MICR171 Midterm III - Hypersensitivities

Type I hypersensitivity

Allergic reactions

Stimulated by IgE binding to IgE receptors FcεRI (Fc epsilon receptor I) on mast cells/basophils

Type I hypersensitivity phases

1. Sensitization - IgE antibody produced response to stimulus and binds to receptors

2. Activation - Cross-linking of receptors by antigen/ligand

3. Effector - Inflammatory mediators released by mast cells, late-phase reaction (accumulation of eosinophils, basophils, lymphocytes, macrophages after 48 hours)

Preformed vs newly synthesized mediators

Preformed (present in granules then released)

• Histamine, serotonin, eosinophilic chemotactic factors (attract eosinophils)

Newly synthesized

• Leukotrienes, thromboxanes, prostaglandins, platelet-activating factor

Type I hypersensitivity therapy/intervention

• Prevention (masks)

• Detection via skin-prick tests

• Desensitization + blocking antibody (incr IgG production)

• Antihistamines (block H1 receptors)

How do histamines function?

Binds to H1 / H2 receptors in cells which causes constriction in muscle cells and separation (vascular permeability) in endothelial cells

Protective role of IgE

Antihelminthic response

When mast cell cross-linking of IgE occurs, serum components brought to site of infection. IgG coats surface of worm and attracts eosinophils

Type II hypersensitivity types

1. Complement mediated - antibody react with cell membrane self-antigen resulting in complement fixation + lysis

2. Antibody-dependent cell-mediated cytotoxicity / ADCC - IgG cells killed by cells with Fc receptors for Ig (NK cells, macrophages, neutrophils, eosinophils)

3. Antibody-mediated cellular dysfunction - antibody binds to cell surface receptor

Type II hypersensitivity conditions

• Transfusion reactions (ABO/Rhesus-incompatibility)

• Erythroblastosis fetalisis

• Myasthenia gravis

Type III hypersensitivity

1) IgG (sometimes IgM) antigen-antibody immune complex forms 2) complexes deposit in tissue without being cleared 3) complement activated, granulocytes are attracted and cause damage with lytic enzymes

• Can be systemic (serum sickness, rheumatic fever) or localized

Type IV hypersensitivity

Sensitization + elicitation stage

• Specific inflammatory TH1 + TH17 cells activated

• Proinflammatory cytokines released by T cells

• Recruitment and activation of antigen-nonspecific inflammatory leukocytes (esp macrophages) that cause damage

Poison ivy, contact dermatitis, tuberculin

Delayed hypersensitivity: maximal 48-72 hours after exposure

Types of delayed hypersensitivity

1. Contact sensitivity - antigen taken up by Langerhans cells in skin then presented to T cells

2. Granulomatous - macrophage unable to destroy pathogen, continues to accumulate and lead to fused epithelial cell clusters

3. Tuberculin-type