PHSC1312 Microbiology/Immunology Lecture 14 T Cell Effector Response

Th1, Th2, Th17

3 subtypes of CD4+ T helper cells

Th1

helper T cell activated in the presence of IL12 and IFN gamma; produce IFN gamma and TNF alpha; induces phagocytosis by macrophages, activates NK cells, causes proliferation of CD8+ T cells; promotes IgG

IL12 and IFN gamma

cytokines that activate Th1 cells

IFN gamma and TNF alpha

cytokines produced by Th1 cells

IgG

Which antibody isotype is promoted by Th1 cells?

intracellular bacteria, protozoa, viruses

Th1 helper cells are primary host immunity effectors against what?

Th2

helper T cell activated in the presence of IL4; produce IL4, IL5, IL9, IL13; induces B cell proliferation and antibody class switching; promotes IgE (and IgG and IgA)

IL4

cytokine that activates Th2 cells

IL4, IL5, IL9, IL13

cytokines produced by Th2 cells

IgE

What is the main antibody isotype promoted by Th2 cells?

extracellular parasites

Th2 helper cells are primary host immunity effectors against what?

Th17

helper T cell activated in the presence of IL1, IL6, and IL23; produce IL17, IL21, IL22, IL23; activates neutrophils and stimulates defensins and other antimicrobials; promotes IgA

IL1, IL6, IL23

cytokine that activates Th17 cells

IL17, IL21, IL22, IL23

cytokines produced by Th17 cells

IgA

What is the main antibody isotype promoted by Th17 cells?

extracellular bacteria and fungi

Th17 helper cells are primary host immunity effectors against what?

CTLs

another name for CD8+ cytotoxic T cells

intracellular infections

What do CTLs respond to by killing infected host cells?

APCs in secondary lymphoid tissue

What primes CTLs?

source of infected tissue

Where do activated CTLs migrate to?

effector activation signal

received by CTLs from any nucleated cell displaying its cognate antigen on an MHC I molecule

IFN gamma

produced by CD8+ T cells to reinforce the cytotoxic response and support innate phagocytes and natural killer cells

Fas FasL

receptor-ligand interaction that triggers apoptosis in a targeted host cell

Fas

protein receptor found on most cells that can interact with a CTL ligand to trigger apoptosis

FasL

ligand expressed on the surface of CTLs that triggers apoptosis if needed when it interacts with a protein receptor on most cells

perforin and granzyme

cytotoxic molecules released by CTLs

perforin

membrane-perturbing molecule that facilitates the delivery of granzymes

facilitate granzyme delivery

What do perforin molecules help do?

granzymes

cytotoxic molecule that initiates an apoptotic death of a cell

absence of activation stimulus

After a threat is resolved, why do a majority of the T cells activated die?

memory cells

cells remaining from the activation pool with a lower threshold of activation and a quicker, more robust cytokine response

lower activation thresholds and quicker more robust cytokine response

features of memory cells

CD4+ T regulatory cells

cells that promote tolerance to self-antigens, produce anti-inflammatory cytokines TGF beta and IL10, and trained in the thymus and induced in the periphery

promote tolerance to self antigens and produce anti inflammatory cytokines

What do CD4+ T regulatory cells do?

TGF beta and IL10

cytokines produced by T regulatory cells

anergy

lack of costimulation signal causing incomplete activation and no response

inducible T regulatory cells

immune cell that develops in the body's tissues as a response to anti inflammatory cytokines and promotes tolerance to antigens

lack of costimulation

What causes anergy?

high affinity for IL2R, CTLA4 stronger affinity for B7 on APC, PD1

surface molecules/signaling checkpoints of regulatory T cells

IL2R

What do regulatory T cells have a high affinity for, allowing them to prevent other T cells from clonally expanding?

CTLA4

receptor on regulatory T cells with a higher affinity than CD28 for B7 on the antigen-presenting cell and disrupts signal 2

higher affinity for B7 ligand on APC than CD28

What is the significance of CTLA4 receptor on regulatory T cells?

stops T cell response

outcome of interaction between CTLA4 receptor on Treg and B7 on APC

PD1

receptor on T regulatory cell surface that interacts with PDL1 or PDL2 on an APC to halt intracellular signaling downstream of CD3 and CD28

PDL1 or PDL2 on APC

What does the PD1 receptor interact with?

halt intracellular signaling downstream of CD3 and CD28

What does PD1 and PDL1 or PDL2 interaction do?