Memory and Tolerance Flashcards

Question

Mechanisms of tolerance?

Answer 1

Inactivation of self-reactive clones Immune regulation Self-epitopes hidden from recognition factors

Answer 2

Checkpoint - does receptor bind self antigens in bone marrow? Those that bind self = clonal deletion or receptor editing

Answer 3

Way of rescuing self reactive cells RAG genes stay active to allow recombination at light chain locus If this creates a non-self binding receptor = rescue If not = deletion

Answer 4

A soluble self-antigen may interact leading to inactivation/anergy, as IgM is not expressed (IgD is, though) and the cell cannot signal, so migrates to the periphery and dies Autoreactivity - cell is ignorant to self-antigens, maybe because they do not bind strongly enough or it is unavailable This leads to a clonally ignorant B cell separated from dangerous self-reactions

Answer 5

Interactions in thymus determine fate | Interactions with antigen on MHCI and II, through 3 CDR loops

Answer 6

T cells dont express TCR on surface, can't recognise self MHC or recognise self-MHC:self-antigens too strongly - removed Useful TCR, recognising self-MHC but not binding self-antigens strongly = kept

Answer 7

Antigen independent quality check, like B cells, checking beta chain rearrangements will express on the surface using a surrogate alpha chain, down regulating RAG

Answer 8

Positive selection If alpha BTCR recognises self-peptides Double positive thymocytes (express CD4 and 8 on surface) interact with self-peptide:MHCI/II Recognition = survival Non-recognition- recovery via receptor editing or death via apoptosis

Answer 9

Is alpha/beta TCR recognition too strong? Single positive cells (i.e. express either 4 or 8) enter medulla, interacting with antigens presented by TFs AIRE and Fexf2 Exact mechanism unclear: affinity hypothesis, where those with intermediate self-peptide affinity survive to exit the thymus

Answer 10

Central removes most dangerous clones, peripheral picks up on the rest

Answer 11

Lack of T cell assistance If T cells cannot recognise self-antigen, even though they are taken up by B cells, T cells wil ignore these and so no plasma cells that recognise self antigens are made This is also evident during affinity maturation in germinal centres, where Tfh cells don't aid

Answer 12

Presenting an antigen in a non-activation context i.e. without co-stimulatory signal is tolerogenic Only signal 1 (antigen) = anergic T cells Induces peripheral Tregs

Answer 13

Induced by antigen and signal 3 induced pTreg = Foxp3+, restrain self-responses thymic derived tTreg = Foxp3+ and - = recognise self and harmless non-self

Answer 14

``` Anti-inflammatory and pro-regulatory cytokines, TGFb, IL10, IL35 Modulate DCs Outcompete effector T cells for IL2 Directly kill T cells Affect transcription of T cells ```

Answer 15

``` Some regions more exposed e.g. the gut, where pathogen antigens are better tolerated Brain Eye Testes Uterus ``` These are enclosed by a physical barrier, blocking lymphatic drainage Low MHCI Suppressive cytokines like TGFb Express FasL for apoptosis of Fas expressing cells

Answer 16

TRauma to one eye = release of the sequestered self antigens, carried to lymph nodes for T cell activation Effector T cells in bloodstream attack both eyes This breaks immune privilege

Answer 17

Use immune suppression to gain immune privilege at the tissue -exploit earlier mechanisms

Answer 18

When tTregs and T cells are triggered in presence of suppressive cytokines, skewing their function

Answer 19

``` Central tolerance Antigen segregation Peripheral anergy Tregs Functional deviation Activation-induced cell death ```