T Cell Function Flashcards
How are T cells contributing to the pathogenesis of periodontitis?
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What are the two types of cell-mediated immunity?
- CD4 helper T cells produce cytokines that activate and recruit other cells
- CD8 cytotoxic T cells kill infected cells with microbes in cytoplasm
Th1 cells
S subset of CD4 T cells; initiate inflammation and immunity by activating macrophages by secreting interferon gamma
Th17 cell
A subset of CD4 T cells that are characterized by production of the cytokine IL-17. They help recruit neutrophils to sites of infection.
describe the discovery of cell-mediated immunity
- Experiment showing transferable from immune animals to naive animals by T cells but not serum
- bacteria were killed in vitro by activated macrophages not T cells
How do helper T cells develop and mediate their function? (overview)
Different cytokines are involved
How is the recognition of antigen by T cell receptor very specific?
T cell clones express TCR that can only recognize one peptide/MHC complex
Though TCR are very specific, presentation of antigen to T cells by APCs is very ___
diverse
How is the presentation of antigen to T cells by APC very diverse?
- several peptides can be presented by different MHC I and MHC II molecules on the surface of the same dendritic cell
- T cells patrol LN in search of DC with the perfect fit
Give the characteristics of CD4 helper T cell subsets
Th1: make IFNgamma and activate macrophages. This targets intracellular pathogens.
Th2: make IL4, IL5, and IL13 and activate eosinophils. This targets parasites (helminths) through IgE
Th17: make IL17 and IL22 and activate neutrophils. This targets extracellular pathogens.
describe the development of T helper effector cells
- different cytokines are produced by DC or other innate cells that have recognized different types of microbes
- the cytokines induce different transcription factors
- transcription factors determine the fate of the helper T cells
development of Th1 cell
- intracellular microbe discovered
- dendritic cell releases IL-12 cytokine, NK cell releases IFN-gamma cytokine
- T cell now antigen-activated and expresses transcription factors T-bet, STAT4, and STAT1
- Th1 cell formed
development of Th2 cell
- helminth (parasite) discovered
- dendritic cell and mast cells and eosinophils involved, release cytokine IL-4
- T cell now antigen-activated and expresses transcription factors GATA-3 and STAT6
- Th2 cell formed
development of Th17 cell
- extracellular fungi or bacteria discovered
- dendritic cell involved, releases cytokines IL-1, IL-6, IL-23, and TGF-beta
- T cell now antigen activated and expresses transcription factors ROR-gt and STAT3
- Th17 cell formed
Function of Th1 cells
Secrete IGNgamma to induce macrophages to kill ingested microbes in classical macrophage activation (enhanced microbial killing)
how are macrophages activated by Th1 cells?
- involves CD40L (on CD4 cell) and CD40 (expressed on APCs - macrophage, dendritic cell, B cells)
- involves IFNgamma secreted by CD4 cell and IFNgamma receptor
- macrophages produce cytokines, up-regulate MHC, costimulatory molecules, and microbicidal activities
what is the response of macrophage activated by Th1 cells?
- secretion of cytokines TNF, IL-1, IL-12, chemokines
- increased expression of MHC and costimulators (B7 molecules)
- killing of phagocytosed bacteria
Function of Th2 cells
- IL4 induces B cells to produce IgE
- IL5 induces eosinophil activation
- mediates worm elimination, mast cell degranulation, intestinal mucus secretion and peristalsis, and alternative macrophage activation (enhance fibrosis/tissue repair)
compare classical and alternative macrophage activation
M1: killing (by ROS, NO, and lysosomal enzymes) and inflammation
M2: tissue repair and inhibit inflammation (happens at end of immune response)
what triggers a monocyte to differentiate into an M2?
IL-13 and IL-4
what triggers a monocyte to differentiate into an M1?
Microbial TLR-ligans, IFNgamma
Functions of TH17 cells
- IL17 mediate recruitment of neutrophil via induction of cytokines/chemokines production from other cells
- IL22 mediates antimicrobial peptides and increased barrier integrity through epithelial cells
- important for extracellular microbes
functions of Tfh cells
- found in the B cell zone
- make IL21 which mediates production of Ig (immunoglobulin) by B cells
How do cytotoxic T cells mediate their function? (overview)
Recognition of antigens and killing via perforin and granzyme FasL
cytotoxic cells of the innate immune response
NK
cytotoxic cells of the adaptive immune response
CD8 T cells
describe the killing by CD8 CTL
- antigen recognition and binding of CTL to target cells: CTL binds to target cells via ICAM-1 (target cells)–LFA-1 (CD8 cell) interaction
- Perforin and granzyme released from granules mediates killing: perforin facilitates entry of granzymes into the cytosol, grandames activate apoptosis
Describe FasL-mediated killing by CD8 CTL
- activated CTL express FasL
- FasL binds to Fas on target cells and induces cell death
- minor role in killing (homeostasis - perforin and granzyme major killers)
describe the cooperation between Th1 cells, CD8 cells, and macrophages in killing intracellular bacteria
- Th1 cells activate macrophage using IFNg to lyse intravesicular microbes
- CD8 kill infected cells with the help from Th1 cells (for cases when microbe is in the cytoplasm and not the phagolysosome)
describe the response of CD8 cells to acute or chronic viral infection
- acute infection induces a protective response; memory T cells form in case re-infected
- chronic infection induces expression of inhibitory molecules and leads to exhaustion
How do Th17 cells play a role in periodontitis?
- Th17 contribute to the inflammation through IL-17 (inflammation already present with neutrophils)
- Th17 induce fibroblasts to produce G-CSF (further neutrophil recruitment and granulopoeisis and mobilization in the bone)
- G-CSF recruit more neutrophils
