Hypersensitivity (inflammatory) reactions
Six types of hypersensitivity have been described. Types I, II, IImI and V are mediated by antibody and type IV and VI by cellular mechanisms. In practice, these reactions may not necessarily occur singly. For example type II –VI may be involved in producing autoimmune diseases. Type I reaction (reaginic/anaphylactic/ immediate hypersensitivity) is an allergic reaction produced within 30 min of exposure to a specific antigen e.g. house dust,, pollens, animal danders or moulds in certain genetically predisposed individuals who are said to be atopic. Prausnitz and Kustner in 1921, showed that the passive transfer of a serum factor (reagin) from an allergic person to the skin of a normal person could produce an immediate wheal and flare reaction in the latter in response to the allergen [25]. The mechanism entails the allergen stimulating B cells to produce specific IgE, with the aid of T helper cells. This IgE, which is allergen-specific binds to mast cells via their Fc receptor . On subsequent exposure, the allergen cross-links the surface bound IgE on the sensitized mast cell that triggers the mast cell to degranulate and release inflammatory mediators (histamine, prostaglandins, slow reacting substance (leukotriene SRS-A)) aimed at destroying the noxious substance. In Type II reactions ( cytotoxic/ membrane reactions), antibodies (IgG or IgM) are produced against antigens on the patient’s own cells. These antibodies interacting via their Fc regions and fixing complement as well as the effector cell can lead to autoimmune diseases, e.g. autoimmune anaemia. Antibodies can also ‘block’ a receptor site preventing its normal function e.g. insulin-resistant diabetes antibodies, or the IgG autoantibodies against the gastric acid-secretory parietal cells (intrinsic factor antibodies) found in pernicious anaemia. In Type III reactions ( immune complex mediated hypersensitivity) there is a hypersensitivity reaction to the immune complexes when not removed by the reticuloendothelial system but deposited in the tissues. Complement is activated and results in inflammatory reactions leading to cellular damage. The soluble complexes are formed when the antigen is in excess as by injecting large amounts of heterogenic serum into the circulation causing ‘serum sickness’ or the precipitation by insoluble complexes when the antibody and antigen are equivalent or in an excess of antibody causing an ‘arthus reaction’ ( a red, oedematous area at site of injection within 4-12h). Complexes are deposited in the bronchial walls in pulmonary asperigillosis, and in the vessels in erythema nodosum. Immune complex formation with aself - antigen occurs in the autoimmune disease such as systemic lupus erythematosus (SLE); Low- grade persistent infection with a weak antibody response to a microbial antigen occurs with viral hepatitis B or staphylococcal infective endocarditis and repeated inhalation of an environmental antigen, e.g. moulds or animal antigen can produce an extensive allergic alveolitis such as farmer’s lung disease with the antibodies being IgG. Type IV reactions ( cell- mediated/ delayed hypersensitivity) reactions) take more than 12 h to develop and can be produced in several ways. The cell recruitment is initially neutrophil in nature (within a few hours) and is followed by lymphocytes and macrophage infiltration (24-48 h). Type IV reactions can be transferred from one animal to another by certain types of lymphocytes but not by serum. The reaction is mediated by a) T delayed hypersensitivity cells ( TD ) that have become sensitized to a particular antigen previously and release lymphokines ( MAF, MIF, Interferon) and interleukins ( IL-1,-2,-3) ; b) T cytotoxic cells (Tc), which directly damage infected target cells, e.g. virus- infected cells, allogenic cells or host cells in graft- versus host disease. Thus, Type IV reactions are seen in association with viral infections and the intracellular bacterial infections- tuberculosis, leprosy and brucellosis and cause severe tissue damage. They are also implicated in autoimmune diseases such as Hashimoto’s thyroiditis and homograft rejection. Type V reaction ( stimulating antibody reaction) is an IgG directed against cell surface antigens that stimulate some cells instead of killing them. This is seen in the pathogenesis of neonatal hyperthyroidism as IgG stimulating antibodies directed against thyroid cells would be capable .of crossing the placenta, or Graves’ disease (hyperthyroidism) in adults where serum IgG behave like TSH and binds to the thyroid TSH receptor producing excessive stimulation of thyroid hormone production. Interestingly, Graves’ disease is associated with other autoimmune disorders such as pernicious anaemia and myasthenia gravis ( acetylcholine receptor antibodies at the nicotinic neuromuscular junction). Interestingly, thymic hyperplasia is found in 70% of myasthenic patients below the age of 40, and a thymic tumour is found in in 10%. Type VI reaction (antibody-dependent, cell- mediated cytotoxicity (ADCC) entails killer lymphocytes (K cells) which lyse target cells coated with antibody. Being activated by antigen-antibody complexes, the K cells interact with the Fc region of cell-bound antibody, and destroy the target cells by the release of proteolytic enzymes. Type VI reactions are also involved in autoimmune diseases, tumour rejection and defence against helminthic parasites. Immuno-pharmacology includes the role of anti-inflammatory (e.g. corticosteroids), immunosuppressive drugs (e.g. corticosteroids, cyclosporine & tracolimus against T cells) and anti-lymphocytic sera in dampening these hypersensitivity reactions and the prevention of transplant/ graft rejection [ 1-4, 26]