The Mechanisms by Which Inflammatory and Hypersensitive Reactions to Parasites Serve as a Defence - Term Paper Example

Using specific examples, compare how inflammatory and hypersensitive reactions to parasites can be a defence of the hosts against the parasites and also a disease problem for the hosts. Abstract Inflammatory and hypersensitive reactions when appropriate are protective as part of the hosts defence against parasites, but may also be detrimental to the host by causing extensive tissue damage, allergy, or autoimmunity. Marcelo U. Ferreira et al (2004) point at the intriguing developments in the antibody antigen reactions that have seen to the development of clinical resistance to interventions against some parasites that has come up due to induced immunity as in the case of the malaria causing parasite. A parasite is “an animal which lives on or in the animal host from where it obtains some form of advantage and often harms it.’’ [Blood et al. 2007] The parasites discussed here mostly refer to helminths, protozoa and arthropods. Inflammation is ‘’a protective response of the animal host caused by cell injury and tissue damage, aiming to eliminate the cause of cell injury and to wall off and remove the injured tissue.’’ [Blood et al. 2007] Cardinal signs of inflammation include the triple response – heat, redness and swelling; and also pain and loss of function. Hypersensitivity is a modified and exaggerated immune reaction of the body to a foreign antigen and is the same as allergy. [Blood et al. 2007] There are different forms of hypersensitivity, namely Type I (immediate anaphylaxis), Type II (cytotoxicity), Type III (immune complex disease) and Type IV (cell-mediated delayed type hypersensitivity). Understanding the dynamics of host/parasite behaviour may be an important point to start any research of any medical or veterinary intervention to boost the animals’ ability to fight back parasitic invasion. The base line however is that it is possible to achieve 100% prevention against pathogenic effects of the parasites if a little and timely immune based intervention can be applied. Introduction An organism’s body has a natural way of responding to undesirable stimuli because of exposure to pathogenic organisms (usually parasites) in the environment. The response can be inflammatory or hypersensitive depending on the causative agent and the magnitude of the effect of the invasion. Inflammation is the quick response of the organism to harmful stimuli such as parasites, damaged cells and other agents that cause irritation to the body manifested through increase in body temperature, swelling, and function loss at the affected area. On the other hand, hypersensitivity refers to the immune reaction of the body against an invading parasite or other pathogenic material. It is undesirable unlike inflammatory reaction as it can lead to body discomfort and even cause diseases to the host. The most common causative agents of inflation and hypersensitivity are parasites which invade the host’s body and cause inflammation to the invaded body area. If it persists then the body responds in a hypersensitive way by forming an antigen antibody reaction with the parasite. Whether the body undergoes inflammation or hypersensitivity the ultimate goal is to eliminate the pathogenic parasite from the invaded tissue. In this paper we consider the mechanisms by which the inflammatory and hypersensitive reactions to parasites serve as a defence against the parasites and also how they can be a disease problem for the hosts. Host-parasite relationship We find different parasites developing their own ways of adjusting their virulence, adapting to the hosts, in order to increase their chances of survival and to reproduce successfully while at the same time causing harm to the hosts which results in automatic inflammatory and hypersensitive responses to their presence by the host. For example ectoparasites and endoparasties develop attachment mechanisms to survive on their host, flies avoid capture by feeding quickly with only a short period of time on the host, while other others like fleas, ticks and mites stay on the host for extended periods of time to feed. In response to the presence of parasites, the host evolves ways of counteracting the invasion of the parasites to limit the damage caused. In this process however, the host may cause harm to itself in the event of severe inflammatory reaction through maybe plucking off the parasite or extreme scratching of the skin. If done with extremism the point of invasion can be opened up for entry of other pathogenic microorganisms. In this way a simple inflammatory reaction due to the release of chemical substances from the neighbouring tissues by competitive antagonism may lead to unprecedented chronic reaction which the host will have to deal with in hypersensitivity. Hypersensitivity can cause pathological reactions which may result in tissue injury induced by humoral or cell mediated immune mechanisms. The most common hypersensitive reactions are the type I, II and III which are mediated by Ab, Ab/Ag complexes with the symptoms occurring within minutes to hours. On the contrary, Type IV hypersensitivity is mediated by T cells and the symptoms are usually delayed for days. Endoparasites are one of the typical type 1 hypersensitivity allergens. In which case they release proinflammatory substances which cause the immunoglobulin E (IgE) to be aggregated due the polyvalence of the type 1 secretion. As such the mast cells are degranulated to release substances like the histamine which are responsible for body reactions like vomiting, coughing, diarrhoea and sneezing in attempt to eliminate the parasite. The acute inflammatory response caused by IgE/mast cells interactions is particularly more immediate and systemic in nature. [Whelan, 2000] The Type III hypersensitivity occurs when there is an overwhelmed phagocytic system because immune complexes are continuously formed leading to their deposition in tissues which activate complement and induce an acute inflammatory response. Direct interaction of the immune complexes with Fc and complement receptors on the neutrophils causes the release of proteolytic enzymes which damage surrounding tissues in the blood vessels, the nephron and body joints. Granulomatous inflammation on the other hand occurs in Type IV hypersensitivity where a collection of T cells and macrophages results from inflammatory mediators such as the IL-1 and TNF-alpha released by macrophages. This inflammation is closely associated with induration, erythema and other tissue damage. Examples of Host defences against parasites: Antibody defence against the extracellular protozoa Invasion of trypanosoma congolense, T.vivax, T. brucei, triggers a body defence reaction in the blood plasma of the animals to the extracellular stages by the production of a parasite-specific antibody from B cells triggered by T-helper cells. In this case IgG and IgM antibodies are bound to the Trypanosoma’s surface antigens causing a direct damage on the parasite by binding the outer cell membrane and leading to its leakage. The classical pathway of complement-mediated lysis which enhances phagocytosis is another means of defence in which the complement C3b that is deposited on the antibody binding to the parasite surface causes it to be opsonised for phagocytosis done by the macrophages present. Activation of Macrophage against intracellular protozoa This occurs on such protozoans where the Type IV hypersensitivity. Resistance to lysosomal enzymes by the protective coat ensures the macrophages of the infected host cannot destroy it. In part the Leishmania antigens produced by the antigen-presenting cells to the T cells leads to their activation. As such nitric oxide released alongside hydrogen peroxide (toxins to most intracellular parasites) increases the effectiveness of the lysosomal enzymes. Immune elimination of gut nematodes The antigen from the worms causes the B cells to secrete IgG1antibody while the T cell secretions activate the goblet cells lining the gut. The worms are metabolically damaged by the antibody while the mucus from goblet cells aids their elimination from the gut system. This expulsion mechanism is aided also by the amines from mast cell degranulation which directly damage the worms. Dermal hypersensitivity against fleas, ticks and mites This is a Type I and IV hypersensitivity in which the immune reaction of dermal hypersensitivity mediates an intense pruritic reaction. mites usually excrete antigens in the host’s epidermis causing the mast cells under the skin to produce histamine which causes an itching inflammatory sensation. This can cause scabies in pigs and dogs in which papules will form in the skin and thicken. It is characterised by excessive grooming and self-trauma, a disease problem for the host. Eosinophil reaction against helminths This is where a host’s response has a limited effectiveness on the parasite in the antibody-mediated cytotoxicity (ADCC). Secretory/excretory antigens produced by the helminths’ larval stages in body organs like the skin and lungs stimulate secretion of IgE and IgG2 from B cellsas well as the production of eosinophil stimulation promoter while eosinophil chemo-attractants are produced by the parasite itself. On the other hand, the adult helminth damages the mesenteric veins leading to chronic granulomatous lesions, and localized thrombophlebitis. [Quinn, 1997] It has been shown experimentally that down-regulation of eosinophilia will occur when larva of extracellular helminths are stationary, adults start laying eggs and when filariae start releasing larvae [Klion, 2003]. In this case body’s hypersensitive reaction to the invasion of the helminthes has limited possibility to eliminate the parasites because of stage developments of the parasite. Eosinophilia can however contribute to the pathogenesis of diseases like hypercoagulability, hypereosinophilic syndrome when eosinophilia levels are too high. This is as a result of secretion of granule proteins like the eosonophil-derived neurotoxins and other pathogenic proteins which facilitate formation of proinflammatory cytokinins that easily attract other inflammatory cells. This may lead to the cardiac involvement which can be fatal [Scheinfeld, 2010]. Most importantly is the release of eosinophil cationic protein which is the main cause of helminth-induced tissue damage. Extreme eosinophilia is more commonly related to parasites with a migrating phase for example the Toxocara canis, Trichuris vulpis and Ancylostoma caninum. [Mackay, 2005] Formation of granuloma against large parasites (extracellular) This is a Type 4 hypersensitivity reaction against extracellular parasites in the human skin, the liver and to other zoonotic infection. This is a response to the chronic availability of antigen from a large parasite where numerous inflammatory cells initially accumulate around parasite causing macrophages to accumulate in large proportions and release fibrogenic factors that activate fibroblasts to produce more collagen. The granuloma walls off the parasite which may die of lack of nutrients or oxygen. Examples of immune evasion by parasites: Acanthocephalan In the presence of helminth worms, the host will often produce a granulomatous reaction which does not help the situation as this will hold the worm even more securely in place in the intestine. For example, the acanthocephalan has a retractable anterior spiny proboscis specially designed so that it can attach itself to the intestine of the host, causing damage to the wall of the intestine. Infected animals may have blood in their faeces. [Matthews, 1998] Ticks Ticks suppress both humoral and cell mediated immunity in their hosts. This happens systemically and also at the feeding site and is caused by factors in saliva. Tick saliva contains much prostaglandin which may be immunosuppressive. Other ticks secrete a histamine binding protein which tends to let the ticks to remain attached and gain a large blood meal over period of several weeks. Babesia The haemoprotozoan, Babesia which is transmitted by hard tick feeds of the Ixodidae family will result in haemoglobinuria (‘red water’), anaemia and fever of the animal hosts. This is done by releasing their proteases and excretory products into their animal hosts. However, the level of disease caused by the parasite also depends on the pathogenicity of the particular babesia species, the age of the host, the level of tick challenge and the immune status of the host. For example, young animals are less likely to get infected with Babesia and this is called inverse age resistance as the case in endemic areas where the young animals acquire their active immunity from colostrums [Urquhart et al. 1996]. Immunity to Trypanosoma is by antibody which binds to cell wall glycoproteins which are antigenic and the immune response to infection from a clone of Trypanosoma will reduce parasite population to low level, but then it recurs again to high level. The fresh population has a different type of glycoprotein that is, they vary their antigens. A new immune response is mounted against this, but the cycle of evasion by variation of these antigens can continue indefinitely to produce cachexia, a chronic wasting disease of trypanosomiasis. Conclusion A survey of the various parasites in the body reveals an in-depth interaction between the host and the parasite with the parasite developing mechanisms of survival and the host developing mechanisms of overcoming the pathogenic effects of the parasite. What is important here is to note that the presence of the parasite inside or outside the body of the host elicits an inflammatory or hypersensitive response against the invasion. In most cases the host by releasing appropriate antibodies against the parasite has been able to counter the pathogenic parasites especially if done in time as the case of the Eosinophil recruitment against extracellular helminths where the limitation of stage development necessitates destruction in the early larval stage of the helminthes. On the other hand some antibody secretions have ended up being detrimental to the host itself and so result in pathogenic substances being formed because of the antigen antibody reactions in the affected cells and tissues. As the case where the proinflammatory substances aggregated immunoglobulin E (IgE) cause the mast cells to degranulate to release histamine which can lead to allergic responses if in uncontrolled state. From all these we can say that the most basic mechanism a body uses to combat pathogenic parasites is by hypersensitive and inflammatory reactions due to antibody-antigen reaction whereby a boost in the body’s immune system can be a natural way to help the body to defend itself against parasites. However it must also be understood that some parasites have some stages of growth that resist any form of distraction and may release antigens whose reaction with the antibodies can result in fatality or simply evade the immunity as the case of the malaria parasite. Such may call for other medical and veterinary interventions. References: Books An Introduction to Parasitology, by Bernard E. Matthews, Cambridge University Press p.106 [Matthews, 1998] Arthropods of Humans and Domestic Animals, by Alan Walker, Chapman & Hall [Walker, 1994] Instant Notes Immunology by P.M. Lydyard, A. Whelan, M.W. Fanger, BIOS Scientific Publishers Ltd [Whelan, 2000] Microbial and Parasitic Diseases of the dog and cat by P.J. Quinn, W.J.C. Donnelly, M.E. Carter, B.K.J. Markey, P.R. Torgerson, R.M.S. Breathnach, W.B. Saunders Company Ltd [Quinn, 1997] Saunders Comprehensive Veterinary Dictionary 3rd edition by D.C. Blood, V.P. Studdert, C.C. Gay, Elsevier Ltd. P. 918, 957,1327 [Blood et al. 2007] Veterinary parasitology, by G. M. Urquhart, J. Armour, J.L. Duncan, A.M. Dunn, F.W. Jennings, 1996 Black well Science Ltd. P. 243 [Urquhart et al. 1996] Journals Antigenic Diversity and Immune Evasion by Malaria Parasites by Marcelo U. Ferreira, Mфnica da Silva Nunes, and Gerhard Wunderlich. Journal of Clinical and Diagnostic Laboratory Immunology. P. 987-995 Vol. 11. Issue No. 6. American Society for Microbiology. [2004] Eosinophils as a marker of systemic disease by Bruce Mackay, Australian College of Veterinary Scientists Science Week [Mackay, 2005] Hypersensitivity Reactions, Delayed by Noah S Scheinfeld and Felix Urman. Feb 2010. Viewed 17th August 2010. < http://emedicine.medscape.com/article/1051555-overview > The Role of eosinophils in host defence against helminth parasites by Amy D. Klion and Thomas B. Nutman, The Journal of Allergy and Clinical Immunology, Vol. 113, Issue 1, p.30-37 [Klion, 2003] Read More