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| − | ==Immunity to parasites==
| + | <big>'''[[Immunity to Parasites]]'''</big> |
| − | The first line of defence against parasitic infection are the effector mechanisms of the innate immune system:
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| − | *'''Macrophages'''- important in the defence against extracellular parasites, macrophages are able to secrete cytokines as well as perform phagocytosis
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| − | **Can act as 'killer cells' through antibody-dependent cell-mediated cytotoxicity, e.g. specific IgG/IgE enhances the ability of macrophages to kill schistosomules
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| − | **The secretion of TNF-alpha:
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| − | ***Activates other macrophages
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| − | ***Renders hepatocytes resistant to malarial infection when in conjunction with IL-1
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| − | ***Can have toxic effects in high amounts
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| − | **When activated by cytokines, killing mechanisms using free radicals and O2-independent toxins (e.g. nitric oxide) are enhanced
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| − | *'''[[Neutrophils - WikiBlood|Neutrophils]]'''- similar properties to macrophages
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| − | **Activated by cytokines such as TNF-alpha, IFN-γ and GM-CSF, [[[[Neutrophils - WikiBlood|Neutrophils]] - WikiBlood|neutrophils]] produce a more intense respiratory burst and extracellular killing is mediated by H2O2
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| − | **Present in parasite-infected inflammatory lesions
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| − | **Express Fc and complement receptors- can participate in antibody-dependent cell-mediated cytotoxicity
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| − | *'''Eosinophils'''- less phagocytic than [[[[Neutrophils - WikiBlood|Neutrophils]] - WikiBlood|neutrophils]], but important in the destruction of larger parasites
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| − | **Most activity is controlled by antigen-specific mechanisms, e.g. binding to worms coated with IgG/IgE increases degranulation
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| − | **The killing of some larvae is enhanced by the activity of mast cells, e.g. antigens released by S. mansoni cause IgE-dependent degranulation of mast cells, the products of which selectively attract eosinophils
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| − | *'''Platelets'''- cytotoxic activity is increased by cytokines such as TNF-alpha and IFN-γ
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| − | **Potential targets include the larval stage of flukes, e.g. ''T. gondii'' and ''T. cruzi''
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| − | **Like other effector cells, platelets express Fc receptors, making them able to perform antibody-dependent cytotoxicity
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| − | Although the innate immune system provides an effective first line of defence, T cells are fundamental in the development of immunity, demonstrated using T-cell deprived mice that fail to resolve otherwise non-lethal infections of, for example, ''T. cruzi''.
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| − | *Both CD4+ and CD8+ cells are required for protection, e.g CD4+ cells protect against the blood stage of a Plasmodium infection (erythrocytes do not express MHC class I), while CD8+ cells are required to mediate immunity against the liver stage (hepatocytes do not express MHC class II).
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| − | *Th1 cells are required to fight intracellular protozoa- the release of IFN-γ activates macrophages to kill the protozoa residing within them
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| − | *Helminth infections require both Th1 and Th2 responses, e.g. during ''S. mansoni'' the secretion of IFN-γ by Th1 cells activates mechanisms that destroy larvae in the lungs, although the Th2 subset, secreting IL-5, predominate
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| − | *Th2 cells are required for the destruction of intestinal worms, where they induce mucosal mast cells and interact with eosinophils
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| − | While cell-mediated immunity is important in tissue infections, such as Leishmania, specific antibodies are important in controlling parasites that live in the bloodstream, e.g. malaria. Mechanisms of antibody-mediated immunity include:
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| − | *Directly damaging protozoa
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| − | *Activating complement
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| − | *Blocking attachment to host cells
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| − | *Enhancing macrophage phagocytosis
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| − | *Involvement in antibody-dependent cell-mediated cytotoxicity
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| − | '''Immunopathology'''
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| − | *The increase in macrophages and lymphocytes in the liver and spleen can lead to swelling of these organs, e.g. visceral leishmaniasis
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| − | *T-cell dependent granulomas forming in organs, e.g. schistosomiasis in the liver
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| − | *The pathology of elephantiasis is thought to be due to changes in the adult filariae in the lymphatic system
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| − | *Formation of immune complexes, e.g. deposition in the kidney during malarial infection
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| − | *Anaphylactic shock caused by IgE production, e.g. after the rupture of hydatid cysts
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| − | *Cross-reaction of antibodies with host tissue, e.g. ''O. volvulus'', the cause of river blindness, expresses an antigen similar to a protein in the retina
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| − | *Excessive production of cytokines, such as TNF-alpha, may contribute to pathology of diseases such as malaria
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| − | '''Evading immune defences''':
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| − | *Selection of innapropriate defences- by exploiting the 'adjuvant' mechanism, some parasites are able to activate the inappropriate helper T cell subset, e.g Leishmania
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| − | *Antigenic variation avoids recognition by antibody and complement, e.g. ''T. brucei''
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| − | *Inhibiting fusion of lysosomes
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| − | *Escaping into the cytoplasm, e.g. ''T. cruzi''
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| − | *Inhibiting respiratory burst, e.g. Leishmania
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| − | *Forming cysts in muscle tissue, e.g. ''T. spiralis''- also develops decay accelerating factor (DAF)
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| − | *Production of antioxidants, e.g. ''W. bancrofti''
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