T Cells And TCRs Flashcards
Where does T cell development occur
Produced in bone marrow
HSC precursor —> thymus to mature (thymocytes)
What does T cell maturation involve
Rearrangement of TCRs
Positive and negative selection (central tolerance)
What is central tolerance
Positive and negative selection
Surviving: thymocytes that recognise MHC I/II —> MHC restriction (positive)
Apoptosis: thymocytes that bind to self-peptides/MHC I/II complexes (negative) —> self tolerance
Describe the processes involved in T cell maturation
- T cells rearrange TCRs genes
- Expression of TCR (alpha-beta or gamma-delta chains)
- Expression of both CD4 and CD8 co-receptors
- Double positive (selection)thymocytes
- generation of single positive thymocytes expressing TCR
What is a Double negative thymocytes
Expresses neither CD4 or CD8
What is a Double positive thymocyte
Express both CD4 and CD8
What is a single positive thymocyte
Expresses one of either CD4 or CD8
What is cluster differentiation (CD(4))
Membrane glycoproteins
Which type of CD molecules do MHC II cells bind to
CD4
Rule of 8, (MHC) 2 x (CD)4 = 8
Which type of CD molecules do MHC I cells bind to
CD8
Rule of 8, MHC (1) x CD(8) = 8
What are TCRs
- Membrane bound glycoproteins similar to Fab fragment
- 2 polypeptide chains: alpha-beta or gamma-delta
- 3 regions: variable V, Constant C and membrane anchoring
- Recognises only protein antigens presented on host cells by MHC I
- T cells DO NOT produce soluble or antigen like molecules
Describe the TCR-alpha locus
Chromosome 14
70-80 V-alpha genes
61 J-alpha gene segments
1 C gene
Describe the TCR beta locus
Chromosome 7
52 V-beta genes
2x (1D gene, 7J genes, 1C gene)
Explain TCR diversity
VDJ recombination - TCRalpha locus: VJ recombination - TCRbeta locus: VDJ recombination of alpha and beta chains Junctional Diversity NO somatic hypermutation
Functions of TCR
Naive TCRs and APC —> signalling cascade —> enhanced T cell cervical —> proliferation —> differentiate into distinct effector and memory Tc and Th subtypes
What is the maturation site for B cells
Bone marrow
Maturation sure for T cells
Thymus (thymocytes)
Difference between antibody and T cell specificity
Antibodies can recognise a variety of organic and inorganic molecules, T cells can only recognise protein antigens
True or false: T cells secrete antibodies
False, B cells do
True or false: T cells can recognise pathogens “By themselves”
False, B cells can, T cells have to have pathogen “presented” (opsonised) to them
What are some similarities between T and B cells
- Appearance, they look exactly the same
- Origin, produced in bone marrow
- TCRs are antibody-like molecules
- Antibodies, BCRs and TCRs are generated by gene recombination
- TCRs are diverse like BCRs and antibodies
- T and B cells undergo clonal expansion after activation
- Antibodies, BCRs and TCRs recognise regions of antigens called epitomes
True or false: the adaptive immune response is launched when the innate response is overwhelmed
True
What are the functions of a cell mediated response
- Cell mediated cytotoxicity through Tc cells
- Activation of cell phagocytes by Th
- Activation of Tc and B cells by Th
- Th - required for development of B and Tc memory cells
What are the functions of CD8 T cells
Recognise antigens on MHC 1 APCs to activate cytotoxic effector functions
Destroy pathogen infected host cells
What is the function of CD4 T cells
Recognise antigens on MHC 2 in APC
Th1: can secrete IL2, TNF-beta, IFN-gamma, cytokines to push class switch
Th2: IL4, IL5, IL6 and IL10 (cytokines) - push B cell class switch
Characteristics of T regulatory cells
Express CD4/CD25 molecules
- recognise antigens on MHC 2 —> immunosuppressive: dominant negative regulation on other lymphocytes
Where do B and T cells circulate
Naive B and T cells patrol the secondary lymphoid organs binding to matching antigens by APC —> Activation
True or false: Professional APCs express antigens in their surface using both MHC I and II molecules
True
True or false: uptake by endocytosis of pathogen leads to simultaneous cross-presentation if viral antigens on MHC 1 and 2 —> activating Th (CD4+) and Tc (CD8+)
True
True or false: dendritic cells can cross-present
True
Describe the mechanism for T cell activation
- Interaction between antigen MHC complex and TCR supported by CD coreceptors
- Interaction between T cell and APC
- APC produce cytokines
True or false: activation if T cells leads to the expression of IL4
False: IL2 turning into an effector or memory cell
What is the role of activated CD4 (Th1) cells
Activate Tc cells
Activate B cells to produce openings —> Activation classical complement
Secrete IL2, IFN-gamma, TNF-alpha
Role of activated CD4 (Th2) cells
Secrete IL4, IL5, IL6 and IL10 Responsible for allergic reactions Help control infection of parasites by: - activating eosinophils and mast cells - switching B cells to produce IgE antibodies
What’s are the 2 processes of CD8 activation
Activation by nature dendritic cells (MHC1 —> IL2 —> Activation)
Activation with help of CD4 cells: CD4 IL2 —> increase in B7 —> CD8 Activation
What is the role of activated (effector) CD8 (Tc) cells
Kill target cells infected with pathogens particularly viruses
Describe the characteristics of the cytotoxic activity of NK and Tc
Fas-independant (perforin/granzymes)
Fas-dependant cytotoxicity
Fas-receptors in surface of target cel
Fas-ligand in surface of NK and Tc cells —> apoptosis
What are the 4 stages of Fas-independent NK and Tc cytotoxicity
- recognition and attachment to target cell
- membrane attack: release of perforin/granzymes
- NK/Tc dissociation
- Target cell apoptosis
