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30 Cards in this Set
- Front
- Back
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Tolerance definition |
set of mechanisms which prevent organisms from responding to self process of eliminating or neutralising self reactive lymphocytes |
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tolerance and age... |
tolerance has to be maintained throughout life |
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if foreign antigens given in perinatal period... |
seen as self in future e.g. non identical twins accepting RBCs skin grafts etc. e.g. pregnancy mother does not reject foreign paternal proteins |
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Central tolerance |
Tolerance that occurs for T cells in the Thymus + Bone marrow |
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Reminder: B cells recognise... T cells recognise... |
B cells - native antigen T cells - peptide fragments presented on either MHC I or MHC II |
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T cell development |
Precursor made in bone marrow development + selection in thymus |
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Reminder: T cells express 2 types of TCR ... |
αβ T cells, MAJORITY gamma delta T cells |
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Thymus basic structure |
cortex medulla organised into lobules by capsular septa |
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Thymus cells |
Thymic stromal cells -Cortical epithelial cells -Medullary epithelial cells -Dendritic cells Cells of Haematopoietic origin -Thymocytes - developing T cells |
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CLINICAL APPLICATION Thymus regression |
most active from neonatal-adolescent early teens thymus starts to regress stroma replaced by adipose |
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route of development in the thymus... |
thymocytes start in the cortex
then as they move into the medulla they undergo selection + development |
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What occurs in the cortex? processes? (2) dominant cell type? which MHC is expressed by ______________ ____________________ ________? |
TCR gene rearrangement Positive selection Reticular epithelial cells are dominant cell →network of fine presses Cortical epithelial cells express MHC II |
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immature thymocytes express both... |
CD4 and CD8 hence said to be CD4+CD8+ |
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Cortico-medullary junction what cells are here? (2) what is their function? |
macrophages, prevent damaged/dying cells moving into the medulla Dendritic cell, negative selection |
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state of thymocytes when they reach the medulla? |
Thymocytes have: undergone TCR gene rearrangement positive selection some negative selection |
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Medulla what happens here? |
additional rounds of negative selection |
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AIRE gene |
expressed by Thymic epithelial cells → transcription of organ specific genes allows thymocytes to be exposed to organ tissue (in the thymus) as part of negative selection |
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Positive selection (simple terms0 |
Can the T cell detect antigens on MHC at all? if it can → progress to cortico-medullary junction |
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Positive selection which cells responsible for this? |
T cells which recognise foreign peptide (i.e. that expressed on MHC) done by cortical epithelial cells i.e. Does the T cell work? Does it detect foreign antigen? |
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Negative selection (simple terms) |
Does the T cell detect self peptides (as foreign)? if yes kill the T cell i.e. Does the T cel detect and attack self peptides? |
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Negative selection |
removes potentially dangerous T cells which recognise self peptides i.e. do not tolerate self → apoptosis |
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Peripheral tolerance: MNEMONIC TIIR |
Threshold response Inappropriate antigen presentation Ignorance Reg T cells
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Peripheral tolerance: Threshold response proteins associated with T cell self regulation? absence of brake? |
T cells can regulate themselves protein associated CD28 is the gas pedal CTLA-4 is the brake pedal if CTLA-4 is absent → severe autoimmune disease as T cells cannot self regulate the CD28 response |
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Peripheral tolerance: Threshold response gas pedal = |
CD28 |
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Peripheral tolerance: Threshold response brake pedal = |
CTLA-4 |
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Peripheral tolerance: Inappropriate antigen presentation |
Dendritic cells → present antigen → activation of T cells dendritic cells give danger signals e.g. LPS from bacteria binds TLR on dendritic cell → full activation of T cell by upregulation of costimulatory molecules self proteins fail to give danger signals although self reactive T cell might recognise self antigens presented, does not become activated CD4 T cell (most important) only recognises MHC II MHC II expression only on: dendritic cells macrophages B cells this means that most tissues cannot directly present own proteins to CD4 T cells |
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Peripheral tolerance: Ignorance |
sites of immune privilege: -eye -testis active suppression of immune responses by cytokines e.g. TGF-β apoptosis - programmed cell death normally these antigens are invisible to immune system |
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Peripheral tolerance: ignorance |
Sympathetic ophthalmia |
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B cell tolerance |
B cells do not have selection process as with the T cells if B cells see antigen before reaching 2º lymphoid tissue usually either inactivated or deleted |
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Major source of B cell tolerance... |
lack of T cell help to mount effective antibody and memory response |
