L19

Question 1

What is type 1 hypersensitivity?

Answer 1

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

Question 2

How do you test for type 1 HST?

Answer 2

IgE skin test = patch/prick tests

RAST = measure allergen specific IgE in blood

Question 3

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

Answer 3

Production of cytokines (AA metabolites)

Eosinophil response

Question 4

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

Answer 4

Mast cells @ tissues

Basophils @ circulation

Question 5

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

Answer 5

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)

Question 6

Is Fc epsilon signaling broad or specific?

Answer 6

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

Question 7

Walk through the normal pathway for IgE production and response.

Answer 7

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)

Question 8

Is IgE normally high or low [ ] in serum?

Answer 8

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

Question 9

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

Answer 9

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

Question 10

Why might someone be predisposed to type 1 HST?

Answer 10

Genetics

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

Question 11

What is anaphylaxis? Mechanism, symptoms, treatment.

Answer 11

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

Question 12

What are the anaphylatoxins?

Answer 12

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

Question 13

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

Answer 13

Due to repeated type 1 HST rxns @ lung

1. Periodic & reversible airway destruction
2. Eosinophils –> chronic bronchial inflam
3. Bronchial SM hypertrophy & hyper-reactive

Question 14

What are the 4 ways you can treat bronchial asthma?

Answer 14

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

Question 15

What is the idea of treating allergies via desensitization?

Answer 15

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

Question 16

How are monoclonal Abs used for allergies?

Answer 16

= Abs against IgE

Neutralize & elim IgE

Question 17

Define an allergen.

Answer 17

= antigen that elicits type 1 HST rxn

Question 18

Define atopy.

Answer 18

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

Question 19

What is type 2 HST?

Answer 19

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

Question 20

What is type 3 HST?

Answer 20

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

Question 21

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

Answer 21

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)

Question 22

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

Answer 22

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

Question 23

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

Answer 23

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

Question 24

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

Answer 24

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

Question 25

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

Answer 25

B/c opsonization and phagocytosis due to Ab targeting

• Autoimmune hemolytic anemia (lose RBCs)
• Autoimmune thrombocytopenic purpura (lose platelets)

Question 26

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

Answer 26

Where BVs branch!!!!
Kidney glomeruli
Joints

Question 27

What is an important examples of type 3 HST diseases?

Answer 27

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

Question 28

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

Answer 28

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

Question 29

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

Answer 29

CD32

Fc gamma R2B