T Cells And TCRs

Question 1

Where does T cell development occur

Answer 1

Produced in bone marrow

HSC precursor —> thymus to mature (thymocytes)

Question 2

What does T cell maturation involve

Answer 2

Rearrangement of TCRs

Positive and negative selection (central tolerance)

Question 3

What is central tolerance

Answer 3

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

Question 4

Describe the processes involved in T cell maturation

Answer 4

• 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

Question 5

What is a Double negative thymocytes

Answer 5

Expresses neither CD4 or CD8

Question 6

What is a Double positive thymocyte

Answer 6

Express both CD4 and CD8

Question 7

What is a single positive thymocyte

Answer 7

Expresses one of either CD4 or CD8

Question 8

What is cluster differentiation (CD(4))

Answer 8

Membrane glycoproteins

Question 9

Which type of CD molecules do MHC II cells bind to

Answer 9

CD4

Rule of 8, (MHC) 2 x (CD)4 = 8

Question 10

Which type of CD molecules do MHC I cells bind to

Answer 10

CD8

Rule of 8, MHC (1) x CD(8) = 8

Question 11

What are TCRs

Answer 11

• 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

Question 12

Describe the TCR-alpha locus

Answer 12

Chromosome 14
70-80 V-alpha genes
61 J-alpha gene segments
1 C gene

Question 13

Describe the TCR beta locus

Answer 13

Chromosome 7
52 V-beta genes
2x (1D gene, 7J genes, 1C gene)

Question 14

Explain TCR diversity

Answer 14

VDJ recombination
- TCRalpha locus: VJ recombination
- TCRbeta locus: VDJ recombination of alpha and beta chains
Junctional Diversity
NO somatic hypermutation

Question 15

Functions of TCR

Answer 15

Naive TCRs and APC —> signalling cascade —> enhanced T cell cervical —> proliferation —> differentiate into distinct effector and memory Tc and Th subtypes

Question 16

What is the maturation site for B cells

Answer 16

Bone marrow

Question 17

Maturation sure for T cells

Answer 17

Thymus (thymocytes)

Question 18

Difference between antibody and T cell specificity

Answer 18

Antibodies can recognise a variety of organic and inorganic molecules, T cells can only recognise protein antigens

Question 19

True or false: T cells secrete antibodies

Answer 19

False, B cells do

Question 20

True or false: T cells can recognise pathogens “By themselves”

Answer 20

False, B cells can, T cells have to have pathogen “presented” (opsonised) to them

Question 21

What are some similarities between T and B cells

Answer 21

• 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

Question 22

True or false: the adaptive immune response is launched when the innate response is overwhelmed

Answer 22

True

Question 23

What are the functions of a cell mediated response

Answer 23

• 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

Question 24

What are the functions of CD8 T cells

Answer 24

Recognise antigens on MHC 1 APCs to activate cytotoxic effector functions
Destroy pathogen infected host cells

Question 25

What is the function of CD4 T cells

Answer 25

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

Question 26

Characteristics of T regulatory cells

Answer 26

Express CD4/CD25 molecules | - recognise antigens on MHC 2 —> immunosuppressive: dominant negative regulation on other lymphocytes

Question 27

Where do B and T cells circulate

Answer 27

Naive B and T cells patrol the secondary lymphoid organs binding to matching antigens by APC —> Activation

Question 28

True or false: Professional APCs express antigens in their surface using both MHC I and II molecules

Answer 28

True

Question 29

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+)

Answer 29

True

Question 30

True or false: dendritic cells can cross-present

Answer 30

True

Question 31

Describe the mechanism for T cell activation

Answer 31

- Interaction between antigen MHC complex and TCR supported by CD coreceptors - Interaction between T cell and APC - APC produce cytokines

Question 32

True or false: activation if T cells leads to the expression of IL4

Answer 32

False: IL2 turning into an effector or memory cell

Question 33

What is the role of activated CD4 (Th1) cells

Answer 33

Activate Tc cells Activate B cells to produce openings —> Activation classical complement Secrete IL2, IFN-gamma, TNF-alpha

Question 34

Role of activated CD4 (Th2) cells

Answer 34

``` 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 ```

Question 35

What’s are the 2 processes of CD8 activation

Answer 35

Activation by nature dendritic cells (MHC1 —> IL2 —> Activation) Activation with help of CD4 cells: CD4 IL2 —> increase in B7 —> CD8 Activation

Question 36

What is the role of activated (effector) CD8 (Tc) cells

Answer 36

Kill target cells infected with pathogens particularly viruses

Question 37

Describe the characteristics of the cytotoxic activity of NK and Tc

Answer 37

Fas-independant (perforin/granzymes) Fas-dependant cytotoxicity Fas-receptors in surface of target cel Fas-ligand in surface of NK and Tc cells —> apoptosis

Question 38

What are the 4 stages of Fas-independent NK and Tc cytotoxicity

Answer 38

- recognition and attachment to target cell - membrane attack: release of perforin/granzymes - NK/Tc dissociation - Target cell apoptosis