495
edits
Changes
→Adaptive Immunity
==Innate Immunity==
==Innate Immunity==
[[File:Helminth Killing edit.png|300px|right|thumb|Helminth Killing - R.J.Francis, RVC 2012]]
[[File:Helmith Killing by Granulocytes.png|250px|right|thumb|Electron Micrograph of Helminth Killing by Granulocytes (G). Adapted from [[http://eprints.adm.unipi.it/527/]] - R.J.Francis, RVC 2012]]
The first line of defence against parasitic infection are the effector mechanisms of the innate immune system. The '''[[Macrophages|macrophages]]''' are important players in the defence against extracellular parasites. This is because macrophages are able to secrete [[Cytokines|cytokines]] as well as perform [[Phagocytosis|phagocytosis]]. In this they can act as 'killer cells' through antibody-dependent cell-mediated cytotoxicity, for example specific [[Immunoglobulins|IgG]]/[[Immunoglobulins|IgE]] enhances the ability of macrophages to kill schistosomules through the interaction of Fc receptors on the surface of the macrophage. Of the secreted cytokines, the secretion of TNFα is of particular importance. This is because TNFα activates other macrophages and can have toxic effects in high amounts. TNFα also renders hepatocytes resistant to malarial infection when in conjunction with IL-1. Cytokine secretion (in particular IFNγ) can also enhance killing by mechanisms using free radicals and O<sub>2</sub>-independent toxins (e.g. nitric oxide).
The first line of defence against parasitic infection are the effector mechanisms of the innate immune system. The '''[[Macrophages|macrophages]]''' are important players in the defence against extracellular parasites. This is because macrophages are able to secrete [[Cytokines|cytokines]] as well as perform [[Phagocytosis|phagocytosis]]. In this they can act as 'killer cells' through antibody-dependent cell-mediated cytotoxicity, for example specific [[Immunoglobulins|IgG]]/[[Immunoglobulins|IgE]] enhances the ability of macrophages to kill schistosomules through the interaction of Fc receptors on the surface of the macrophage. Of the secreted cytokines, the secretion of TNFα is of particular importance. This is because TNFα activates other macrophages and can have toxic effects in high amounts. TNFα also renders hepatocytes resistant to malarial infection when in conjunction with IL-1. Cytokine secretion (in particular IFNγ) can also enhance killing by mechanisms using free radicals and O<sub>2</sub>-independent toxins (e.g. nitric oxide).
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==Adaptive Immunity==
==Adaptive Immunity==
Although the innate immune system provides an effective first line of defence, [[T cells|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''.
Although the innate immune system provides an effective first line of defence, '''[[T cells|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<sup>+</sup> and CD8<sup>+</sup> cells are required for protection, e.g CD4<sup>+</sup> cells protect against the blood stage of a Plasmodium infection (erythrocytes do not express MHC class I), while CD8<sup>+</sup> cells are required to mediate immunity against the liver stage (hepatocytes do not express MHC class II).
*Both CD4<sup>+</sup> and CD8<sup>+</sup> cells are required for protection, e.g CD4<sup>+</sup> cells protect against the blood stage of a Plasmodium infection (erythrocytes do not express MHC class I), while CD8<sup>+</sup> cells are required to mediate immunity against the liver stage (hepatocytes do not express MHC class II).
*T<sub>H</sub>1 cells are required to fight intracellular protozoa - the release of IFN-γ activates macrophages to kill the protozoa residing within them
*T<sub>H</sub>1 cells are required to fight intracellular protozoa - the release of IFNγ activates macrophages to kill the protozoa residing within them
*Helminth infections require both T<sub>H</sub>1 and T<sub>H</sub>2 responses, e.g. during ''S. mansoni'' the secretion of IFNγ by T<sub>H</sub>1 cells activates mechanisms that destroy larvae in the lungs, although the T<sub>H</sub>2 subset, secreting IL-5, predominate. IL-5 is responsible for the eosinophilia associated with parasite infections.
*Helminth infections require both T<sub>H</sub>1 and T<sub>H</sub>2 responses, e.g. during ''S. mansoni'' the secretion of IFNγ by T<sub>H</sub>1 cells activates mechanisms that destroy larvae in the lungs, although the T<sub>H</sub>2 subset, secreting IL-5, predominate. IL-5 is responsible for the eosinophilia associated with parasite infections.
*T<sub>H</sub>2 cells are required for the destruction of intestinal worms, where they induce mucosal mast cells and interact with [[Eosinophils|eosinophils]]
*T<sub>H</sub>2 cells are required for the destruction of intestinal worms, where they induce mucosal mast cells and interact with [[Eosinophils|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:
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
*Directly damaging protozoa
*Activating complement
*Activating [[Complement|complement]], and the subsequent Membrane Attack Complex
*Blocking attachment to host cells
*Blocking attachment to host cells
*Enhancing macrophage phagocytosis
*Enhancing macrophage [[Phagocytosis|phagocytosis]]
*Involvement in antibody-dependent cell-mediated cytotoxicity
*Involvement in antibody-dependent cell-mediated cytotoxicity
=='''Immunopathology'''==
=='''Immunopathology'''==
The immunopathology is the damage resulting from an immune response to the parasites. Examples include:
*The increase in macrophages and lymphocytes in the liver and spleen can lead to swelling of these organs, e.g. visceral leishmaniasis
*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
*T-cell dependent (T<sub>H</sub>1 and T<sub>H</sub>17) 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
*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
*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
*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
*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
*Excessive production of cytokines, such as TNFα, may contribute to pathology of diseases such as malaria
=='''Evading immune defences'''==
=='''Evading immune defences'''==
Parasites can evade an immune response from the host by changing the antigens presented to the host, produce antigens that mimic the host's antigens and can produce down-regulating factors which suppress or modify the host's immune responses. Having a rapid turnover of their surface coat when host cells bind and by being able to live in sites which are protected from the host's immune response allow parasites to establish themselves in a particular species.
Parasites can evade an immune response from the host by changing the antigens presented to the host, produce antigens that mimic the host's antigens and can produce down-regulating factors which suppress or modify the host's immune responses. Having a rapid turnover of their surface coat when host cells bind and by being able to live in sites which are protected from the host's immune response allow parasites to establish themselves in a particular species.
*Selection of innapropriate defences- by exploiting the 'adjuvant' mechanism, some parasites are able to activate the inappropriate helper T cell subset, e.g Leishmania
*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''
*Antigenic variation avoids recognition by antibody and complement, e.g. ''T. brucei''
*Inhibiting fusion of lysosomes
*Inhibiting fusion of lysosomes
*Escaping into the cytoplasm, e.g. ''T. cruzi''
*Escaping into the cytoplasm, e.g. ''T. cruzi''
*Inhibiting respiratory burst, e.g. Leishmania
*Inhibiting respiratory burst, e.g. Leishmania
*Forming cysts in muscle tissue, e.g. ''T. spiralis''- also develops decay accelerating factor (DAF)
*Forming cysts in muscle tissue, e.g. ''T. spiralis'' - also develops decay accelerating factor (DAF)
*Production of antioxidants, e.g. ''W. bancrofti''
*Production of antioxidants, e.g. ''W. bancrofti''