Re: allergy feed back loop/AUTOIMMUNITY

[Guest guest]

Themes > Science > Life Sciences > General Biology > Immunology > The Immune

System & Disease > Autoimmunity > How are autoimmune reactions initiated?

In the last lecture we mentioned that some antigens are hidden away from the

immune system in immunologically privileged sites. When trauma or other events

cause damage to the barriers which protect such special sites this can lead to

the release of novel autoantigens and the production of autoantibodies. In the

case of autoimmune sympathetic opthalmia, damage to one eye leads to subsequent

autoimmune attack on the contralateral eye.

T cell bypass

This concept embodies the idea that autoimmunity can arise as a result of T cell

tolerance being bypassed. This might occur in a number of ways

modification. This can happen when a small molecule (eg a drug) binds to a

protein and alters an MHC- binding peptide so that it becomes a neoantigen

recognised by T cells. This provides T cell help, through linked recognition,

for antibody production which need not be (and usually is not) directed against

a neodeterminant.

inflammation. During an inflammatory response an immunostimulatory environment

is created by the release of cytokines which recruit and activate professional

antigen presenting cells and provide support for T cell activation rather than

anergy. As a result autoreactive T cells which were anergic or ignorant may

become activated. This concept is central to >Matzinger's Danger Hypothesis<

(see lec 11).

molecular mimicry is a rather specialised version of the above in which an

epitope of an invading microorganism cross-reacts with a self protein. The T

cell help provided by the other microbial antigens permits the activation of B

cells which make an crossreactive antibody which either escaped tolerance or

which acquires sufficient self reactivity through somatic mutation and selection

driven by the cross-reactive antigen.

http://www.cartage.org.lb/en/themes/Sciences/LifeScience/GeneralBiology/Immunolo\

gy/ImmuneSystemDisease/Autoimmunity/Autoimmunereactions/Autoimmunereactions.htm

[Guest guest]

2009 FASEB

CD8+ T cells and neuronal damage: direct and collateral mechanisms of

cytotoxicity and impaired electrical excitability

http://www.fasebj.org/cgi/content/abstract/23/11/3659

Collateral Bystander Damage by Myelin-Directed CD8+ T Cells Causes Axonal Loss

http://ajp.amjpathol.org/cgi/content/abstract/175/3/1160

CITED FROM

Naïve CD8 T-cells initiate spontaneous autoimmunity to a sequestered model

antigen of the central nervous system

http://brain.oxfordjournals.org/content/131/9/2353.abstract

http://en.wikipedia.org/wiki/Naive_T_cell

Immune Regulation of Autoreactive T Cells

http://www.bcm.edu/neurology/msrl/immune_regulation.html

Role of Microbial Infection in the Pathogenesis of MS

http://www.bcm.edu/neurology/msrl/microbial_infection.html

Postthymic maturation influences the CD8 T cell response to antigen

http://www.pnas.org/content/106/12/4799.abstract

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Neutrophils Process Exogenous Lymphocytes

Presentation of Peptides to T MHC Processing Pathway for

Bacteria Via an Alternate Class I

http://www.jimmunol.org/cgi/reprint/167/5/2538.pdf

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Chapter 8: Antigen Processing and Presentation

Ag recog by T cells REQUIRES presentation by MHC on a cell membrane (MHC

restriction)

Pathways for Ag presentation:

a) Class I MHC assoc. with peptides from endogenous Ag's

Class II MHC assoc with peptides from exogenous Ag's

--

AG PRSENTATION,MHC 1,MHC 11

http://pathmicro.med.sc.edu/2009-immpdf/12Agprocessing.pdf

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B-T CO-OPERATION

http://rheuma.bham.ac.uk/teaching/immunology/l12.htm

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Antigen-Specific Blockade of Lethal CD8 T-Cell Mediated Autoimmunity in a Mouse

Model of Multiple Sclerosis1

http://www.jimmunol.org/cgi/content/full/182/10/6569

TASK1 modulates inflammation and neurodegeneration in autoimmune inflammation of

the central nervous system

http://brain.oxfordjournals.org/content/132/9/2501.abstract

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http://www.sciencemag.org/cgi/content/abstract/249/4971/918

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[Guest guest]

Program: Molecular basis, diagnosis and therapy of IgE-mediated allergy

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Titel Molecular basis, diagnosis and therapy of IgE-mediated allergy

Abstract Three areas cover the major activities of the group:

immuno-epidemiology, allergen-characterization and humoral immune-response. In

the first area, cross-sectional studies were started up in the frame of an

Integrated Project under FP6 in Ghana and Indonesia to study the role of

infections in the development of (food) allergies. These studies are coordinated

by LUMC and our group is responsible for the serum analysis for allergy. In the

second area, a new family of food allergens was identified that is linked to oil

bodies in nuts and seeds: oleosins. These allergens were purified and cloned and

expressed. The importance of this group of allergens is that they are overlooked

in current diagnostic tests because they are removed during defatting steps used

in the production of diagnostic extracts. Their addition will improve diagnostic

tests in the future. In the third area we have for the first time demonstrated

by in vivo challenges with transgenic human lactoferrin (produced in rice) that

IgE antibodies against plant glycans have no biological activity (do not induce

mediator release). Assays were set up to investigate whether this is explained

by avidity or by valency of the interaction between IgE and allergen.

Period 01/2008 - unknown

http://www.onderzoekinformatie.nl/en/oi/nod/onderzoek/OND1332342/

Program: Role of dendritic cells in the orchestration of immunity and tolerance

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Titel Role of dendritic cells in the orchestration of immunity and tolerance

Abstract Optimal defense against pathogens requires adaptive immunity in which

specialized antigen-specific effector T helper (Th1, Th2, Th17) cell subsets

play an important role. The action of these effector Th cells types is controled

by regulated by T regulatory (Tr) cells, which prevents excessive host tissue

damage, autoimmunity and allergy. The optimal balance between selected

protective effector and tolerogenic Tr cells is orchestrated by

antigen-presenting dendritic cells by expressing molecules that enable naïve T

cells to become Th1, Th2, Th17 or Tr cells. We have proposed the concept that

the expression pattern of these T cell polarizing molecules by dendritic cells

is flexible and depends on how these dendritic cells have been conditioned by

micro-environmental factors, such as pathogen-associated molecules or host

tissue reactivity factors. In close collaboration with the Depts. Dermatology,

Retrovirology, Rheumatology, Gastroenterology, ENT, Experimental Immunology and

Pediatric Pulmonology of the AMC we study this immunoregulatory role of

dendritic cells in homeostasis and disease. In the previous period we defined

the pathway utilized by dendritic cells to orchestrate anti-bacterial Th17

cell-mediated responses and documented that fact that epidermal skin dendritic

cells lack receptors for bacteria-associated molecules, marking the epidermis as

an immunopriviliged area for skin commensals.

Period 01/2008 - unknown

http://www.onderzoekinformatie.nl/en/oi/nod/onderzoek/OND1332374/

Autoimmunity, Polyclonal B-Cell Activation and Infection

The effect of polyclonal B-cell activation, brought about by injections of a

B-cell activator - lipopolysaccharide from Gram-negative bacteria—is sufficient

to cause autoimmune disease in an immunologically normal host

http://lup.sagepub.com/content/1/2/63.abstract