T cells lecture 1 Flashcards
Adaptive immunity is
Gradual response - over a few days
Targets specific pathogens
Highly diverse antigen receptors
Immunological Memory
Where do T cells arise?
Bone Marrow
Where do T cells mature?
Thymus
Function of T cells
Kill infected cells
Help B cells
Kill tumour cell
What do T cells not produce?
Antibody
Surface receptors are called?
TCR
T cell receptors
How are infected cells recognised?
MHC molecules
On antigen-presenting cells (APCs)
What kills infected cells?
Cytotoxic T cells
How can T cells identify infected cells?
Small pathogenic proteins expressed on surface of infected cells
Lymphocytes
B cells
T cells
Specific T cells found in blood periphery
CD4+
CD8
Other subset of T cell
T regulators
T cells are initially
Naive T cell type
T helper Cell
CD4+
CD4+ function
against intracellular bacteria + parasite
Help CD8+
Promote humoral immune defense
CD4 secreted molecules
IFN-Y
IL-2-4-5-10-13
CD8+ is?
Cytotoxic T cell
CD8+ secreted molecules
Perforin
Granzymes
IFNy
Function of CD8+
Activated - cytotoxic
Kill virus-infected cells
Kill tumour cells
How do T cells recognize an infected cell?
TCR
Structure of TCR
Heterodimer - a,b chains
Each chain has 2 domains -
- one variable
- one constant domain
What molecules does the TCR associate with
CD3
Function of CD3?
Allows signal to be fed into the cell
CDR
Complementarity Determining Regions
How many CDRs in TCR
3
Where are CDRs found?
Variable region of TCR
How does TCR interact with APCs?
MHC molecule recognised and binds to peptides from bacteria and virus.
Why is T cell receptor diverse?
Allows T cells to recognise many specific pathogens
How do T cells generate diversity to recognise many pathogens?
VDJ recombination
TCR locus
Many genes
Rearrange to make many receptors
VDJ recombination at the a locus
Join V segment to J segment
Loci
a-chain locus
b-chain locus
v
variable region
J
Joining region
D
Diversity segment
C
constant segment
CDR loops are more diverse in?
B chain
B locus: Where does recombination takes place?
Recombination Signal Sequences
RSS
B locus: enzyme
VDJ recombinase enzyme
B locus: most important enzyme
RAG1
RAG2
Expressed in lymphocytes of T + B cell
RAG1 + RAG2
Enzymes cut open DNA for recombination to occur
What segmentd join at the most variable region?
D
J
Why segments join at D and J genes?
Junction diversity
Extra nucleotides are added when DNA segments join
Segment corrosponds to which loop of the TCR?
CDR3
Combination Diversity
From different combination of gene segments
Junction diversity
Addition of nucleotides when recombination occurs
Steps of VDJ recombination occuring at signal sequences
RAG complex cleaves signal sequences
DNA hairpins forms
RAG complex with Artemis = hairpin single stranded
New nucleotides are added
Ends paired and repaired - coding joint
How TCR detect pathogens?
MHC molecules
MHC
Major Histocompatibility Complex
Antigen Presentation
MHC bind proteins from virus/bacteria (antigenic peptides)
Present them to T cells
-can bind to self peptides from the cell
MHC-1
3 extra cellular domain
a2 a1
a3 b2
Peptide binding = a2 a1
B2 microglobulin
MHC II
Peptide binding a1 and b1
a1 b1
a2 b2
MHC 1
Nucleated cell
Present endogenous antigens
Display self proteins, virus proteins, intracellular pathogen
Present to cytotoxic (CD8)
MHC II
Antigen presenting cells (APCs)
Present exogenous antigens (extracellular, external)
Phagocytosis, receptor mediate endocytosis
Present to CD4 Helper T cells
Where do peptides bind?
MHC cleft
1 - 8-10 aa
II - 13-25 aa
MHC genes are…
Highly polymorphic
