MODULE 6 - Immunology III Flashcards
what controls the speed of the cellular immune response?
amount/availability of antigen + costimulation + cytokines
what is the most important cytokine for expanding B cells and T cells?
IL-2 - T cells
IL-6 - B cells
what controls the magnitude of the cellular immune response (i.e. how big the clonal burst is)?
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)
what drives the resolution of the cellular immune response?
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
what do regulatory T cells (Tregs) do?
suppress T cell activation
suppress T cell proliferation
suppress T cell differentiation
all they do is suppress
what are the two main subsets of Tregs?
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
what do Tregs express?
Foxp3 (transcription factor)
high levels of IL-2 receptor alpha chain (CD25)
Co-inhibitory molecule CTLA-4
why can Tregs outcompete other cells around them for growth factors?
they express high levels of CD25 (IL-2 receptor alpha chain)
what does CTLA-4 do?
co-inhibitory molecule able to bind CD80 and send inhibitory signals rather than costimulatory signals
where is Foxp3 expression induced in Tregs?
in thymus for Trees (thymus derived Tregs)
in periphery for pTregs (peripheral Tregs) (can be driven by TFG-beta)
what does Foxp3 do?
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
where are Tregs found?
throughout the body
how do Tregs suppress?
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
what does IL-10 do?
suppress T cell cytokine production and reduces APC MHC expression (turns of APCs)
what does TGF-beta do?
blocks T cell cytokine production
stops their abilities
what does IL-35 do?
suppress T cell proliferation
what does it mean when we say CD4 helper cells are heterogenous?
multiple subsets of them w different jobs
are CD4 effector T helper cells terminally differentiated?
no
they can change to other subsets depending on cytokine environment
e.g. pTregs
cause they have a high degree of plasticity
what drives T helper cell subset/lineage commitment?
master regulator transcription factors
what might happen if Tregs are made less effective?
expansion phase is faster and to greater extent
contraction phase slower to resolve
what is IPEX?
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)
how do you treat IPEX?
immunosuppressants
bone marrow transplant
what do Tregs in the gut associated lymphoid tissue (GALT) do?
suppress immune responses to gut microflora
this why IPEX commonly results in gut inflammation
what does Treg depletion enhance T cell response to and how?
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
how can purposely increasing Treg numbers be useful?
treating autoimmune disease
decreases chance of graft rejection
how can purposely decreasing Treg numbers be useful?
helps fight cancers as immune system fights as hard as possible
improves vaccination
where do short lived plasma cells live?
in the lymph node or spleen
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
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
