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==Introduction==

 

=Immune Tolerance=

Immunological tolerance occurs when there is unresponsiveness towards particular antigens, so any further immune responses are prevented or suppressed. Tolerance is required to prevent:

Immunological tolerance occurs when there is unresponsiveness towards particular antigens, so any further immune responses are prevented or suppressed. Tolerance is required to prevent:

* Potentially harmful inflammatory responses towards innocuous substances, such as air-borne or food molecules

* Potentially harmful inflammatory responses towards innocuous substances, such as air-borne or food molecules

==Mucosal tolerance==

==Mucosal tolerance==

Mucosal tolerance is the systemic unresponsiveness towards antigens administered across mucosal surfaces. The highest antigenic load of the body surfaces occurs in the GI tract, so mucosal tolerance is also sometimes referred to as oral tolerance. When oral tolerance towards food antigens breaks down, inflammatory responses are induced. [[Regional Lymphoid Tissue - Anatomy & Physiology|Gut associated lymphoid tissue]] is important in the development of oral tolerance: animals that lack [[Peyer's Patches - Anatomy & Physiology|Peyer’s patches]] and mesenteric lymph nodes do not develop oral tolerance. It is thought the liver and spleen may also play a role.

Mucosal tolerance is the systemic unresponsiveness towards antigens administered across mucosal surfaces. The highest antigenic load of the body surfaces occurs in the GI tract, so mucosal tolerance is also sometimes referred to as oral tolerance. When oral tolerance towards food antigens breaks down, inflammatory responses are induced. [[Regional Lymphoid Tissue - Anatomy & Physiology|Gut associated lymphoid tissue]] is important in the development of oral tolerance: animals that lack [[Peyer's Patches - Anatomy & Physiology|Peyer’s patches]] and mesenteric lymph nodes do not develop oral tolerance. It is thought the [[Liver - Anatomy & Physiology|liver]] and [[Spleen - Anatomy & Physiology|spleen]] may also play a role.

In the GI tract, high doses of antigen can cause anergy or cell death. Low doses can induce a T cell response where the antigen is taken up and presented, inducing a Th2-like cell response which produces cytokines that suppress the Th1 inflammatory response, such as IL-10 and TGF-beta. 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'''.

In the GI tract, high doses of antigen can cause anergy or cell death. Low doses can induce a T cell response where the antigen is taken up and presented, inducing a Th2-like cell response which produces cytokines that suppress the Th1 inflammatory response, such as IL-10 and TGF-beta. 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 Factors of Innate Immune System|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 [[:Category:Allergic Respiratory Diseases|allergic]] and [[Autoimmune Diseases - Introduction#Autoimmune diseases|autoimmune]] responses

==Regulatory T Cells==

==Regulatory T Cells==

Regulatory T cells are unique in their use of a transcription repressor known as FoxP3 which is encoded by a gene on the X chromosome; rare deficiencies in FoxP3 are characterised by autoimmunity, primarily towards gut tissue, the thyroid, pancreative beta-cells and the skin. Sufferers are unable to produce regulatory T cells and the only known treatment is a bone marrow transplant from a MHC-identical sibling.

Regulatory T cells are unique in their use of a transcription repressor known as FoxP3 which is encoded by a gene on the X chromosome; rare deficiencies in FoxP3 are characterised by autoimmunity, primarily towards gut tissue, the thyroid, pancreative beta-cells and the skin. Sufferers are unable to produce regulatory T cells and the only known treatment is a bone marrow transplant from a MHC-identical sibling.

==Test yourself with the Immunology Flashcards==

[[Immune tolerance flashcards - Wikiblood|Immune tolerance flashcards]]

|flashcards = [[Immune Tolerance Flashcards|Immune tolerance flashcards]]

|literature search =[http://www.cabdirect.org/search.html?q=title:(%22immune+tolerance%22)+OR+title:(%22t+cell+tolerance%22)+OR+title:(%22mucosal+tolerance%22)&fq=sc:%22ve%22 Immune Tolerance publications]

[[Category:Immunology]]

[[Category:Immunology]]