IMMUNOLOGICAL TECHNIQUES
Laboratory tests vary widely in clinical immunology. Some are essential for diagnosis while others useful in subclassifying disorders. Finally, some are of research interest only but may add to our immunological armamentarium in the future. In this regard, it is important to understand that these tests do vary in their sensitivity and specificity.
TYPE IV: DELAYED
T cells drive this reaction when they react with antigen and release TH1 cytokines. The cytokines in turn attract other cells, such as macrophages, which release their lysosomal enzymes. Histologically, the lesions consist of lymphocytes, macrophages, and occasionally eosinophillic polymorphonuclear leucocytes, leading to a chronic lesion of necrosis fibrosis and granulomatosus reaction. An excellent example of this reactivity is seen when PPD is injected into the skin of a person who has been previously infected with the tuberculosis organism.
TYPE III: IMMUNE COMPLEX
These reactions result from the presence of either circulating immune complexes in the tissues. Deposition of immune complexes depends on their size, charge, local concentration of complement, and perhaps most important the nature of the antigen. An excellent example of this type of reaction is the arthritis reaction in which antigen is injected into the skin of an animal previously sensitized to the same antigen and has produced antibody to that antigen. The preformed antibody goes to the site of the injected antigen and forms a complex, thereby inducing complement activation and neutrophil attraction. The result is intense local inflammation, hemorrhage and necrosis, There are numerous examples of this type of hypersensitivity reaction, including serum sickness, glomerulonephritis and systemic lupus erythemathosus.
TYPE II: CELL BOUND
These reactions are initiated by antibody reacting with antigen on the cell membranes. IgM and IgG can be involved in these reactions. Clinical examples include organ-specific autoimmune diseases and immune hemolytic anemia. The role of autosensitized T cells in some diseases such as rheumathoid arthritis and multiple sclerosis have been postulated, but the evidence for their involvement is far from clear. In Grave’s disease (hyperthyroidism), autoantibodies have a primary pathogenic but specific reactive T cells are also present. However, it is not clear whether the T cells exert a primary role in stimulating antibody production or are really secondary to the tissue damage.
HYPERSENSITIVITY REACTIONS
TYPE I: IMMEDIATE
These reaction are those that involve antigens that react with IgE bound to tissue mast cells or basophils. Activation of the mast cell results in the release of large amounts of pharmachologically active substances. These reactions are rapid (hence immediate) and if injected into the skin a “wheel and flare” reaction can be seen within five to ten minutes. Most antigens stimulating IgE are either inhaled or ingested. A perfect example of the inhaled antigen is ragweed pollen. The IgE production requires helper T cells and T-cell-derived cytokines. IL-4 and IL-13 stimulate IgE production while IFN-γ is inhibiting. Many factors regulate the balance between help and suppression, including route of administration, physical nature of the substance, and the genetic background of either animals or humans. In the latter, there s a family tendency to these reactions but exact genetic factors are still ill defined.
TISSUE DAMAGE PATHWAY
Although the major function of the components of the immune system is to neutralize or destroy the invading organisms or antigen, these reaction often cause “bystander” tissue damage as well. These are called hypersensitivity reactions, and Gell and Coombs conveniently divided them into five types.
The use of an antibody-coated target to destroy foreign target cells is called antibody-dependent cell-mediated cytotoxicity, or ADCC. This killing is dependent on the recognition by cells bearing Fc receptors and includes monocytes, neutrophils and NK cells. These cells do not need simultaneous recognition by MHC molecules. The mechanisms of killing most likely involve the release of cytoplasmic components of the target cells and perforin, but additional factors are also probably involved.
