HTHSCI 1DT3 Lecture Notes - Lecture 16: Tryptophan, Il2Rb, Enteropathy
23 Jun 2018
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Induction of tolerance to self-antigens
Adaptive immunity is present in all jawed vertebrates & is mediated by the RAG recombination
system
In terms of the receptor regions i.e. the Fab segment, BCRs and TCRs are almost identical
TCRs/BCRs
Each loop of the TCR is a complementarity-determining loop
The CDR1, 2 and 3 regions are variable
CDR1 and CDR2 have multiple copies; in B cells they can be altered by affinity maturation
CDR3 diversity is generated by V(D)J recombination (gene rearrangement)
Diversity is induced in both alpha and beta chains (I.e. there are two variable region in CDR3
BCRs recognise a characteristic of the conformation shape of a whole or ‘native’ antigenic
protein
TCRs recognise T cell epitopes, which are internal linear structures generated by antigen
processing
The T cell system has involved to ‘look inside’ the cell as MHC presents an external
representation of the internal contents
Induction of self-tolerance
T cells regulate the B cell community hence self-tolerance induction in T cell compartments is
key
In bone marrow transplants donor T cells are transferred to recipient and recognition of non-self
produces a damaging AI response (GvHD). These T cells are important to attack the leukaemia
hence the graft-host response cannot be completely avoided. Hence standard practise is now to
remove some T cells before transplantation and re-infuse them post-transplantation, allowing
them to attack the leukaemia at this stage
Mechanisms of self-tolerance
1) Central tolerance: not 100% effective hence autoreactive T cells are present in the peripheral
cell repertoire
2) Raised activation threshold in the periphery
3) T cell anergy: on recognition of the antigen without co-stimulation
4) T regulatory cells
5) Lymphocytes have cell intrinsic curtailing of autoreactivity via negative feedback, expression of
inhibitory co-receptors and downregulation of receptor expression
6) Danger hypothesis (requirement for DAMPs as well as PAMPs) adds another level of immune
regulation
Central tolerance
T cell development in the thymus is a complex process, influenced by the thymic
microenvironment which contains:
DCs
Macrophages
Cortical epithelial cells
Medullary epithelial cells
…And fibroblasts in the stroma
find more resources at oneclass.com
find more resources at oneclass.com
Document Summary
Adaptive immunity is present in all jawed vertebrates & is mediated by the rag recombination system. In terms of the receptor regions i. e. the fab segment, bcrs and tcrs are almost identical. Each loop of the tcr is a complementarity-determining loop. The cdr1, 2 and 3 regions are variable. Cdr1 and cdr2 have multiple copies; in b cells they can be altered by affinity maturation. Cdr3 diversity is generated by v(d)j recombination (gene rearrangement) Diversity is induced in both alpha and beta chains (i. e. there are two variable region in cdr3. Bcrs recognise a characteristic of the conformation shape of a whole or native" antigenic protein. Tcrs recognise t cell epitopes, which are internal linear structures generated by antigen processing. The t cell system has involved to look inside" the cell as mhc presents an external representation of the internal contents. T cells regulate the b cell community hence self-tolerance induction in t cell compartments is key.
