Hypersensitivity reactions mediated by antibodies fall into different types. These are: anaphylactic reaction, cytotoxic hypersensitivity, Immune complex mediated tissue damage, T-Cell-mediated hypersensitivity, stimulatory hypersensitivity and antibody dependent cell-mediated cytotoxic mechanism (ADCC). What are they?
Type 1: Anaphylactic reaction
Initial introduction of the antigen (e.g, penicillin) leads to the production of cytotoxic antibodies (mainly IgE) in sensitive persons. These are attached to the surface of mast cells.
On subsequent exposure, the antigen reacts with the preformed antibodies, causing mast cell degranulation and release of histamine serotonin, and slow reacting substance (SRSA). This may lead to asthma due to broncho-constriction, or anaphylactic shock due to wide-spread capillary dilatation.
Allergens such as pollens, house dust and fungi react with cell bound IgE of the respiratory tract leading to bronchial asthma or hay fever. Allergens from food may cause urticaria.
Type I hypersensitivity reaction occurs within 30 minutes of exposure to the allergens. Such reaction can be abolished by drugs like adrenaline and disoduim cromoglycate which prevent the release of histamine. Antihistamines compete with the released histamine for effector sites. Repeated introduction of the allergen in small doses results in hyposensitization.
Type II: Cytotoxic hypersensitivity
Certain drugs may complex with membrane proteins of blood cells leading to production of auto-antibodies. These antibodies can lyse the blood cells through the action of complement. Hemolytic anemia caused by alpha methyl dopa, agranulocytosis produced by amidopyrine and thrombocytopenia induced by chlorothiazides are examples of this mechanism.
Type III: Immune complex mediated tissue damage
The continued presence of antigen causes persistent antibody production. Antigen antibody complexes form and circulate in the blood. These heavy molecules are entrapped in the blood vessels, renal glomeruli, lungs, skin and joints.
Complement system is activated through the alternate pathway. The complement degradation products attract polymorphs and macrophages and an inflammatory reaction sets in with resultant damages to the tissues. Platelet aggregation occurs and these microthrombi lead to vascular occlusion and ischemia. If the antibody is in excess, the complexes are rapidly precipitated and tend to be localized at the site of entry of antigen. This leads to Arthus type reaction. If an antigen is injected intradermally into a hyper-immuned animal, erythema and edema occur at the site of the injection.
This reaction reaches a peak in 3-8 hours, and is referred to as intermediate type skin reaction. Farmer’s lung is the classical example of localized type III reaction. On the other hand, if antigen is in excess, soluble complexes are formed which precipitate in all tissues, giving rise to the serum sickness type of reaction. The lumpy granular precipitates seen in renal glomeruli in post-streptococcal glomerulonephritis are due to systemic type III reaction.
Type IV: T-cell-mediated hypersensitivity reaction
This is also called delayed type hypersensitivity in which a slow erythematous indurated lesion develops after an intradermally injected tuberculin (or similar antigen) on an individual.
Thyroid cells are normally stimulated by TSH through a membrane associated receptor. The long acting thyroid stimulator (LATS) which is an antibody against some components if the receptor also produces TSH like activity but it is more prolonged. The continued stimulation of LATS leads to hyperthyroidism. Similarly, anti-lymphocyte globulin is stimulatory to lymphocytes in appropriate conditions.
Type VI: Antibody dependent cell-mediated cytotoxic mechanism (ADCC)
This mechanism does not require complement activity. The effector cells are neither T nor B cells but are called K cells. The specificity of this reaction resides in the antibody molecule. Only very small amounts of antibody are required to produce this reaction and therefore this mechanism is effective in areas where antibody concentration may be minimal, e.g, at the site of solid tumors. The full significance of this mechanism has not been known.