Immunology Chapter 7 – The development of T lymphocytes
B-cell vs T-cell
B-cell:
Development in Bone marrow – generation BCR – negative selection
Secondary lymphoid organs – positive selection – naïve B cells
Activation by intact antigen -- Isotype switching and affinity maturation
Effector (plasma cell) and memory B cells
T-cell:
Development in Thymus – generation TCR – positive and negative selection
Secondary lymphoid organs – naïve T cells
Activation by processed antigen via MHC plus peptide
Effector and memory T cells
T-cell development
T-cell precursors travel from bone marrow to medulla
thymus via the blood circulation --> T-cells develop and
mature in the cortex of the thymus (primary lymphoid
organ) (thymocytes):
Uncommitted progenitor --> T-cell progenitor -->
CD8 – CD4- thymocyte with pre-TCR (double
negative) --> CD8+ CD4+ thymocyte with TCR
(double positive) --> CD8+ or CD4+ thymocyte with TCR (single positive)
TCR development
During the somatic recombination there are 2 checkpoints:
1. First checkpoint in double negative: test whether the
beta chain of TCR is functional
2. Second checkpoint in double positive: test whether the
alpha chain of TCR is functional – this occur
repeatedly until exhausting just like the BCR light-
chain
Critical selection on TCR recognizing self MHC presenting non-self-peptides.
Occurs in the thymus:
1. Positive selection: binding TCR to self MHC presentation of both MHCI and
MHCII peptide-complexes by cortical epithelial cells
MHC restriction occurs here: recognition MHC by TCR
During positive selection CD4+ vs CD8+ thymocyte fate is determined
based on binding of:
o MHCI – CD8+
o MHCII – CD4+
a. Only 2% of total T cell pool will recognize self MHC isotypes --> they
will move further to negative selection
b. Rest will die via apoptosis
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