Hypersensitivity Reactions

Front 1

What factors are released in the immediate response of a type I?

Back 1

-Histamine
-Chymotryptase
-TNF-a

Front 2

Histamine's role in immed. response?

Back 2

incr. vascular permeability, incr smooth muscle contraction

causes wheal, swelling

Front 3

Chymotyptase role in immed response?

Back 3

-digestion of ECM components -- "remodelling"

Front 4

TNF-a role in immed response?

Back 4

incr. expression of adhesion molecules on endothelial cells, incr overall inflammatory response

Front 5

What is released in the late response?

Back 5

-cytokines
-chemokines
-leukotrienes

Front 6

Cytokine role in late response?

Back 6

IL13, IL4 for Th2 response
IL3,5 and GM-CSF stimulate eosinophil production in bone marrow

Front 7

Chemokine role in late response? Which chemokine?

Back 7

MIP-1 recruits neutrophils, macrophages, monocytes

Front 8

Leukotriene role in late response?

Back 8

same as histamine, but much more potent

Front 9

What comprises the eosinophil immedate response?

When does this occur in relation to the rest of the type I reaction?

Back 9

they degranulate as well, release MBP (for parasites)

BUT unless eosinophils happen to be nearby where the reaction is taken place, they must be recruited from the bone marrow, which would take place after the late phase response in the big picture of Type I reactions

Front 10

What comprises the eosinophil late response?

Back 10

They function to increase the overall inflammatory response

-in time leading up to late response they synthesize prostaglandins, cytokines, leukotrienes which they then release

Front 11

What elements are in place to control eosinophil involvement

Back 11

Normally number is low since they're so toxic

IL-5 from Th2 cells increases their production in bone marrow

They migrate to site in response to eotaxin made by activated endothelial cells

FcER on their surface must be induced so they're not degranulated willy nilly

Front 12

What does major basic protein do to mast cells and basophils?

Back 12

causes further degranulation

Front 13

What kind of immune response (which effector cell) do allergens favor?

Which IL favors IgE production

Back 13

Allergens favor Th2 responses

Th2s then produce IL-4, which cause IgE to be made

Front 14

What happens if you get type I reaction activation in the blood stream?

Back 14

system anaphylaxis
GI- cramps, vomiting, diarrhea
Respiratory- airways close down
Vasculature- incr. permeability = swelling, loss of blood pressure, reduced O2 delivery to tissues, shock

Front 15

What is the result of a mild type I reaction in the airway?

Back 15

allergens diffuse across mucus membranes and activate mucosal mast cells

allergic rhinitis- runny nose, itchy, watery eyes

Front 16

More severe type I rxn in airways?

Back 16

allergic asthma

allergens get farther down, mast cells activated in lower airways, causes airway obstruction

over time, get chronic response mediated by cytokines/eosinophils-- chronic presence of CD4 Th2s, neutrophils, eosinophils

Front 17

Type I on skin?

Chronic type I on skin can lead to?

Back 17

hives/urticaria
mast cells activated in deeper subcutaneous tissue-- more diffuse swelling (angioedema)

chronic- atopic dermatitis, eczema

Front 18

What are the treatment strategies

Back 18

Avoidance
Drugs (antihistamines, corticosteroids, cromolyn sodium- prevents mast cell degranulation)
Desensitization (Allergy immunotherapy)
Try to switch from Th2 to Th1 response

Front 19

What is a type II hypersensitivity rxn-- what's it mediated by? What's it against

Back 19

Mediated by IgG, against cell surface proteins or tissue proteins

Front 20

Four examples of Type II reactions

Back 20

Penicillin allergy
Erythroblastosis fetalis
Autoimmune affecting cell function (myasthenia gravis)
Goodpastures

Front 21

Factors involved in penicillin allergy

Back 21

Penicillin
-Ab binds to RBC/Pen, activates complement AND allows opsonization to occur

-Get hemolytic anemia, thrombocytopenia

Front 22

Factors involved in goodpastures (3 things that can happen)

Back 22

-Ab to basement membrane can activate classical complement pathway
-Bound Ab and C3b can opsonize tissue and activate macs, neutrophils
-Bound Ab can induce ADCC by NK cells

Front 23

What autoimmune diseases are result of type II reactions?

How could you treat them?

Back 23

Graves, myasthenia gravis, goodpastures,

plasmapheresis or mAb against specific Igs

Front 24

What four things can induce a type III reaction?

Back 24

persistent infection
autoimmune reaction (body interprets as persistent infection because can't get rid of self Ag)
Inhalation- IgG is induced instead of IgE, get immune complexes forming in alveolar wall upon long term exposure
Systemic administration of Ig for passive immunity- induces body to develop anti-Ig Ab

Front 25

What's the common factor among these four things?

Back 25

immune complex formation/accumulation

Front 26

What are the steps of immune complex formation and damage?
-complex formation first induces what two things?
-then these cause other things to happen

Back 26

-small complexes don't get cleared, deposit in vessel walls
-activate classical complement pathway
-activate macs and neutrophils

Front 27

What do activated macrophages do?

Back 27

secrete TNF-a, L-1, which cause tissue damage and recruit more neutrophils

Front 28

What does complement activation do?

Back 28

Anaphylatoxins induce mast cell and basophil degranulation= increased vascular permeability

then more complexes can get further into vessel wall

complement components also recruit PMNs

Front 29

Immune complexes also cause what?

Back 29

platelet aggregation

Front 30

What do PMNs do to vessel wall

Back 30

release lysosomal enzymes, cause wall damage

Front 31

What do enzymes and tissue damage result in?

Back 31

fever, pain in local site, urticarial rash because of deposition in skin vessels

Front 32

Two common types of Type IV reactions?

Back 32

DTH reaction - eg, TB skin test (ag is protein)
Contact sensitivity- Ags are metal ions, haptens

Front 33

What type of cells initiate Type IV reactions?

Back 33

Tc, Th1, Th2

Front 34

What types of cells cause the damage in Type IV reactions?

Back 34

Tc, macrophages, eosinophils

Front 35

What's different about this than the other reactions (in the amt of Ag required)

Back 35

requires 100-1000 times more Ag to elicit response

takes 1-3 days

Front 36

Why does Type IV take so long to elicit a response?

Back 36

relies on memory T cells...these must proliferate...

Front 37

Granulomatous reaction

Back 37

Ag induces a Type IV response, so effector T cells attack it, but they can't eliminate it

Ag gets surrounded by macrophages, w/lymphocytes surrounding periphery

necrosis can occur because of ischemia