Immunology/microbiology Review

Front 1

Arm of the immune system:
Barriers: Anatomic, Physiologic, Phagocytic (monocytes, neutrophils, macrophages), Inflammatory events

Back 1

Innate Immune System

Front 2

Arm of immune system that present intrinsically, nonspecific, no memory, and limited diversity

Back 2

Innate Immune System

Front 3

Arm of the immune system:
Lymphocytes (T & B cells) and plasma cells (end cells of B-lymphocyte differentiation); Antigen Presenting Cells (macrophages, B cells, dendritic cells)

Back 3

Adaptive Immune System

Front 4

Arm of immune system that is inducible, specific, has memory, extensive diversity, self versus non-self distinction, self-limiting

Back 4

Adaptive Immune System

Front 5

antibodies produced by B lymphocytes bind to pathogens and assit w/ phagocytosis

Back 5

Opsonization

Front 6

What activates complement

Back 6

Antibodies produced by plasma cells bind to pathogen and activation copmlement

Front 7

Gram Stain
"Im positively BLUE over you!"

Back 7

Gram-positive = BLUE

Front 8

Gram Stain
"No (negative) RED commies!!"

Back 8

Gram-negative = RED

Front 9

6 Classic Gram (+) bacteria

Back 9

2 cocci, 4 bacilli
(1) Streptococci (strips)
(2) Staphylcocci (clusters)
2 Spore-forming bacilli
(3) Bacillus
(4) Clostridium
2 Bacilli
(5) Corynebacterium
(6) Listeria

Front 10

Only Gram (-) cocci

Back 10

Neisseria
diplococcus (looks like 2 coffee beans kissing)

Front 11

Only spirial shaped Gram (-) organisms

Back 11

Spirochetes: Treponema, Borrelia, Leptospira

Front 12

Bacterial organism that does not have a cell wall

Back 12

Mycoplasma, have a simple cell membrane

Front 13

Gram (+) Organisms with branching filamentous growth

Back 13

Actinomyces (anaerobic)
Nocardia (partially acid-fast)

Front 14

Gram (-) Rods

Back 14

Enterics (E. coli, Shigella, Salmonella, Yersinia, Klebsiella, Proteus, Enterobacter, Serratia, Vibrio, Campylobacter, Helicobacter, Pseudomonas, Bacteroids)
Haemophilus
Bordatella
Legionella
Yersinia
Francisella
Brucella
Pastuerall
Gardenerella

Front 15

Pleomorphic Gram (-) organisms

Back 15

Chlamydia
Rickettsiae

Front 16

Gram (+) and Gram (-) Oligate Aerobes

Back 16

Use glycolysis, TCA cycle, & electron transport chain w/ O2 as final electron acceptor, have catalase, peroxidase, superoxide dismutase
Gram (+): Nocardia, Bacillus cereus
Gram (-): Neisseria, Pseudomonas, Bordetella, Legionalla, Brucella
Acid-Fast: Mycobacterium

Front 17

Gram (+) and Gram (-) Facultative Anaerobes

Back 17

Aerobic, use O2 as an electron acceptor in their electron transfer chain, have catalase & superoxide dismutase, CAN grow in absence of oxygen using fermentation for energy
Gram (+): Staphylcoccus, Bacillus anthracis, Corynebacterium, Listeria, Actinomyces
Gram (-): Most gram (-) rods

Front 18

Gram (+) and Gram (-) Microaerophilic

Back 18

Use fermentation as energy & have no electron transport system, can tolerate low levels of O2 b/c they have superoxide dismutase (no catalase)
Gram (+): Streptococcus (some spp are facultative anaerobes)
Gram (-): Spirochetes (Treponema, Boerrelia, Leptospira), Campylobacter

Front 19

Gram (+) and Gram (-) Oligate Abaerobes

Back 19

Fermentation for energy, no enzymes to break down Oxygen
Gram (+): Clostridium
Gram (-): Bacteroides

Front 20

Chemoheterotrophs

Back 20

all medically important bacteria, use chemical & organic compounds, such as glucose for energy

Front 21

Obligate intracelluar organisms

Back 21

not capable of the metabolic pathways for ATP syn & must steal ATP from their host, they live in their host cell & can't survive w/o a host --> Energy Parasites
Ex: Chlamydia, Rickettsia

Front 22

Facultative intracelluar organisms

Back 22

bacteria that are phagocytosed by host's macphs & neutrophils & survive w/in the WBCs unharmed, they inhibit phagosome-lysosome fusion, thus escaping hydrogen peroxide & superoxide radicals
Ex: Listeria monocytogenes, Slamonella typhi, Yersinia, Francisella turlarensis, Brucella, Legionella, Mycobacterium

Front 23

Endotoxins are only present in Gram (-) bacteria w/ one exception

Back 23

Listeria monocytogenes

Endotoxin is a piece of the outer membrane lipopolysaccharide (LPS), Lipid A

Front 24

Where do all cells from the immune system arise from

Back 24

Pluripotent stem cell

Front 25

What signal to the pluripotent stem cell causes it to differentiate into the Lymphoid stem cell & what will it make

Back 25

IL-7;
Makes NK Cells, B-cells, T-cells
Lymphoid cells (except NK cells) are in the adaptive branch)

Front 26

What signal to the pluripotent stem cell causes it to differentiate into the Myeloid stem cell & what will it make

Back 26

GM-CSF, IL-3
Makes RBCs, Platelets, Basophils, Mast cells, Eosinophils, Neutrophils, Monocytes, Macrophages, & Dendritic Cells
-Myeloid cells are in the innate branch

Front 27

What are the signals for myeloid stem cell to differentiate into Eosinophil progenitor, Megakaryocyte, & Erythroid Progenitor

Back 27

Myeloid Progenitor:
IL-5 --> Eosinophil progenitor: IL-5 --> Eosinophil
Thrombopoietin --> Megakaryocyte --> IL-11 --> Platelets
Erythropoietin --> Erythroid Progenitor --> Erythrocyte

Front 28

What myeloid cell is found in the bloodstrem, kidney bean-shaped nucleus, CD14 (+), is phagocytic & differentiates into tissue macrophages

Back 28

Monocyte

Front 29

What myeloid cell is found in tissues, has a ruffled membrane, cytoplasm w/ vacuoles & vesicles, CD14 (+), performs phagocytosis & secretes cytokines

Back 29

Macrophage

Front 30

What myeloid cell is found in the Epithelia & tissues, has long cytoplasmic arms, functions include antigen capture, transport, & presentation

Back 30

Dendritic Cell

Front 31

What myeloid cell is found in the bloodstrem, has a multi-lobed nucleus & small pink granules, performs phagocytosis & activation of bactericidal mechanisms

Back 31

Neutrophil

Front 32

What myeloid cell is found in the bloodstrem, bilobed nucleus & large pink granules, & acts to kill antibody-coated parasites

Back 32

Eosinophil

Front 33

Lymphoid cell found in the bloodstream, lymph nodes, spleen, submucosa & epithelim, large, dark nucles w/ small rim of cytoplasm

Back 33

B cells, T cells

Front 34

CD19, CD20, CD21 (+) & produces antibody

Back 34

B-cells

Front 35

CD3, CD4 (+), helps regulate immune responses

Back 35

T helper cells

Front 36

CD3, CD8 (+), kill altered or infected cells

Back 36

Cytotoxic T cells

Front 37

Lymphoid cell found in the bloodstream, large cytoplasmic granules, CD16, CD56 (+) & what is it's fcn

Back 37

Natural Killer Lymphocyte: kills tumor/virus cell targets or antibody coated target cells

Front 38

Lymphoid cell found lymph nodes, spleen, mucosal-associated lymphoid tissues, and bone marrow, small dark nucleus, intensely staining golgi apparatus

Back 38

Plasma Cell

Front 39

End cell of B-cell differentiationm produce antibody

Back 39

Plasma Cell

Front 40

Myeloid cell found in the bloodstream, has a bilobed nucleus w/ large blue granules, it is nonphagocytic & releases pharmacologically active substances during allergic responses

Back 40

Basophil

Front 41

Myeloid cell found in tissues, mucosa, & epithelia, has a small nucleus & cytoplasm is packed with large blue granules, releases granules containing histamine, etc. during allergic responses

Back 41

Mast Cell

Front 42

When is a mature B lymphocyte classified as a Naive B-cell

Back 42

when it has not yet come in contact with antigen

Front 43

What are the naive B-cell antigen receptors

Back 43

IgM and IgD

Front 44

What are the naive T-cell antigen receptors

Back 44

T-cell receptor (TCR) made of alpha and beta chains

Front 45

What makes up the antigen receptor of the B lymphocyte

Back 45

Membrane-bound Immunoglobulin, has a 4-chain glycoprotein molecule that serves as the basic monomeric unit for each of the distinct Ab molecules, has two identical halves, each componsed of a long, Heavy chain (mu for IgM, delta for IgD) & a shorter, light chain (kappa or lambda), a "hinge" region joins the heavy chains

Front 46

What does the variable region on the N-terminus of heavy and light chains determine

Back 46

Idiotype = antigen specificity

Front 47

What does the constant region on the C-terminus of heavy and light chains determine

Back 47

Isotype = class of Ig which determines what you are going to do w/ the Ag bound in terms of function and biological effects

Front 48

What lymphocyte cells recognize unprocessed antigens & which cell recognizes cell-bound peptides

Back 48

B-Cell: unprocessed antigens
T-Cell: cell-bound peptides

Front 49

What is the B-cell signal transduction complex composed of

Back 49

Heterodimer of Ig-alpha & Ig-beta on each side of the receptor, and CD19 & CD21 co-receptors (lower threshold of Ags)

Front 50

What is the T-cell signal transduction complex composed of

Back 50

multichain structure called CD3

Front 51

Membrane Marker for B-cells

Back 51

CD19, CD20, CD21

Front 52

membran marker for T-cells (T helper & cytotoxic T cells)

Back 52

CD3

Front 53

How are heavy chain variable domains of antigen receptors produced

Back 53

B-lymphocyte progenitors select randomly & in the absence of stimulating antigen to recombine 3 gene segments, designated variable (V), diversity (D), & joining (J) to produce unique sequences of amino acids in the variable domains (VDJ recombination)

Front 54

How are light chain variable domains of antigen receptors produced

Back 54

B-lymphocyte progenitor preforms random rearrangement of two types of gene segments (V & J) to encode the variable dome of LC
-mRNA molecules are created which joins this variable domain sequence to mu or delta constant domains

Front 55

What is the fcn of terminal deoxyribonucleotidyl transferase (Tdt)

Back 55

while HC segments are undergoing recombination, this enzyme randomly inserts bases (w/o a template on the complementary strand) at the jcns of V, D, & J segments)
-not active during light chain rearrangement

Front 56

What is N-nucleotide addition

Back 56

When Terminal deoxyribonucleotidyl transferase (Tdt) enzyme randomly inserts bases (w/o a template on the complementary strand) at the jcns of V, D, & J segments)

Front 57

How many chances does a cell have to produce a functional heavy (or beta) chain

Back 57

Two
(1) VJD rearrangments
(2) rearranging gene segments of the homologous chromosome
-if it fails to make a functional protein from the rearrangement of segments on either chrom the cell undergoes apoptosis

Front 58

Allelic Exclusion

Back 58

Once a functional product has been acheived by one of these rearrangements the cell shuts off the rearrangement and expression of the other allele on the homologous chromosome
--> process ensures that B & T lymphocytes synthesize only one specific antigen-receptor per cell

Front 59

What is used as a marker for early stage T- & B- cell development in Acute Lymphoblastic Leukemia

Back 59

Tdt

Front 60

What is the first set of constant domains for the heavy chain of Ig that is transcribed

Back 60

IgM, then IgD

Front 61

Omenn Syndrome (clinical outcome of failed gene rearrangment)

Back 61

AR, missense mutation in rag genes, causing rag enzymes to only have partial activity
-Lack of B cells (below limits of detection)
-Marked decrease in T cells
-Characterized by early onset, failure to thrive, red rash (generalized), diarrhea, & severe immune deficiency

Front 62

Severe Combined Immunodeficiency (SCID), (clinical outcome of failed gene rearrangment)

Back 62

AR, Nill mutations in rag1 or rag2 genes, no rag enzyme activity
-Total lack of B and T cells
-Total defects in humoral & cell-mediated immunity

Front 63

What and where are the primary lymphoid organs

Back 63

Sites of lymphoid-cell development (lymphopoieisis)
-Bone Marrow
-Thymus

Front 64

What and where are the seconary lymphoid organs

Back 64

Sites of antigen exposure
-Spleen
-Lymph nodes
-Mucosal-associated lymphoid tissues

Front 65

What do cells whose idiotype has too great an affinity for normal cellular molecules undergo in the bone marrow and the peripherhy

Back 65

Bone marrow: Clonal Deltion
Peripherhy: Clonal Anergy

Front 66

What T-cells are allowed to leave the bone marrow

Back 66

T-cells that are selectively unresponsive to self-antigens (tolerant)

Front 67

What does the outer cortex & Inner medulla of the thymus contain

Back 67

Outer cortex: packed with immature T-cells
Inner medulla: where T-cells pass into as they mature
-both are laced w/ a network of epithelial cells, dendritic cells, & macphages, which interact physically with the developing thymocytes

Front 68

Where are MHC antigens expressed & what are their gene products

Back 68

Expressed at high density on the surface of cells of the thymic stroma
Class I: HLA-A, -B, -C
Class II: HLA-DP, -DQ, -DR

Front 69

alpha chain plus beta-2 microglobulin, codominantly expressed, expressed on all nucleated cells of the body, CD8 cells
What Antigen Class?

Back 69

MHC-Class I

Front 70

Alpha and Beta chains, expressed codominantly, present on APC's, CD4 cells
What Antigen Class?

Back 70

MHC-Class II

Front 71

Positive Selection

Back 71

TCRs capable of binding with low affinity; cells with "good" receptors

Front 72

Failure of Positive Selection

Back 72

those that fail to recognize self-MHC at all; cells with "useless" receptors

Front 73

Negative Selection

Back 73

those that bind to strongly to self MHC molecules will be induced to undergo apoptosis; cells with "bad" receptors

Front 74

"helper" T cells (TH)

Back 74

CD4+ cells that recognize class II MHC

Front 75

Cytotoxic T cells (CTLs)

Back 75

CD8+ cells that recognize class I MHC

Front 76

What secondary lymphoid organ is designed to initate immune responses to tissue-borne antigens

Back 76

Lymph nodes (small nodular aggregates found along lymphatic channels of body)
-filters tissue fluid
-Outer cortex Follicles = B-cell areas
-Paracortex = T-cell area
-Inner Medulla = Macrophages

Front 77

What secondary lymphoid organ is designed to initate immune responses to blood-borne antigens

Back 77

Spleen (filters blood)

Front 78

What is the pathway of lymphatic circulation

Back 78

Each LN is surrounded by a fibrous capsule punctured by an afferent lymphatic --> bring lymph into subcapsular sinus --> fluid percolates thru outter cortex (B-cell area) --> paracortex (T-cell area) --> inner medulla (macph) --> medullary sinus --> efferent lymphatic (memory cells exit) --> thoracic duct --> vena cava --> circulate

Front 79

What is the pathway of circulation through the spleen

Back 79

Splenic artery --> Arterioles surrounded by Periarteriolar lymphoid sheath, PALS (T-cell areas), Lymphoid follicles surrounded by rim of lymphocytes & macph attached nearby (B-cell areas) --> vascular sinusoids (Red pulp) --> splenic vein --> Portal circ

Front 80

How to lymphocytes leave the bloodstream to enter lymph nodes?

Back 80

High endothelial venules (HEVs)
-L-selectins on lymphocytes bind to addressins on the HEV, & chemokine receptors mediate the homing of specific cells to specific areas
-Naive T cells home to LN paracortex or splenic PALS
-Naive B cells migrate into LN follicles, & in spleen create a corona outisde the T-cell area

Front 81

For a molelcule to be an immunogen/antigen, what 3 basic critera must it meet

Back 81

-It must be recognized as foreign
-Must have a certain degree of chemical complexity
-Must have a molecular weight of at least 5,000 to 10,000 Kd

Front 82

Portion of the Antigen that has 3-D complementarity with the idotype of a B-cell receptor or a TCR

Back 82

Epitope/Antigenic Determinent of the Antigen

Front 83

What is a Haptan

Back 83

Single Antigenic Determinants
-they are to small to be recognized by the immune system to elicit an immune response
-however, they can become conjugated to body proteins (the carrier, i.e. RBCs) & the hapten-carrier conjugate serves as the immunogen for the ensuing allergic response

Front 84

What is the first response to invasion

Back 84

Acute Inflammatory Response, represents the response of the innate immune system
-First step is to activate the vascular endothemium in the breached epithelium barrier
-Cytokines & other inflam mediators are released to induce expression of selectin-type adhesion molecules

Front 85

What is the first to bind to inflamed endothelium in acute inflammatory response

Back 85

Neutrophils, they peak at about 6 hours
-Monocytes, macphs, & even eosinophils may arrive 5-6 hours later in response to neutrophil-released mediators

Front 86

What are 4 sequential steps required for Extravasation of Phagocytes

Back 86

(1) Rolling: Phagocytes (mucin-like adhesion mol) attach loosely to E-selectin on endothelium (force of bf in area causes cell to detach & reattach repeatedly --> rolling)
(2) Activatipn by Chemoattractants: Chemokines (i.e. IL-8, C5a, N-formyl peptides) bind R on phagocyte surface & trigger G-protein mediated activating signal --> induce confirmational change in integrins on phagocyte to inc affinity for Ig adhesion molecules on endothelium
(3) Arrest & Adhesion: Interaction b/w Integrins & Ig-CAMS mediates tight binding
(4) Transendothelial Migration: phagocyte extends pseudopodia thru vessel wall & extravasates into tissues & exhibit chemotaxis

Front 87

Leukocyte Adhesion Deficiency

Back 87

rare AR w/ absence of CD18 (common Beta-2 chain of integrin molecules)
-an inability of their leukocytes to undergo adhesion-dependent migration into sites of inflam
-1st Indication: Omphalitis (swelling & reddening around stalk of umbilical cord)
-suffer recurrent, chronic bacterial infections, have abnormally high # of granulocytes in their circ (cant migrate --> abscess & pus formation dont occur)

Front 88

Method of Diagonising Leukocyte Adhesion Deficiency

Back 88

Evaluating expression (or lack) of the beta chain (CD18) of the integrin by flow cytometry

Front 89

Substances that are chemoattractive to neutrophils

Back 89

IL-8, complement split product C5a, Leukotriene B4, Formyl methionyl peptides

Front 90

Process of Phagocytosis involves

Back 90

(1) Extension of pseudopodia to engulf attached material
(2) Fusion of pseudopodia to trap the material in a phagosome
(3) Fusion of phagosome w/ a lysosome to create a phagolysosome
(4) Digestion
(5) Exocytosis of digested contents

Front 91

Opsonization is enhancement of phagocytosis with

Back 91

Opsonins:
-IgG
-C3b

Front 92

How Staphylococcus aureus impede opsonization

Back 92

Protein A of S. aureus impededs opsonization by binding to Fc component of IgG

Front 93

What is respiratory burst

Back 93

During phagocytosis, this metabolic process activates a membrane bound oxidase that generates oxygen metabolites which are toxic to ingested microorganisms

Front 94

What reduces oxygen to superoxide anion, which generates hydroxyl radicals and hydrogen peroxide, which are microbicidal

Back 94

NADPH oxidase

Front 95

What is in the lysosome that acts on hydrogen peroxide & chloride ions to produce hypochlorite (active ingredient in household bleach), which is microbicidal

Back 95

Myeloperoxidase

Front 96

What are the lysosomal contents of phagocytes that contain oxygen-independent degradative materials

Back 96

-Lysozyme (digests bacterial cell walls by cleaving peptidoglycan)
-Defensins (circular peptides that form channels in bacterial cell membranes)
-Lactogerrin (chelates iron)
-Hydrolytic enzymes

Front 97

Intracellular Killing Mechanisms include:

Back 97

Oxygen-Dependent Killing:
-Toxic Oxygen Metabolites (NADPH oxidase)
-Toxic Halide Radicals (Myeloperoxidase)
Oxygen-Independent Killing
-Lysosomal Contents
-->Lysozyme
-->Defensins
-->Lactogerrin
-->Hydrolytic enzymes

Front 98

Inherited deficiency in the production of one of several subunits of NADPH oxidase that eliminates the phagocyte's ability to produce many critical O2-dependent intracellular metabolites

Back 98

Chronic Granulomatous Disease: sufferent from chronic, recurrent infections w/ catalase (+) organisms (Staph, Klebsiella, Serratia, Aspergillus)

-Myeloperoxidase & Lysosomal content killing mech remain intact & they can fight over catalase (-) organisms

Front 99

Nitroblue tetrazolium (NBT) reduction test or Neutrophil oxidative index can be used for what

Back 99

Failures of phagocytic cells to generate oxygen radicals
--> used in Chronic Granulomatous Disease

Front 100

4 bacteria that produce exotoxins that increase levels of cAMP (cAMP mnemonic)

Back 100

c = cholera (Vibrio cholera)
A = anthrax (Bacillus anthracis)
M = Monteczuma's revenge (popular name for enterotoxigenic E. coli)
P = Pertussis (Bordetella pertussis)

Front 101

How is the MHC I molecule loaded with peptides

Back 101

Endogenous Pathway (i.e. Obligate IC pathogens, viral proteins)
-Proteins synthesized in cytosol are degraded in proteasomes into peptides
-Peptides are transported thru a peptide transporter, TAP complex into ER
-Bind to freshly syn MHC class I proteins
-Exocytosed & Transported to cell memb & presented to CD8+

Front 102

How is the MHC II molecule loaded with peptides

Back 102

Exogenous Pathway (i.e. EC
pathogens, Bacteria)
-Taken up into cell by APC's (small bacterial peptides w/in a vesicle)
-MHC II in ER are plugged w/ invarient chain, leave ER through exocytosis
-MHC II & nacterial vesicle fuse --> phagolysosome
-Dec acidity & component of phagolysosome cause invarient chain to degrade & opens up peptide binding groove
-Peptides in the vesicle are then loaded into the MHC II groove
-transported to cell surface of APC to be presented CD4+

Front 103

What is the invarient chain

Back 103

it is located on MHC class II molecules, blocks the peptide-binding groove so no normal cellular peptides can accidently be attracted there

-macph has both class I and class II binding sites since it is nucleated & an APC

Front 104

What 3 signals are needed for T-cell activation

Back 104

(1) Binding of TCR to MHC II/peptide commplex
(2) Costimulatory Molecules
-CD4 binds MHC II
-CD8 binds MHC I
-LFA-1 binds ICAM-1
-CD2 binds LFA-3
-CD28 binds B7
(3) Cytokines
-IL-2, IL-1, IL-6, TNF-alpha

Front 105

How do CD4 & CD8 act as costimulatory molecules

Back 105

the coreceptors for MHC classes II and I), tranduces activating signals to the T cells

Front 106

How do Integrins on T-cells (LFA-1) & IgCAMs on APCs (ICAM-1) act as costimulatory molecules

Back 106

they increase cell-cell adherence, so the cytokines can go back and forth

-also done by IgCAMs on T cells (CD2) binding to Integrins (LFA-3) on APCs

Front 107

What triggers the upregulation of B7

Back 107

Pathogen binding to innate receptors (e.g. TLR molecules) along w/ antigen recognition

Front 108

What does CD28 on T cells binding to B7 on APC trigger

Back 108

the transcription of several cytokines

Front 109

What is the most important growth factor for T cells, that stimulates the proliferation of clones of T cells specific to that antigen

Back 109

IL-2
-the proliferation of naive T cells in response to antigen recognition is mediated by an autocrine growth pathway, the responding T cell secretes its own growth-promoting cytokine, IL-2, & also expresses the receptor molecules for it

Front 110

What are the effector mechanisms controlled by Th cells

Back 110

-Antibody synthesis (Th2)
-Macrophage Activation (Th1)
-Cytotoxic T-cell kills (Th1)
-NK cell killing

Front 111

What cytokine causes macrophages to become activated

Back 111

IFN-gamma

Front 112

What are superantigens

Back 112

Viral or bacterial proteins that cross-link the variable Beta domain of a TCR to an alpha chain of MHC II
-Cross-linkage provides an activating signal that induces T-cell activation & proliferation in absence of Ag-specific recognition of peptides in MHC II groove

Ex: Staphylococcal enterotoxins, Toxic-Shock Syndrome Toxin-1 (TSST-1), Streptococcal pyrogenic exotoxins

Front 113

Where do superantigens bind on the TCR/MHC II complex and what are the consequences of this

Back 113

They bind outside the Ag-binding cleft, they activate any clones of T cells expressing a particular variable Beta sequence & thus cause polyclonal activation of T cells resulting in overproduction of IFN-gamma
--> IFN-gamma activates macphs --> overexpression of proinflam cytokines (IL-1, IL-6, TNF-alapha) --> systemtic toxicity

Front 114

What are the 2 major & 2 minor classes of Th cells that can arise from the naive T lymphocyte (Th0)

Back 114

Th2: promote humoral immunity
Th1: promote CMI
Treg: regulate T cell activity
Th17: tissue damage assoc w/ autoimmune disease

Front 115

What stimulates the differentiation of Th0 into Th1 cells

Back 115

By microbes that stimulate a strong initial innate immune response w/ resultant production of IL-2, IFN-gamma, & TNF-beta

Caused by Intracellular Pathogens, Bacteria (i.e. Listeria, mycobacteria), & some parasites (i.e. Leishmania)

Front 116

What stimulates the differentiation of Th0 into Th2 cells

Back 116

Absence of innate immune stimuli, caused by Extracellular pathogens (i.e. Bacteria, helminths, response to allergens)
-promote humoral immunity, help make Abs, & help w/ class switching
-produced IL-4, IL-5, IL-6, IL-10, IL-13, TGF-beta

Front 117

What is the role of IL-4, IL-5, and IL-10 in the Th2 response to Extracellular Pathogens

Back 117

IL-4: Promotes class-switching to IgG & IgE, inhibits Th1 pathway to prevent differentiation to cause activated macphs
IL-5: promotes class-switching to IgA
IL-10: inhibits Th1 pathway to prevent differentiation to cause activated macphs

Front 118

What is the role of IL-2 & IFN-gamma in the Th1 response to Intracellular Pathogens

Back 118

IL-2: required for CTL to become cytotoxic
IFN-gamma: Activate macrophages & shuts down Ab response from Th2

Front 119

What is the role of Treg cells produced from differentiation of Th0 cells

Back 119

Regulate (inhibit) T cell fcn
-ID'd by constitutive expression of CD25 on surface & expression of TF FoxP3
-secrete inflammaiton inhibiting cytokines, IL-10, & are ciritical for the prevention of autoimmunity

Front 120

What is the role of TH17 cells produced from differentiation of Th0 cells

Back 120

believed to play a role in the tissue damage assoc w/ some autoimmune diseases
-ID'd by expression of TH RORgammat & production of pro-inflam cytokine IL-17

Front 121

What type of leprosy has a strong Th1 response which is capable of eradicating the intracellular pathogens by granuloma formation

Back 121

Tuberculoid Leprosy
-there is some damage to skin & peripheral nerves, but disease progresses slowly, if at all, & the pt survives

Front 122

What type of leprosy has a strong Th2 response

Back 122

Lepromatous Leprosy
-Th2 response is turned on, & because of reciprocal inhibition, the cell-mediated response is depressed
-pts develop Abs to the pathogen that are not protective & mycobacteria multiply inside macphs
-few macular lesions w/ multiple nodular lesions from bacterial overgrowth in tissues causing loss of sensation
-Hypergammaglobulinemia may occurs

Front 123

What mediates humoral immunity

Back 123

Antibodies syn by B lymphocytes & secreted by their fully differentiated end cell, the plasma cell
-directed toward the defense against EC microbes or toxins

Front 124

What is needed for B-cell contact w/ Th cells (B lymphocyte activation)

Back 124

-MHC II/peptide presentation
-Costimulatory Molecules (B7 is upregulated on the B lymphocytem making them effective presenters of Ag to Th cells in the area --> form a conjugate --> Th cell is activated & induced to a Th2 cell)
-CD40/CD40L binding (CD40L on surface of Th2 cell is upregulated & it interacts w/ CD40 on B cells)

Front 125

What are the 3 signals needed for B cell activation

Back 125

(1) MHC II/peptide presentation (Ag entering 2' lymphoid organs binds to & cross-links the idiotypes of these memb-R)
(2) CD40/CD40L binding (CD40L on surface of Th2 cell is upregulated & it interacts w/ CD40 on B cells)
(3) Release of Th2 cytokines

Front 126

Th2 cytokines induce B-cell

Back 126

-Differentiation into Ab secreting cells
-Memory cells
-Class Switching

Front 127

Thymus Independent Antigens

Back 127

-Contain no peptides (can't be recognized by T-cells)
--> i.e. Lipopolysaccharide from cell envelop of Gram (-) bacteria & polycapsular antigens
-Stimulate only IgM
-Create no memory
--> Response is generally weaker than the response to other classes of antigen

Front 128

What are B-cell mitogens

Back 128

Directly cause mitosis regardless of the cell's antigenic specificity
-Mitogens activate many clones of B cells & are used clinically to assess lymphocyte fcn

Front 129

What is isotype switching

Back 129

The progression of new antibody isotypes produced by B cells is defined by the sequence of constant domain coding in the B-lymphocute DNA & each isotype immunoglobulin is designed w/ a different effector fcn in mind (dictate effector fcn of Ab molecule)
-directed by Th2 cells

Front 130

What occurs if an Ab molecule is digested with Papain

Back 130

Cleavage occurs above the disulfide bonds that hold the heavy chains together
-generates 3 seperate fragments
--> 2 are called Fab (Fragment Antigen Binding), monovalent & capable of binding
--> 1 is Fc (Fragment Cystallizable)

Front 131

What occurs if an Ab molecule is digested with Pepsin

Back 131

Generates 1 large fragment called F(ab')2 & a digested Fc fragmet
--> F(ab')2 is divalent & is capable of binding & bridging

Front 132

What is the bridging of Ags by Ab molecules required for

Back 132

-Agglutinatinon of particulate antigens (RBCs and latex beads) or
-The precipitation of soluble antigens

--> IgG and F(ab')2 fragments both have a valence of 2 and can bridge b/w antigens

Front 133

What is the first immunoglobulin that can be produced by a B cell w/ or w/o T-cell help & why

Back 133

IgM
Coding for the constant domains of the heavy chain IgM (mu chains) are the 1st sequences downstream from the coding for the idiotype of the molecule

Front 134

How does IgM exist on the surface of a B cell vs IgM secreted by plasma cells

Back 134

Surface: Monomer
Secreted: Pentamer, help together in an extremely compact form by a J chain

Front 135

Ig that has a plasma valence of 10, fcns in trapping of free antigen, and has the highest avidity of all Ig's

Back 135

IgM

Front 136

What Ig has the highest affinity

Back 136

IgG

-interaction b/w the variable regions (Fab region) and the Antigen

Front 137

What Ig is the most efficient at activating complement, is not an opsonin, and does not mediate ADCC

Back 137

IgM

Front 138

What is used as a measure of primary response (acute infection)

Back 138

IgM

Front 139

What will convalescent serum consist of

Back 139

Mostly IgG's w/ subthreshold levels of IgM

Front 140

What is needed for class-switching to take place

Back 140

T-cell
CD40L
Cytokines

Front 141

When and where does class-switching occur

Back 141

Occurs during the immune response & occurs in the germinal centers (only formed during an immune response)

Front 142

How is isotype-switching induced

Back 142

B lymphocyte receives cytokine signals from the activated Th2 cells in the secondary lymphoid organs

Front 143

What is isotype switching & how does it occur

Back 143

It is the changing of the Hc constant domains to classes of Ab w/ new & different effector fcns
-by rearranging the DNA encoding the constant regions of Hc by activating switch regions that cause the intervening DNA to be looped out, excised, & degraded
-idiotype is then joined to a new constant region domain coding, & an Ab w/ identical Ag specificity but a new effector fcn is produced

Front 144

What are the clones of proliferating antigen-specific B cells

Back 144

Germinal centers in the follicles of the lymph nodes & spleen

Front 145

What is it called when during intense proliferative response of the B cell, randome mutations in the coding of variable domain region may occur which can create a single point mutation in the Ab idiotype

Back 145

Somatic Hypermutation

Front 146

Clonal Selection

Back 146

overtime clones of cells w/ high receptor affinity will begin to predominate in the germinal center and causes affinity maturation

Front 147

Affinity Maturation

Back 147

Predominance of clonses capable of producing Ab's w/ increasing affinity for the antigen
--> Although isotype switching will necessarily dec the avidity of the preponderance of Ab molecules as the immune response evolves, it will be substituded by an inc in Ab affinity over time

Front 148

X-linked Hyper-IgM Syndrome

Back 148

Characterized by deficiency of IgG, IgA, & IgE, and elevated levels of IgM
-Peripheral blood of infected pts has high #'s of IgM-secreting plasma cells, as well as autoantibodies to neutrophils, platelets, & RBCs
-they fail to make germinal centers during a humoral immune response
-defect is in gene encoding CD40L --> no CD40L expressed on Th cells --> o costimulatory signal for B-cell response to T-dependent Ags & only IgM is produced

Front 149

Children with what condition suffer recurrent respiratory infections, esp those caused by Pneumocystis jiroveci

Back 149

X-linked Hyper-IgM Syndrome

Front 150

Major Ab produced after IgM, exists in 4 subisotypes, activates complement, opsonizes, & mediates ADCC, & actively transported across the placenta

Back 150

IgG

Front 151

Most is produced in the submucosa, dimer w/ a J chain, inhibits binding of adhesive substances to mucosal surfaces, important component of breast milk

Back 151

IgA

Front 152

What cytokines cause isotype switching to IgA

Back 152

IL-5 & TGF-beta

Front 153

What contains Th2 cells that assists in IgA production

Back 153

MALT (mucosal-associated lymphoid tissues)
-the homing of specific memory cells to epithelial & mucosal surfaces leads to the production of these specialized lymphoid aggregations along these barriers

Front 154

Where is MALT located

Back 154

Tonsils, Peyer's patches, & numerous less well-organized lymphoid accumulations in the Lamina Propria

Front 155

What receptor does IgA bind to so it is able to get into the submucosa

Back 155

Poly Ig Receptor on the basolateral side of the epithelium
-it binds specifically to the J chain & transports the dimer across the cell & dumps it out into the mucosa

Front 156

Secretory Component Function

Back 156

When IgA is released into the mucosa, it steals the Poly Ig Receptor & that becomes the secretory component
Functions:
-Transepithelial Transport
-Protection from proteolytic cleavage

Front 157

What cytokines cause isotype switching to IgE

Back 157

IL-4 and IL-13

Front 158

Ig that is the so-called homocytotrophic Ab b/c it binds directly to FcSigma receptors present on mast cells & basophils (w/o binding Ag)

Back 158

IgE

Front 159

Mediates immediate type I allergic reactions & protects against parasites

Back 159

IgE

Front 160

What is the Ig that match the heavy chains
Mu
Gamma
Alpha
Delta
Sigma

Back 160

Mu: IgM
Gamma: IgG
Alpha: IgA
Delta: IgD
Sigma: IgE

Front 161

Order of abundance of serum IgG

Back 161

IgG (650-1,500) > IgA (75-390) > IgM (40-345) > IgD & IgE (trace)

Front 162

Complement activation of classic pathway Ig

Back 162

IgM, IgG

Front 163

Opsonization Ig

Back 163

IgG

Front 164

Antibody-dependent cell-mediated cytotoxicity (ADCC)

Back 164

IgG

Front 165

Placental Transport Ig

Back 165

IgG

Front 166

Naive B-cell Antigen receptor

Back 166

IgM, IgD

Front 167

Memory B-cell antigen receptor (only one can be present)

Back 167

IgG, IgA, IgE

Front 168

Triggers mast cell granule release

Back 168

IgE

Front 169

In what type of deficiency do patients usually present w/ recurrent pyogenic infections w/ extracellular pathogens, absence of Ig's for opsonization & have a major problem w/ complement activation

Back 169

Immunodeficiencies involving B Lymphocytes
-The T-cell Immune System is intact, & T-cell activies against IC pathogens, delayed-type hypersensitivity & tumor rejection are normal

Front 170

Has two pathways of activation, enhances inflammation, enhances phagocytosis, & causes lysis

Back 170

The Complement System

Front 171

Anaphylatoxins

Back 171

C3a, C4a, C5a
-C3a & C5a can bind directly to mast cells & basophils causing degranulation & release of Histamine

Front 172

Main chemotactic complement protein

Back 172

C5a

Front 173

Main complement protein opsonin & Ab opsonin

Back 173

C3b and IgG

Front 174

What complement protein is responsible for clearance of immune complexes

Back 174

C3b

Front 175

How is the Alternative Complement Pathway initiated

Back 175

By simple attraction of the early factors to the surface of microbes
-Bacterial polysaccharides & LPS of the cell envelope of Gram (-) bacteria

Front 176

How is the Classical Complement Pathway initiated

Back 176

Activated by Antigen-Antibody complexes
-Both IgG & IgM, but IgM is most efficient

Front 177

Physiologic control on classical complement activation at the level of

Back 177

C1, C3, & C5

Front 178

Physiologic control on alternative complement activation at the level of

Back 178

C3, C5

Front 179

Deficiencies in membrane attack complex results in recurrent infections of

Back 179

Neisseria

Front 180

Uncontrolled complement activation at the mucosa surfaces cause edema & pain

Back 180

Hereditary angioedema, deficiency of complement regulatory components

Front 181

The absence of regulatory proteins causes paroxysms of hemolysis of RBCs and the resultant hemoglobinuria

Back 181

Paroxysmal Nocturnal Hemoglobinuria, deficiency of complement regulatory components

Front 182

What removed activated T cells after the Primary Immune Response

Back 182

Activation-Induced Cell Death (AICD)

Front 183

What type of B Lymphocytes have the highest affinity of Ig

Back 183

Memory Lymphocytes: Highest affinity
Activated/Effector Lymphocytes: Increasing affinity
Naïve Lymphocytes: Low affinity

Front 184

What type of T Lymphocytes have the highest amount of IL-2 Receptor Expressed

Back 184

Activated/Effector Lymphocytes have the highest amount
Naïve & Memory Lymphocytes have the lowest amounts

Front 185

Where do Memory Lymphocytes tend to home too

Back 185

Home in a tissue-specific fashion, presumably returning to the type of tissue in which they first encountered Antigen

Front 186

Where do Activated/Effector Lymphocytes tend to home too

Back 186

Areas of active inflammation b/c of their expression of cell adhesion molecules such as LFA-1

Front 187

Where do Naïve Lymphocytes tend to home too

Back 187

Regions of secondary lymphoid organs specific for their cell type

Ex: T cells to paracortical areas

Front 188

What mediates Activation-Induced Cell Death (AICD)

Back 188

Mediated thru the Fas pathway
-Trimerization of the Fas molecule expressed on the surface of activated T cells w/ the Fas ligand molecule on neighboring cells initiates a signal-transduction cascade that leads to apoptosis of the Fas-bearing cell

Front 189

As pathogens are eliminated by effector mechanisms & the system is slowly returning to its baseline quiescent state what is generated?

Back 189

Immunologic memory, important b/c:
-avoids expending E on the generation of cells & molecules no longer needed & that may be potentially harmful in absence of invading stimulus
-“resets” the baseline homeostatic function of immunologic organs

Front 190

How is B cell activity stopped after the Primary Immune Response

Back 190

B lymphocyte differentiation into plasma cells is antigen-dependent, & as Ag disappears, the stimulus for differentiation is removed. Plasma cells only live 2 weeks & when they die they are not replaced from the differentiation B-cell pool, the response wanes

Front 191

How do Memory B lymphocytes differ from Naïve B Lymphocytes

Back 191

They have undergone isotype switching, & will have surface IgG, IgA, or IgE isotype & enter a resting stage of the cell cycle

Front 192

What is the time lag after immunization & the peak response for a Primary Response vs a Secondary Response

Back 192

Primary Response: 5-10 days, small peak
Secondary Response: 1-3 days, large peak

Front 193

What is the passive means of Natural Immunity

Back 193

Placental IgG transport, colostrum

Front 194

What is the goal of passive immunization

Back 194

Elicitation of protective immunity and immunologic memory

Front 195

What is the goal of passive immunization

Back 195

Transient protection or alleviation of existing condition

Front 196

What is the immunization protocol for a Primary Response vs a Secondary Response

Back 196

Primary Response: high dose of antigen (often w/ adjuvant)
Secondary Response: low dose of antigen (often w/o adjuvant)

Front 197

What is the inducing agent for a Primary Response vs a Secondary Response

Back 197

Primary Response: All immunogens
Secondary Response: Protein Antigens

Front 198

What is the Antibody Isotype & Antibody Affinity for a Primary Response vs a Secondary Response

Back 198

Primary Response: IgM, then IgG, variable to low antibody affinity
Secondary Response: Increasing IgG, IgA, or IgE, high Ab affinity (affinity maturation)

Front 199

What is the morphology of Naïve Lymphocytes, Activated/Effector Lymphocytes, Memory Lymphocytes

Back 199

Naïve Lymphocytes: Small, little cytoplasm
Activated/Effector Lymphocytes: Large, more cytoplasm
Memory Lymphocytes: Small

Front 200

What is the active means of Natural Immunity

Back 200

Recovery from infection

Front 201

What is the passive means of Artificial Immunity

Back 201

Horse antivenin against black widow spider bite, snake bite
Horse antitoxin against botulism, diphtheria
Pooled human immune globulin versus hepatitis A & B, measles, rabies, varicella zoster, or tetanus
“Humanized” monoclonal antibodies versus RSV

Front 202

Recommended age for Diphtheria, Tetanus, Pertussis vaccine, DTaP

Back 202

15-18 months, 4-6 years

Front 203

Recommended age for Varicella vaccine, Varicella series

Back 203

Varicella: 12-15 months, 4-6 years
Varicella Series: 7-18 years

Front 204

Recommended age for Measles, Mumps, Rubella vaccine, MMR, MMR series

Back 204

MMR: 12-15 months, 4-6 years
MMR series: 7-18 years

Front 205

Recommended age for Influenza vaccine

Back 205

6 months on, yearly

Front 206

Recommended age for Inactivated polio vaccine, IPV, IPV series

Back 206

IPV: 6-18 months, 4-6 years
IPV series: 7-18 years

Front 207

Recommended age for Pneumococcal vaccine, PCV

Back 207

12-15 months, 2-6 years at high-risk

Front 208

Recommended age for Haemophilus influenza type B, Hib

Back 208

12-15 months

Front 209

What is the active means of Artificial Immunity

Back 209

Hepatitis B component vaccine
Diphtheria, tetanus, pertussis toxoid vaccine
Haemophilus capsular vaccine
Polio live or inactivated vaccine
Measles, mumps, rubella attenuated vaccine
Varicella attenuated vaccine

Front 210

Recommended age for Hepatitis B vaccine, HepB, HepB series

Back 210

Hep B: 1-2 months, 6-18 months
HepB Series: 7-18 years

Front 211

What are the risks associated with passive immunotherapy

Back 211

From induction of antibodies from other species:
-IgE production (can cause systemic anaphylaxis)
-Type III Hypersensitivity (generate IgG or IgM anti-isotype Ab’s which form complement-activating immune complexes
From induction of antibodies from humans:
-Anti-allotype Antibodies (elicit response against minor Ig polymorphisms, allotypes)

Front 212

What is the vaccine & vaccine type for B. pertussis

Back 212

DTP, DTaP, Toxoid plus filamentous hemagglutinin

Front 213

What viral vaccines can cause infections in immunocompromised host

Back 213

Attenuated (Live): sometimes
Killed: no
Component: no

Front 214

What viral vaccines can revert to a pathogenic form

Back 214

Attenuated (Live): possibly
Killed: no
Component: no

Front 215

What is the vaccine & vaccine type for N. meningitidis

Back 215

MCV, 4 capsular serotypes (Y, W-135, C, A)

Front 216

What is the vaccine & vaccine type for S. pneumoniae

Back 216

Pediatric: PCV, 7 capsular serotypes & protein
Adult: PPV, 23 capsular serotypes

Front 217

What is the vaccine & vaccine type for H. influenzae

Back 217

Hib, Capsular polysaccharide and protein

Front 218

What is the vaccine & vaccine type for C. tetani

Back 218

DTP, toxoid

Front 219

Recommended age for Hepatitis A vaccine, HepA & HepA series

Back 219

HepA (2 doses) 12-23 months
HepA series 2-18 years

Front 220

What is the vaccine & vaccine type for C. diphtheriae

Back 220

DTP, toxoid

Front 221

Recommended age for Meningococcal vaccine

Back 221

2-18 years (high risk 2-10 years)

Front 222

What viral vaccines have potential for contamination with other viruses

Back 222

Attenuated (Live): yes, high
Killed: reduced
Component: no

Front 223

Why are live attenuated viruses only given after 12 months of age?

Back 223

Residual maternal antibodies would inhibit replication & the vaccine would fail

Front 224

What vaccines are contraindicated in pt’s with egg allergies

Back 224

Influenza
MMR
Yellow Fever

Front 225

What vaccines are contraindicated in pregnancy

Back 225

Rubella (MMR)

Front 226

What are the component vaccines of active immunization

Back 226

Hepatitis B
HPV

Front 227

What are the live viral vaccines of active immunization

Back 227

Mrr. V.Z. Mapsy
-Mumps
-Rotavirus
-Rubella
-Varicella Zoster
-Measles
-Adenovirus (pathogenic [not attenuated] respiratory strains given in enteric coated capsule
-Polio (Sabin)
-Small Pox
-Yellow Fever
(all by adenovirus is attenuated)

Front 228

What are the killed viral vaccines of active immunization

Back 228

RIP-A (Rest In Peace Always – the killed viral vaccines)
-Rabies (killed human diploid cell vaccine)
-Influenza
-Polio (Salk)
-A Hepatitis

Front 229

What viral vaccines have immunogenicity

Back 229

Attenuated (Live): High (CMI & HMI)
Killed: Lower (HMI)
Component: Middle

Front 230

What viral vaccines have special storage

Back 230

Attenuated (Live): yes, viable organisms
Killed: no
Component: no

Front 231

In cases where children are at exceptionally high risk exposure to a pathogen, they are sometimes given earlier than 6-9 months of age, what is most often needed in these cases

Back 231

The need for repeated booster inoculations

Front 232

What is colostrum so important

Back 232

Infant only has 20% of adult IgA at 12 months

Front 233

What is the only isotype useful in diagonising infections in an neonate

Back 233

IgM

Front 234

Why do normal infants have few infections during the 1st few months

Back 234

Maternal IgG

Front 235

When do children w/ immune deficiencies become ill

Back 235

When maternal IgG is low

Front 236

What do vaccines need to elicit in order for an immune response to display immunogenic memory

Back 236

Th cells
-live viral vaccines elicit CMI & HMI
-killed viral vaccine elicit antibodies

Front 237

What type of vaccine is generally required for enveloped viruses

Back 237

Live vaccines

-Killed vaccines are generally sufficient for naked viruses

Front 238

What two vaccines are examples of Recombinant antigen vaccines

Back 238

Hepatitis B & HPV
-Hep B: the gene coding for HBsAg is inserted into yeast cells, which then release this molecule into the culture medium, the molecule is then purified & used as the immunogen in the vaccine

Front 239

What substances increase the immunogenicity of an antigen when administered with it

Back 239

Adjuvants

Front 240

What effects can adjuvants exert

Back 240

Prolonging antigen persistance (Aluminum potassium sulfate)
Enhancing costimulatory signals (muramyl dipeptide)
Inducing granuloma formation
Inducing nonspecific lymphocyte proliferation (LPS & synthetic polyribonucleotides)

Front 241

What is an allotype

Back 241

Minor amino-acid sequence variations in rgw constant domains of Hc and Lc Ig's
There expression is genetically determined, & repeated exposure to a foreign allotype can cause production of antibodies which recognize these sequence variations

Front 242

Th1 cells primed in the lymph nodes and spleen serve to provide the cytokine stimuli to activate 3 potential effector cells to destroy infected or altered cells

Back 242

Macrophages
CTLs
NK cells

Front 243

What arm of the immune response is designed to identify and eradicate antigenic stimuli that arise from inside the cells of the body

Back 243

Cell-mediated Immune response

Front 244

Kill intracellularly, killing is enhanced by IFN-gamma, TNF-alpha, and TNF-beta, cause granulomas & necrosis of surrounding tissues

Back 244

Macrophages

Front 245

When Th1 cells activate macrophages and cause tissue damage, the result is

Back 245

Delayed-type hypersensitivity (DTH)

Front 246

What assay is often used to measure the pts ability to mount a CMI response

Back 246

DTH skin testing, i.e. Mantoux test, Lepromin Test

Front 247

What does CTL stimulation require

Back 247

-Non-self peptide/class I MHC
-IL-2 (secreted by Th1 cell to enhance differentiation & cloning)
-IFNs increase MHC expression (make targets more susceptible to killing)

Front 248

What is the process by which CTLs kill their target in the Degranulation pathway

Back 248

(1) Attachment to the target (mediated by TCR, CD8, LFA-1 integrin)
(2) Activation (cytoskeletal rearrangment to concentrate granules against attached targets)
(3) Exocytosis of granule contents (perforin & granzymes)
(4) Detachment from the targets

Front 249

CTLs kill by

Back 249

-Perforins
-Cytokines (TNF)
-Granzymes

Front 250

What are two mechanisms by which CTL killing can occur

Back 250

(1) Degranulation with perforin & granzymes
(2) TNF/TNF receptor interaction (FasL on CTL binding to Fas on target cells)

Front 251

kill tumor cells & virus infected cells, kill by granzymes and perforin, enhanced by IFN-alpha, IFN-beta, and IL-12, inhibited by MHC class I, counted with CD16 & CD56

Back 251

NK cells

Front 252

NK cell markers

Back 252

CD16 and CD56

Front 253

NK cells (#1), macrophages, monocytes, neutrophils, eosinophils, target recognition via IgG, killing by lytic enzymes, TNF, perforin

Back 253

Antibody-Dependent Cell-mediated Cytotoxicity (ADCC)

Front 254

What are the 2 mechanisms NK cells kill in CMI

Back 254

(1) cells that do not have class I MHC
(2) Target recognition via IgG (ADCC)

Front 255

What is the special case where IgE (not IgG) can mediate ADCC

Back 255

When the target is a parasitic worm

Front 256

Effector cells in CMI CD markers
CTL
NK cell
Macrohphage

Back 256

CTL: TCR, CD3, CD8, CD2
NK cell: CD16, CD56, CD2
Macrohphage: CD14

Front 257

Effector cells in CMI, Antigen Recognition
CTL
NK cell
Macrohphage

Back 257

CTL: Specific, TCR
NK cell: ADCC (specific for IgG), otherwise recognizes lectins
Macrohphage: nonspecific

Front 258

Effector cells in CMI, MHC recognition required for killing
CTL
NK cell
Macrohphage

Back 258

CTL: Yes, class I MHC
NK cell: No, MHC I recognition inhibits
Macrohphage: No

Front 259

Effector cells in CMI, effector molecoles
CTL
NK cell
Macrohphage

Back 259

CTL: Perforin, Granzymes, Cytokines (TNF-beta, IFN-gamma)
NK cell: Perforin, Granzymes, Cytokines (TNF-beta, IFN-gamma)
Macrohphage:TNF-alpha (IL-1, IL-6), Enzymes (NADPH oxidase, myeloperoxidase), NO, oxygen radicals

Front 260

What virus downregulates class I MHC & also produces a "decoy" MHC class I molecule

Back 260

CMV

Front 261

Deficiency in NADPH oxidase, failure to generate superoxide anion & other O2 radicals, recurrent infection w/ catalase-positive bacteria & fungi

Back 261

Chronic Granulomatous Disease (CGD)

Front 262

Absence of CD18, recurrent & chronic infections, failure to form pus, & do not reject umbilical cord stump, often have a lot of gingivostomatitic

Back 262

Leukocyte adhesion deficiency

Front 263

Granule structural defect, recurrent infection w/ bacteria, chemotactic & degranulation defects; absent NK activity, partial albinism

Back 263

Chediak-Higashi syndrome

Front 264

Pt w/ albinism & an immune deficiency

Back 264

Chediak-Higashi syndrome

Front 265

Deficiency of essential enzyme in hexose monophosphate shunt, same Sx as CDG with assoc anemia

Back 265

Glucose-6-phosphate dehydrogenase (G6PD) deficiency

Front 266

Granule enzyme deficency with mild or no Sx, cell is unable to generate hypochlorite

Back 266

Myeloperoxidase defiency

Front 267

Th1 cells can't make IFN-gamma, neutrophils dont respond to chemotactic stimuli, coarse facies, cold abscesses, retained primary teeth, increased IGE, eczema

Back 267

Job's Syndrome

Front 268

Deficiency of BTK, blocks B-cell maturation, low Ig's of all classes, no circulating B cells, B-cell maturation in bone marrow stopped at pre-B stage, normal CMI; Tx w/ monthly gamma globulin replacments, ABX for infection

Back 268

Bruton X-linked Hypogammaglobulinemia

Front 269

Deficiency of CD40L on activated T cells, high serum titers of IgM w/o other isotypes, normal B & T-cell numbers, susceptibility to EC bacteria & oppurtunists, Tx w/ ABX & gammaglobulins

Back 269

X-linked Hyper-IgM syndrome

Front 270

Deficiency of IgA, repeated sinopulmonary & GI infections, Tx w/ ABX not Ig's

Back 270

Selective IgA deficiency (most common)

Front 271

Molecular defect is unknown, onset in late teens to early 20's, B cells present in peripheral blood, Ig levels dec w/ time, inc autoimmunity, inc atopy, Tx w/ ABX

Back 271

Common Variable Immunodeficiency

Front 272

Delayed onset of normal IgG syn, detected in 5th to 6th month of life; resolves by 16-30 months; susceptibility to pyogenic bacteria; Tx w/ ABX & in severe cases gammaglobulin replacement

Back 272

Transient Hypogammaglobulinemia of Infance

Front 273

What is the normal immunologic event that does not occur in pts w/ X-linked Hyper-IgM syndrome

Back 273

Isotype Class switching

Front 274

Deficiency in Classic Pathway, marked inc in immune complex diseases, increased infections w/ pyogenic bacteria

Back 274

Deficiency in C1q, C1r, C1s, C4, C2,

Front 275

Deficiency in both complement pathways, very severe recurrent bacterial infections & immune complex disease

Back 275

Deficiency in C3,

Front 276

Defiency in both complement pathways, recurrent meningococcal & gonococcal infections

Back 276

Deficiency in C5, C6, C7, or C8

Front 277

Deficiency in complement regulatory proteins, overuse of C1, C4, or C2, with edema at mucosal surfaces

Back 277

Deficency in C1- inhibitor --> Hereditary Angioedema

Front 278

What are the Selective T-cell deficiencies

Back 278

DiGeorge Syndrome
MHC class I Deficiency
Bare Lymphocyte Syndrome (MHC class II Deficiency)

Front 279

Failure of formation of 3rd & 4th pharyngeal pouches, thymic aplasia, Facial abnormalities, hypoPT, cardiac malformations, depression of T-cell #'s & absence of T-cell responses

Back 279

DiGeorge Syndrome

Front 280

Failure of TAP 1 molecules to transport peptides to ER, CD8+ T cells deficient, CD4+ T cells normal, recurrent viral infections, normal DTH, normal Ab production

Back 280

MHC class I Deficiency

Front 281

Failure of MHC class II expression, defects in transcription factors, T cells present & responsive to nonspecific mitogens, no GVDD, deficient in CD4+ T cells, hypogammaglobulinemia

Back 281

Bare Lymphocyte Syndrome (MHC class II Deficiency)

Front 282

What is the only Ab Isotype present in DiGeorge Syndrome

Back 282

IgM
-T-cells are needed for IgG, IgA, and IgE Ab production

Front 283

What are the combined partial B- and T-cell deficiencies

Back 283

Wiskott-Aldrich Sydrome
AtaxiaTelangiectasia

Front 284

Defect in cytoskeletal glycoprotein, X-linked, defective responses to bacterial polysaccharides & depressed IgM, gradual loss of humoral & cellular responses, thrombocytopenia, & eczema

Back 284

Wiskott-Aldrich Sydrome

Front 285

Defect in kinase involved in cell cycle, ataxia, telangiectasia (capillary distortions in eye), Deficiency of IgA & IgE production

Back 285

AtaxiaTelangiectasia

Front 286

Present with Triad of Sx: Immunodeficiency, Eczema, Thrombocytopenia

Back 286

Wiskott-Aldrich Sydrome

Front 287

What is the complete functional B- and T-cell deficiency and what are the subtypes

Back 287

Severe Combined Immunodeficiency (SCID)
-Defects in common gamma chain IL-2 receptor (present in IL-4,IL-7, IL-9, IL-15), X-linked
-Adenosine Deaminase Deficiency (results in toxic metabolic products in cells)
-rag1 or rag2 gene nonsense mutations

Front 288

What Severe Combined Immunodeficiency (SCID) subtype has total absence of B and T cells

Back 288

rag1 or rag2 gene nonsense mutations

Front 289

Severe Combined Immunodeficiency (SCID) subtype that present with chronic diarrhea; skin, mouth, and throat lesions; opportunisitc (fungal) infections; low levels of circulating lymphocytes; cells unresponsive to mitogens

Back 289

-Defects in common gamma chain IL-2 receptor (present in IL-4,IL-7, IL-9, IL-15), X-linked
-Adenosine Deaminase Deficiency

Front 290

Early in HIV infection where does the virus bind

Back 290

-D-type retrovirus attaches to CD4 receptors on host cells (Th cells, macphs, microglial)
-CCR5 chemokine receptor on the macrophage

Front 291

Late in HIV infection where does the virus bind

Back 291

CXCR4 chemokine receptor on the T-cells

Front 292

What gene is responsible for HIV virulence by making infected cells less susceptible to CTL killing

Back 292

Nef gene product, downregulates class I MHC expression

Front 293

What HIV characteristic is responsible for eliminating cell- and antibody-mediated immunity

Back 293

Direct cytopathic effect on lymphocytes & macrophages

Front 294

What HIV characterisitic inhibits cytokine syn in both infected & uninfected cells

Back 294

Tat gene product

Front 295

What does Immune deviation toward the Th2 in HIV cause?

Back 295

Inhibits potentially protective CMI responses and produces Abs that can mediate ADCC, resulting in further elimination of TH cells

Front 296

What results from the antigenic drift of gp120

Back 296

Evades antibody mediated effector mechanisms and exhausts individuals immune capacity

Front 297

What results from the heavy glycosylation of gp120

Back 297

Hides potentially protective epitopes from immune recognition

Front 298

What is the reservoir for HIV infection

Back 298

Macrophage

Front 299

If you have pt that has known sexual encounters w/ HIV (+) individuals, uses no protection or prophylaxis and has never been HIV (+), what molecule is responsible for this

Back 299

CCR5 mutation
-Homozygous = immune
-Heterozygous = slows clinical course

Front 300

What is caused by excessive responses to foreign antigens, or failure of self-tolerance (autoimmunity)

Back 300

Hypersensitivity disease

Front 301

What do all hypsensitivity reactions have in common

Back 301

-The first exposure to the antigen "sensitizes" the lymphocyes
-Subsequent exposures elicit a damaging rxn
-The response is specific to a particular antigen or a cross-reacting substance

Front 302

IgE mediated, protective response to helminth, atopic/allergic individuals develop this response to inappropriate stimuli

Back 302

Type I (immediate) Hypersensitivities

Front 303

Primary mediators of Type I hypersensitivity

Back 303

Mediators that are already made & stored in the granule
-Histamine
-Heparin
-Eosinophil chemotactic Factor A (multiple chemokines)

Front 304

Histamine of Type I hypersensitivity

Back 304

Smooth muscle contraction; inc vasc permeability

Front 305

Heparin of Type I hypersensitivity

Back 305

Anticoagulant

Front 306

Eosinophil chemotactic Factor A of Type I hypersensitivity

Back 306

Chemotactic

Front 307

Secondary mediators of Type I hypersensitivity

Back 307

Newly synthesized from Arachidonic Acid
-Prostaglandin D2, E2, F2alpha
-Leukotrienes C4, D4, E4 (lipoxygenase pathway)
-Leukotriene B4

Front 308

Prostaglandin D2, E2, F2alpha
of Type I hypersensitivity

Back 308

Inc Smooth muscle contraction & vasc permeability

Front 309

Leukotrienes C4, D4, E4 of Type I hypersensitivity

Back 309

Inc Smooth muscle contraction & vasc permeability

Front 310

Leukotriene B4 of Type I hypersensitivity

Back 310

Chemotactic for neutrophils

Front 311

What is responsible for the late-phase rxn of Type I hypersensitivity

Back 311

Arachidonic Acid cascade --> breakdown of phospholipids in membrane that get shuttled through this pathway

Front 312

Allergens: Trees, grasses, dust, cats, dogs, mites
Clinical Findings: Edema, Irritation, mucus in nasal mucosa

Back 312

Allergic rhinitis (Hay Fever), Type I hypersensitivity

Front 313

Allergens: Insect stings, drug reactions
Clinical Findings: Bronchial & tracheal constriction, complete vasodilation & death

Back 313

Systemic Anaphylaxis, Type I hypersensitivity

Front 314

Allergens: Milk, eggs, fish, cereals, grains
Clinical Findings: Hives & GI problems

Back 314

Food allergies, Type I hypersensitivity

Front 315

Allergens: In vivo skin testing for allergies, insect bites
Clinical Findings: local skin edema, reddening, vasodilation of vessels

Back 315

Wheal & Flare, Type I hypersensitivity

Front 316

Allergens: Inhaled materials
Clinical Findings: Bronchial & tracheal constriction, edema, mucus production, massive inflammation

Back 316

Asthma, Type I hypersensitivity

Front 317

What is the development of Immediate-Hypersensitivity Reaction

Back 317

(1) First exposure to allergen
(2) Th2 release of IL-4 & IL-13 stimulates B cells to produce IgE; class switching occurs
(3) B cell produces IgE immunoglobulin; it attaches to Fc receptor on mast cell
(4) Second Exposure to allergen
(5) Allergen cross-links several IgE molecules on mast cell & cell degranulates releasing powerful chemicals

Front 318

Type I Effector Cells

Back 318

Mast Cells
Basophils
Eosinophils

Front 319

Activated Mast Cell (or basophil) effects:
Biogenic amines (histamine)
Lipid Mediators (PAF, PGD2, LTC4)
Cytokines (TNF)
Enzymes (trypase)

Back 319

Biogenic amines (histamine): Vascular leakage, bronchoconstriction
Lipid Mediators (PAF, PGD2, LTC4): Bronchoconstriction, intestinal hypermotility, inflammation, tissue damage
Cytokines (TNF): Inflammation
Enzymes (trypase): Tissue damage

Front 320

Eosinophil Effects:
Cationic granule proteins (major basic protein, eosinophil cationic protein)
Enzymes (eosinophil peroxidase)

Back 320

Cationic granule proteins (major basic protein, eosinophil cationic protein): kill of parasites & host cells
Enzymes (eosinophil peroxidase): tissue remodeling, kill of parasites & host cells

Front 321

How antibodies in Type II Hypsensitivities cause tissue damage

Back 321

(1) May opsonize or activate the copmlement system
(2) May recruit neutrophils and macrophages that cause tissue damage
(3) May bind to normal cellular receptors and interfere with their fcn

Front 322

Tissue-specificc autoantibodies, opsonize or activate copmlement, recruit inflammatory cells, interfere with cellular fcn

Back 322

Type II Hypsensitivities

Front 323

What are the types of Cytotoxic Type II Hypsensitivities

Back 323

Autoimmune Hemolytic Anemia (HDNB)
Acute Rheumatic Fever
Goodpasture System
Transfusion Reaction
Autoimmune Thrombocytopenic purpura

Front 324

Ab to RBC membrane proteins (Rh, I, Ags) --> Opsonization, phagocytosis, & complement-mediated destruction of RBCs --> Hemolytic anemia

Back 324

Autoimmune Hemolytic Anemia (HDNB), Cytotoxic Type II Hypsensitivity

Front 325

Ab against stretococcal cell-well Ag; Ab cross-reacts w/ myocardial Ag --> inflammation, macrophage activation --> myocarditis arthritis

Back 325

Acute Rheumatic Fever, Cytotoxic Type II Hypsensitivity

Front 326

Ab against type IV collage in basement membrane of kidney glomeruli & lung alveoli --> complement- & Fc-receptor mediated inflammation --> Nephritis, lung hemorrhage, linear Ab depositons on IF

Back 326

Goodpasture System, Cytotoxic Type II Hypsensitivity

Front 327

Ab against ABO blood glycoproteins --> IgM isohemagglutinins formed naturally in response to normal bacterial flora cause opsonization + complement activation --> hemolysis

Back 327

Transfusion Reaction, Cytotoxic Type II Hypsensitivity

Front 328

Ab against platelet membrane proteins --> Ab-mediated platelet destruction through opsonization & complement activation --> bleeding

Back 328

Autoimmune Thrombocytopenic purpura, Cytotoxic Type II Hypsensitivity

Front 329

What are the types of Non-cytotoxic Type II Hypsensitivities

Back 329

Myasthenia Gravis
Graves disease
Type II (non-insulin dependent diabetes)
Pernicious Anemia

Front 330

Ab against ACh receptor --> Ab inhibits ACh binds, downmodulates receptors --> Muscle weakness, paralysis

Back 330

Myasthenia Gravis, Non-cytotoxic Type II Hypsensitivity

Front 331

Ab against TSH receptor --> Ab-mediated stimulation of TSH receptors --> Hyperthyroidism followed by Hypothyroidism

Back 331

Graves disease, Non-cytotoxic Type II Hypsensitivity

Front 332

Ab against Insulin receptor --> Ab inhibits binding of insulin --> Hyperglycemia

Back 332

Type II (non-insulin dependent diabetes), Non-cytotoxic Type II Hypsensitivity

Front 333

Ab against instrinsic factor of gastric parietal cells --> Neutralization of intrinsic factor, decreased absorption of Vit B12 --> abnormal erythropoiesis, anemia

Back 333

Pernicious Anemia, Non-cytotoxic Type II Hypsensitivity

Front 334

How is Type II Hypsensitivity different from Type III Hypsensitivity

Back 334

In Type II Hypsensitivity as the disease progresses, complexes of Antigen & antibody may cause localized damage, but these complexes do not circulate so the damage is localized to the specific tissue

Front 335

Anti-RhD + IgG, formed in Rh- mother carrying an Rh+ child, first preganancy sensitizes, Ab crosses placenta and injures subsequent fetuses, prevent w/ RhoGAM

Back 335

Hemolytic disease of the Newborn (HDNB) a.k.a. Erythroblastosis fetalis, Type II Hypsensitivity

Front 336

What is RhoGAM and when is it used

Back 336

A preparation of human Anti-RhD IgG antibody, used to prevent hemolytic disease of the newborn in an Rh- mother
-it is given at 28 weeks gestation & again w/in 72 hours after birth
-this Ab effectively eliminates the fetal Rh+ cells before they can generate RhD-specific memory B cells in the mother

Front 337

Systemic damage, Immune complexes activate complement, self or foreign Antigens

Back 337

Type III Hypsensitivity

Front 338

What are examples of Type III Hypsensitivities

Back 338

Systemic Lupus Erythematosus
Rheumatoid Arthritis
Poststreptococcal Glomerulonephritis
Serum Sickness
Arthus Reaction

Front 339

Abs against dsDNA, Sm, & other nucleoproteins --> nephritis, arthritis, vasculitis, butterfly facial rash

Back 339

Systemic Lupus Erythematosus, Type III Hypsensitivity

Front 340

Target antigen is Rheumatoid Factor --> joint pain, erosions

Back 340

Rheumatoid Arthritis, Type III Hypsensitivity

Front 341

Target antigen is streptococcal cell wall Ags (may be "planted" in GBM) --> Nephritis, "lumpy-bumpy deposits"

Back 341

Poststreptococcal Glomerulonephritis, Type III Hypsensitivity

Front 342

Caused by various proteins (i.e. giving immunoglobulins or anti-venom) --> Arthritis, vasculitis, nephritis

Back 342

Serum Sickness, Type III Hypsensitivity

Front 343

Caused by any injection protein --> Localized pain & edema

Back 343

Arthus Reaction, Type III Hypsensitivity

Front 344

What is Rheumatoid Factor

Back 344

Your own IgM against your own IgG that is specific to the Fc portion

Front 345

Delayed-type (48-72 hours), CD4+ Th1 cells mediate, activate macrophages, cause inflammation, common in chronic intracellular infections

Back 345

Type IV Hypsensitivity

Front 346

What are examples of Type IV Hypsensitivities

Back 346

Tuberculin test (PPD)
Contact Dermatitis
Hashimoto's thyroiditis
Insulin-dependent diabetes mellitus (Type I)
Multiple Sclerosis
Guillain-Barre Syndrome
Celiac Disease

Front 347

PPD (tuberculin & mycolic acid) --> Indurated skin lesion (granuloma)

Back 347

Tuberculin test (PPD), Type IV Hypsensitivity

Front 348

Nickel, poison ivy/oak, catechols, hapten/carrier --> vesicular skin lesions, pruritis, rash

Back 348

Contact Dermatitis, Type IV Hypsensitivity

Front 349

Unknown Ag in thyroid --> Hypothyroidism

Back 349

Hashimoto's thyroiditis, Type IV Hypsensitivity

Front 350

Islet-cell antigens, insulin, glutamic acid decarboxylase, etc --> Polydipsia, Polyuria, Polyphagia, Ketoacidosis

Back 350

Insulin-dependent diabetes mellitus (Type I), Type IV Hypsensitivity

Front 351

Target antigen is streptococcal cell wall Ags (may be "planted" in GBM) --> Nephritis, "lumpy-bumpy deposits"

Back 351

Poststreptococcal Glomerulonephritis, Type III Hypsensitivity

Front 352

Caused by various proteins (i.e. giving immunoglobulins or anti-venom) --> Arthritis, vasculitis, nephritis

Back 352

Serum Sickness, Type III Hypsensitivity

Front 353

Caused by any injection protein --> Localized pain & edema

Back 353

Arthus Reaction, Type III Hypsensitivity

Front 354

What is Rheumatoid Factor

Back 354

Your own IgM against your own IgG that is specific to the Fc portion

Front 355

Delayed-type (48-72 hours), CD4+ Th1 cells mediate, activate macrophages, cause inflammation, common in chronic intracellular infections

Back 355

Type IV Hypsensitivity

Front 356

What are examples of Type IV Hypsensitivities

Back 356

Tuberculin test (PPD)
Contact Dermatitis
Hashimoto's thyroiditis
Insulin-dependent diabetes mellitus (Type I)
Multiple Sclerosis
Guillain-Barre Syndrome
Celiac Disease

Front 357

PPD (tuberculin & mycolic acid) --> Indurated skin lesion (granuloma)

Back 357

Tuberculin test (PPD), Type IV Hypsensitivity

Front 358

Nickel, poison ivy/oak, catechols, hapten/carrier --> vesicular skin lesions, pruritis, rash

Back 358

Contact Dermatitis, Type IV Hypsensitivity

Front 359

Unknown Ag in thyroid --> Hypothyroidism

Back 359

Hashimoto's thyroiditis, Type IV Hypsensitivity

Front 360

Islet-cell antigens, insulin, glutamic acid decarboxylase, etc --> Polydipsia, Polyuria, Polyphagia, Ketoacidosis

Back 360

Insulin-dependent diabetes mellitus (Type I), Type IV Hypsensitivity

Front 361

Myelin basic protein, proteolipid protein --> progressive demyelination, blurred vision paralysis

Back 361

Multiple Sclerosis, Type IV Hypersensitivity

Front 362

Peripheral nerve myelin or ganglioside --> ascending paralysis, peripheral nerve demyelination

Back 362

Guillan-Barre Syndrome, Type IV Hypersensitivity

Front 363

Unknown specificity of pathogenic T cells --> Gluten sensitive enteropathy

Back 363

Celiac Disease, Type IV Hypersensitivity

Front 364

What is the Ab, complement, and Effector cells of Type I (immediate) Hypersensitivity rxns

Back 364

Ab: IgE
Complement: No
Effector Cells: Basophil, mast cell

Ex: Hay fever, atopic dermatitis, insect venom sensitivity, anaphylaxis to drugs, some food allergies, allergies to animals & animal products, asthma

Front 365

What is the Ab, complement, and Effector cells of Type II (cytotoxic) Hypersensitivity rxns

Back 365

Ab: IgG, IgM
Complement: Yes
Effector Cells: PMN, macrophages, NK cells

Ex: Autoimmune or drug-induced hemolytic anemia, transfusion rxns, HDNB, hyperacture graft rejection, Goodpasture's disease, Rheumatic Fever

Front 366

What is the Ab, complement, and Effector cells of Type II (non-cytotoxic) Hypersensitivity rxns

Back 366

Ab: IgG
Complement: No
Effector Cells: None

Ex: Myasthenia gravis, Graves disease, Type 2 DM

Front 367

What is the Ab, complement, and Effector cells of Type III (Immune Complex) Hypersensitivity rxns

Back 367

Ab: IgG, IgM
Complement: Yes
Effector Cells: PMN, macrophages

Ex: SLE, RA, polyarteritis nodosa, poststreptococcal GN, Arthus rxn, Serum sickness

Front 368

What is the Ab, complement, and Effector cells of Type IV (Delayed, DTH) Hypersensitivity rxns

Back 368

Ab: None
Complement: No
Effector Cells: CTL, Th1, Macrophages

Ex: Tuberculin test, TB, Leprosy, Hashimoto thyroiditis, poison ivy (contact dermatitis), acute graft rejection, GVHD, IDDM

Front 369

How do you differentiate b/w Multiple Sclerosis and Myasthenia Gravis

Back 369

MS: Spastic paralysis
MG: weakening paralysis

Front 370

What is a common infection causing Guillain-Barre Syndrome

Back 370

Campylobacter

Front 371

Failure of self-tolerance, Genetics (class II MHC), Environment (infections), Hormones

Back 371

Autoimmunity

Front 372

What is the key factor in the development of autoimmunity

Back 372

the recognition of self-antigens by autoreactive lymphocytes, which then become activated, proliferate, and differentiate to produce effector cells and cytokines that cause tissue injury

Front 373

What is among the strongest genetic associations w/ development of autoimmune disease?

Back 373

class II MHC genes

Front 374

HLA allele in Rheumatoid Arthritis

Back 374

DR4

Front 375

HLA allele in Insulin-dependent DM (Type I)

Back 375

DR3/DR4

Front 376

HLA allele in Multiple Sclerosis, Goodpasture's

Back 376

DR2

Front 377

HLA allele in SLE, Psoriasis, IBD, Reiter's syndrome

Back 377

DR2/DR3

Front 378

HLA allele in Ankylosing Spondylitis

Back 378

B27

Front 379

HLA allele in Celiac Disease

Back 379

DQ2 or DQ8

Front 380

HLA allele in Graves disease

Back 380

B8

Front 381

Immune responses may recruit leukocytes and increase of expression of costimulators which activate T lymphocytes that are not specific for the infectious pathogen

Back 381

Bystander activation

Front 382

Antigens of a microbe cross-react w/ or mimic self antigens

Back 382

Molecular Mimicry

Front 383

Can expose self antigens that are normally concealed from immune cells

Back 383

Inflammation and associated damage

Front 384

Infections can trigger autoimmunity through

Back 384

-activating bystanders
-molecular mimicry
-inflammatory damage

Front 385

What is the mainstain of therapy for hypersensitivity disease directed at

Back 385

Modification of T-cell function
-inhibit T cell proliferation
-inhibit T cell function
-kills T cells
-antagonize damaging products

Front 386

What therapy for immune diseases inhibits T cell proliferation

Back 386

Cyclosporine

Front 387

What therapy for immune diseases inhibit T cell function

Back 387

Corticosteroids

Front 388

What therapy for immune diseases kills T cells

Back 388

Cyclophosphamie

Front 389

What therapy for immune diseases are antagonists to proinflammatory cytokines or costimulatory molecules

Back 389

Monoclonals or binding proteins

Front 390

How are monoclonal antibodies produced?

Back 390

By fusing antigen-specific spleen cells with myeloma cells --> this causes the production of identical, monospecific Abs b/c they are all produced by a single, cloned, parent cell

Front 391

Clinical use of Abciximab

Back 391

Antiplatelet: Antagonist of IIb/IIIa receptors

Front 392

Clinical use of Infliximab

Back 392

RA & Crohn's disease: binds TNF

Front 393

Clinical use of Trastuzumab

Back 393

Breast CA: antagonists to ERB-B2

Front 394

Clinical use of Dacliximab

Back 394

Kidney Transplants: Blocks IL-2 receptors

Front 395

Clinical use of Muromonab

Back 395

Kidney Transplant: blocks allograft rejection, blocks CD3

Front 396

Clinical use of Palivizumab

Back 396

Respiratory syncytial virus: blocks RSV fusion protein

Front 397

Clinical use of Rituximab

Back 397

Non-Hodgkin Lymphoma: binds CD20

Front 398

When tissue is moved from one location to another in the same individual

Back 398

Autografts (Autologous grafts)

Ex: Skin grafting in burns or Coronary Artery Replacement with Saphronous veins

Front 399

Skin grafting in burns or Coronary Artery Replacement with Saphronous veins

Back 399

Autografts

Front 400

Transplants b/w genetically identical individuals (monozygotic twins)

Back 400

Isografts (Syngeneic grafts)

Front 401

Grafts transplants b/w genetically different members of the same species

Back 401

Allogeneic grafts

Ex: Kidney Transplant

Front 402

Kidney Transplant

Back 402

Allogeneic grafts

Front 403

Grafts transplanted b/w members of a different species

Back 403

Xenogeneic grafts

Ex: Baboon heart into human child

Front 404

Baboon heart into human child

Back 404

Xenogeneic grafts

Front 405

All grafts except what are identified as foreign invading proteins and destroyed by Graft rejection

Back 405

Autografts

Front 406

Graft Rejection Effectors

Back 406

CTLs
Macrophages
Antibodies

Front 407

Effector Phase of Rejection

Back 407

Th cytokines play a critical role in stim macph, Cytotoxic T cell, & Ab-mediated killing
-IFNs, TNF-alpha & -beta all inc the expression of class I MHC
-IFN-gamma inc the expression of class II MHC, as well as increasing the susceptibility of cells in the graft to MHC-restricted killing

Front 408

Types of Graft Rejection

Back 408

Hyperacute
Accelerated
Acute
Chronic

Front 409

Caused by a bone marrow transplants where grafted T cells attack the host, Sx include Rash, jaundice, diarrhea, GI hemorrhage

Back 409

Graft-verus-Host-Disease (GVHD)

Front 410

Tissue Compatibility testins

Back 410

ABO Blood typing
Mixed Lymphocyte reaction (class II)
Microtoxicity test (class I)

Front 411

Routine HLA Typing

Back 411

HLA-A
HLA-B
HLA-DR
-these are the only loci that appear to predict the likelihood of rejection of the transplantq

Front 412

Microtoxicity test (class I)

Back 412

Using antisera against specific class I antigens
-Lymphocytes from the donor or recipient are mixed w/ different antisera
-If Abs recognize their specific epitope on the cells they will be bound there & addition of complement will result in cell lysis
-the lysis of cells is monitored by adding a dye that will penetrate cells whose memb have become leaky from the actions of complement

Front 413

Mixed Lymphocyte reaction (class II)

Back 413

-Lymphocytes from one individual being tested are irradiated so that they cannot proliferate but will act as stimulator cells for the presentation of MHC antigens
-the other individual's cells are added to the culture & uptake of tritrated thymidine is used as an indicator cell proliferation
-if the MHC class II antigens are different, proliferation will occur, if they are the same, no proliferation will occur

Front 414

Cyclosporin A

Back 414

Prevention of acute allograft rejection
-drug inhibits IL-2 & also IL-2 receptors, thereby effectively preventing lymphocyte proliferation

Front 415

Capsules:
Some Killers Have Pretty Nice Capsules

Back 415

Streptococcus pneumoniae
Klebsiella pneumoniae
Haemophilus influenza
Pseudomonas aeruginosa
Neisseria meningitidis
Cryptococcus neoformans

Front 416

Primary mechanism of adherence in most gram (-) cells

Back 416

Pili/fimbriae

Front 417

Primary mechanism of adherence in gram (+) cells

Back 417

Teichoic acids

Front 418

Cleaves Fc portion may coat bacteria & bind them to cellulara Fc receptors

Back 418

IgA proteases
Destruction of mucosa IgA

Ex: Neisseria, Haemophilus, S. pneumoniae

Front 419

Chelate and import iron

Back 419

Siderophores

Front 420

Surface proteins that allow an organism to bind and invade normally non-phagocytic human cells, escaping the immune system

Back 420

Invasin

Ex: Yersinia pseudotuberculosis (organism causing diarrhea)

Front 421

Tunnel from the bacteria to the host cell (macrophage) that delivers bacterial toxins directly to the host cell

Back 421

Type III Secretion Systems

Ex:E. coli, Salmonella species, Yersinia species, P. aeruginosa, Chlamydia

Front 422

What is the toxic portion of LPS

Back 422

Lipid A

Front 423

What toxins are the inhibitors of protein synthesis

Back 423

Corynebacterium diptheriae (Diphtheria toxin)
Pseudomonas aeruginosa (Exotoxin A)
Shigella dysenteriae (Shiga toxin)
Enterohemorrhagic E. coli (Verotoxin, a shiga-like toxin)

Front 424

Mode of action of Diphtheria toxin

Back 424

ADP ribosyl transferase; inactivates eEF-2; 1' targets: heart/nerves/ epithelium
--> inhibits eukaryotic cell protein cell synthesis

Front 425

Mode of action of Exotoxin A (pseudomonas aeruginosa)

Back 425

ADP ribosyl transferase; inactivates eEF-2; 1' target: liver
--> inhibits eukaryotic cell protein cell synthesis

Front 426

Mode of action of Shiga Toxin (Shigella dysenteriae)

Back 426

Interferes w/ 60S ribosomal subsunit
inhibits protein cell synthesis in eukaryotic cells

Front 427

Mode of action of Verotoxin (EHCH)

Back 427

Interferes w/ 60S ribosomal subsunit
inhibits protein cell synthesis in eukaryotic cells

Front 428

What are the neurotoxins

Back 428

Clostridium tetani (Tetanus Toxin)
Clostridium botulinum (Botulinum Toxin)

Front 429

Mode of action of Tetanus Toxin

Back 429

Blocks release of the inhibitory neurotransmitters glycine & GABA
-inhibits protein syn in euk cells

Front 430

Mode of action of Botulinum Toxin

Back 430

Blocks release of ACh
-inhibitos cholinergic synapse

Front 431

What are the superantigens

Back 431

Staphylococcus aureus (TSST-1)
Streptococcus pyogenes (Exotoxin A a.k.a. erythrogenic or pyrogenic toxin)

Front 432

What are the cAMP inducers

Back 432

Enterotoxigenic E. coli (Heat labile toxin (LT))
Vibrio cholerae (Cholera toxin)
Bacillus anthracis (Anthrax toxin)
Bordetella pertussis (Pertussis Toxin)

Front 433

Mode of Action of Heat Labile Toxin (LT, ETEC)

Back 433

LT stim an adenylate cyclase by ADP ribosylation of GTP binding protein

Front 434

Mode of Action of Anthrax Toxin

Back 434

EF = edema factor = adenylate cyclase
LF = lethal factor
PA = protective antigen

Front 435

Mode of Action of Pertussis Toxin

Back 435

APD ribosylates Gi, the negative regulator of adenylate cyclase --> inc cAMP
-Histamine-sensitizing Lymphocytosis promoting Islet activating

Front 436

What are the cytolysins

Back 436

Clostridium perfringens (Alpha toxin)
Staphylcoccus aureus (Alpha toxin)

Front 437

What is Mode of Action of Alpha toxin in Clostridium perfringens

Back 437

Lecithinase
-damages cell membranes; myonecrosis

Front 438

What is Mode of Action of Alpha toxin in Staphylcoccus aureus

Back 438

Toxin intercalates forming pores
-cell memb becomes leaky

Front 439

Outer membrane

Back 439

Gram (-) only
Hydrophobic memb:
LSP = endotoxin
-Lipid A = toxic moiety
-PS = immunogenic portion
Outer membrane proteins: attachment, virulence
Protein porins: Passive transport

Front 440

Teichoic acids present in

Back 440

Gram (+) only
-immunogenic, induces TNF-alpha, IL-1, attachment

Front 441

Mycolic acids present in

Back 441

Acid-fast only
Resistance to drying and chemicals

Front 442

Periplasmic space present in

Back 442

Gram (-) only

Front 443

Endospores present in

Back 443

Gram (+) only
-Keratin coat, calcium dipicolinate
Resistance to heat, chemicals, & dehydration

Front 444

What bacterial growth phase:
Initial phase
Detoxifying medium
Turning on enzymes to utilizae medium

Back 444

Lag Phase
-Number of cells at beginning = number of cells at end of lag phase

Front 445

What bacterial growth phase:
Rapid exponential growth

Back 445

Log Phase
-Generation time = time it takes one cell to dividie into two

Front 446

What bacterial growth phase:
Nutrients used up
Toxic products like acid and alkali begin to accululate

Back 446

Stationary Phase
-# of new cells = # of dying cells

Front 447

Medium that selects for certain bacteria by inclusion of special nutrients &/or ABX

Back 447

Selective medium

Front 448

Medium on which different bacteria can be distinguished by differences in colonial morphology or color

Back 448

Differential medium

Front 449

Thioglycote Medium

Back 449

Anaerboes

Front 450

Loffler's coagulated and serum (S) and Tellurite agar (D)

Back 450

Corynebacterium

Front 451

Eosin methylene blue (D) and MacConkeys (D)

Back 451

Enteric Bacterium

Front 452

Hektoen enteric agar (D) and Xylose-lysine-deoxychocolate agar

Back 452

Enteric pathogens

Front 453

TCBS (Thiosulfite Citrate Bile Salts Sucrose agar) (S)

Back 453

Vibrio cholerae (likes alkaline growth medium)

Front 454

Charcoal-yeast extract agar (CYE agar) (S)

Back 454

Legionella

Front 455

Lowennstain-Jensen medium (S)

Back 455

Mycobacterium

Front 456

Chocolate agar

Back 456

Neiserria from normally sterile sites, Haemophilus

Front 457

Thayer-Martin selective medium (S)

Back 457

Neiserria from site with normal floar

Front 458

Cholesterol nd purines and pyrimidines growth requirement

Back 458

Mycoplasma

Front 459

Cysteine growth requirements

Back 459

Francisella, Brucella, Legionella, Pasteurella

Front 460

X (protoporphyrin) and V (NAD)

Back 460

Haemophilus (influenzae and aergypticus require both)

Front 461

Require oxygen
Have no fermentative pathways
Generally produce superoxide dismutase

Back 461

Obligate aerobes
-Mycobacterium
-Pseudomonas (Bacillus)

Front 462

Requires low but not full oxygen tension

Back 462

Microaerophilic
-Campylobacter
-Helicobacter

Front 463

Will respire aerobically until oxygen is depleted and then ferment or respire anaerobically

Back 463

Facultative Anaerobes
-Most bacteria, e.g. Enterobacteriacae

Front 464

Lack superoxide dismutase
Generally lack catalase
Are fermenters
Cannot use O2 as terminal electron acceptor

Back 464

Obligate Anaerobes
-Actinomyces
-Bacteroides
-Clostridium

Front 465

Types of DNA that may be found in bacteria

Back 465

Bacterial DNA
Plasmid DNA
Bacteriophage DNA

Front 466

Where are all essential & nonessential bacterial genes located

Back 466

Essential : bacterial chromosome
Nonessential: bacterial plasmid

Front 467

Episome

Back 467

subclass of plasmids
may be integrated into the bacterial DNA
Have insertion sequences matching those found on bacterial chromosomes

Front 468

2 processes available to stabilize "new" DNA

Back 468

Homolgous recombination
Site-Specific recombination

Front 469

mechanism to incorportate short, linear pieces of DNA into the chromosome
must be some sequence homology
recombinase A is required
there is one-to-one exchange of DNA

Back 469

Homolgous recombination

Front 470

mechanism used to combine circular pieces of DNA
-Plasmids
-Temperate phages
-Transposons
Requires NO homology
No DNA is lost
Requires restriction endonucleases

Back 470

Site-Specific recombination

Front 471

3 major roles of Site-Specific recombination

Back 471

Integration of fertility factor to make an Hfr cell
Integration of temperate phage DNA into a bacterial chromosome to create a prophage
Movement and insertion of transposons

Front 472

DNA can be transferred from bacterium to bacterium by

Back 472

Conjugation
Transformation
Transduction

Front 473

How do you get new genetic combinations in bacteria

Back 473

Gene transfer followed by stabilization of genes (recombination)

Front 474

What is competent bacteria

Back 474

capable of binding and importing free DNA from the enivornment

Front 475

Requires free DNA
Requires competent cells
Captured DNA is incorporated by homologous recombination

Back 475

Transformation

Front 476

Gene transfer from donor (F+ or Hrf cell) to recipient (F- cell) during cell-to-cell contact

Back 476

Conjugation

Front 477

What controls conjugation

Back 477

Fertility factors (in plasmid or episome form)

Front 478

oriT (origin of transfer)

Back 478

A single strand break occurs here, this is where transfer of the single strand begins
the other strand remains and it is quickly restored to double strandedness
A plasmid must have this region to be transferrable by conjugation

Front 479

Donor cells in which fertility plasmid is in its free state

Back 479

F+ cells

Front 480

Donor cells in which fertility factor has inserted itself into the bacterial chromosome

Back 480

Hfr cells

Front 481

F+ x F- cross

Back 481

one strand of the entire plasmid is transferred
it results in a "sex change" of the recipient

Front 482

Hfr x F- cross

Back 482

Chromosomal genes clostest to oriT are transferred
Transferred genes must be stabilized by homologous recombination
No "sex change" occurs as the bridge does not remain long enough to transfer the tra operon