Immune tolerance

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Immune tolerance or immunological tolerance is the process by which the immune system
does not attack an antigen.
[1]
It can be either 'natural' or 'self tolerance', in which the body
does not mount an immune response to self antigens, or 'induced tolerance', in which
tolerance to external antigens can be created by manipulating the immune system. It occurs in
three forms: central tolerance, peripheral tolerance and acquired tolerance.
Genetic defects in these processes lead to autoimmunity, such as in Autoimmune
polyendocrine syndrome type 1 (APS-1) and immunodysregulation polyendocrinopathy
enteropathy X-linked syndrome (IPEX).
Contents
1 Central tolerance
2 Peripheral tolerance
3 Acquired tolerance
4 Immune tolerance to allografts
5 See also
6 References
7 External links
[edit] Central tolerance
Central tolerance occurs during lymphocyte development and operates in the thymus and
bone marrow. Here, T and B lymphocytes that recognize self antigens are deleted before they
develop into fully immunocompetent cells, preventing autoimmunity. This process is most
active in fetal life, but continues throughout life as immature lymphocytes are generated.
In mammals the process occurs in the thymus (T cells)
[2][3]
and bone marrow (B cells), when
maturing lymphocytes are exposed to self antigens. Self antigens are present in both organs
due to endogenous expression within the organ and importation of antigen due to circulation
from peripheral sites. In the case of T cell central tolerance, additional sources of antigen are
made available in the thymus by the action of the transcription factor AIRE.
Positive selection occurs first when naive T-cells are exposed to antigens in the thymus. T-
cells which have receptors with sufficient affinity for self-MHC molecules are selected.many
self protein antigens are processed and presented by thymic antigen presenting cells (APCs)in
association with self MHC. Other cells that do not show sufficient affinity to self-antigens
will undergo a deletion process known as death by neglect which involves apoptosis of the
cells. The positive selection is a classical example of the importance of some degree of
autorreactiveness. This does not occur in B cells.
Negative selection of T-cells with a very high affinity of self-MHC molecules are induced to
anergy, or lineage divergence to form T-regulatory cells. This process also occurs during B
cell development.
[edit] Peripheral tolerance
Peripheral tolerance is immunological tolerance developed after T and B cells mature and
enter the periphery. The T cells that leave the thymus are relatively but not completely
safe.Some will have receptors(TCRs) that can respond to self antigens that:
1. are present in such high concentration that they can bind to "weak" receptors
2. the T cell did not encounter in the thymus (such as, tissue-specific molecules like
those in the islets of Langerhans, brain or spinal cord)
Those self reactive T cells that escape intrathymic negative selection in the thymus can inflict
cell injury unless they are deleted or effectively muzzled in the peripheral tissue. Several
back mechanism silence such potentially auto reactive T cells are known to exist. They
include following:
Anergy
Activation-induced cell death
Peripheral supression cell death
[edit] Acquired tolerance

This section needs additional citations for verification. Please help improve this
article by adding citations to reliable sources. Unsourced material may be challenged
and removed. (May 2011)
Acquired or induced tolerance refers to the immune system's adaptation to external antigens
characterized by a specific non-reactivity of the lymphoid tissues to a given antigen that in
other circumstances would likely induce cell-mediated or humoral immunity. One of the most
important natural kinds of acquired tolerance is immune tolerance in pregnancy, where the
fetus and the placenta must be tolerated by the maternal immune system.
In adults, tolerance may be induced by repeated administration of very large doses of antigen,
or of small doses that are below the threshold required for stimulation of an immune
response.
[citation needed]
Tolerance is most readily induced by soluble antigens administered
either intravenously or sublingually, but specially orally.
[citation needed]
Immunosuppression also
facilitates the induction of tolerance.
[citation needed]

In clinical practice, acquired tolerance(induced tolerance) is important in organ
transplantation, when the body must be forced to accept an organ from another individual.
The failure of the body to accept an organ is known as transplant rejection. To prevent
rejection, a variety of medicines are used to produce induced tolerance.
[4]

One of the most important forms of acquired tolerance is oral tolerance.
[5]
Oral tolerance, the
specific suppression of cellular and/or humoral immune reactivity to an antigen by prior
administration of the antigen by the oral route, probably evolved to prevent hypersensitivity
reactions to food proteins and bacterial antigens present in the mucosal flora.
[6]
It is of
immense immunological importance, since it is a continuous natural immunologic event
driven by exogenous antigen. Due to their privileged access to the internal milieu, antigens
that continuously contact the mucosa represent a frontier between foreign and self
components. Oral tolerance evolved to treat external agents that gain access to the body via a
natural route as internal components without danger signals, which then become part of self.
Failure of oral tolerance is attributed to the development and pathogenesis of several
immunologically based diseases, including inflammatory bowel disease (Crohn's disease and
ulcerative colitis).
[edit] Immune tolerance to allografts
There are many instance in which an allograft may be accepted without the use of
immunosuppressive measure. Obviously, in the case of tissue that lack alloantigen, such as
cartilage or heart valve, there is no immunological barrier to transplantation. However there
are also instances in which the strong predicted response to an allograft does not occur. There
are two general cases in which an allograft may be accepted. One is when cells or tissue are
grafted to a so-called privileged site that is sequestered from immune surveillance. The
second is when a state of tolerance has been induced biologically, usually by previous
exposure to the antigen of the donor in a manner that cause immune tolerance rather than
sensitization in the recipient.
[7]

[edit] See also
Central tolerance
CD22
sialic acid acetylesterase
[edit] References
1. ^ Pontell, Emile B. (2008). Immune tolerance research developments. New York:
Nova Biomedical. ISBN 1-60456-209-9.
2. ^ Sprent J, Kishimoto H (2001). "The thymus and central tolerance". Philos Trans R
Soc Lond B Biol Sci 356 (1409): 60916. doi:10.1098/rstb.2001.0846. PMC 1088448.
PMID 11375064. //www.ncbi.nlm.nih.gov/pmc/articles/PMC1088448/.
3. ^ Hogquist K, Baldwin T, Jameson S (2005). "Central tolerance: learning self-control
in the thymus". Nat Rev Immunol 5 (10): 77282. doi:10.1038/nri1707.
PMID 16200080.
4. ^ Hurakadle, Kobkate Lalalpure (2011), Textbook bof Pharmaceutical Biotechnology,
pp. 2223, ISBN 81-312-2828-2
5. ^ Mayer L, Sperber K, Chan L, Child J, Toy L (2001). "Oral tolerance to protein
antigens". Allergy 56 (s67): 125. doi:10.1111/j.1398-9995.2001.00904.x.
PMID 11297999.
6. ^ Wiener HL (October 2000). "Oral tolerance, an active immunologic process
mediated by multiple mechanisms". Journal of Clinical Investigation 106 (8): 9357.
doi:10.1172/JCI11348. PMC 314352. PMID 11032852.
//www.ncbi.nlm.nih.gov/pmc/articles/PMC314352/.
7. ^ richard a. goldsby, thomas j. kindt, barbara a. osborne, janis kuby (2003),
immunology, pp. 494, ISBN 978-0-7167-3331-7
[edit] External links
Immune Tolerance Network
International Conference on Immune Tolerance
Immune+tolerance at the US National Library of Medicine Medical Subject Headings
(MeSH)
v
t
e
Immunology: Lymphocytic adaptive immune system and complement

Lymphoid
Antigens
Antigen
o Superantigen
o Allergen
Hapten
Epitope
o Linear
o Conformational
Mimotope
Antigen presentation/Professional APCs:
Dendritic cell
Macrophage
B cell
Immunogen


Antibodies
Antibody
o Monoclonal antibodies
o Polyclonal antibodies
o Autoantibody
o Microantibody
Polyclonal B cell response
Allotype
Isotype
Idiotype
Immune complex
Paratope


Immunity vs.
tolerance
action: Immunity
Autoimmunity
Alloimmunity
Allergy
Hypersensitivity
Inflammation
Cross-reactivity
inaction: Tolerance
o Central
o Peripheral
o Clonal anergy
o Clonal deletion
o Tolerance in pregnancy
Immunodeficiency


Immunogenetics
Affinity maturation (Somatic hypermutation
Clonal selection)
V(D)J recombination
Junctional diversity
Immunoglobulin class switching
MHC/HLA



Lymphocytes
Cellular (T cell)
Humoral (B cell)
NK cell


Substances
Cytokines
Opsonin
Cytolysin


Complement
Anaphylatoxins


M: LMC cell/phys/auag/auab/comp,
igrc
imdf/ipig/hyps/tumr proc, drug (L3/4)

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