MODULE 6 - Immunology III

Question 1

what controls the speed of the cellular immune response?

Answer 1

amount/availability of antigen + costimulation + cytokines

Question 2

what is the most important cytokine for expanding B cells and T cells?

Answer 2

IL-2 - T cells

IL-6 - B cells

Question 3

what controls the magnitude of the cellular immune response (i.e. how big the clonal burst is)?

Answer 3

amount/availability of antigen + costimulation + cytokines + naive precursor frequency (number of cells you have initially i.e. you have more if you have memory cells)

Question 4

what drives the resolution of the cellular immune response?

Answer 4

antigen/pathogen clearance + lack of costimulation + decreased cytokines

i.e. antigen availability goes down as you clear pathogen so less APCs stimulated so less cytokines produced

Question 5

what do regulatory T cells (Tregs) do?

Answer 5

suppress T cell activation

suppress T cell proliferation

suppress T cell differentiation

all they do is suppress

Question 6

what are the two main subsets of Tregs?

Answer 6

thymic Tregs (tTregs) - develop in thymus, 10% of your CD4 T cells

induced peripheral Tregs (pTregs) - normal CD4 T cells that are induced to become Tregs in the periphery

Question 7

what do Tregs express?

Answer 7

Foxp3 (transcription factor)

high levels of IL-2 receptor alpha chain (CD25)

Co-inhibitory molecule CTLA-4

Question 8

why can Tregs outcompete other cells around them for growth factors?

Answer 8

they express high levels of CD25 (IL-2 receptor alpha chain)

Question 9

what does CTLA-4 do?

Answer 9

co-inhibitory molecule able to bind CD80 and send inhibitory signals rather than costimulatory signals

Question 10

where is Foxp3 expression induced in Tregs?

Answer 10

in thymus for Trees (thymus derived Tregs)

in periphery for pTregs (peripheral Tregs) (can be driven by TFG-beta)

Question 11

what does Foxp3 do?

Answer 11

interfere with IL-2 production after T cell activation by forming complexes with transcription factors that drive IL-2 production

is key component of Tregs

Question 12

where are Tregs found?

Answer 12

throughout the body

Question 13

how do Tregs suppress?

Answer 13

metabolic disruption - outcompeting other T cells with high affinity IL-2 receptor (CD25)

IL-2 required to activate T cells and allow them to proliferate and survive

cytolysis with granzyme A and B (kills T effector cells)

produce suppressive cytokines (IL-10, IL-35 and TGF-beta) (TGF-beta can be surface bound and secreted, others secreted)

CTLA4 binds CD80 and CD86 on APCs with higher affinity than CD28 so outcompetes other T cells and makes DCs produce things that are toxic to T cells

Question 14

what does IL-10 do?

Answer 14

suppress T cell cytokine production and reduces APC MHC expression (turns of APCs)

Question 15

what does TGF-beta do?

Answer 15

blocks T cell cytokine production

stops their abilities

Question 16

what does IL-35 do?

Answer 16

suppress T cell proliferation

Question 17

what does it mean when we say CD4 helper cells are heterogenous?

Answer 17

multiple subsets of them w different jobs

Question 18

are CD4 effector T helper cells terminally differentiated?

Answer 18

no

they can change to other subsets depending on cytokine environment

e.g. pTregs

cause they have a high degree of plasticity

Question 19

what drives T helper cell subset/lineage commitment?

Answer 19

master regulator transcription factors

Question 20

what might happen if Tregs are made less effective?

Answer 20

expansion phase is faster and to greater extent

contraction phase slower to resolve

Question 21

what is IPEX?

Answer 21

where people have Foxp3 deficiency

causes systematic autoimmunity

caused by mutation in Foxp3 gene

Foxp3 nessecary for development and function of Tregs (and it interfere with IL-2 production)

Question 22

how do you treat IPEX?

Answer 22

immunosuppressants

bone marrow transplant

Question 23

what do Tregs in the gut associated lymphoid tissue (GALT) do?

Answer 23

suppress immune responses to gut microflora

this why IPEX commonly results in gut inflammation

Question 24

what does Treg depletion enhance T cell response to and how?

Answer 24

enhances T cell response to TB infection

because it won’t outcompete other T cells with CD25 so increases cytokine production but doesn’t effect pathogen load

Question 25

how can purposely increasing Treg numbers be useful?

Answer 25

treating autoimmune disease

decreases chance of graft rejection

Question 26

how can purposely decreasing Treg numbers be useful?

Answer 26

helps fight cancers as immune system fights as hard as possible

improves vaccination

Question 27

where do short lived plasma cells live?

Answer 27

in the lymph node or spleen

Question 28

where do long lived plasma cells live?

Answer 28

in the bone marrow

here they receive survival signals from stromal cells

long-lived plasma cells are a source of long-lasting high affinity class-switched antibody

Question 29

what are memory B cells?

Answer 29

arise from germinal centre reaction

have inherited genetic changes from germinal centre reaction (so express high affinity antibody and are class switched)

express higher levels of MHCII and co-stimulatory molecules than naive B cells

populate spleen and lymph nodes and circulate through blood

divide slowly or not at all

express surface Ig but don’t secrete unless antibody