Immunoparasitology & Allergy Flashcards
Hygiene hypothesis
If exposed to helminth worms early in childhood = establishes immune system to prevent hypersensitivity
- treated asthma but at what cost..
Hypersensitivity
- Undesirable (damaging, discomfort in, fatal) reactions produced by a “normal” but over-reacting immune system
- requires a pre-sensitized immune state (prior exposure to antigen)
- Types I - IV based on mechanisms involved and time required for reaction to occur
Immediate vs Delayed Hypersensitivity
Immediate:
- Type I, II, III
- antibody-mediated
- 5 minutes to 10 hours
Delayed:
- Type IV
- T cell-mediated
- 24 to 48 hours
4 sources of allergens
- Inhaled:
- pollen, dander, mold, feces (ie. dust mites) - Injected:
- insect venom, vaccines, drugs, therapeutics - Ingested:
- food, orally-administered drugs - Contact:
- leaves, synthetic chemicals, industrial metals
Type I Hypersensitivity
- itching to death
- IMMEDIATE: 15 to 30 minutes
- exogenous antigen = IgE production
- mast cell or basophil involvement
- skin, eyes, nasopharynx, lungs, and GI tract
NOTE: parallels helminth worm infections
Mechanism: Type I Hypersensitivity
- production of IgE in response to certain antigens/ allergens
- IgE have a high affinity for Fc on mast cells + basophils = bound IgE “waits”
- **second exposure = antigen cross-links with bound IgE = degranulation of mast cells
- granules include vasoactive amines and potent inflammatory mediators
Effects of degranulation
Pro-inflammatory:
- constricts smooth muscle in lung and GI
- vasodilation
- increases permeability of small blood vessels
- increases mucus secretion
- prevents clotting
Cytokines released during degranulation
IL-4, IL-13 = ampifies Th2 response
IL-5 = eosinophil production = amplifies inflammatory response and tissue destruction
TNF-a = promotes inflammation and cytokine production
Anaphylaxis
- sudden, severe, potentially fatal, allergic reaction
- can involve skin, lungs, GI, cardiovascular
- symptoms within minutes
- asthma and hay fever are risk factors
Localized Anaphylaxis examples
- hay fever; pollen, dust mite feces
- asthma; dander, pollen, dust mite feces
- acute urticaria; animal hair, insect bites
- food allergy; peanuts, milk, eggs, shellfish
Systemic Anaphylaxis: cause
- drugs (penicillin)
- venoms (bee sting)
- food (peanuts)
= potentially fatal
Treatment for mild vs severe systemic anaphylactic shock
Mild = Anti-histamines
Severe = Epinephrine
Type II Hypersensitivity
- allergen/ antigens on cell surface (self) = IgG or IgM
- antibodies bind target = immune cells with Fc receptors recognize antibodies
= Antibody-Dependent Cell-mediated Cytotoxicity (macrophages, granulocytes, NK cells)
= bound Ab to Ag can also activate complement (classical)
Type II Hypersensitivity examples
- rheumatic fever: antibodies against bacteria (S. pyogenes) cross-reacts with antigens found on heart valves
- HDFN (Rh incompatibility)
- transfusion reactions
Type III Hypersensitivity
- soluble antigens (non-self) = IgG and IgM bind = immune complexes*
-
immune complexes are normally cleared by spleen and liver BUT failure of removal = Type III hypersensitivity
= immune complexes deposited in blood vessels and organs = activates complement and neutrophils = tissue damage/ destruction
*NOTE: multiple antibodies interacting with multiple antigens
Serum Sickness
[target antigen] = [antibodies]; point of equivalence allows formation of immune complex = Type III hypersensitivity
SLE
Systemic Lupus Erythematosus:
- associated with Type III Hypersensitivity
= chronic systemic autoimmune disease
= “butter-fly rash” on face
= damaged kidney due to infiltration of immune complexes
Type IV Hypersensitivity
- DELAYED; occurs >24 hours after antigen exposure
- mediated by activated immune cells (ie. CD4+ T helper cells, NOT ANTIBODIES)
Type IV Hypersensitivity: mechanism
- antigen = activates T helper = pro-inflammation
- CD4+ T cell secretes cytokines = excessively activates and recruits other immune cells (macrophages and neutrophils) = tissue damage
Type IV Hypersensitivity examples
- Tuberculin test
- TB granuloma
- poison ivy
