Hypersensitivity Flashcards
Allergen
innocuous antigen that does not normally cause disease
common sources of allergens
inhaled, injected, ingested, and contacted
Type 1 hypersensitivity
immediate type hypersensitivity is mediated by igE and mast cells
3 phases of type 1 hypersensitivity
sensitization, immediate response, and late phase response
sensitization
APC presents antigen to MHC II–> MHC II presents to a naive CD4+ t cell–> this differntiates into th2 because of th2 bias–> th2 produces IL-4, IL-5, IL-13
purpose IL-4 (and IL-13)
class switching igE
purpose of IL-5 (IL-3)
eosinophil maturation/activation
sensitization steps after th2 produces IL-4, IL-5, IL-13
th2 cells help B cells differentiate into IgE producing B cells–> IgE unload onto FcE receptors on mast cells–>mast cell becomes pre-armed
atopy
exaggerated tendency to mount an IgE response to allergens; an atopic patient will have elevated serum IgE and eosinophils
causes of atopy
genetic–> IgE binding and th2 bias increase atopic tendency; pollution; hygiene hypothesis
second- immediate phase
crosslinking of IgE by the antigen which causes mast cell activation and degranulation within seconds (explosive degranulation of mast cells)
primary mediators of immediate phase
histamines and proteases (like tryptase and chymase)
effect of primary mediators (minutes)
vasodilation (permeability), smooth muscle spasm, and mucus secretion with tissue damage
secondary mediator 1 = things cleaved from membrane phospholipids (eicosanoids) (15 min- hours)
leukotrienes, prostaglandins, and platelet activating factor (which is a chemotactic agent that brings in eosinophils, basophils, and neutrophils)
effect of secondary mediators 1
vasodilation and permeability; smooth muscle spasm; chemotaxis of neutro, baso and eosinophil
secondary mediators 2= cytokines (hours)
not preformed; have to be transcribed into mRNA and made into proteins and then secreted by the mast cells;
help prolonged activation
IL-4 and IL-5 help in maturation of eosinophils and MIP1 alpha and beta are involved in recruitment of macrophages
Phase 3- late response
mediated by eosinophils that are circulating in the blood and must be recruited to the site of infection by factors of macrophages
eosinophils are recruited by
eotaxin (lung epithelium, fibroblasts, smooth muscle) and leukotriene B4 (mast cells)
eosinophils are activated by
IL-5
eosinophils can ________ inflammation in ___________ of antigen
sustain; in the absence of …..whereas mast cells are only activated in the presence of antigen
four sites of mast cells aka first line of defense
eye, nose; lung; gi; and skin—-skin and mucosal surfaces
disease symptoms are determined by
the route of allergen entry and the site of activation of the tissue resident mast cells
actute urticaria
route: skin or systemic; mast cell activation in upper dermis; and disease = increase vascular permeability, edema, and inflammation
angioedema
route: mucosal surfaces or systemic; mast cell activation in the dermis, subcutaneous tissue and/or mucosa; disease = edema and inflammation …. this is what is dangerous in vocal cords or upper airways
allergic asthma cause
elevateed IgE levels, eosinophil
mast cell activation in the lung
triggered by specific allergens
anaphylaxis
route: systemic; anaphylactic shock = systemic vasodilation, BP drop, arrythemia, brady or tachycardia, cardiac arrest
treatment of anaphylaxis
epinephrin for cardiovascular
b2 receptor agonist (salbutamol) for brochospasm
type 2 hypersensitivity
antibodies mostly IgG bind either cells or ECM
2 principle mechanisms that cause hypersensitivity type 2
binding to cells = phagocytosis or lysis and recruitment of neutrophils causing inflammation is if it binds to ECM
mechanism behind type 2 hypersensitivity
RBC presents a non-self antigen that activates complement, which opsonized the RBC–> c3b receptor along with fcgamma receptor (antibody) on macrophage recognize the opsonized particle and phagocytose it
this can cause anemia as well as low levels of circulating platelets
type 2 hypersensitivity happens most commonly with
transfusion reactions and drug allergies
2 other instances where type 2 hypersensitivity plays in:
eryhthroblastosis fetalis and drug allergies where some drugs alter the cell surface molecules that can then be targets for antibody responses
explain mechanism of antibodies (IgG) having hypersensitivity type 2 to ECM
macrophages through Fcgamma receptor recognize antigen on the surface of a matrix and they bind to it, along with complement. c5a recruits neutrophils to the site. the neutrophils then release lysozymes and ROS
best examples of type 2 hypersensitivity from ECM’s
acute rheumatic fever (antibodies to the streptococcus pyogenes wall proteins that bind to cardiac glycoprotein)
goodpasture syndrome- antibody to collagen of basement membrane in kidneys and lungs
type 3 hypersensitivity reaction
immune complexes are formed between a soluble antigen and IgG antibody (the IC are then deposited on the wall of the blood vessel and cause inflammation- vasculitis)
Phase 1 of hypersensitivity type 3
antigen–> recognized serum proteins by t cells–> stimulate b cells–> stimulate production of antibodies which are secreted (takes about a week)
Phase 2 of hypersensitivity type 3
immune complexes form from the reaction of the antibodies and the serum proteins (which is what makes the serum proteins go down in the graph). IC deposition preferentially happens in kidney glomeruli, joints, skin, and serosal surfaces
phase 3 of hypersensitivity type 3
IC deposited in blood vessel causes activation of complement activation, neutrophil recruitment, and neutrophil activation
diseases of hypersensitivity type 3
serum sickness- systemic application of soluble proteins and depending on where IC deposits stick to determines clinical signs. this can look like type 1 but the difference is that it is delayed onset
arthurs reaction- local immune complex activation (can happen with repeated exposure to a vaccine)
arthurs is local as opposed to systemic
hypersensitivity pneumonitis- farmer’s lung- hay dust/ mold spores
poststreproccocal glomerularnephritis; reactive arthritis (post infection)
SLE (LUPUS) is the classic type 3 hs reaction
type 4 hypersensitivity reactions
delayed hypersensitivity reaction mediated by t cells
mechanism behind type 4 hypersensitivity reacion
antigen is taken up by APC, they present them to cd4+ t cells which differentiate into TH1 cells; th1 cells then secrete the th1 characteristic cytokines; cytokines and chemokines cause severe inflammation through recruitment and activation of macrophages along with lysozymes, radicals, and vasoactive mediators
typical th1 cytokines
IFN gamma- activates macrophages, vascular adhesion molecules
INF alpha- causes local tissue destruction
chemokines (IL-8) recruits macrophages
example of a DTH reaction
poison ivy or contact dermatitis from nickel
2 ways that urushiol causes the poison ivy reaction we see
modification of extracellular proteins–> uptake by langerhans cells (DC) –> presentation via MHC class II –> activation of CD4+ Th1 cells
uptake by epidermal cells and modification of intracellular proteins –> presentation via MHC class 1 –> activation of CD8+ T cells
