T cell Differentiation

Question 1

Th1

Answer 1

Polarized by IL-12; IL-18; IFN-y
Effector cytokines produced: IFN-y and TNF

Master gene transcription regulator = t-bet

Secrete IFN-y which activates macrophages to beomce M1 angry macrophages which avidly injest and kill bacteria and other foreign invaders.

Macrophages release cytokines that can intesify inflammation (TNF-a and IL-1)

T cell recognizes and macrophage removes.

Can also cause contact hypersensitivity

Question 2

Th17

Answer 2

Polarized by TGF-B, IL-1, IL-6, IL-23
Effector cytokines produced: IL-17 and IL-22

Master gene transcription regulator = Ror-yt

Main job is to cause inflammation –> similar to Th1, but even more intense (Also linked to autoimmune)

Also activate M1 macrophages at sites of infx.

Biggest role is maintaining the integrity of mucosal surfaces.

Question 3

Th2

Answer 3

Polarized by IL-4
Effector cytokines produced: IL-4, IL-5, and IL-13

Master gene transcription regulator = GATA-3

IL-4 and IL-13 attract and activate mphages to become alternatively activated or M2. These are healing macrophages (debris removal, scar formation, walling off pathogens that M1’s haven’t killed.

IL-4 and IL-5 are chemotactic for eosinophils (specialized for killing parasites/protozoa/worms)

Also give rise to Th2-like Tfh cells which w/ their high amounts of IL-4 push to B cells to make class switch from IgM/IgD to IgE

Question 4

Tfh

Answer 4

Polarized by: IL-6 and IL-21
Effector cytokines produced: IL-4 and IL-21

Master gene transcription regulator = BCL-6

Migrate to follicles of the cortex where B cells are. There they help B cells that have recognized antigen to differentiate into plasma cells.

Secrete cytokines to direct B cells from IgM to IgG, IgA, or IgE. (Tfh in gut –> IgA or spleen switch B cells to IgG).

Question 5

Treg

Answer 5

Polarized by IL-2 and TGF-B
Effector cytokines produced: IL-10 and TGF-B

Master gene transcription regulator = FOX-P3

Tregs are a small population of T cells, but very potent. One Treg can suppress up to 1,000 other Th cells.

W/o these you get autoimmune –> IPEX

Question 6

HLA B27

Answer 6

90x more likely to get ankylosing spondyltis. (Joe Girardi put the Yankees on his back to win the 27th world series. also yankelosing spondylitis)

Also psoriasis, inflammatory bowel disease, reiter’s

Question 7

HLA DR2

Answer 7

130x times more likely to have narcolepsy (Doctor’s go to sleep)

Also MS, hay fever and SLE.

Question 8

HLA - A3/B14

Answer 8

90x more likely to have hemochromatosis (you can still have ABs even if you eat pi as long as you pump IRON)

Question 9

HLA - DQ2/GQ8

Answer 9

Celiac’s disease (celiac’s can’t go 2 DQ)

Question 10

HLA DR3

Answer 10

Type I DM, Grave’s disease (Dr’s 3rd shift is graveyard shift, and he’s craving sugar by then)

Question 11

HLA DR4

Answer 11

RA and Type I DM (4 finger’s on RA w/ ulnar deviation)

Question 12

B 53

Answer 12

Protects against malaria (p53 doesn’t protect against malaria, but B53 does)