MODULE 6 - Immunology III Flashcards

1
Q

what controls the speed of the cellular immune response?

A

amount/availability of antigen + costimulation + cytokines

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2
Q

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

A

IL-2 - T cells

IL-6 - B cells

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3
Q

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

A

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)

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4
Q

what drives the resolution of the cellular immune response?

A

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

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5
Q

what do regulatory T cells (Tregs) do?

A

suppress T cell activation

suppress T cell proliferation

suppress T cell differentiation

all they do is suppress

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6
Q

what are the two main subsets of Tregs?

A

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

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7
Q

what do Tregs express?

A

Foxp3 (transcription factor)

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

Co-inhibitory molecule CTLA-4

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8
Q

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

A

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

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9
Q

what does CTLA-4 do?

A

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

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10
Q

where is Foxp3 expression induced in Tregs?

A

in thymus for Trees (thymus derived Tregs)

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

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11
Q

what does Foxp3 do?

A

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

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12
Q

where are Tregs found?

A

throughout the body

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13
Q

how do Tregs suppress?

A

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

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14
Q

what does IL-10 do?

A

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

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15
Q

what does TGF-beta do?

A

blocks T cell cytokine production

stops their abilities

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16
Q

what does IL-35 do?

A

suppress T cell proliferation

17
Q

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

A

multiple subsets of them w different jobs

18
Q

are CD4 effector T helper cells terminally differentiated?

A

no

they can change to other subsets depending on cytokine environment

e.g. pTregs

cause they have a high degree of plasticity

19
Q

what drives T helper cell subset/lineage commitment?

A

master regulator transcription factors

20
Q

what might happen if Tregs are made less effective?

A

expansion phase is faster and to greater extent

contraction phase slower to resolve

21
Q

what is IPEX?

A

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)

22
Q

how do you treat IPEX?

A

immunosuppressants

bone marrow transplant

23
Q

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

A

suppress immune responses to gut microflora

this why IPEX commonly results in gut inflammation

24
Q

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

A

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

25
how can purposely increasing Treg numbers be useful?
treating autoimmune disease decreases chance of graft rejection
26
how can purposely decreasing Treg numbers be useful?
helps fight cancers as immune system fights as hard as possible improves vaccination
27
where do short lived plasma cells live?
in the lymph node or spleen
28
where do long lived plasma cells live?
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
29
what are memory B cells?
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