Lecture # 18 T cell Effector Function Flashcards
How many signals activate naive T cells?
1 TCR: MHC-Peptide interaction; # 2 CD28:B7-1/B7-2 interactions; #3 cytokine signals delivered by APCs
Signal 1 without signal 2 induces______
Anergy
Why are CD4 cells important in CD8 cell activation?
1) CD4+ by definition are helper T cells 2) CD4 sends signals to the APC that then upregulates 4-1BBL to interact with 4-1BB on CD8 Cells; CD4+ cells also help by producing cytokines that stimulate CTL differentiation (through the APCs)
What receptors are lost to keep T lymphocytes out of lymph nodes?
CCR7,CD69 and L-Selectin
What receptors do DCs express that are important for T cell activation?
1) MHC bound with its peptide 2) B7-1 and B7-2; One cell must deliver each signal
Where does co-stimulation occur?
Stimulation occurs in the draining lymph nodes
How many days does it take for activated T cells to differentiate into effector cells?
4-5 days
What cytokine does Th1 T cells make? What is its function?
IFN g; activates macrophages; IgG production; fights against intracellular microbes
What cytokine does Th2 T cells make? What is its function?
IL-4 (helps B cells make antibodies) ; IL-5; IL-13; Activate mast cells, eosinophilsl IgE production; “alternative” macrophage activation; works against helminthic parasites; plays a role in autoimmune disease; tissue damage associated with chronic infections.
What cytokine does Th17 T cells make? What is its function?
IL-17 (acts on neutrophils); neutrophilic, monocytic inflammation; fights against extracellular bacteria and fungi
What cytokine does CD4 + Treg make? What is its function?
TGF-B inhibits DC and activated T cells; plays a role in autoimmune inflammatory disease
Th1 differentiation
;Th1 cells require IL-12 and IFNg signaling through those cytokine R induce STAT 4 and STAT 1, which upregulates T-bet and switches on T cell expression of IFN-g and IL-12R—this “fixes” development of Th1 lineage; IL-12 (DC) and IFN g (NK) are produced when viruses and bacteria interact with DCs and NK cells.
T-bet
master transcription factor that induces the expression of interferon gamma in Th1 cells
STAT 4 and STAT 1
transcription factors that work with T-bet to induce expression of IFN g
Th2 differentiation
Worms and some other parasites induce IL-4 that push Th2 differentiation; • Th2 cells require IL-4, signaling through this cytokine R induces STAT6, which upregulates GATA-3 and switches on T cell expression of IL-4—this “fixes” development of Th2 lineage
Th17 differentiation
Bacteria and fungi induce IL-6 and TGF-b that push Th17 differentiation (Extracellular pathogens); Th17 cells require TGF-b and IL-6, signaling through those cytokine R induce STAT3 which upregulates RORgT. RORgt leads to the production of IL-21; Th17 cells produe IL-17 and IL-22
In the absence of infection, how are Tregs induced?
In the absence of infection, Treg cells are induced by DC production of TGF-b and low IL-6; • Treg cells require TGF-b, which upregulates FoxP3 and switches on T cell expression of TGF-b and IL-10—this “fixes” development of Treg lineage
How are Tregs produced?
Produced naturally in the thymus during thymocyte development and are inducible during immune response-develop from naïve CD4 cells and downregulate immune responses after antigen is cleared by downregulating IL-2 or inhibiting antigen presentation
How do TH1 cells activate macrophages?
Th1 effectors recognize pathogen peptide in class II and send signals to Mf through CD40 and IFN-g signals ; CD4 effectors provide additional activating signals to Mf to help kill intracellular pathogens; Macrophages and NK cells are induced to produce ROS, NO to kill pathogens and also produce inflammatory cytokines.
How do Th2 cells handle worm (parasitic infections)?
Th2 responses induces IL-4 and IgE production(that activate mast cells) and IL-5 (which activates eosinophils) ; IL-4 and IL-13 also have effects on macrophages for tissue repair; also contribute to airway allergies and asthma
How do TH17 cells combat Bacteria and Fungi?
Th17 responses induce neutrophils – help with anti-bacterial and anti-fungal responses; Important at barrier sites-gut immunity
What cytokine does Th1 cell make?
IFNg; which helps to activate macrophages; intracellular microbe defense
What cytokine does Th2 cell make?
IL-4; helps B cells make antibodies; helminthic parasites and allergies/IgE
What cytokine does Th17 cell make?
IL-17; which acts on neutrophils; extracellular fungi and bacteria
What cytokine does Treg cell make?
TGF-B; inhibits DC and activated T cells
Signal 3 for Treg
TGF-B, which upregulates FoxP3, causing expression of IL-10 and TGF-B
Signal 3 for Th17 cells
TGF-B; IL-6; signaling through STAT3, which upregulates RORgt leading to IL-17/22 expression
Signal 3 for Th1 cells
IL-12 (DC); IFNg (NK cells); signaling through STAT1/4, which upregulates T-bet, leading to IFNg and IL-12R
Signal 3 for Th2 cells
IL-4; signaling through STAT6, which upregulates Gata-3
Tuberculoid Leprosy vs lepromatous leprosy
T. Leprosy- Th1 response mounted, low levels of bacteria; L.leprosy- Th2 responses, ineffective, high levels of bacteria
Immunological Synapse formation
1) LFA-1 binds to ICAM on APC 2) CD8+ cell produces Granzymes and perforin that kill infected cells
pSMAC
LFA-1:I-CAM1
cSMAC
TCR, CD4, CD28, MHC:Peptide
