Diebel Week 5

Question 1

Describe the four different types of Treg effector mechanisms used to control the proliferation and actions of other T cell populations

Answer 1

1. Immunosuppressive cytokines
   a. Production of IL-10, 35, and TGFbeta → causes effector T cell cycle arrest
2. IL-2 consumption
   a. Soaks up IL-2 with IL-2R (aka CD25) → Treg =
   CD4+ and CD25+ !!
3. Cytolysis
   a. FAS mediated killing with granzymes
4. Modulation of DC maturation and function
   a. Treg tells DC (via CTLA4–CD80/86) to convert
   trytophan to kynurenin, which is a lymphocyte
   toxin

Question 2

IL-10

Answer 2

Made by Treg and Th2 cells for suppression of T cell effector cells
1) Blocks IL-2
2) Global down-regulation of T cell cytokines
3) Down regulates MHC II expression
(blocking the ability to become active)

Question 3

IL-12

Answer 3

(IFNgamma – made by Th1 à angry macrophages – which make IL-12)
Produced by macrophages and dendritic cells
Supports survival and growth of Th1 cells
Blocks the growth of Th2 CD4+ cells

Question 4

IL-35

Answer 4

Made by Treg
Increases Treg expansion and increased IL-10 production
TGFbeta + IL-35 converts Th1 to Treg

Question 5

TGF-β

Answer 5

Made by Treg
Increases Treg expansion and increased IL-10 production
TGFbeta + IL-35 converts Th1 to Treg

Question 6

IL-35 and TGF-β Combination

Answer 6

TGFbeta + IL-35 converts Th1 to Treg

Question 7

CCR7

Answer 7

Requirement for immature T cells (from marrow) to migrate to thymus

Question 8

CD25

Answer 8

CD25 = IL-2R
CD25- = naïve
CD4+ and CD25- = Effector CD4+ T cells (Th1, Th2, Th17, Tfh)
CD4+ and CD25+ = CD4+ Treg

Question 9

describe the four different types of B cell tolerance mechanisms

Answer 9

1. Clonal deletion
   a. Induction of apoptosis via inhibition of survival signals or activation of death receptors
2. Receptor editing
   a. Continued V(D)J recombination to avoid self reactivity
3. B-cell intrinsic mechanisms
   a. Anergy, downregulation of the BCR, upregulation of CD5
   b. Lack of T cell help or survival factors

Question 10

Which cell(s) produce… IL-2

Answer 10

T cells (both CD4+ and CD8+) – promotes proliferation and growth

supports growth and expansion of most T cell populations and NK cell and B cells via IL-2R (=CD25+)

Question 11

Which cell(s) produce… IL-4

Answer 11

Th2, NKT, Mast cells –
B cells → proliferation and isotype switching
T-cell → promotes Th2 production

Question 12

Which cell(s) produce… IL-5

Answer 12

secreted by Th2 cells, mast cells, and eosinophils

Promotes differentiation of B cells and IgA production. Also promotes eosinophil production.

Question 13

Which cell(s) produce… IL-13

Answer 13

Made by Th2 IL-4 and IL-13 which attracts and activates macrophages, but in a different way than IFNγ does → involved via M2 macrophage cells in repair and healing.

Question 14

Which cell(s) produce… IL-17

Answer 14

Made by Th17 → promotion of M1 “angry” macrophage response

Question 15

Which cell(s) produce… IFNgamma

Answer 15

secreted by Th1 cells, cytotoxic T cells, dendritic cells, and NK cells

Question 16

Which cell(s) produce… TNFalpha/beta

Answer 16

Alpha → secreted mainly by macrophages

Beta → secreted by Treg