Lecture 11 - Uzonna Flashcards
(38 cards)
Define tolerance.
SPECIFIC unresponsiveness to an antigen induced by the exposure of the specific lymphocyte to that antigen.
Define self tolerance.
Immunologic unresponsiveness to self antigens
Define tolerogens.
Antigens that induce tolerance
Define immunodeficiency.
Developmental or maturational defects in lymphoctye populations and/or function
Define immunosuppression.
Active or passive inhibition of immune response in an otherwise immunologically competent host
What are the two signals required for lymphocyte activation?
What does signal 1 alone result in?
Specific recognition of antigen (between TcR/pep/MHC or BcR/Ag)
&
non-specific signal microbially induced molecules on/from APC.
Signal 1 alone leads to unresponsiveness, anergy, deletion, and apoptosis.
What happens if a lymphocyte’s encounter with an antigen leads to…
Activation?
Tolerance?
Ignorance?
Proliferation and differentiation
Anergy and apoptosis
No response
Describe self/non-self discrimination in terms of tolerance of the immune system.
Adaptive immune system needs to respond to specific and targeted foreign antigens without responding to self. This is achieved by early and continuous presence of self-antigens. Important for self tolerance and control of autoimmunity.
What is self tolerance?
Immunologic unresponsiveness to self antigens
Briefly describe medawar’s classical graft experiment.
Performed on mice regarding skin grafts.
- Strain A skin on Strain B mouse = rejection
- Strain A cells on neonate Strain B mouse and Strain A skin graft on said mouse after 6 months = accepted
- Strain A cells on neonate strain B mouse and strain C skin graft on said mouse after 6 months = rejected
What are the general characteristics of tolerance?
Immune response affected only by antigens used to induce tolerance
Tolerance may be transient/permanent
Must be established at clonal level (T and /or B cell specific)
Tolerance may be induced to self/foreign Ag.
Tolerance is highly _____.
Antigen specific
How is tolerance inducible?
Foreign antigens may be administered in a way that induces tolerance.
What are the factors that influence development of tolerance?
Host status of immune system Form/nature of antigen (soluble vs. aggregates) Size of antigen immunogenicity Route of antigen administration Dose of antigen
What is positive T cell selection?
When double positive T cells are able to recognize MHC class I or II molecules by DCs in cortex of thymus.
What is negative T cell selection?
When double positive T cells showed too strong an interaction with self peptides presented by MHC molecules in thymus. They undergo cell death.
What are the two main types of tolerance?
Central and peripheral
What falls under the central tolerance umbrella?
Negative selection
Development of Tregs
Receptor editing of B cells
What falls under the peripheral tolerance umbrella?
Regulatory cells and suppression
Anergy/ignorance
Exclusion from lyphoid follicles (B cells)
What are the locations, targets, and mechanisms of central T cell tolerance?
Location: Generative lymphoid organ - Thymus
Target: immature lymphocytes
Mechanisms: Neg selection, deletion, reg cells
What are the locations, targets, and mechanisms of peripheral T cell tolerance?
Location: Peripheral/secondary lymphoid organs
Targets: mature lymphocytes
Mechanisms: Anergy, deletion, immunosuppression, T regs
Define anergy and how it happens.
Anergy is the functional inactivation of T lymphocytes. This is achieved by the recognition of an antigen without adequate levels of secondary signalling via lack of co-stimulatory molecules in APC (B7). Expression of inhibitory CTLA-4.
What is AICD and what causes it?
it is Activation induced Cell Death - deletion of a cell.
Repeated activation of a mature T lymphocyte by self antigen without second signal will result in AICD.
Which cells are involved in immune suppression?
How do they do this?
Most reg T cells (CD4+CD25+FoxP3+)
They mediate their function through soluble factors like IL-10 and TGFbeta and direct interation through inhibition of activation and differentiation and effector functions of T cells.
