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Flashcards in L19 Deck (29)
1

What is type 1 hypersensitivity?

↑IgE coats mast cells & basophils
Immediate response
Faster & larger response when +antigen

2

How do you test for type 1 HST?

IgE skin test = patch/prick tests
RAST = measure allergen specific IgE in blood

3

Because type 1 HST is a fast response, what is the pathophys that causes the delayed (late phase) response of this reaction?

Production of cytokines (AA metabolites)
Eosinophil response

4

What is the difference between mast cells and basophils in a type 1 HST reaction?

Mast cells @ tissues
Basophils @ circulation

5

What receptor does IgE bind? Explain how the receptor gets a response.

Fc epsilon
- @ mast cells, basophils, eosinophils
1. Receptors CROSS LINK
2. Conformational change
3. Lyn +P ITAM
4. ITAM recruits Syk
5. Release
- Granules (immediate rxn)
- Cytokines & AA metabolite secretion (late phase rxn)

6

Is Fc epsilon signaling broad or specific?

Broad - binds the Fc region of IgE - doesn't care which specific antigen is on the other end
Specific allergic reactions occur b/c of entry site - GI vs lungs vs. skin

7

Walk through the normal pathway for IgE production and response.

Allergen binds B cell
B cell recruits Th2 (activated by innate response to allergen)
- Th2 promotes IgE isotype switching of B cell
B cell --> IgE plasma cell against that allergen
Secretes IgE
Bound IgE + mast cell
Mast cell release of granule products (immediate reaction) & cytokines (late phase reaction)

8

Is IgE normally high or low [ ] in serum?

LOW
Moves into tissues to coat mast cells/basophils when not responding to allergen
How these cells get signals to pre-form granules so there can be an immediate response when an allergen presents

9

What are the effects of immediate mast cell/basophil products vs late phase products?

All released at same time - different time frame of action
Immediate = vacular leak, broncho-constriction, GI motility
- Vasoactive amines: vasodilate & SM contraction
- Proteases: tissue damage
Late phase = tissue remodeling and inflam
- Cytokines: inflam, WBC recruit
- AA metabolites: vasodilate & SM contract

10

Why might someone be predisposed to type 1 HST?

Genetics
- Make more IgE for same antigen
- Different cytokines to change Th2 differentiation (preferentially)
- Mutations in Fcepsilon

11

What is anaphylaxis? Mechanism, symptoms, treatment.

Mechanism = extreme type 1 HST
Symptoms:
- Bronchial constriction
- Edema
- CV collapse (hypotension)
Treat w/ EPI !!!!

12

What are the anaphylatoxins?

C5a, C3a, C4a - inflam members of complement cascade
From MAST CELLS
↑SM contract
↑vasc perm

13

What is bronchial asthma? What is the triad of symptoms?

Due to repeated type 1 HST rxns @ lung
1. Periodic & reversible airway destruction
2. Eosinophils --> chronic bronchial inflam
3. Bronchial SM hypertrophy & hyper-reactive

14

What are the 4 ways you can treat bronchial asthma?

1. Cromolyn - stabilizes mast cells so don't degran easily
2. Leukotriene antagonists (phosphodiesterase inhibitors) block bronchial SM constrict
3. Corticosteroids - ↓cytokines --> ↓inflam
4. Epi (inhaler) broncho-dilator

15

What is the idea of treating allergies via desensitization?

Slowly ↑allergen exposure in small doses
Make more IgG than IgE
IgG binds Fcgamma R2B receptor = inhibitory against B cells (can't make IgE)
May also see T2h tolerance - less class switching

16

How are monoclonal Abs used for allergies?

= Abs against IgE
Neutralize & elim IgE

17

Define an allergen.

= antigen that elicits type 1 HST rxn

18

Define atopy.

Likelihood of a person to have an allergic response to something
Why you're allergic to peanuts and I'm not

19

What is type 2 HST?

IgM/G
2 = cy-2-toxic
- Excess Ab --> complement & MAC
When bound @ cell surface - local tissue damage
More common in auto-immune

20

What is type 3 HST?

IgM/G
Ab-antigen in CRICULATION deposit in BVs
- Defective CR1 b/c usually helps clear immune complexes from the blood
- Ab+antigen+complement --> MAC --> neutrophil attraction
Deposits happen in shared areas --> predictable symptoms

21

What is goodpasture syndrome? What type of HST is it?

Auto-immune - type 2 HST
Ab against basement membrane (collagen)
@ Glomeruli --> nephritis and hematuria
- Fc receptor on glomerular membrane --> binds IgG --> inflammation and tissue destruction via complement
@ Lung alveoli --> lung hemorrhage & hemoptysis (coughing up blood)

22

What is pemphigus vulgaris? What type of HST is it?

Type 2 HST
Ab against desmosomes in epidermal cell jxns
Form skin vesicles

23

What is Graves disease? What type of HST is it?

Ab for TSH receptor
Stimulates receptor w/o hormone
Effects of hyperthyroidism (bulging eyes!!)

24

What is Myasthenia Gravis? What type of HST is it?

T2 HST rxn
Ab binds ACh receptor @ NMJ --> no muscle contraction
Eyelid droop

25

What are 2 type 2 HST diseases that could lead to anemia & bleeding?

B/c opsonization and phagocytosis due to Ab targeting
- Autoimmune hemolytic anemia (lose RBCs)
- Autoimmune thrombocytopenic purpura (lose platelets)

26

Where are common deposit locations of Ab-antigen complexes in type 3 HST?

Where BVs branch!!!!
Kidney glomeruli
Joints

27

What is an important examples of type 3 HST diseases?

Systemic lupus erythematosus (SLE) = Ab against DOUBLE STRANDED DNA

28

What are 3 ways to treat chronic (type 2 & 3) HST diseases?

1. Corticosterioids - limit inflam damage
2. Plasmapheresis - remove bad Abs in blood
3. IVIG - giving preformed IgG
- Binds Fc gamma R2b = inhibits B cells switching
- Bind IgE directly to ↑removal from body
- ↓IL4

29

Which receptor yields B cell inactivation (anti-inflam)?

CD32
Fc gamma R2B