6: Adaptive immunity, T cells & antigen presentation 🏁 Flashcards
The t cell receptor
- resembles an IgG Fab fragment (α- and β-chain)
- is never secreted
- C-region with transmembrane region
- V-region with antigen binding site
How do get the TCR diversity and how high is it?
somatic recombination in thymus (VDJ)
- variable segments: ~70α, 52β
- diversity segment: 0α, 2β
- joining segments: 61α, 13β
-> need to pair α and β doubles diversity potential
junctional diversity is reached by random nucleotide addition at the joins between V, D and J
2.5x10^7 different T cell clones in humans
potential 10^12 different T cells
Origin of T Cells?
- come from bone marrow
- mature in Thymus
Thymus degrades with age -> only reservoir of naive T-cells and no new once at one point
Major Histocompatibility Complex (MHC)
- what is it?
- what is it needed for?
-
MHC is general term in human: HLA
-MHC-I -> HLA-A, HLA-B, HLA-C - MHC-II -> HLA-DR, HLA- GQ, HLA-DP
each human expresses one of each
- highly polymorphic genes on chromosome 6
- important for T cell development (selection)
- important for self-, PAMP- and DAMP-recognition
Where are antigens processed?
- intracellular pathogens (and self-peptides) are degraded in cytosol -> peptides enter ER and bind to MHC-I
- extracellular pathogens are phago-/endocytosed -> degradation of proteins and binding to MHC-II in phagolysosome or endocytotic vesicles
What does MHC restriction mean?
- only one of the generated peptides can bind to MHC and be presented
- T cell response only to the immunodominat antigen epitope
- TCR activation depends on correct antigen and correct MHC
What are the TCR co receptors and what is there function?
CD4 and CD8
- they increase the sensitivity by 100 fold
- they determine the function and interaction:
- CD4 -> T helper cells, MHC-II
- CD8 -> cytotoxic T cells, MHC-I
T cell development
in Thymus
- negative selection to recognise non-self peptides
- positive selection to recognise host MHC molecules
—> TCR recognises self MHC and non-self antigen
what is alloreactivity?
recognition of foreign MHC as non-self antigen (e.g. Transplantation)
MHC expression on cells?
MHC-I is expressed on all nucleated cells and increased by cytokines
MHC-II:
Name cytokine classifications and some examples
Do you really want that?
pro-inflammatory: IL-1/2/6/8/12…, TNF-α, IFN-γ
anti-inflammatory: IL-10/35, TGF-β, (IL-4)
What are cytokines good for?
They are important for T effector cell differentiation from naive Th0 cells:
example:
high IL-2 -> cell proliferation
low IL-4 -> Th2 differentiation, also supported by IL-10
IFN-γ -> Th1 differentiation
they can also have diverse effects in different target cells
Name infections where Th1/Th2 cells determine the outcome
- Leishmania major: Th1 activates Macrophages leading to cell mediated immunity and recovery, Th2 inhibits Macrophage activation
- Mycobacterium leprae: Th1 response -> patient lives, Th2 response -> patient dies
What are the subsets of CD4 T cells and what is there purpose?
Th0: naive CD4 T cell
TFH: B cell helper
Th1: Intracellular pathogens, autoimmunity (proinflammatory)
Th2: Extracellular parasites, allergy, asthma
Th17: Extracellular bacteria, Fungi, Autoimmunity (proinflammatory)
iTreg: (Down-)regulation of immune response, Immune tolerance, Lymphocyte homeostasis
in more detail: TFH
- determine immunoglobulin class switch and promote B cell survival
- essential for formation of germinal center
- important for positive selection of high affinity B cell clones
required for B cell memory
