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Created page with 'The first line of defence against parasitic infection are the effector mechanisms of the innate immune system: *'''Macrophages'''- important in the defence against extracellular …'
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''
[[Category:Parasites]]
*'''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''
[[Category:Parasites]]