4. Adaptive Immune Response: T Cells Flashcards
How do T cells recognise antigen? Which CD molecules can this associate with?
T cell receptor (TCR), CD4 or CD8
Where do T cells develop?
Thymus (grow in bone marrow like every other cell, then move and develop in thymus)
What happens when T cells become mature?
Will either become CD4+ or CD8+
What do most CD4+ T cells do?
Helper T cells (help other immune system cells to carry out function) or regulatory T cells (suppress unwanted immune responses)
What do most CD8+ T cells do?
Cytotoxic T Cells (cytotoxic)
What are the two versions of T Cell receptor?
(most are) alpha-beta TCR (Alpha and beta chains), may also be gamma-delta TCR (lesser)
T cells may be one or the other of these
Basically all T cells are alpha-beta
What is the structure of the TCR?
Heterodimer (alpha and beta chains), each with a variable and constant region
Variable region gives T cell specificity - recognises particular peptide-MHC combination
Constant region
Transmembrane segment
Short cytoplasm tail
How are the domains of the TCR stabilised?
Intrachain disulphide bond, chains linked together by interchain disulphide bond
How do MHCs vary between individuals?
Bits that vary are in the groove that binds the peptide, other bits do not vary between individuals (non-polymorphic)
What part of the MHC does CD4/8 bind?
The non-polymorphic side (non varying part)
What MHC does CD8 bind to and which does CD4 bind to?
CD8 - MHCI
CD4 - MHCII
No exception
How do TCRs send signals into the cell?
Through the CD3 coreceptor complex (CD3delta, epsilon gamma and zeta chain)
ITAMs on the zeta chains are phosphorylated by Lck causing a signalling cascade which ends up in T cell activation (only if co-stimulation occurs)
There is antigen specificity of the TCR
What is an ITAM?
Immunoreceptor tyrosine based activation motif - present on the CD3 co-receptor complex
How is variability of TCRs created?
Unique genetic recombination of TCR genes (only found in lymphocytes)
What occurs to the TCRs/T cells after genetic recombination? What are the two forms of selection?
Selection occurs in the thymus (checking that T cells are useful)
Positive selection - check that our T cell receptors recognise own MHC version
Negative selection - check if recognise foreign peptides
What happens if you only send a signal through the CD3 and TCR?
Inactivation of T lymphocyte - Anergy
What co-stimulation is required to activate T cell?
Additional interactions e.g. CD80 and CD86 molecules
What additional co-stimulation of T cells may occur?
Through cytokines leads to additional co-stimulation
What happens when T Cell is activated (3)?
Proliferate and expand in number, carry out effector function (e.g. kill cells), form memory cells
What are the various types of helper T Cell? What do they express?
Th1 cell - produce cytokines such as interferon gamma, interleukin 2 and TNF beta - involved in helping cytotoxic T lymphocytes/ macrophages to carry out functions, help B cells produce antibody, inhibit Th2 cells
Th2 cell - produce IL-4, 5, 10, 13 - specialised in making B cells make antibody, inhibit Th1
Th17 cell - produce IL-17, 22
Tfh - produce IL-21 and ICOS - help B cells produce antibody in germinal centres in secondary lymphoid tissues
Describe CD4 Treg and CD8 Tc
Treg: produce TGFbeta, IL-10, 35 - suppress unwanted immune response
Tc: produce perforin, granzymes, fas ligand - kill infected cells
What are the co-stimulatory molecules of the Th1 cell?
CD86, CD28, CD40 - activates Th1 cell causing secretion of gamma interferon which in turn superactivates macrophages
How do helper T cells help cytotoxic T cells?
Th1 secrete IL-6, 2 which activate cytotoxic T cell
How do cytotoxic T lymphocytes (CTL) kill cells?
2 mechanisms - identical to NK cells
Fas/Fas-ligand pathway - Fas-ligand of CTL binds to Fas
Granzyme pathway - release of granzymes and perforin (similar to C9) - perforin makes pores to insert granzymes
Net result of either pathway is activation of caspases which set off programmed cell apoptosis destroying the infected cell to be taken up by phagocytic macrophages
