essay 3 - allergic reactions - definition, types and pathogenesis

define allergic reaction

• an altered sensitivity to a specific antigen//allergen.

hypersensitivity

• Disorders caused by immune responses are called hypersensitivity reactions

• Hypersensitivity reactions are abnormal and excessive responses of the activated immune system that cause harm and injury to the host tissues

List the types of allergic reactions

• Type I - anaphylactic - IgE mediated

• Type II - cytotoxic - IgG/IgM mediated

• Type III - immune complex - AgAb mediated

• Type IV - delayed types - T cell mediated

• Type I - anaphylactic - IgE mediated

• The outcome depends on location and degree of exposure, e.g localised response is hayfever, while a systemic response is anaphylaxis

1. an individual is exposed to a specific allergen and develops IgE antibodies which attach to mast cells. These mast cells are now called sensitised mast cells

2. upon re-exposure to the same allergen, the allergen attaches to the IgE antibodies on the mast cells, stimulating mast cell degradation and releasing histamine and other chemical mediators such as leukotrienes and prostaglandins

3. these chemical mediators, mainly histamine, cause vasodilation of the blood vessels and increased capillary permeability, bronchiole constriction and nerve irritation leading to itching and pain. A combination of these (mainly respiratory and circulatory) leads to severe oxygen deficit to the brain leading to generalised collapse and loss of consciousness

• the treatment for types 1 hypersensitivity reactions are antihistamines, epinephrine injection and glucocorticoids in cases of severe or prolonged allergic reaction

• Type II - cytotoxic - IgG/IgM mediated

1. the immune system is exposed to a cell surface natigen (may be intrinsic or extrinsic)

2. body produces IgG or IgM antibodies against this antigen and they bind to the target cell surface, which leads to 3 possible mechanism (the mechanism depends on the target antigen and disease context)

A) cell destruction = complement is activated leading to opsonisation or direct cell lysis. e.g in case of mismatched blood transfusion

B) inflammation = complement is activated, specifically complement fragments C3A and C5A which recruit neutrophils and monocytes causing tissue inflammation and injury e.g goodpasture syndrome (anti-glomerular basement membrane disease)

C) Cellular dysfunction = antibody binds to receptors on target cells and alters the cell function. This may block receptors (e.g Myasthenia Gravis) or it maly stimulate receptors (e.g Graves disease)

• Type III - immune complex - AgAb mediated

1. soluble Ag binds to Ab and forms immune complexes within circulation

2. these complexes deposit in tissues and they activate the complement system which recruits neutrophils to the site causing inflammation

3. the neutrophils release enzymes and reactive oxygen species causing tissues damage and necrosis

• e.g Artus reaction, post streptococcal reaction and serum sickness

• Type IV - delayed types - T cell mediated

1. First exposure to the antigen causes antigen presenting cells to present the antigen to CD4 T cells

2. upon re-exposure the memory T cells recognise the antigen and actuate CD4 (release cytokines, recruit and activate immune cells) and CD8 (directly kill target cells)

3. activated macrophages and immune cells cause inflammation and injury locally which appears 24-72 hours after

• E.g hasimotos, mantoux TB test