Difference between revisions of "Immunity to Parasites"
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==Innate Immunity== | ==Innate Immunity== | ||
| − | + | The first line of defence against parasitic infection are the effector mechanisms of the innate immune system. | |
| − | + | ||
| − | The first line of defence against parasitic infection are the effector mechanisms of the innate immune system. The '''[[Macrophages| | + | The '''[[Macrophages|Macrophages]]''' are important in the defence against extracellular parasites. This is because macrophages are able to secrete [[Cytokines|cytokines]] as well as perform 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 TNF-&alpha& is of particular importance. This is because TNF-&alpha& activates other macrophages and can have toxic effects in high amounts. TNF-alpha also renders hepatocytes resistant to malarial infection when in conjunction with IL-1. |
| − | + | *****When activated by cytokines, killing mechanisms using free radicals and O2-independent toxins (e.g. nitric oxide) are enhanced | |
| − | + | *'''[[Neutrophils|Neutrophils]]'''- similar properties to macrophages | |
| − | + | **Activated by cytokines such as TNF-alpha, IFN-γ and GM-CSF, [[Neutrophils|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|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 | ||
==Adaptive Immunity== | ==Adaptive Immunity== | ||
| − | Although the innate immune system provides an effective first line of defence, | + | 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 | + | *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 | + | *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: | 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 | + | *Activating complement |
*Blocking attachment to host cells | *Blocking attachment to host cells | ||
| − | *Enhancing macrophage | + | *Enhancing macrophage phagocytosis |
*Involvement in antibody-dependent cell-mediated cytotoxicity | *Involvement in antibody-dependent cell-mediated cytotoxicity | ||
=='''Immunopathology'''== | =='''Immunopathology'''== | ||
| − | |||
*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 | + | *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 | *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 | + | *Excessive production of cytokines, such as TNF-alpha, 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'' | ||
Revision as of 15:32, 17 May 2012
Innate Immunity
The first line of defence against parasitic infection are the effector mechanisms of the innate immune system.
The Macrophages are important in the defence against extracellular parasites. This is because macrophages are able to secrete cytokines as well as perform phagocytosis. In this they can act as 'killer cells' through antibody-dependent cell-mediated cytotoxicity, for example specific IgG/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 TNF-&alpha& is of particular importance. This is because TNF-&alpha& activates other macrophages and can have toxic effects in high amounts. TNF-alpha also renders hepatocytes resistant to malarial infection when in conjunction with IL-1.
- When activated by cytokines, killing mechanisms using free radicals and O2-independent toxins (e.g. nitric oxide) are enhanced
- Neutrophils- similar properties to macrophages
- Activated by cytokines such as TNF-alpha, IFN-γ and GM-CSF, 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, 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
Adaptive Immunity
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
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
- 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
Also see Adaptive Immunity to Parasites