struggle areas

Question 1

How are TH1 cells produced

Answer 1

receive IL-12 and IFN-y from DCs, express master transcription factor Tbet, produces IL-2, TNF-a, IFN-y

Question 2

How are TH2 cells produced

Answer 2

receive IL-4, express master transcription factor GATA-3, produces IL-4, IL-5 and IL-13

Question 3

How are TH17s produced

Answer 3

receive IL-6, TGF-B, IL-21, express master transcription factor ROR-yt, produces IL-17, IL-22

Question 4

What are the anti-viral cytokines?

Answer 4

IFN-y, IL-12

Question 5

What does vitamin D upregulate on T cells

Answer 5

Selectin ligands (E, and P), CCR10 and 4 for receptors expressed in the skin

Question 6

What does vitamin A upregulate on T cells

Answer 6

a4b7, CCR9 attracted to MAdCAM and CCL25

Question 7

TH1 effector functions

Answer 7

ACTIVATE MACROPHAGES
can kill
produce IL-2 to promote proliferation, chemotaxis

Question 8

TH2 effector functions

Answer 8

remember it is involved in allergies! so it activates eosinophils and recruits mast cells

also involved in epithelial turnover, tissue remodelling and mucus production

Question 9

Effector functions of TH17 cells

Answer 9

involved in chemotaxis, neutrophil production (good for bacterial infections!), epithelial turnover and production

Question 10

Function of FRCs in T cell activation

Answer 10

fibroblastic reticular cells produce a netowrk to facilitate interactions of T cells and DCs, produce CCL19/21 which is the ligand for CCR7

Question 11

Requirements for naive vs memory t cells

Answer 11

naive: IL-7 and MHC
Memory: IL-15 and IL-7

Question 12

what markers do long-lived memory cells produce

Answer 12

IL-7R
Doesn’t need KLGR1

Question 13

Central memory receptors

Answer 13

CD62L+
CCR7+
High proliferative potential, low effector function

Question 14

Effectors memory receptors + characteristics

Answer 14

CD62L-
CCR7-
CCR5+
high effector function and recirculation

Question 15

Tissue resident memory characteristics

Answer 15

CD62L-
CCR7-
CD103+/-
CD69+
High effector function, no recirculation

Question 16

escape mechanisms: low immunogenicity

Answer 16

fails to activate t cells
MHC molecule formed by HLA-I and beta2m
mutations in HLA-I is associated with poor survival

Question 17

mechanisms for escape: absence of co-stim

Answer 17

failure to co-stimulate tolerize T cells, makes them treat tumour as self

Question 18

how do tumours create an immunosuppressive environment

Answer 18

secrete TGF-beta, IL-10, IDO and expresses PDL-1
IDO is an enzyme that catalyses tryptophan (essential amino acid for t cells)

Question 19

what cells express AIRE

Answer 19

medullary epithelial cells

Question 20

what stromal cells conduct positive selection

Answer 20

thymic cortical epithelial cells

Question 21

What do DN1 thymocytes need to enter thymus

Answer 21

NOTCH signalling and HEV

Question 22

What lymphatics does lymph enter and exit through and what are they

Answer 22

lymphatics are high endothelial venules that are used by cells in the circulation to enter LNs
efferent lymphatic = exit
afferent lymphatic = arrives

Question 23

what breaks down proteins in endosomal compartments

Answer 23

Low pH: H+ pump +ATPases
Reduction of S-S bonds by GILT
proteases (range of redundant cathepsins)

Question 24

what are the three Adoptive cell therapies?

Answer 24

• CAR-T
• TCR-T
• TIL

Question 25

downsides of CAR-T

Answer 25

poor infiltration into tumour tissues, releases cytokines to try and break barrier but can cause cytokine storm ~ treated with IL-6

Question 26

What are the three main purposes of monoclonal antibodies

Answer 26

- opsonising - deliver toxins - inhibit checkpoints

Question 27

examples of conjugated toxin therapy

Answer 27

anti-cd30: gets internalised and cleaved in the endosome releases toxin that targets microtubules anti-cd20: conjugated with radionucleotide

Question 28

prophylactic vaccines

Answer 28

preventative. used for oncogenic viruses including HBV and HPV gardasil = virus like particle subunit vaccine

Question 29

therapeutic vaccines

Answer 29

treat. can involve oncolytic viruses that mainly infect tumour cells that have faulty defences against viruses e.g. T-VEC: engineered herpes simplex virus that targets melanoma

Question 30

unconventional t cells

Answer 30

- y/delta express a different receptor, associated with tumour response, activated in a MHC independent manner - MAIT Recognise microbial derived vitamin B metabolites presented by MR1 NKT: expresses NK markers, either expresses CD4 or none, can recognise lipids in CD1d