Slide1 l.jpg
1 / 11

Peripheral tolerance and Immunoregulation..

Uploaded on:
Category: General / Misc
Peripheral tolerance and Immunoregulation. Dr. C. Piccirillo Canada Research Chair Department of Microbiology & Immunology McGill University MIMM-414A Lecture 1- Oct. 20, 2006 Why T cell regulation?
Slide 1

Fringe resistance and Immunoregulation. Dr. C. Piccirillo Canada Research Chair Department of Microbiology & Immunology McGill University MIMM-414A Lecture 1-Oct. 20, 2006

Slide 2

Why T cell regulation? How does the resistant framework avoid self-reactivity while keeping up reactivity to trespassers/non-self? White blood cell regulation without administrative T cells? Concealment of autoreactive T cells Control invulnerability to enteric microorganisms Limit histopathology

Slide 3

Self/non-self separation Turn of the twentieth century 1901: Ehrlich and Morgenroth Immunized goats with RBC from another goat to presume that host safe reactions react to outside antigens. They authored the Latin saying: awfulness autoxicus Why did the goats create autoAb to their own particular RBC? 1938-Traub incited resistance by infusing LCMV in utero into mice delivering a disease that was extensive in life. 1949-Macfarlane Burnet: proposed that the creature's age at the first's season experience with antigen was the basic determinant in the affectation of resilience. 1953: Medawar actuated invulnerable resistance to skin allografts in mice by neonatal infusion of allogeneic cells. Counteractive action or inability to mount reaction to self-segments?

Slide 4

Immunological resilience A condition of useful lethargy for a specific antigen. May happen in the setting of a non-provocative safe reaction. Resistance is a dynamic procedure.

Slide 5

Central resistance to a great extent controls self/non-self separation. Thymic deletional procedures are wasteful. Moderate-high liking TCR/pMHC cooperations - > clonal erasure Low-direct TCR/pMHC communications - > determination No connection disregard and passing BMDC included in clonal cancellation (cortico-medullary intersection) T cell maturational state is critical (nature,site and how) Role of AIRE (AutoImmune Regulator) Autoreactive T cells leave thymus and exist in outskirts. Nonattendance of malady recommends instrument of dynamic concealment.

Slide 6

Multiple instruments guarantee fringe T cell resilience. Lack of awareness: life structures, lymphatics, Ag crypticity, benefit Deletion : cross-presentation of Ag by BMDC results in death (eg;CD8+) Anergy: Insufficient co-incitement on self-tissues Clonal weariness: CD8+ T cells in incessant viral contaminations Immune deviation: shift from provocative to mitigating cytokine generation (eg; Th1-Th2). Actuation prompted cell passing (AICD): Fas/FasL (IL-2) = Death Peripheral resilience is a versatile procedure.

Slide 7

Tolerance to Self Antigen sequestration (lens of eye, spermatozoa) Low MHC expression (i.e. hepatocytes) Immune Response to Foreign Antigens Influence of Antigen Dose (low zone, high zone), timing/term of introduction, courses, nature of antigen , protein > CHO >> lipids , vicinity of adjuvants Influence of Antibody input restraint (IgG represses IgM), differential antigen tying proclivity Factors favoring resistance Age, neurological and endocrine elements, Nutritional status, MHC Haplotypes

Slide 8

Acquired Tolerance In numerous cases, test lethargy may be interceded by silencer (T) cells , which effectively keep a safe reaction. Unique examinations of Gershon and Kondo (1970) demonstrated that T cells were needed for resilience actuation. In addition, T cells from tolerant mice stifled B cells from typical mice. Dynamic concealment by T cells additionally found in a few reactions under Ir quality control and in the regulation of IgE reactions (Tada). Concealment normally instigated by systemic organization of antigen-coupled to self cells; course of infusion is essential (i.v. favors; intradermal gives contact sharpening). Silencer T cells produce components. These elements may act specifically on T/B targets. Can be adaptively exchanged.

Slide 9

Infamous Suppressor T cells Suppressor or Regulatory lymphocytes Patrol fringe, hushing self-responsive T cells and look after resistance. 1970’s-mid 80’s Gershon, Kondo, Tada….. Forbidden of T “suppressor” cells CD8+ Complex administrative systems mapping to I-J (inside of the MHC) Molecular cloning of TCR and MHC baffled in T cell hybridomas emitting “suppressor factors” No identifiable cell surface marker No clone or cell lines with silencer movement No antigen particular silencer variable quality recognized Transient phenotype

Slide 10

The silencer's rebirth T cell More inquiries than answers. Questions ? n Number of productions * 1 1995 - Present Answers

Slide 11

A system of CD4 + administrative T cells control safe reponses. Thymic CD4 + T cell pool Thymically-determined normally happening CD4 + CD25 + Treg cells (nTreg ) Peripherally-instigated CD4 + Treg cells ( iTreg ) Foxp3 + GITR + CTLA-4 + CD25 + TCR + Peripheral separation signals CD25 GITR CTLA-4 Foxp3 CD25 +/ - GITR +/ - CTLA-4 +/ - Foxp3 +/ - APC _ Activated Effector T cell Autoimmunity Transplantation Tumor Immunity Infectious illness Piccirillo et al. Patterns in Immunol. 2004. .:tsli