Hypersensitivity Reaction - Essay Example

? Hypersensitivity Reactions Hypersensitivity Reactions Hypersensitivity reactions refer to reactions by the normal immune systemsthat are undesirable. They include autoimmunity and allergies. The reactions could be occasionally fatal, uncomfortable, or damaging. In order for hypersensitivity reactions to occur, they need the host to be in a state of pre-sensitization. Gell and Coombs classified these reactions into four groups. These are: allergy, antibody dependent hypersensitivity, immune complex disease, delayed hypersensitivity disease, and autoimmune disease. This paper aims to review the immunological mechanisms giving rise to the four groups of hypersensitivity. It also compares and contrasts hypersensitivity reactions caused by antibodies and those caused by T-lymphocytes, while also discussing the clinical consequences of each of the reactions using examples. Hypersensitivity reactions can be divided into type I-IV, based on the various involved mechanisms. Type I, often associated with allergy, is mediated by IgE. IgE triggers basophil and mast cell degranulation cross linking with antigen. Type II occurs on binding of the host’s cells to antigens, which marks them for destruction (Phillips, 2006 p89). Mediation is by IgG and IgM antibodies. Type III hypersensitivity triggering occurs due to aggregates of IgM, IgG, complement proteins, and antigens deposited in tissues. Type IV hypersensitivity’s mediation is by macrophages, monocytes, and T cells. Infectious diseases and autoimmune involve this hypersensitivity in their reactions. Most hypersensitivity injuries develop due to interactions between antibodies and antigens or between sensitized T-lymphocytes and antigens. The general symptoms accompanying the reaction depend on the involvement of either T-lymphocytes, or antibodies. During antibody involvement, immediate hypersensitivity results, while T-lymphocyte involvement results in delayed hypersensitivity reaction. Immediate hypersensitivity includes immune complex reactions, cytotoxic reactions, allergic reactions, and anaphylaxis. Delayed hypersensitivity includes infection allergies and contact dermatitis. Antibody Mediated Hypersensitivity vs. T-lymphocyte Mediated Hypersensitivity Antibody mediated hypersensitivity depends on the antigen nature, its frequency, and antigen contact route (Phillips, 2006 p11). It also depends on antibody type that reacts with the antigen. The initial antigen dose is known as sensitizing dose. On exposure, a latent period follows. Later, a dose of the same antigen, referred to as shocking or eliciting dose, sets off the reaction. This results in tissue damage. In T-lymphocyte mediated hypersensitivity, T-lymphocytes function rather than antibodies. These T-lymphocytes function in cell mediated immunity. They produce Lymphokines, which stimulate macrophage influx in order to perform phagocytosis. This results in immune response exaggeration. For both antibody mediated and T-lymphocyte mediated hypersensitivity reactions, local tissue destruction results. However, destruction of tissue by T-lymphocyte mediation occurs via phagocytosis. For antibody mediated hypersensitivity, reactions begin minutes after antigen administration (Phillips, 2006 p31). On direct administration of the antigen directly to the tissue, for example, injection or bee stings, a systemic reaction occurs. For instance, anaphylactic shock may result. When the contact involved is superficial, involving epithelial tissue, a localized reaction results, for example, hay fever and asthma. These reactions can also be referred to as atopy or allergy. T-lymphocyte mediated hypersensitivity, on the other hand, requires one day or more in order to develop. It can manifest in the form of infection allergy, such as in the tuberculin test (Phillips, 2006 p34). A second manifestation of T-lymphocyte mediated hypersensitivity is contact dermatitis. Large blister like lesions accompany the reaction, with vesicles surrounded by redness. The vesicles usually itch intensely. Allergens act as the antigens that elicit antibody mediated hypersensitivity, particularly when involvement of local allergic reactions exists (Phillips, 2006 p33). Penicillin molecules, included in the group of haptens, could be involved when bound to larger molecules of proteins. Allergens for this class of include animal dander, pollen grains, dust, feathers, and food. For T-lymphocyte mediated hypersensitivity, allergens involved include plant substances like poison oak, disinfectants, cosmetics, and metals such as mercury and nickel (Phillips, 2006 p35). Clinical Consequences of Hypersensitivity Antibody mediated hypersensitivity reactions can be divided into three classes. These include type I, II, and III hypersensitivity. Type 1 hypersensitivity, also referred to as anaphylactic or immediate hypersensitivity, invo0lves the skin (eczema and urticaria), eyes, nasopharynx, bronchopulmonary tissues, and the GIT. The reactions normally last between fifteen to twenty minutes, with symptoms ranging from death to minor inconveniences. Sometimes, its onset may be delayed, by between ten to twelve hours (Castells, 2011 p45). IgE mediates immediate hypersensitivity. The mast cell, or the basophil, is the primary cell in this hypersensitivity. Platelets modify and/or amplify reactions, as do eosinophils and neutrophil. Then mechanism involves the production of IgE preferentially in response to antigens, also known as allergens. Individuals prone to this hypersensitivity produce more TH2 cells preferentially, which in turn secrete IL-13, IL-5, and IL-4. These interleukins favour switching of IgE class. IgE has a high affinity for its receptors on basophil and mast cells (Castells, 2011 p45). Subsequent exposure to the allergen causes the cell bound IgE to cross-link, triggering various pharmacologically active substances to be released (Doan et al, 2008 p34). Triggering of mast cells requires these IgE Fc receptors to be cross-linked. Calcium ion influx precedes degranulation of mast cells, which is a vital process. Ionophores, which lead to an increase in cytoplasmic calcium ions, promote degranulation, while agents that cause depletion of cytoplasmic calcium lead to Degranulation suppression. Mast cells could also be triggered by anaphylotoxins like c5a, chemicals like codeine, emotional stress, and exercise. While reactions mediated without allergen-IgE interaction by the same agents produce similar symptoms, they cannot be called hypersensitivity reactions. Platelet activation factor amplifies the reaction, leading to aggregation of platelets and release of histamine, vasoactive amines, and heparin. ECF-A and neutrophil chemotactic factors act as an attraction for neutrophil and eosinophils respectively (Frederic et al, 2010 p10). These cells act in the release of necrosis causing hydrolytic enzymes. The local reaction may also be controlled by release of PG-E, histaminases, and arylsulphatase. Cyclic nucleotides also modulate this hypersensitivity reaction. Substances that alter levels of cGMP and cAMP alter symptoms of allergy (Frederic et al, 2010 p10). Type II hypersensitivity affects various tissues and organs. Allergens in this hypersensitivity involve endogenous antigens, though haptens with the ability to attach to the membrane of the cell can also trigger it (Frieri & Brett, 2009 p22). Examples of this hypersensitivity disorder include thrombocytopenia, granulocytopenia, and haemolytic anaemia. The reaction lasts for minutes to hours. IgG or IgM classes of antibodies primarily mediate the reaction. The lesions formed consist of neutrophil, complement, and antibodies. Treatment involves immunosuppressive and anti-inflammatory agents. Type III hypersensitivity may involve single organs like kidneys, lungs, and joints, or may be general, for example, serum sickness. The reaction takes approximately three to ten hours after antigen exposure. Soluble immune complexes mediate the reaction (Kenneth et al, 2011 p25). This involves class IgG, though class IgM may be involved too. Antigens could be exogenous or endogenous. The antigen does not attach to the involved organ and is soluble. The primary components include complements (C3a, 5a, and 4a), and immune complexes. Platelets cause the damage, as do neutrophils. Primarily, the lesion contains immune complex deposits, neutrophils, and complement. In the later stages, infiltration by macrophages may lead to healing. Disease production and determination of the involved tissue depends on antibody affinity and immune complex size (Kenneth et al, 2011 p25). T-lymphocyte mediated hypersensitivity can also be referred to as type IV hypersensitivity, which causes erythemal and induration. It works in the pathogenesis of infectious diseases and autoimmune diseases, as well as granulomas. Mechanisms of damage include macrophages, monocytes, and T-lymphocytes (Phillips & Mario, 2006 p61). Tc led to direct damage while TH1 secrete cytokines, which in turn activate Tc and recruit macrophages and monocytes. They then activate these cells. This activation leads to most of the damage. Lymphokines involved include IL-2, interferon gamma, monocytes chemotactic factor, and TNF beta/alpha. Bibliography Castells, Mariana C: Anaphylaxis and hypersensitivity reactions. Totowa, N.J: Human, 2011. Doan, Thao T, Roger Melvold, and Carl Waltenbaugh: Concise medical immunology. Baltimore, MD: Lippincott Williams & Wilkins, cop., 2008. Frederic P. Miller, Agnes F. Vandome, John McBrewster: Hypersensitivity. Saarbrucken: VDM Verlag Dr. Mueller e.K., 2010. Frieri, Marianne, and Brett Kettelhut: Food hypersensitivity and adverse reactions: a practical guide for diagnosis and management. New York: M. Dekker, 2009. Kenneth M. Murphy, Paul Travers, Mark Walport: Janeway's Immunobiology. Oxford: Garland Science, 2011. Phillips, Michael, and Mario R Escobar: Hypersensitivity. New York: Plenum Press, 2006. Sherman, William Bowen: Hypersensitivity. Philadelphia: Saunders, 2008. Thomas J. Kindt, Richard A. Goldsby, Barbara Anne Osborne, Janis Kuby: Kuby Immunology. Gordonsville: W.H. Freeman, 2006. Read More