L19 Flashcards
What is type 1 hypersensitivity?
↑IgE coats mast cells & basophils
Immediate response
Faster & larger response when +antigen
How do you test for type 1 HST?
IgE skin test = patch/prick tests
RAST = measure allergen specific IgE in blood
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
What is the difference between mast cells and basophils in a type 1 HST reaction?
Mast cells @ tissues
Basophils @ circulation
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)
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
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)
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
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
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
What is anaphylaxis? Mechanism, symptoms, treatment.
Mechanism = extreme type 1 HST Symptoms: - Bronchial constriction - Edema - CV collapse (hypotension) Treat w/ EPI !!!!
What are the anaphylatoxins?
C5a, C3a, C4a - inflam members of complement cascade
From MAST CELLS
↑SM contract
↑vasc perm
What is bronchial asthma? What is the triad of symptoms?
Due to repeated type 1 HST rxns @ lung
- Periodic & reversible airway destruction
- Eosinophils –> chronic bronchial inflam
- Bronchial SM hypertrophy & hyper-reactive
What are the 4 ways you can treat bronchial asthma?
- Cromolyn - stabilizes mast cells so don’t degran easily
- Leukotriene antagonists (phosphodiesterase inhibitors) block bronchial SM constrict
- Corticosteroids - ↓cytokines –> ↓inflam
- Epi (inhaler) broncho-dilator
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
How are monoclonal Abs used for allergies?
= Abs against IgE
Neutralize & elim IgE
Define an allergen.
= antigen that elicits type 1 HST rxn
Define atopy.
Likelihood of a person to have an allergic response to something
Why you’re allergic to peanuts and I’m not
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
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
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)
What is pemphigus vulgaris? What type of HST is it?
Type 2 HST
Ab against desmosomes in epidermal cell jxns
Form skin vesicles
What is Graves disease? What type of HST is it?
Ab for TSH receptor
Stimulates receptor w/o hormone
Effects of hyperthyroidism (bulging eyes!!)
What is Myasthenia Gravis? What type of HST is it?
T2 HST rxn
Ab binds ACh receptor @ NMJ –> no muscle contraction
Eyelid droop
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)
Where are common deposit locations of Ab-antigen complexes in type 3 HST?
Where BVs branch!!!!
Kidney glomeruli
Joints
What is an important examples of type 3 HST diseases?
Systemic lupus erythematosus (SLE) = Ab against DOUBLE STRANDED DNA
What are 3 ways to treat chronic (type 2 & 3) HST diseases?
- Corticosterioids - limit inflam damage
- Plasmapheresis - remove bad Abs in blood
- IVIG - giving preformed IgG
- Binds Fc gamma R2b = inhibits B cells switching
- Bind IgE directly to ↑removal from body
- ↓IL4
Which receptor yields B cell inactivation (anti-inflam)?
CD32
Fc gamma R2B
