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Chapter 11 –Hypersensitivity

Dr. Hafez Sumairi

Learning outcomes

1.What are the mechanisms of different types ofhypersensitivity reactions?

2.What are the major clinical and pathologic featuresof diseases caused by these reactions, and whatprinciples underlie treatment of such diseases?

Hypersensitivity

• Hypersensitivity reactions are the injurious, or pathologic, immunereactions in response to

• First, responses to foreign antigens• Infectious• Non infectious

• Second, directed against self (autologous) antigens, as a result of the failureof self-tolerance

• Responses against self antigens are termed autoimmunity,• Disorders caused by such responses are called autoimmune diseases.

Types of hypersensitivityreactionsHypersensitivity reactionsare classified on the basisof the principalimmunologic mechanismthat is responsible fortissue injury and disease

Immediate hypersensitivity• Also called allergy, or atopy

• Hay fever, food allergies, bronchial asthma, andanaphylaxis, pollen, certain foods, insect venoms,animal dander, or penicillin

• Activation of TH2 cells and production of IgEantibody

• Antigens that elicit allergic reactions often are calledallergens

• Two of the cytokines secreted by TH2 cells,interleukin-4 (IL-4) and IL-13, stimulate Blymphocytes specific for the foreign antigens toswitch to IgE-producing plasma cells.

Immediate hypersensitivity• Activation of mast cells and secretion

of mediators

• This process of coating mast cells withIgE is called sensitization

• When mast cells sensitized by IgE areexposed to the allergen, the cells areactivated to secrete their mediators

• The major amine is histamine

• TNF, IL-4, Chemokines

• IL-5, IL-13

Clinical syndromesand therapy

Therapy forimmediatehypersensitivity• The therapy for immediate

hypersensitivity diseases isaimed at inhibiting mastcell degranulation,antagonizing the effects ofmast cell mediators, andreducing inflammation

Diseases caused byantibodies andantigen-antibodycomplexes• Vasculitis, arthritis, and nephritis

• Autoantibodies against self antigensresults from a failure of self-tolerance

• Rheumatic fever

• Post-streptococcal glomerulonephritis

• EpsteinBarr virus

• Malaria

Diseases caused byantibodies andantigen-antibodycomplexes• Mechanisms of tissue injury and disease

by1. Inducing local inflammation, they may

2. Bind to and promote the destruction ofcells

3. interfere with normal cellularfunctions

Human antibody-mediated diseases(type IIhypersensitivity)

Immune complexdiseases (type IIIhypersensitivity)

Diseases caused by Tlymphocytes• The autoimmune reactions usually are

directed against cellular antigens withrestricted tissue distribution

• T cell–mediated autoimmune diseasestend to be

• Limited to a few organs and

• Usually are not systemic

• Contact sensitivity

• Tuberculosis

• Superantigens• Superantigens bind to invariant parts of T

cell receptors on many different clones ofT cells, regardless of antigen specificity,thereby activating these cells.

Delayed-type hypersensitivity (DTH)

• It occurs 24 to 48 hours after an individual previously exposed to aprotein antigen is challenged with the antigen

• In different T cell–mediated diseases, tissue injury is caused byinflammation induced by cytokines that are produced mainly byCD4+ T cells or by killing of host cells by CD8+ CTLs

• DTH reactions are manifested by infiltrates of T cells and bloodmonocytes in the tissues, edema and fibrin deposition caused byincreased vascular permeability in response to cytokines produced byCD4+ T cells

Delayed-typehypersensitivity(DTH)• Clinical syndromes and therapy

• Chronic inflammatory diseases that areinitiated by immune reactions are calledimmune-mediated inflammatorydiseases

• Antagonists of TNF

• Block costimulators such as B7 andantagonists against receptors forcytokines such as IL-1, IL-6, and IL-17

• B cell depletion with anti-CD20

Thank you