Hypersensitivity Flashcards
1
Q
Type I hypersensitivity
A
- immediate
- mediated by IgE
- commonly called allergies or atopic disorder
- atopic individuals are 10-40% of the pop and are genetically susceptible and generally have higher levels of IgE and eosinophils
- clinical manifestations depend on the route of entry on the antigen and location of the responding cells
2
Q
common sources of allergens
A
- inhaled
- injected
- ingested
- contacted
3
Q
commonalities between allergens
A
- relatively low MW
- highly soluble
- stable proteins carried on particles
- contain peptides that can be presented by MHC class II
- effective at activating TH2 cytokines especially IL4 and stimulating and IgE response
4
Q
require initial sensitization
A
- antigen activation of TH2 cells and stimulation of IgE class switching in B cells
- production of IgE
- binding of IgE to FcRepsilon on mast cell
5
Q
subsequent exposures
A
- allergen binds to IgE bound to mast cell
- releases chemical mediators for immediate ration
- cytokines cause late phase reaction 2-4 hours later
- can also cross link IgG, or C5a can bind to complement receptors
- mast cells also have TLRs-can be turned on in response to LPS
6
Q
contents of mast cell granules
A
- histamine
- TNF
- tryptase
- chemokines-CCL3- brings monocytes
- lipid activators-leukotrienes
7
Q
two phases
A
- immediate response is wheal and flare- swelling from leakage and engorgement with RBCs
- late phase is more widespread swelling and inflammation
8
Q
effects of mast cell mediators
A
-vascular leakage
-bronchoconstriction
-intestinal hypermobility
^ from amines and lipid mediators
-inflammation-cytokines
-tissue damage-enzymes
9
Q
SRS-A
A
- slow releases substance of anaphylaxis
- mixture of leukotrienes produced during response
10
Q
serotonin
A
vascular perm
11
Q
TNF
A
expression of adhesion molecules on endothelial cells
12
Q
mediators bring in
A
- IF cells
- basophils
- eosinophils
- reciprocally regulated- TGFb and IL3 increase basophils and decrease eosinophils
- IL5 and GM-CSF increase eosinophils
- usually low levels until activated, then can expresses IgE FcR
13
Q
granulocytes and parasites
A
- promotes expulsion of parasites by increased peristalsis and mucous
- kills parasites and host cells and helps with tissue remodeling
14
Q
responses to subQ allergen
A
- insect saliva
- low dose
- activates mast cells
- increase vascular perm and localized swelling
- urticaria is localized, deeper more diffuse swelling is angiodema
- mechanism in skin testing for allergies (RAST assay for allergen specific IgE)
15
Q
responses to inhaled allergen
A
- allergic rhinitis
- antigen taken in by APC activates TH2 cells which make IgE first time via IL4
- second time inhaled and antigen activates local mucosal mast cells
- causes blood vessel perm and activation of epithelium
- eosinophils recruited (IL5 and GM-CSF) and enters nasal passages with mucous
16
Q
allergic asthma
A
- acute-mucosal mast cell captures antigen
- IF mediators contract smooth muscle, increase mucous secretion from airway epithelium and increase BV perm
chronic
- mediated by cytokines and eosinophil products
- can occur in absence of allergen- other irritants like cold or smoke
- leads to tissue remodeling and mucous plugs
TH2 cells-IL13?
17
Q
reactions to adsorbed antigen
A
- food
- ingestion activates mucosal mast cells in gut
- release histamine, which acts on epithelium, BV, and smooth muscle
- antigen diffuses into blood vessels and is widely distributed causing urticaria
- smooth muscle contraction is vomiting and diarrhea
- fluid flows into gut lumen
18
Q
responses to systemic allergin
A
- systemic anaphylaxis
- drugs, serum, venom, peanuts
- epipen-tight junctions, relaxes smooth muscle, activates heart
- antigen in bloodstream enters tissues and activates CT mast cells throughout the body
- mast cells degranulate and release IF mediators
- drop in BP is fatal
- contracts airway
- cramps and vomiting
19
Q
genetic predisposition
A
- MHC and non MHC
- TcR
- IL4
- IL4R
- IgE Receptor
- structural variants
- increases the immune response
20
Q
hypersensitivity doubled
A
-hygiene and low parasites
21
Q
hygiene hypothesis
A
- poorer hygiene results in exposure to Tg1 inducing infections which protect against allergy
- little allergy seen in worm infections in developing countries that need TH2?
22
Q
counter regulation hypothesis
A
- infections lead to production of IL10 and TGFb which downregulates TH1 and TH2
- less hypersensitivity
- clean and genetic=allergies
23
Q
treatment for type I sensitivity
A
- avoid the allergen
- treat symptoms with antihistamines, corticosteroids, singulair, epi, albuterol
- desensitization-controlled exposure to increased dose of antigen over time leads to IgA and G antibodies which block binding of allergen to IgE
- allergenic peptide vaccination to anergize allergen specifiv T cells
- anti IgE
- block effectors-anti cytokines
24
Q
Type II, III, IV
A
- may occur in response to foreign antigen
- also when an individuals immune system reacts against autologous or modulated self antigens
- impacted by genetic susceptibility and environmental factors
25
Q
Type II
A
- antibodies bind to a cell associated antigen or cell surface receptor and fix antigen
- penicillin modifies proteins on RBCs and IgG binds to it
- leads to lysis or complement and phago
- when platelets its thrombocytopenia
- significant in ABO transfusions- we have antiA, B or both
26
Q
Type III
A
- large quantities of soluble antigens and their antibodies develop and form large latticed immune complexes
- isotype, valency, charge, and ability to fix complement determine IC pathogenicity
- latticed immune complexes are pathologically capable of depositing systemically in any of a variety of tissue sites, creating downstream cellular damage with many different clinical presentations
- serum sickness
- kidney problems
27
Q
arthus reaction
A
- locally injected antigen in immune individual with IgG
- local immune complex formation activates complement, C5a binds to a receptor on mast cell
- the antibody complex also binds to the mast cell and induces degranulation
- local IF, increased fluid and protein release, phago, blood vessel occlusion
- PMNs attracted and produce lysosomal enzymes
- tetanus booster at less than 5 years
28
Q
serum sickness
A
- occurs after the development of antibody, 7-10 days
- may occur after large amounts of foreign protein such as antisera for snake bite, mouse antibodies, streptokinase
- second time can happen 1-3 days
29
Q
type IV
A
- delayed type from proteins leading to local skin swelling
- contact type from poison ivy leading to local epidermal reaction
- gluten sensitive-atrophy in small bowel and malabsorption
- TH1 cells important-chemokines, IFN gamma, TNFa and LT, IL3 and GM-CSF
30
Q
delayed type sensitivity
A
- antigen introduced subQ and processed by APCs
- TH1 recognizes and releases cytokines
- T cells, phago, fluid and protein to site
- PPD
31
Q
contact hypersensitivity
A
- CD4 cells activate other immune cells while CD8 cells kill chemical reacted cells that display foreign antigen
- poison ivy toxin modifies our skin protein
- first time ok, second time lots of active T cells
32
Q
treatment of type 2,3,4
A
- avoid antigen
- reduce the impact of the immune response with antiinflammatories, steroids
- reduce immune response in general (steroids) or specifically (target B and T cells)
- induce regulation of the response (Treg)
- block the effector mechanisms of allergic response cytokines, co stim molecules
33
Q
Type IV
A
TH1 cells
chemokines, IFN gamma, TNFa and LT, IL3 and GM-CSF
