Bio 230 Lecture Notes

Chapter 17. Immunological Disorders and Tests

Immune Disorders

Type I. Immediate hypersensitivity: due to allergen exposure. e.g., hay fever, asthma.

Allergen: allergy-inducing foreign antigens or haptens. e.g., pollen, dust, molds, grain, nuts, antibiotics
Localized and systemic anaphylaxis (immediate, exaggerated, possibly fatal allergic reactions)
Mechanism: IgE mediated. Allergen activates IgE production through APC (antigen presenting cells) and T-helper cells; IgE has strong affinity to basophils and mast cells, which become sensitized on first exposure; on secondary exposure, the sensitized mast cells release histamines, activating inflammation
Treatment: the use of denatured allergens to stimulate IgG response, intercepting allergens from reaching IgE-attached mast cells.

Type II. Cytotoxic hypersensitivity: due to mismatched antigens on the red blood cells. e.g., transfusion reactions (ABO and Rh types)

Mechanism of ABO transfusion reaction: A-type individuals have Type A antigens on the red blood cells and anti-B antibodies (IgM) in serum; transfusion using B-type blood (which has B antigen on the red blood cells) causing the phagocytosis or lysis of red blood cells.

Type III. Immune-Complex hypersensitivity: due to an excess of antigen-antibody complexes. e.g., rheumatoid arthritis
Type IV. Cell-mediated/Delayed hypersensitivity: T cell (not antibody) responses to allergens. e.g, contact dermatitis due to poison ivy

Auto-antibodies: antibody against self-antigens
Examples: juvenile diabetes (autoimmunity against insulin), rheumatoid arthritis (autoimmunity against joint tissues), lupus
Mechanisms of autoimmunity

Genetic propensity (family history)
Molecular mimicry: auto-antibodies induced by parasite antigens that are similar to self-antigens
B cell mutations
Failure in clonal deletion
Viral components integrated with host membranes

Types of transplantation: autograft (self), isograft (twins), allograft (unrelated individuals), xenograft (different species)
Transplant rejection caused by T cell-mediated destruction of non-self tissues
Histocompatibility antigens: body's self antigens, encoded by major histocompatibility complex (MHC) genes. There are four MHC (or HLA) loci on chromosome 6. The MHC loci are the most diverse in the human genome: each locus having numerous alleles in human populations, such that even siblings (except identical twins) have different MHC antigens.
Tissue typing test for the matching of strong-reacting MHC allelic types.
Immunosuppression treatment during transplantation: X-ray or cytotoxic drugs to kill off immune cells

Primary immunodificiency: congenitally defective T or B cells
Secondary immunodificiency: caused by infection (e.g., HIV), lymphoma (cancer of immune/lymphoid cells), or immunosuppression treatments

Source of pathogen-specific antibodies: traditionally obtained by vaccinating an animal (horse, goat) and then harvesting he antibodies from its blood. Now antibodies are obtained in vitro by monoclonal antibody (Mab) techniques
Two types of diagnostic tests

Direct tests: test the presence of a pathogen. Diagnostic agents: antibodies for a pathogen.
Inderect tests: test the presence of antibodies against a pathogen. Diagnostic agents: anti-antibodies. More sensitive than direct tests since pathogens are rarely present in serum while infections produce antibodies in serum. Production of antibodies in the serum resulting from infection (or immunization) is called "seroconversion".

Precipitation reactions: Ab-Ag complexes form precipitation in zone of equivalence. Examples are precipitin ring test, immunodiffusion tests (in agrose gel) and immunoelectrophoresis (faster diffusion driven by electrophoresis). Gel-based techonologies are able to detect the presence of multiple antibodies against an antigen
Agglutination reactions: clumping of solid particles (e.g., microbial cells or soluble antigens attached to particles). Examples are agglutination tests, hemagglutination (clumping of red blood cells)
Neutralizaiton reactions: blocking of harmful effects of toxins or viruses

Fluorescent-antibody (FA) techniques: Ab-Ag complex detection using fluorescein-labeled antibodies. Direct FA detects antigen in a patient sample, indirect FA detects antibody in patient serum
Radioimmunoassay (RIA): the use of radioactively-labeled antibodies
Enzyme-linked immunosorbent assay (ELISA): Ab-Ag complex detection using enzyme-linked antibodies. Direct ELISA detects antigen; indirect ELISA detects antibody. Able to produce visible color changes without the use of UV (in FA) or photo-film (in RIA).
Western blot: confirmatory tests for the presence of a pathogen (direct test) or seroconversion (testing the presence of antibodies against pathogens antigens). Separation of serum proteins by electrophoresis->transfer to cellulose paper->hybridization using tagged antibodies->washing away unbound antibodies->visualization of antigen-antibody complexes