Mcp: Unit 8

Front 1

List the 5 major (classes/isotypes) of immunoglobulins?

Back 1

Note the heavy chains associated with each Ig.

Front 2

Which immunoglobulin (Ig) is most common in blood?

Back 2

IgG

Front 3

Which Ig is the "first responder" or always secreted first in an immune response?

Back 3

IgM

Front 4

Draw the general structure of an antibody. Indicate/describe: the antigen binding sites, N-termini, C-termini, light chains, heavy chains, variable region, constant region, and hinge region.

Back 4

Antibodies are made from 4 polypeptides--2 heavy chains and 2 light chains which are linked by disulfide bonds. N-termini contains the variable (V) region, including the antigen binding site, which is reason for diverse antigen binding specificity. C-termini contain the constant region which binds to other body cells, and hinge region (on select Igs).

Front 5

What are the 3 main antibodies present in blood, lymph and connective tissue?

Back 5

IgM, IgA, IgG

Front 6

Describe the role of IgG

Back 6

Main function is to facilitate engulfment and destruction of extracellular microorganisms/toxins by phagocytes (aka opsonization). Also works in concert with complement. It has the longest has the longest half life in blood.

Front 7

What immunoglobulin triggers immune hypersensitivity reaction (in developed countries)?

Back 7

IgE. Its constant region binds tightly to mast cell receptors triggering strong inflammatory response (i.e. to parasitic worms or other organisms).

Front 8

What 2 immunoglobulins are expressed as cell surface receptors on circulating naive B-lymphocytes?

Back 8

IgM and IgD

Front 9

What is lipopolysaccharide (LPS)? What effects does it have in the immune system, both locally and systemically?

Back 9

LPS is major cell-surface component of gram negative bacteria and an endotoxin. Local infection stimulates acute inflammatory response (increased vascular permeability, WBC infiltration, and swelling). Systemic infection induces fever, headache, vomiting and septic shock. Septic shock decreases BP and cardiac output. It may also lead to DIC and/or ARDS.

Front 10

Describe the structure of LPS noting its antigenic and endotoxic components.

Back 10

LPS has a hydrophobic lipid-rich end and a hydrophilic polysaccharide-rich end which is antigenic and a determinant of the O antigen. The endotoxicity of the molecule resides in Lipid A region.

Front 11

Describe the characteristics of LPS endotoxin that make it difficult to get rid of (cleanly remove).

Back 11

Front 12

Describe the key immune system mediators in response to LPS endotoxin and their primary effects. Which three are most critical?

Back 12

Most critical: TNF, IL-1, and IL-6

Front 13

Describe the interrelated effects of the 3 key mediators (trio) in the endotoxic immune response.

Back 13

Front 14

List the primary and secondary immune organs.

Back 14

Primary: Bone marrow, Thymus; Secondary: Spleen, Lymph nodes, Tonsils/adenoids, Peyers patches, appendix.

Front 15

Describe the major cell types involved in immune response.

Back 15

B cell: a lymphocyte derived from lymphoid precursor; differentiates into plasma cells that secrete antibody upon infection; T cell: regulates the immune response, kills infected cells; Macrophage: phagocytic cell resident in tissues that kills foreign particles; Monocyte: a macrophage equivalent that circulates in blood--becomes a macrophage when it enters tissue. PMNs: neutrophils engaged in phagocytosis of foreign particles. These make up large portion of WBC. Eosinophils: important for killing worms--with major basic protein. Basophil: unknown function; Mast cell: release of histamine.

Front 16

Define the lag (aka inductive or latent) phase of the (antibody) immune response.

Back 16

The lag or latent phase is the period of time after initial exposure to an immunogen before antibody can be detected.

Front 17

Describe the primary and secondary immune response in terms of antibody production phases.

Back 17

After exposure to a immunogen, there is a lag phase followed by a exponential increase in pathogen-specific antibody. This antibody production reaches a peak and then plateaus (steady state). The steady state period is followed by a steady decline or decay of antibody in the serum. Upon secondary exposure to the immunogen (or vaccine), there is a significantly shorter lag time and more robust pathogen-specific antibody production. This is called the secondary or "memory" response.

Front 18

List the 7 ways that the secondary immune response differs from the primary immune response.

Back 18

1. Shorter lag time
2. Higher rates of antibody synthesis
3. Higher peak antibody titer
4. Longer persistence of antibody
5. A predominance of IgG class molecules
6. Higher affinity of antibody
7. Requires less antigen

Front 19

Describe the B-lymphocyte repertoire.

Back 19

The B-cell repertoire consists of individual B-cells that express only 1 of many idiotypes (variable region) of immunoglobulin on their surface. The collection of B-cells expressing different Igs constitute the full repertoire of antibody specificities.

Front 20

Describe the process of clonal selection in B-cells.

Back 20

When naive B-cells encounter an antigen that corresponds to its surface bound Ig it binds and is then activated with T-cell help. This causes the B-cells to proliferate (making daughter cells) and also differentiate into plasma cells that secrete antibody. As immune response continues, there is increasing selection of those B-cells that have the highest affinity for antigen (and thus a higher antibody specificity).

Front 21

Helper T-cells are distinguished by what surface antigen?

Back 21

CD4

Front 22

What is a hapten?

Back 22

A small molecule that cannot induce an antibody response on its own. It may induce a response when it is bound to a carrier protein.

Front 23

Describe the differences in how B-cells vs. T-cells view/interact with antigens.

Back 23

T-cells mostly react to antigens that are proteins or peptides. They will react with the antigen of the surface of antigen presenting cells or with MHC and co-stimulatory molecules. Once activated they will proliferate and then stimulate B-cells. B-cells may recognize/mount antibody response to a protein carrier or a hapten. Once activated by T-cells, B-cells may differentiate into plasma cells or memory cells; Other T-cell factors cause the switch from IgM to IgG production.

Front 24

What are T-independent antigens? What types of molecules are part of this class?

Back 24

T-independent antigens are immunogens that do not require T-cell help to produce and immune response. These are usually polymeric molecules with a large number of repeating subunits that can cause cross-linking of the Ig on the B-cell. They may also be polyclonal activators of B-cells that provide a mitogenic signal to the B-cell ( thought to work through TLRs).

Front 25

What is an antigen presenting cell (APC)? What features or actions are required for a cell to be considered an APC?

Back 25

APC function is to intiate interaction with antigen via endocytosis, phagocytosis or interaction with complement (C3b receptor mediated or preexisting), or receptors. APC process the antigen (digest) and then present its fragment on the cell surface with MHC class II antigens. Additionally, the APC must express MHC class II antigens on its surface, provide a second or co-stimulatory signal (B7). Note: B-cells can do these things too.

Front 26

Which cells are considered excellent antigen presenting cells?

Back 26

Dendritic cells, Langerhans cells, mononuclear phagocytic cells.

Front 27

List the 5 most important ROS inclusive of the RNOS. Which ones are primary and which are secondary. Draw the chemical structure for each. Which ones are free radicals.

Back 27

Primary ROS: Superoxide and Nitric oxide (primary RNOS). The others are secondary ROS.

Front 28

Write the metabolic synthesis rxns for the following ROS: superoxide.

Back 28

Front 29

Write the metabolic synthesis rxns for the following ROS: Nitric oxide.

Back 29

Front 30

List the 13 vitamins and their common names.

Back 30

Front 31

List the fat soluble vitamins.

Back 31

Vitamins: A, D, E, K

Front 32

List the water soluble vitams.

Back 32

Vitamins: B1, B2, B3, B5, B6, B9, B12, Biotin, C

Front 33

Vitamins are classified according to absorption/transport and not function. For each of the listed fat-soluble vitamins, indicated key classification features: A, D, E, K.

Back 33

Vitamin A: chromophore, hormone, antioxidant; Vitamin D: hormone; Vitamin E: antioxidant; Vitamin K: coenzyme involved in carboxylation, calcium and clotting.

Front 34

Vitamins are classified according to absorption/transport and not function. For each of the listed water-soluble vitamins indicate key classification features: C, B complex (B1-3, B5-6, B9, B12), Biotin.

Back 34

Vitamin C: antioxidant, a collagen/cross-linking cofactor; Vitamin B1-3, B5-6, Biotin: energy releasing (oxphos)
Vitamin B9, B12: hematopoietic

Front 35

List the primary functions for each of the fat-soluble vitamins? Note the deficiencies associated with each.

Back 35

Vitamin A: deficiency results in night blindness and keratomalacia (softening of cornea); Vitamin E: deficiency results in damage to cell membranes, leakage of cell contents leading to myopathies, neuropathies, and liver necrosis but no MAJOR disease. Note: preemies/LBW and those with fat malabsorption predisposed to Vit E deficiency. Vitamin K: deficiency associated with increased prothrombin time and easy bruisability. Note Vitamin antagonists are anticoagulants.

Front 36

List the associated functions/enzymes for each of the water soluble vitamins. Note the deficiencies associated with each.

Back 36

Front 37

Summarize the key functions of Vitamin A.

Back 37

Front 38

What are the precursors for vitamin A? What are the main derivatives of the Vitamin A family? Which of the derivatives is active in vision? Which of the derivatives is active gene transcription for growth/development?

Back 38

Front 39

What are the key functions of Vitamin D?

Back 39

Front 40

What are the 2 inactive provitamins of Vitamin D? Describe their conversion to active Vitamin D.

Back 40

Front 41

List the 3 major macrominerals.

Back 41

Calcium, Magnesium, and Phosphorous

Front 42

List the 9 microminerals.

Back 42

Chromium, Copper, Cobalt, Fluorine (aka Fluoride), Iodine, Iron, Manganese, Molybdenum, Selenium, and (Zinc).

Front 43

List the 4 hormones that regulate calcium homeostasis. Indicate their primary roles in maintaining this homeostasis.

Back 43

Front 44

Describe the mechanism of calcium homeostasis, specifically the action of the 4 regulatory hormones.

Back 44

Front 45

What is the significance of Chromium (Cr) to metabolism?

Back 45

Front 46

Describe how copper deficiency leads to anemia. Compare/contrast to iron-deficiency anemia.

Back 46

Front 47

How are minerals classified in terms of daily allowance?

Back 47

Macrominerals:> 100-200 mg per day required;
Microminerals: <100-200 mg per day required.

Front 48

Describe the general biologic function of minerals.

Back 48

Participate in metal ion catalysis (many are metal ions);
-Facilitate nucleic acid stabilization (esp. Mg+)
-Assist with protein folding (i.e. zinc fingers)

Front 49

List the 15 essential minerals and for each indicate its function(s) and any diseases that result from deficiency.

Back 49

Front 50

Describe the role and effects of calcium in the body.

Back 50

Front 51

Describe the absorption and transport of dietary calcium.

Back 51

Calcium is absorbed in the intestines by active transport. Vitamin D is required for via calcium binding protein, calbindin.

Front 52

Describe the process of bone remodeling by osteoblasts and osteoclasts and role of the major calcium-related hormones.

Back 52

Front 53

Define the differences between osteoporosis and osteomalacia.

Back 53

Osteoporosis: mineralization is normal, bone mass reduced.
Osteomalacia: mineralization is reduced, bone mass is normal.

Front 54

List the dietary sources of Vitamin D? Where is Vitamin D stored in the body?

Back 54

Vitamin D is obtained from fortified dairy products and oily fish. Most vitamin D, however, can be obtained from the action of sunlight on provitamins in the skin. Vitamin D is stored in fat depots throughout the body.

Front 55

Describe/characterize the Vitamin D deficiencies: Rickets (in children) and osteomalacia (adults).

Back 55

Rickets is a disorder of cartilage cell growth and enlargement of the epiphyseal growth plates and accumulation of undermineralized bone matrix giving soft, pliable bones (i.e. bowing of knees). Osteomalacia is a demineralization of preexisting bone that results in softer bones more susceptible to fracture.

Front 56

What is the result of Vitamin D toxicity (>50,000 IU per day).

Back 56

Very high serum calcium that leads to aberrant calcification of soft tissues (i.e. formation of kidney stones which can lead to kidney failure).

Front 57

What is the biologic role of Vitamin E? Where is it found in the body? Major dietary sources?

Back 57

Vitamin E acts as an antioxidant-- a free radical scavenger (alpha tocopherol is potent ROS scavenger). It also prevents oxidation of LDL, thereby helping to reduce risk of CVD. Vitamin E is found in cell membranes, circulating lipoproteins and fat deposits (mostly). Dietary sources: vegetable oils.

Front 58

List the 2 key members of the Vitamin E family(there are 8 naturally occuring forms). Which is the form that is actively maintained in the body? Which 2 homologs are the major forms found in blood plasma.

Back 58

Front 59

Deficiencies in Vitamin E result in what types of problems?

Back 59

Damage to cell membranes, leakage of cell contents resulting in myopathies, neuropathies and liver necrosis. No major Vitamin E deficiency is know. Note: preemies and persons with fat malabsorption are predisposed to Vitamin E deficiency.

Front 60

What are contraindications to Vitamin E supplementation?

Back 60

Large doses of Vitamin E can interfere with Vitamin K metabolism during anticoagulant therapy and this increases risk for bleeding.

Front 61

What is the biological function of Vitamin K?

Back 61

Vitamin K is crucial for blood clotting. It is a cofactor for the conversion of glutamate residue to carboxyglutamate residue in the synthesis of calcium binding proteins including coagulation factors: II (prothrombin), VII, IX, and X. Factor II (prothrombin) synthesis occurs in liver and is proenzyme of thrombin.

Front 62

Dietary sources of Vitamin K? How is it produced, absorbed and stored/found in the body? What are the 2 naturally occurring forms?

Back 62

Vitamin K is absorbed in the small intestine and incorporated into chylomicrons, and distributed to tissues via low density lipoproteins. It is present in tissues in small amounts and there is little long-term storage. Naturally occuring forms: Vit K1 and Vit K2.

Front 63

What are the symptoms/signs of Vitamin K deficiency?

Back 63

Vitamin K deficiency leads to increased prothrombin time which is associated with easy bruisability. Recall Vitamin K antagonists are given in anticoagulant therapy to prevent thromboembolism.

Front 64

What is the recommended dietary intake of Vitamin K?

Back 64

There is no recommended allowance for Vitamin K because of the variable contribution from the diet and intestinal synthesis.

Front 65

List the 9 water-soluble vitamins and give their common names, cofactor form and diseases caused by their deficiency.

Back 65

Front 66

Why are the B-complex vitamins considered a complex?

Back 66

Front 67

What is the biologic role of vitamin C (aka ascorbate)?

Back 67

Vitamin C is a strong reducing agent, an antioxidant, and a cofactor in hydroxylation reactions. It is a required cofactor for enzymes that catalyze the hydroxylation of proline and lysine residues during-collagen synthesis (cross linking).

Front 68

What are the dietary sources of vitamin C? How is it absorbed?

Back 68

Fruits and veggies; It is absorbed by a sodium dependent mechanism.

Front 69

Deficiency in Vitamin C leads to what disease? What are the common signs of the disease?

Back 69

Scurvy; it is a defect in collagen synthesis. Symptoms: corkscrew hairs, impaired wound healing, malformed teeth, and capillary rupture.