Adaptive Immunity- T cells

Question 1

what is the purpose of MHC class1 and 2?

Answer 1

they are cell surface receptors specialised in presenting antigens - (only peptide antigens)

Question 2

what recognizes MHC-peptide complexes?

Answer 2

they are rexognized by T cells -

T cell receptors (TCR) recognize these peptides, binds them, and becomes activated

Question 3

what type of T cell does MHC class 2 activate?

What type of T cell does MHC class 1 activate?

Answer 3

MHC class 2= T helper cell

MHC class 1 = Cytotoxic T cell

Question 4

does one T cell recognize many different peptides… or only one?

Answer 4

only one-

they are highly specialized, however there are 10^8 unique TCRs in the body

Question 5

Once T cells recognize a MCH-peptide complex, what occurs?

Answer 5

once activated, clonal expansion occurs-

T cells must interact with other cells and generate memory T cells that live for more than 20 years

Question 6

Where to T cells develop?

Answer 6

they develop in the Thymus (primary lymphoid tissue) into naive T cells

this is where TCR rearrangment occurs

selection process

differentiation into CD4/CD8 lineage

Question 7

where are T cells activated?

Answer 7

they are activated whenever they come across a matching MHC class peptide complex -this occurs in Lymph nodes

clonal expansion then occurs - differentiation into effector cell

Question 8

what is the T cell effector function?

Answer 8

happens in any tissue

direct killing of tumor or infected cell - it also recruits help

Question 9

Where are T cells formed in the first 8 weeks gestation vs. at 15 weeks gestation?

Answer 9

8 weeks = in the thyroid gland and the bones

15 weeks - in the intestines?, spleen and lymph nodes

Question 10

what are the three checkpoints for maturing T cells in the thymus?

Answer 10

1. do you have a T Cell receptor?
   
   • • Cells at this point are also CD4 and CD8 positive
   • • CD4 and CD8 are co- receptors
2. Can you recognise self MHC?
   
   • •Positive selection also down-regulates either CD4 or CD8, depending on whether interaction occurred with MHC class I (CD8) or class II (CD4)
   • • Results in single positive CD4 and CD8 T cell
   • retains T cells that recognize self
3. Do you recognise self antigen (negative selection)?
   
   • Does the TCR bind to self-peptide too tightly – APOPTOSIS
   • Does the TCR bind weakly/moderately - LIVES
   • negative selection = eliminates T cells that recognise self peptide too tightly - protects against autoimmunity

Question 11

how are there millions of T cell with different specificities if we only have about 30,000 genes in total ?

Answer 11

gene rearrangement - random and variable TCR molecules with unique specificities

Question 12

what two signals are required to activate T cells?

Answer 12

Signal 1 = specific MHC-peptide complex molecule detected

• CD4 coreceptor interacts with residues on the side of the MHC

Signal 2= costimulatory receptors (B7 or CD80/CD86) on APCs are upregulated and interact with the CD28 (always present on T cells)

once these conditions are met, T cell activation occurs

Question 13

What do activated T cells produce?

Answer 13

they produce the cytokine interleukin 2- IL2

IL2 is a T cell growth factor -

Question 14

What effect does IL2 have on T cells ?

Answer 14

it proliferates and exapnds T cell clones

Question 15

If you wnat to supress T cell activation or activity what do you target? What drug does this?

Answer 15

you supress IL2- this is what Tacrolimus does - it pevents IL2 expression as an immunosuppressive drug -

Question 16

What are the T cell effector functions?

Answer 16

CD8= cytotoxic T cells - only recognize MHC Class 1 , directly kill virally infected or tumor cells

CD4 T helper cells - only recognize MHC class 2 - help active B cells and macrophages via cytokine production and interaction

Question 17

How do cytotoxic T cells kill?

Answer 17

they bind to the MHC class 1 molecule with a processed antigen

they are packed full of vesicles with toxic enzymes for killing

once the cytotoxic T cell is activated perforin (perforates cells) and granzymes (proteolytic enzymes) are released that destroy structural cytoskeleton proteinas and degrade DNA

Question 18

what are the two key functions of T helper cells?

Answer 18

1. interact with B cells to activate them - produce antibodies
2. production of cytokines to drive the immune repsonse - cytokines will activate T and B cells and macrophages to clear infection, cytokines produced depend on infection agent

Question 19

What are the different subsets of T helper cells?

Answer 19

TH1

TH2 and

TH17

Question 20

What differentiates the TH1, TH2 and TH17 subsets of T helper cells?

Answer 20

they all produce different cytokines based on the type of infection present

TH1= IFNgamma- IgG production for intracellular microbes- associated with chronic infections

TH2= IL4,5,13- IgE production for heminth parasites - associated with allergies

TH17= IL17A, IL17F, IL22 - neutrophilic monocytic inflamation associated with autoimmune diseases

Question 21

What is DiGeorge Syndrome?

Answer 21

a deletion on the chromosome 22 leads to severe neuromuscular defects and hypothyroidism - no T cells

this has severe developmental and cardiac defects as well as immune disfuntion

Question 22

What is SCID?

Answer 22

severe combined immunodeficiency

• majority due to mutations in the receptor for IL2- common gamma chain - T cells can’t proliferate in response to IL2 -
• normal B cell numbers however
• also a part of other cytokine receptors so severe defects