2-Hypersensitivity Reactions Flashcards
hypersensitivity reaction
definiton
host response to antigen that dev into deleterious effects like tissue damage and death
types
I = allergy, anaphylaxis
II = antibody mediated cytotoxicity
III = immune complex disease
IV = delayed type hypersensitivity, only one not cell mediated
type I
general
rapidly progressing immune rxn thru antigen bindning IgE coated basophils or mast cells
‘immediate hypersensitivity’
i.e. respiratory allergies, allergic asthma, hives, food, anaphylaxis
allergens
anaphylaxis induced by insect venom, penicillin, seafood, nuts
allergens go directly into blood stream or rapidly absorbed from gut so systemic mast cell activation
acute urticaria
aka wheal and flare
allergy testing, insect bites, animal hair
seasonal rhinoconjuctivitis
pollen (ragweed, grass, tree)
dust mite feces
asthma
dander, pollen, dust mite feces
food allergy
fish, shellfish, peanuts, tree nuts, milk, soy, eggs, wheat
atopy
inc tendency to dev allergies
atopic indivs make IgE to allergens instead of parasites so physiologic resp to parasites usually in skin, airways, gut same as allergic
Th2 resp so no inflamm
hygiene hypothesis
dec exposure to pathogens early in life > TH2 immunity and IgE instead of TH1 so allergy/asthma inc in developed countries
respiratory allergens
small moles carried on larger particles like pollen grains or mite feces
-soluble allergen elutes/diffuses into mucosa at very small doses
-transmucosal delivery in very low doses so effective elicit TH2 IgE resp
basophils
characteristics
part of peripheral blood WBC
-purple staining, granules present
-non phagocytic
-related to mast cells so prominent in allergies/anaphylaxis
dev of anaphylaxis
- first exposure = IgE antibodies made
- IgE binds Fc receptors on basophils and mast cells
- subsequent exposure to allergen binds surface bound IgE and release granule contents, memory resp
- granules have vasoactive compounds so edema and SM contraction, 2-30 min after exposure
mast cell granule contents
- histamine - bronchial SM contract + inc vascular permeability
- proteases- act matrix metalloproteinases to cleave tissue matric proteins = damage
- TNF alpha - promote inflamm
- eosinophils- acc of esoins locally or in blood will counteract effects of histamine
leukotrienes
LTC/D/E4
-most potent substance cause SM contraction and inc vascular permeability
-released more slowly and longer effect than histamine
eosinophils
acc in nasal and bronchial mucosa in resp allergies and in intestinal mucosa during worm infections
attach to worms and release granules with hydrolytic enzs
late phase response
6-8 hours after immediate rxn thru secretion of prostaglandins, leukotrienes, chemokines, cytokines
-2nd phase of SM contraction
-sustained edema
-recruit eosins and TH2 cells
-remodel tissue i.e. SM hypertrophy and hyperplasia
treatments for type I
- epinephrine- only one that reverses anaphylaxis, binds beta adrenergic receptors
- antihistamines-bind hista receptors
- cromolyn sodium- block degranulation
- theophylline- block degranulation
- repeated subq allergen infections so IgE dec and IgG inc
- humanized mouse anti-IgE antibody- binds IgE to prevent binding to receptors
beta = Gs so inc cAMP and relax SM, tighten juctions, stim heart
type I general
antibody mediated cytotoxicity uses IgM, IgG antibodies vs cell surface or ECM antigens
-opsonize and phagocytosis of cells, complement and Fc receptor mediated inflamm, act leukocytes
hemolytic disease of newborn
Mo makes IgG to Rh antigen expressed by RBCs of child
-assume Mo Rh neg and baby Rh pos
1. first Rh pos child stims immune resp but not affected
2. later Rh pos child - Mo IgG will cross placenta and destroy RBCs in spleen and liver of child = mild symptoms or still birth
use anti-Rh antibodies to prevent sensitization
non-cytotoxic reactions
- graves disease- antibodies to TSH receptor = overprod of thyroid hormones > hyperthyroidism
- myasthenia gravis - antibodies to Ach receptor blocks nerve impulse transmission
type III general
immune complex disease induced by
1. autoimmune diseaes like lupus, SLE
2. serum sickness
3. drug rxns - penicillin
4. infectious disease- subacute endocarditis, chronic viral hepatits, poststrep nephritis
5. inhaled allergens- mold spores, hay dust
system is overwhelmed
pathogenesis
antibody + antigen = immune complex
-antigen must persist for long periods time for disease to dev
-medium size immune complexes cause problems bc lodge in tissue and act complement > C5a > neutrophil acc
-lysosomal enz damage tissue = fever, urticaria, arthritis, lymph node enlarge, proteinuria
serum sickness
prototype immune complex disease
-as conseq of repeat injection of foreign serum
1. horse anti-tetanus
2. horse antirabies
3. antiserum to snake venoms
4. antilymphocyte globulin
