T Cell Activation and Generation of Effector T Cells

Question 1

Where are the microbes that B lymphocytes target?

Answer 1

➝ extracellular

Question 2

Where are the microbes that T lymphocytes target?

Answer 2

➝ intracellular

Question 3

Describe T cell activation briefly?

Answer 3

➝ Generated in bone marrow and they undergo maturation in the thymus
➝ mature naive T cells are released from the thymus into the blood
➝ recirculate between blood and peripheral lymphoid orangs
➝ if they encounter antigens that they recognise lymphocyte activation,proliferation and differentiation occurs

Question 4

How do naive mature T cells become mature?

Answer 4

➝ Ag recognition

➝ activation, proliferation and differentiation into effector T cells and memory T cells

Question 5

What are T cells designed to fight?

Answer 5

➝ Intracellular bacteria
➝ viruses
➝ cancer cells

Question 6

How do T cells recognise antigens?

Answer 6

➝ after processing and presentation

Question 7

What do αβ TCR recognise?

Answer 7

➝ peptides

Question 8

What do γδ T cells recognise?

Answer 8

➝ antigens that are not peptides

Question 9

How do T cells recognise antigens?

Answer 9

➝ via their T cells receptor

Question 10

What is the structure of αβ TCR ?

Answer 10

➝ one alpha chain and one beta chain

Question 11

What is the structure of a γδTCR?

Answer 11

➝ one gamma and one delta chain

Question 12

What is each chain made up of?

Answer 12

➝ 1 variable domain and one constant domain

Question 13

What is the antigen binding site made up of?

Answer 13

➝ Vα and Vβ

Question 14

What domains are homologous in TCR and BCR?

Answer 14

➝ V and C domains

Question 15

What T cells have αβ TCR?

Answer 15

➝ CD4 and CD8 T cells

Question 16

What T cells have γδ TCR?

Answer 16

➝ all other T cells

Question 17

What do MHC molecules display?

Answer 17

➝ peptides from processed Ag

Question 18

What does MHC I present to and what is its structure ?

Answer 18

➝ CD8+ T cells

➝composed of α and β2 microglobulin

Question 19

What does MHC II present to and what is its structure?

Answer 19

➝CD4+ T cells

➝composed of α and β chain

Question 20

What cells express MHC I?

Answer 20

➝ all nucleated cells

Question 21

What cells express MHC II?

Answer 21

➝ APC

➝ dendritic cells, macrophages

Question 22

What are human MHC molecules called?

Answer 22

➝ HLA (human leukocyte antigen)

Question 23

What are the MHC I HLAs?

Answer 23

➝ HLA-A
➝ HLA-B
➝ HLA-C

Question 24

What are the MHC II HLAs?

Answer 24

➝ HLA-DP
➝ HLA-DQ
➝ HLA-DR

Question 25

What forms the peptide binding groove in MHC I?

Answer 25

➝ two alpha chains

Question 26

What forms the peptide binding groove in MHC II?

Answer 26

➝ alpha 1 and beta 1 chain

Question 27

What cells are the only ones capable of presenting to naive T cells?

Answer 27

➝ dendritic cells

Question 28

What do macrophages present to?

Answer 28

➝ previously activated effector T cells

Question 29

What do CD8+ T cells recognise?

Answer 29

➝ antigens displayed by nucleated cells

Question 30

Where are dendritic cells found?

Answer 30

➝ mucosa ➝ skin ➝ tissues

Question 31

What are dendritic cells in the skin called?

Answer 31

➝ Langerhans cells

Question 32

What are the 5 functions of dendritic cells?

Answer 32

``` ➝ Capture microbes ➝ transport microbes from tissue to draining lymph nodes ➝ process microbes into antigens ➝present antigens to naive T cells ➝ activate naive T cells ```

Question 33

What are the three signals dendritic cells use for naive T cell activation?

Answer 33

➝ TCR recognising antigen ➝ Co-stimulation ➝ Cytokine signals

Question 34

Describe how naive T cells are activated by dendritic cells?

Answer 34

➝ the first signal is the TCR recognising the antigen and the peptide in combination with MHC ➝ it needs a second signal called co-stimulation ➝ this is done by the ligation of the co-stimulatory receptor CD28 (on the T cell) by the co-stimulatory molecules CD80/86 (on the APC) ➝ the third signal is via the cytokines

Question 35

What do the cytokines secreted by the dendritic cell to activate the naive T cell depend on and what do they determine?

Answer 35

➝ The type of infection | ➝ it determines what type of effector the activated T cells differentiate into

Question 36

What happens if only the first signal occurs?

Answer 36

➝ no response ➝ anergy ➝ tolerance

Question 37

What does infection do to the APCs?

Answer 37

➝ increases the antigen presenting functions and increases the expression of co-stimulatory molecules and of MHC

Question 38

What cytokines does the APC need to produce to make a TH1 cell?

Answer 38

➝ IL-12 | ➝ IFN gamma

Question 39

What do TH1 cells induce?

Answer 39

➝ macrophage co-operation

Question 40

What do TH2 cells induce?

Answer 40

➝ B cell and eosinophil/mast cell co-operation

Question 41

What are the 4 functions of macrophages?

Answer 41

➝ Phagocytose microbes ➝ Antigen presentation to effector CD4+ T cells ➝ activation of TH1 cells ➝ TH1 cells activate macrophages to kill ingested microbes

Question 42

What cells can present to CD8+ T cells?

Answer 42

➝ all nucleated cells

Question 43

What are CD8+ cells specialised to do?

Answer 43

➝ recognise viral antigens and proteins | ➝ eliminate cells infected by viruses/ malignant cells

Question 44

What can CD8+ recognise antigens from in addition to all nucleated cells?

Answer 44

➝ microbes that have been phagocytosed if the antigens escape from the phagosome into the cytosol

Question 45

What antigens are presented to CD4+ T cells?

Answer 45

➝ exogenous antigens are taken up in cells, processed and presented by MHC II

Question 46

What are the three things that can happen to exogenous pathogens?

Answer 46

➝ taken up by phagocytes ➝ eliminated via killing in phagocytes ➝ eliminated by antibodies (neutralisation, opsonisation and complement activation)

Question 47

What cell types does CD4+ help?

Answer 47

➝ Macrophages (TH1) | ➝ B cells (TH2)

Question 48

Describe how a bacterial peptide is presented onto MHC II in 14 steps?

Answer 48

1)A macrophage takes up a bacteria into an endosome 2)The bacteria is broken down 3)The proteins from the bacteria are contained within the endosome and are fused with a lysosome 4)Enzymes cleave the proteins which produce peptides 5)MHC molecules are produced in the ER, if there is nothing to fill the peptide region then the molecule is unstable and MHC gets degraded 6)In the ER the newly generated MHC molecules are conjugated with the invariant chain that has a fragment that stabilises the groove 7)The complex of MHC and the invariant chain leaves the ER and into the golgi into an exocytic vesicle 8)While the vesicle is travelling to the surface it ends up in the late endo-lysosomal compartment where the peptides from the bacteria are 9)The invariant chain gets destroyed by the low pH of the lysosome except for one small fragment called CLIP which remains in the groove 10)The compartment expresses another molecule (HLA-DM) that is a class II MHC molecule, it is not involved in antigen presentation but in freeing the groove of the MHC to allow it to load the peptides. 11)The HLA-DM has a higher affinity for CLIP and it ‘steals’ away from the MHC II 12)The MHC II has a free groove now that the bacterial peptide can enter in 13)If the MHC II cannot find a peptide it will be degraded 14If a bacterial peptide has entered then the MHC II will be stabilised and it will leave via a vesicle and is fused on the plasma membrane

Question 49

What antigens are presented to CD8+ T cells?

Answer 49

➝ cytosolic antigens (viruses,mutated proteins in cancer cells)

Question 50

Describe how viral proteins are presented on MHC I in 9 steps?

Answer 50

1) There is an infected APC or an epithelial cells (viruses can infect any nucleated cell) 2) There is a virus growing in the cytosol with proteins of the virus present in the cytosol 3) During a viral infection, cells develop proteasomes that are specialised in recognising viral proteins 4) They take up viral proteins and break them down into peptides 5) The peptides are imported into the ER via a transporter called TAP 6) MHC I is generated in the ER 7) The MHC I has a free grove so the peptides can fit 8) If the MHC I finds a peptide that fits in the groove, it is stabilised and it can leave, if it doesn’t find a peptide it gets degraded 9) If a peptide is found it leaves via an exocytic vesicle to the membrane and presents on the surface of the cell for recognition by CD8+

Question 51

What are the three types of effector T cells?

Answer 51

➝ T helper cells ➝ Cytotoxic T lymphocytes ➝ Regulatory T cells

Question 52

What are the 4 types of T helper cell and what are their functions?

Answer 52

``` ➝ TH1 - help phagocytes kill ingested microbes ➝ TH2 - help eosinophils/mast cells to kill helminths ➝ TH17- role in defense against bacteria & fungi ➝ TFH - help B cells class switch ```

Question 53

What do Regulatory T cells express?

Answer 53

➝ CD4 ➝ CD25 ➝ FOXP3

Question 54

What are the two cytokines that induce differentiation into TH1 and what kind of cells produce them?

Answer 54

➝ IL-12 and IFN gamma | ➝ APC infected with bacteria

Question 55

What is the main cytokine produced by TH1?

Answer 55

➝ IFN gamma

Question 56

What are the 4 roles of TH1?

Answer 56

➝ MAIN :activate phagocytes and stimulates destruction of intracellular pathogens ➝ OTHER : stimulate production of IgG antibodies and phagocytosis of microbes

Question 57

What are the cytokines that induce differentiation of TH2 and what kind of cells produce them?

Answer 57

➝ IL-4 ➝ IL-25 ➝ IL-33 ➝ APC infected with helminths

Question 58

What are the 3 cytokines produced by TH2?

Answer 58

➝ IL-4 ➝ IL-5 ➝ IL-13

Question 59

What are the 4 main roles of TH2?

Answer 59

➝ help B cells produce IgE ➝ IgE opsonises helminths ➝ activates eosinophils & mast cells ➝ eosinophils & mast degranulation and killing of helminths

Question 60

What disease is TH1 present in?

Answer 60

➝ autoimmunity | ➝ chronic inflammation

Question 61

What disease is TH2 present in?

Answer 61

➝ Allergy

Question 62

What diseases is TH17 present in?

Answer 62

➝ autoimmunity | ➝ inflammation

Question 63

What diseases is TFH present in?

Answer 63

➝ autoimmunity

Question 64

How do effector T cells leave the activation site?

Answer 64

➝ via blood

Question 65

In what way do CD8+ T cells kill cells and why?

Answer 65

➝ antigen-specific | ➝ contact- dependent so uninfected/healthy cells are not killed

Question 66

What 2 cytolytic molecules do CD8+ T cells use?

Answer 66

➝ Perforin - forms pores and delivers granzymes | ➝ granzymes A,B,C initiate apoptosis

Question 67

What is CD8+ T cell killing mediated by?

Answer 67

➝ the death receptor pathway Fas/FasL