HTHSCI 1DT3 Lecture Notes - Lecture 15: Phagocytosis, Natural Killer Cell, Nzr Ab Class

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The adaptive immune system – marco purbho
Adaptive immunity = describes the immune response to unique antigen
Evolved evolutionarily late
αβTCRs have alpha and beta chains, and recognise processed antigen as peptide on the MHC
molecules ONLY ON APCs, by contacts with both peptide and MHC molecule
BCRs have 2 heavy (beta) chains and two light (alpha) chains, cross-linked by covalent bonds,
and recognise whole native antigen
Both have highly variable antigen-recognising sequences; there is not enough room in the
genome to encode them all thus gene rearrangement confers the variability
B cells
Originate in the BM
Specific for one antigen
When BCR activated, B cells proliferate, differentiate to plasma cells, produce antibodies
Antibodies are the same as (membrane-bound) BCRs, but in a soluble form
Structure of BCR / Abs
40 Variable segments– 1-5 Joining segments – 1-25 Diversity segments ONLY ON THE HEAVY CHAIN –
Constant region
- the Variable, Joining and Diversity sequences are on chromosomes 22, 4, and 14 respectively
Gene Rearrangement
1) Joining and Diversity regions re-arrange first; Recombination Activating Gene -1 and -2 (RAG-1,
RAG-2) enzymes involved
- RAG enzymes carry out recombination at coding joints.
-This is imprecise i.e. nucleotides can be randomly added or subtracted
- this can lead to non-functional arrangement, but is useful in increasing the diversity of the
regions – it is estimated 10^ possible BCR combinations exist
2) Variable region rearranges to the JD region
Maturation
Heavy chain expressed on pre-BCR with surrogate light chain  triggers signalling cascade to
terminate heavy chain rearrangement
If expression cannot occur due to non-functional arrangement  signalling cascade to switch to
rearrangement of heavy chain gene on other chromosome (2 chances for functional heavy chain
to be created)
Light chain expressed with heavy chain to test autoreactivity
Naïve B cell thus formed
Exits BM and migrates to LN to await antigenic challenge
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Document Summary

Adaptive immunity = describes the immune response to unique antigen. Tcrs have alpha and beta chains, and recognise processed antigen as peptide on the mhc molecules only on apcs, by contacts with both peptide and mhc molecule. Bcrs have 2 heavy (beta) chains and two light (alpha) chains, cross-linked by covalent bonds, and recognise whole native antigen. Both have highly variable antigen-recognising sequences; there is not enough room in the genome to encode them all thus gene rearrangement confers the variability. When bcr activated, b cells proliferate, differentiate to plasma cells, produce antibodies. Antibodies are the same as (membrane-bound) bcrs, but in a soluble form. 40 variable segments 1-5 joining segments 1-25 diversity segments only on the heavy chain . The variable, joining and diversity sequences are on chromosomes 22, 4, and 14 respectively. Joining and diversity regions re-arrange first; recombination activating gene -1 and -2 (rag-1, Rag enzymes carry out recombination at coding joints.

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