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=Immune Tolerance=
=Immune Tolerance=
* To prevent an immune attack against host tissue- described as '''self-tolerance'''
* To prevent an immune attack against host tissue- described as '''self-tolerance'''
=T Cell Tolerance=
==T Cell Tolerance==
During T cell development within the thymus, genes encoding the T cell receptor are rearranged, resulting in adult cells that are able to recognise antigen fragments displayed by the host MHC molecule. Some receptors however will be self-reactive, i.e. they bind too strongly to antigens expressed by the host's own tissues ('''autoantigens'''). As these cells will induce immune reactions that could be damaging to the host ([[Autoimmune Diseases - Introduction#Autoimmune diseases|Autoimmunity]]), they must be deleted or suppressed.
During T cell development within the thymus, genes encoding the T cell receptor are rearranged, resulting in adult cells that are able to recognise antigen fragments displayed by the host MHC molecule. Some receptors however will be self-reactive, i.e. they bind too strongly to antigens expressed by the host's own tissues ('''autoantigens'''). As these cells will induce immune reactions that could be damaging to the host ([[Autoimmune Diseases - Introduction#Autoimmune diseases|Autoimmunity]]), they must be deleted or suppressed.
==Central Tolerance==
===Central Tolerance===
[[Image:Thymic selection of t cells.jpg|thumb|right|150px|Negative selection of t cells- copyright Brian Catchpole]]
[[Image:Thymic selection of t cells.jpg|thumb|right|150px|Negative selection of t cells- copyright Brian Catchpole]]
*Takes place within the thymus
*Takes place within the thymus
**During negative selection, cells passing through the corticomedullary junction and thymic medulla once again encounter MHC molecules, on epithelial cells, dendritic cells and macrophages, this time bound to self-peptide. Cells bearing receptors that bind too strongly to this complex are deleted through mechanisms that induce apoptosis.
**During negative selection, cells passing through the corticomedullary junction and thymic medulla once again encounter MHC molecules, on epithelial cells, dendritic cells and macrophages, this time bound to self-peptide. Cells bearing receptors that bind too strongly to this complex are deleted through mechanisms that induce apoptosis.
==Peripheral Tolerance==
===Peripheral Tolerance===
It is inevitable that some self-reactive T cells will get through the thymic selection process and into the periphery, as:
It is inevitable that some self-reactive T cells will get through the thymic selection process and into the periphery, as:
*Some self-antigens are not expressed in the thymus
*Some self-antigens are not expressed in the thymus
* In the case of self-antigens, autoimmune diseases such as diabetes are caused by Th1 cells and can be prevented by 'antigen-primed' Th2 cells.
* In the case of self-antigens, autoimmune diseases such as diabetes are caused by Th1 cells and can be prevented by 'antigen-primed' Th2 cells.
=Mucosal tolerance=
==Mucosal tolerance==
Mucosal tolerance is the systemic unresponsiveness towards antigens administered across the mucosal surfaces
Mucosal tolerance is the systemic unresponsiveness towards antigens administered across the mucosal surfaces
*As the highest antigenic load of the body surfaces occurs in the GI tract, it is also known as oral tolerance
*As the highest antigenic load of the body surfaces occurs in the GI tract, it is also known as oral tolerance
**It is thought the liver and spleen may also play a role
**It is thought the liver and spleen may also play a role
==Mechanisms==
===Mechanisms===
*High doses of antigen can cause anergy or cell death
*High doses of antigen can cause anergy or cell death
*Low doses can induce a T cell response:
*Low doses can induce a T cell response:
***Although the cellular response is antigen-specific, the cytokines released are not. TGF-beta is known to inhibit the proliferation and function of B-cells, cytotoxic T cells and NK cells. This means tolerance induction to one antigen suppresses an immune response to a second associated antigen- this mechanism has been used to suppress some autoimmune diseases by feeding with an antigen isolated from the affected tissue. This is known as ‘’bystander suppression’’.
***Although the cellular response is antigen-specific, the cytokines released are not. TGF-beta is known to inhibit the proliferation and function of B-cells, cytotoxic T cells and NK cells. This means tolerance induction to one antigen suppresses an immune response to a second associated antigen- this mechanism has been used to suppress some autoimmune diseases by feeding with an antigen isolated from the affected tissue. This is known as ‘’bystander suppression’’.
==Other mucosal surfaces==
===Other mucosal surfaces===
*Nasal deposition of some peptides can be used to induce tolerance, controlling both humoral and cellular responses
*Nasal deposition of some peptides can be used to induce tolerance, controlling both humoral and cellular responses
*Administration of antigen in aerosol form to the lung has been used to control both allergic and autoimmune responses
*Administration of antigen in aerosol form to the lung has been used to control both allergic and autoimmune responses
==Regulatory T Cells==
=Regulatory T Cells=
A number of cell populations identified during studies on autoimmunity and organ transplantation have shown the capacity to suppress responses to self-antigen and regulate rejection. Although once considered a tentative theory, this form of tolerance is now considered a major mechanism in the protection of host tissue from immune attack.
A number of cell populations identified during studies on autoimmunity and organ transplantation have shown the capacity to suppress responses to self-antigen and regulate rejection. Although once considered a tentative theory, this form of tolerance is now considered a major mechanism in the protection of host tissue from immune attack.
[[Image:T reg cells.JPG|thumb|right|150px|Regulatory T cells- copyright Brian Catchpole]]
[[Image:T reg cells.JPG|thumb|right|150px|Regulatory T cells- copyright Brian Catchpole]]
==[[Immune tolerance flashcards - Wikiblood|Immune tolerance flashcards]]==
==[[Immune tolerance flashcards - Wikiblood|Immune tolerance flashcards]]==
[[Category:Immunology]]