Lecture outline :

Important definitions

Hypersensitivity reactions

Are harmful antigen-specific immune responses , occur when an individual who has been primed by an innocuous antigen subsequently encounters the same antigen , produce tissue injury and dysfuntion.

Allergen:

The antigens that give rise to immediate hypersensitivity

Atopy:

The genetic predisposition to synthesize inappropriate levels of IgE specific for external allergens

Types of Hypersensitivity

1. Type I Hypersensitivity

2. Type II Hypersensitivity

3. Type III Hypersensitivity

4. Type IV Hypersensitivity

5. Type V Hypersensitivity

Type I Hypersensitivity (Anaphylactic) Reactions/Allergy:

Occur within minutes of exposure to antigen

Antigens combine with IgE antibodies

IgE binds to mast cells and basophils, causing them to undergo degranulation and release several mediators:

Histamine:

Prostaglandins:

Leukotrienes:

Anaphylactic shock: Massive drop in blood pressure. Can be fatal in minutes.

Exposure to an allergen activates B cells to form IgE secreting plasma cells

Secreted IgE molecules bind to Fce receptors on mast cells

A subsequent exposure to the allergen results in crosslinking of the bound IgE which triggers the release of various compounds

Examples

Atopy

Anaphylaxis

Asthma

Type II Hypersensitivity (Cytotoxic) Reactions / antibody-dependent :

Involve activation of complement by IgG or IgM binding to an antigenic cell.

Antigenic cell is lysed

Transfusion reactions:

ABO Blood group system: Type O is universal donor. Incompatible donor cells are lysed as they enter bloodstream.

Rh Blood Group System: 85% of population is Rh positive. Those who are Rh negative can be sensitized to destroy Rh positive blood cells.

Hemolytic disease of newborn: Fetal cells are destroyed by maternal anti-Rh antibodies that cross the placenta.

Examples

Autoimmune hemolytic anemia

Thrombocytopenia

Erythroblastosis fetalis

Goodpasture's syndrome

Type III Hypersensitivity (Immune Complex) Reactions:

Involve reactions against soluble antigens circulating in serum.

Usually involve IgA antibodies.

Antibody-Antigen immune complexes are deposited in organs, activate complement, and cause

inflammatory damage.

Glomerulonephritis: Inflammatory kidney damage.

Occurs with slightly high antigen-antibody ratio is present.

Insect bites—if an individual has been previously sensitized and has circulating antibodies, the initial reaction will be type I at the site of the bite and 4-8 hours later a type III reaction might develop

Arthus reaction: deposits of immune complexes draw neutrophils, leading to an accumulation of fluid (edema) and RBC’s (erythema)

Severity of the reaction varies from mild swelling and redness to tissue necrosis

Type III reactions can also be generalized (as opposed to localized to a specific tissue)

Large amounts of circulating antigen can form immune complexes which are not easily cleared by phagocytic cells

Examples

Serum sickness

Arthus reaction

Systemic lupus erythematosus (SLE)

Type IV (Cell-Mediated) Reactions/Delayed-type hypersensitivity/ antibody-independent :

Involve reactions by TD memory cells.

First contact sensitizes person.

Subsequent contacts elicit a reaction.

Reactions are delayed by one or more days (delayed type hypersensitivity).

Delay is due to migration of macrophages and T cells to site of foreign antigens.

Reactions are frequently displayed on the skin: itching, redness, swelling, pain.

Tuberculosis skin test

Poison ivy

Metals

Latex in gloves and condoms (3% of health care workers)

Anaphylactic shock may occur.

APC resident in the skin process antigen and migrate to regional lymph nodes where they activate T cellsSensitised T cells migrate back to the the skin where they produce cytokines which attract macrophages which cause tissue damage

Many contact dermatitis reactions are mediated by TH1 cells

The molecules (such as pentadecacatechol) complex with skin proteins and this complex is then internalized by antigen presenting cells, processed and presented with Class II MHC molecules which are recognized by appropriate TH1 cells and which are now “sensitized” to pentadecacatechol

Subsequent exposure to pentadecacatechol will activate these TH1 cells and induce cytokine production; approximately 48 to 72 hours after this second exposure macrophages accumulate at the site and release lytic enzymes that cause the redness and pustule formation of poison oak exposure

Examples

Contact dermatitis

Mantoux test

Chronic transplant rejection

Multiple sclerosis

Type V Hypersensitivity / Auto immune:

This is an additional type that is sometimes (often in Britain) used as a distinction from Type 2

Instead of binding to cell surface components, the antibodies recognize and bind to the cell surface receptors , which either prevents the intended ligand binding with the receptor or mimics the effects of the ligand, thus impairing cell signaling

Examples

Grave's disease

Myasthenia Gravis

Hashimoto's thyroiditis

Systemic lupus erythematosus

Learning objectives:

  • Define Hypersensitivity , allergen , immunogen , Allergy , Atopy
  • Types of hypersensitivity
  • Allergic response and role of mast cells in allergy
  • Arthus reaction
  • Process and mechanism of delayed type hypersensitivity