Hypersensitivity reactions

hypersensitivity reaction

heightened and/or inappropriate response

4 major types of hypersensitivity reactions

type I, II, III, IV

Type I hypersensitivity reaction

immediate type hypersensitivity (allergy, asthma, IgE mediated)

Type II hypersensitivity reaction

Cytotoxic (anti-body mediated) hypersensitivity (Rh mismatch Ig-mediated C’ activation)

Type III hypersensitivity reaction

Immune complex hypersensitivity (serum sickness, vasculitis, AG-Ab complexes) (serum sickness=med allergy)

Type IV hypersensitivity reaction

Delayed type hypersensitivity (TB skin test, Tdth (Th1) cells)

2 phases of allergy

sensitization and effector phase

Sensitization phase

• exposure to antigen/allergen

• production of IgE

• binds to mast cells and basophils

Effector phase

• IgE binds to allergen/antigen

• IgE crosslinking results in mast cell degranulation

• release pharmacologically-active mediators

IgE production and genetics

• APC produces cytokines (help guide immune response)

• Th2 are especially important for allergy reactions

• IL-4 promotes B cells to switch to produce IgE antibodies

Atopic individual

one that is prone to allergy

allergen

a non-parasitic Ag that stimulates IgE

Relative dosage of allergen

the amount of allergen exposure that can influence production of IgG or IgE

Preformed chemical mediators of allergies

• histamine

• increases vascular permeability and smooth muscle contraction

Newly formed chemical mediators of allergies

• occurs in 30-60 seconds

• leukotrienes (esp LTE4)

• increase vascular permeability and pulmonary smooth muscle contraction

• 1000x more potent that histamine

Allergic reaction symptoms

• dependent on allergen exposure site

• wheal and flare reaction

• bronchoconstriction

• mucous secretion

• vasodilation (shock)

Wheal-and-flare reaction

• skin becomes itchy (pruritus) and experience erythema (redness)

• basically an inflammatory reaction

3 main types of treatment of allergies

• anti-histamine-anti-leukotriene

• desensitization

• anti-IgE therapy

Anti-histamine/anti-leukotriene treatment

block the binding of histamine/leukotriene to target cells

desensitization treatment

low dose of allergen to stimulate immune system to produce IgG

anti-IgE therapy treatment

remove IgE antibodies, to prevent binding to FceR

2 Assays for IgE-mediated allergies

• skin test

• radioimmunoassay

Skin test

• small amount of potential allergens exposed on skin

• may cause a severe reaction

radioimmunoassay

• detect allergen/antigen specific IgE in serum (need purified allergens)

• start with fixed amount of radioactivity, then reduce to form precipitate

Type II hypersensitivity

produce antibody to antigen found on cells

ex: blood transfusion reactions

Ab-mediated cytotoxicity

• C’ activation of ADCC

• ABs bind to cell surface, activate C’, then are lysed

Transfusion reactions

• Abs are produced against determinants on blood cells

• ex: inject type B into type A (anti-B Abs bind to B=activate C’=cell lysis)

Human blood groups

• ABO

• 2 antigens (A/B)

• 4 blood types, A,B,AB,O

Isohemagglutinins

-’natural antibodies’ IgM

-serum from type A that agglutinates cells from B

Rh

2 major types, Rh+ (85%) and Rh- (15%)

universal blood donor type

blood type O- (has no antigens for donor immune system to attack)

universal blood recipient

blood type AB (no antigens to attack donor cells)

Hemolytic disease of the newborn (HDN) (type II hyper sens)

• erythroblastosis fetalis

• maternal IgG (anti-Rh abs) crosses placenta to into fetal RBCs

• causes C’ activation and destruction of fetal blood cells

HDN treatment

• RhoGAM- given soon after delivery

• reduces risk of sensitization to <1%

Immune complex disease (type II hyper sens)

• ex: serum sickness, lupus, arthus reaction

• large AG-Ab complexes (IgG>IgM)

• complex localizes in kidney, blood vessel walls

  • activate C’=cell destruction=stimulate ADCC

type III hypersensitivity

1. introduce Ag and form immune complexes

2. C’ activation, chemotaxis of inflammatory cells (mast cells, neutrophils)

3. release more inflammatory mediators

4. destruction of cells in area (esp endothelial)

Delayed-type hypersensitivity (type IV)

• DTH response: CD4+ and T cells stimulate inflammation

• influx of inflammatory cells (esp macrophages)

• initial symptoms after 24 hours, peaks at 48-72 hours

• ex: TB test and poison oak stimulation

TB skin test

• tuberculin reaction: inject PPD

• is previously exposed, memory Tdth (Th1) present and are activated —>stimulate local inflammation

summary of 4 types of hypersensitivity reactions