Difference between revisions of "Immunity to Parasites"
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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 …') |
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| − | + | 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 first line of defence against parasitic infection are the effector mechanisms of the innate immune system | + | **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''. | |
| − | Although the innate immune system provides an effective first line of defence, | + | *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). |
| − | *Both CD4 | + | *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 |
| − | *Helminth infections require both | + | *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''' | |
| − | |||
*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 | + | *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''': | |
| − | + | *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'' | ||
| − | |||
| − | |||
[[Category:Parasites]] | [[Category:Parasites]] | ||
| − | |||
| − | |||
Revision as of 19:51, 17 May 2010
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- similar properties to macrophages
- Activated by cytokines such as TNF-alpha, IFN-γ and GM-CSF, [[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]], 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