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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]]==