277 Chapter 18 Immune Disorders Allergy (Hypersensitivity): Allergen: How does an allergen enter the body? 3I, 1C

277 Antibody-Mediated Cell-mediated (Immediate-type) (Delayed-type) 1. Few seconds to 1. one to several days 24 hours. 2. Involves the release 2. No of histamine. 3. Occurs in blood 3. Anywhere vessels, connective tissues and smooth muscles.

Antibody-mediated Cell-mediated (Immediate-type) (Delayed-type) 4. Can be transferred 4. No with serum that contains IgE. 5. Cannot be transferred 5. Can be transferred with lymphocytes. with lymphocytes. 6. Type I, type II and 6. Type IV type III.

278 Physiology of IgE-mediated Allergy: 1. Allergen enters the body. 2. The immune system produces IgE. 3. The IgE attaches to the mast cell and basophil. 4. The cells are described as being sensitized.

Insert figure 16.3 Cellular reactions A schematic view of cellular reactions during the type I allergic response. (1-6) sensitization, (7-10) provocation.

278 5. The next time the same allergen enters the body again. 6. The allergen connects to the IgE. 7. The binding activates the cells to undergo degranulation. 8. The chemical mediators (histamine, bradykinin, serotonin, leukotriene, heparin) are released from the sensitized cells. It is due to these chemicals that cause the allergic reaction.

Atopic dermatitis (eczema): Food allergy: Drug allergy: 279 Type I Allergy Atopic Diseases: Hay fever: Asthma: Atopic dermatitis (eczema): Food allergy: Drug allergy: Anaphylaxis (anaphylactic shock):

280 Diagnosis of Type I Hypersensitivity: Skin testing: Desensitization or hyposensitization: IgG removes allergen from the system. IgE combines with allergen and prevents it from reacting with the mast cells. Allergen induces clones of suppressor T cells which block the production of IgE by B cells.

Diagnosis of Allergy Important to determine if a person is experiencing allergy or infection Skin testing

281 Type II Allergy Mismatch in: ABO system: Blood transfusion Rh system: Erythroblastosis fetalis

281 Blood Types Agglutinogens Agglutinin A A B B B A AB A and B None O None A and B Recipient ------- Antibody? Donor ----------- Antigen? Compare Antigen and Antibody Homologous ---- Reaction (clumping) Incompatible (cannot donate blood)

Interpretation of blood typing.

282 Type III (immune complex-mediated) Allergy Mechanisms: The immune complexes precipitate in the basement membranes of epithelial tissues. The neutrophils release lysosomal granules to digest the tissues and cause a destructive inflammatory conditions.

283 Type III Allergy Arthus reaction (antibody excess): Serum sickness (antigen excess): Hypersensitivity Pneumonitis: Glomerulonephritis: Rheumatoid Arthritis: Systemic Lupus Erythromatosus (SLE):

Figure 18.9 The crippling distortion of joints characteristic of rheumatoid arthritis.

Figure 18.10 The characteristic facial rash of systemic lupus erythematosus.

284 Type IV/Delayed-Type Allergy Infectious Allergy (Allergy of Infection): Contact Dermatitis:

Figure 18.11 A positive tuberculin test, a type IV hypersensitivity response.

Figure 18.12 Allergic contact dermatitis, a type IV hypersensitivity response.

285 Major histocompatibility complex (MHC or HLA): Type I and type II genes are responsible for recognition of self and regulation of immune response. Host-versus-graft reaction: Graft-versus-host reaction:

285 Type IV (Delayed or Cell-mediated) Hypersensitivity: Graft rejection Classes of Grafts: Autograft: Isograft (Syngraft, syngenic, isogenic): Allograft (Homograft): Xenograft (Heterograft):

Types of grafts Figure 18.13

286 Tissue Typing: Mixed lymphocyte reaction (MLR): Tissue typing: a. Lymphoagglutination b. Lymphocytotoxicity

286 Causes of Autoimmune Diseases: Estrogen may stimulate the destruction of tissues by cytotoxic cells. Maternal cells may cross placenta and trigger an autoimmune disease in the fetus. Fetal cells may cross placenta and trigger autoimmunity in mother.

286 4. The sequestered antigen theory During embryonic development, some tissues are hidden behind anatomical barriers and cannot be detected by the immune system. Eventually their antigens are exposed due to infection, trauma or deterioration. They are then attacked by our immune system.

287 5. The clonal selection theory The forbidden clones (the lymphocytes that can react with our tissues) are supposed to be eliminated. If they survive, they will attack our own tissues.

287 Theory of molecular mimicry 7. Theory of viral infection

288 Examples of Autoimmune Diseases Autoimmunity Affecting Blood Cells: Autoimmune hemolytic anemia Autoimmunity Affecting Endocrine Organs: Type I diabetes mellitus (juvenile-onset diabetes): Type II diabetes (maturity-onset, non-insulin- dependent diabetes): Graves’disease: against thyroid gland; excessive thyroid hormone (results in goiter)

288 C. Autoimmunity Affecting Nervous Tissue: Multiple sclerosis (MS): Autoimmunity Affecting Connective Tissue: Rheumatoid arthritis

288-289 Immunodeficiency Diseases: I. Primary Immunodeficiency Diseases: 1. Chronic granulomatous disease 2. Agammaglobulinemia (Hypogammaglobulinemia): 3. DiGeorge syndrome (thymic aplasia): 4. Severe combined immunodeficiency (SCID):

289 Secondary Immunodeficiency Disease: Autoimmunodeficiency syndrome (AIDS):

David, the bubble boy, with severe combined immunodeficiency.

Primary immunodeficiency diseases.