Author, Donkey, Bureaucrats, Administrators
53,803
edits
Changes
no edit summary
Line 11:
Line 11:
−==Immunity to parasites==+The first line of defence against parasitic infection are the effector mechanisms of the innate immune system:
−*'''Macrophages'''- important in the defence against extracellular parasites, macrophages are able to secrete cytokines as well as perform phagocytosis
−**Can act as 'killer cells' through antibody-dependent cell-mediated cytotoxicity, e.g. specific IgG/IgE enhances the ability of macrophages to kill schistosomules
−**The secretion of TNF-alpha:
−***Activates other macrophages
−***Renders hepatocytes resistant to malarial infection when in conjunction with IL-1
−***Can have toxic effects in high amounts
−**When activated by cytokines, killing mechanisms using free radicals and O2-independent toxins (e.g. nitric oxide) are enhanced
−*'''[[Neutrophils - WikiBlood|Neutrophils]]'''- similar properties to macrophages
−**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
−**Present in parasite-infected inflammatory lesions
−**Express Fc and complement receptors- can participate in antibody-dependent cell-mediated cytotoxicity
−*'''Eosinophils'''- less phagocytic than [[[[Neutrophils - WikiBlood|Neutrophils]] - WikiBlood|neutrophils]], but important in the destruction of larger parasites
−**Most activity is controlled by antigen-specific mechanisms, e.g. binding to worms coated with IgG/IgE increases degranulation
−**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
−*'''Platelets'''- cytotoxic activity is increased by cytokines such as TNF-alpha and IFN-γ
−**Potential targets include the larval stage of flukes, e.g. ''T. gondii'' and ''T. cruzi''
−**Like other effector cells, platelets express Fc receptors, making them able to perform antibody-dependent cytotoxicity
−
−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''.
−*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).
−*Th1 cells are required to fight intracellular protozoa- the release of IFN-γ activates macrophages to kill the protozoa residing within them
−*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
−*Th2 cells are required for the destruction of intestinal worms, where they induce mucosal mast cells and interact with eosinophils
−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:
−*Directly damaging protozoa
−*Activating complement
−*Blocking attachment to host cells
−*Enhancing macrophage phagocytosis
−*Involvement in antibody-dependent cell-mediated cytotoxicity
−
−'''Immunopathology'''
−*The increase in macrophages and lymphocytes in the liver and spleen can lead to swelling of these organs, e.g. visceral leishmaniasis
−*T-cell dependent granulomas forming in organs, e.g. schistosomiasis in the liver
−*The pathology of elephantiasis is thought to be due to changes in the adult filariae in the lymphatic system
−*Formation of immune complexes, e.g. deposition in the kidney during malarial infection
−*Anaphylactic shock caused by IgE production, e.g. after the rupture of hydatid cysts
−*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
−*Excessive production of cytokines, such as TNF-alpha, may contribute to pathology of diseases such as malaria
−
−'''Evading immune defences''':
−*Selection of innapropriate defences- by exploiting the 'adjuvant' mechanism, some parasites are able to activate the inappropriate helper T cell subset, e.g Leishmania
−*Antigenic variation avoids recognition by antibody and complement, e.g. ''T. brucei''
−*Inhibiting fusion of lysosomes
−*Escaping into the cytoplasm, e.g. ''T. cruzi''
−*Inhibiting respiratory burst, e.g. Leishmania
−*Forming cysts in muscle tissue, e.g. ''T. spiralis''- also develops decay accelerating factor (DAF)
−*Production of antioxidants, e.g. ''W. bancrofti''
−
<big>'''[[Immunity to Parasites]]'''</big>
−