T Cell Immunity Flashcards
what signals stimulate dendritic cell maturation in BACTERIAL infections
TLR agonists (like PAMPs) induce CYTOKINE production by epithelial cells and tissue macrophages; the cytokines stimulate dendritic cell maturation
what signals stimulate dendritic cell maturation in VIRAL infections
- type I interferons promote dendritic cells maturation
AND - TLR agonists induce cytokine production, promoting dendritic cell maturation
what are the PRIMARY T-cell activators
dendritic cells
characteristics of immature dendritic cells
-tissue resident, quiescent
-HIGHLY endocytic
-LOW level of expression of costimulatory molecules and HLA
-POOR stimulators of T cells
characteristics of mature dendritic cells
-migrates to LYMPH NODES
-endocytosis is shut down
-HIGH level expression of costimulatory molecules and HLA
-HIGHLY stimulatory for T cells
where do mature (activated) dendritic cells present their antigens to T cells
in the PARACORTEX (T-cell rich area) of the lymph nodes
how do T cells enter the paracortex of lymph nodes
across high-endothelial venules (HEVs)
*circulating T cells “hop” from one dendritic cell to another, looking for their antigen
*if they don’t find it, they leave and continue to circulate through the blood
*T cells that encounter their antigen proliferate and differentiate into effector cells
what is the first type of interaction between dendritic cells and T cells
adhesion molecule interactions (low-affinity)
*LFA-1 on T cell interacts with ICAM-1 on APC
-if T cell does not recognize, then T cell leaves
*if T cell DOES recognize, then LFA-1 changes conformation and increases affinity to prolong cell-cell contact
what are the 3 signals necessary for T-cell activation by antigen-presenting cells (APCs)
- TCR recognition of HLA-bound epitope & CD4/8 association with class I/II HLA (signal 1)
- interaction of CD80/86 (B7-1 or B7-2) on the dendritic cell with CD28 on the T cell (signal 2)
- activated T cells need inflammatory cytokines or type I interferon to be functional (signal 3)
signal 1 in T-cell activation
TCR recognition of HLA-bound epitope & CD4/8 association with class I/II HLA
*interaction via adhesion molecule interaction (LFA-1 on T cell with ICAM on dendritic cell)
signal 2 in T cell activation
interaction of CD80/86 (B7-1 or B7-2) on the dendritic cell with CD28 on the T cell
*CD28 interaction leads to:
a. increased IL-2 transcription (growth factor for T cells) and mRNA stability
b. increased Bcl-xL (anti-apoptotic protein)
what is the major advantage of the CD80/86 - CD28 interaction in the activation of naive T cells (signal 2)
prevention of clonal amplification of T cells bearing TCRs that recognize self-peptides (minimize self-reactivity)
role of CTLA-4 during T cell activation
CTLA-4 on T cells competes with CD28 for CD80/86 to prevent over-activation
CTLA-4 inhibitors
*sometimes CTLA-4 inhibitors are used as therapy to prevent T cells from self-regulating, creating a more robust immune response to tumor burden
activation and proliferation of CD8+ T cells
- secrete IL-2 (a T-cell growth factor)
- upregulate the high-affinity IL-2 receptor
*the secreted IL-2 binds the IL-2 receptor, promoting T-cell growth and proliferation - signals from the dendritic cell (IL-12 or type I interferon) give the T cells the ability to lyse cells and produce cytokines of their own (perforins & granzymes)
activation and proliferation of CD4+ T cells
- express IL-2 receptor and secrete IL-2
- CD40-L expression (helps activate B cells)
- assume a CD4+ fate, based on which signal 3 they received
function of activated CD8+ T cells
*target cells for destruction in which cytoplasmic localized pathogens (e.g. viruses) are present
*directly kill virus-infected and tumor cells via perforin and granzymes (similar to NK cells)
fates of activated CD4+ T cells
- CD4+ Th1 cell
- CD4+ Th2 cell
CD4+ Th1 cells
activate macrophages to kill vesicle-bound pathogens and enhance the expression of certain IgG isotypes
*secretes IFN-gamma, TNF-alpha, and Il-2
*Th2 signals INHIBIT Th1
CD4+ Th2 cells
promote the activation of B cells and the expression of certain IgG isotypes
*secretes IL-4, IL-5, IL-6, IL-10, and IL-13
*Th1 signals INHIBIT Th2
regulatory T cells
help maintain specific immune tolerance by suppressing CD4 and CD8 T-cell effector functions
*produce anti-inflammatory cytokines
*kill self-reactive cells
thymic aplasia (DiGeorge Syndrome) - 22q11 deletion
-leads to an absent thymus (and absent parathyroids)
CATCH-22:
*cleft palate
*abnormal facies
*thymic aplasia
*conotruncal abnormalities (tetralogy of Fallot)
*hypocalcemia
*22q11 deletion
what signal 3 induces differentiation into a Th1 cell
IFN-gamma & Il-12
what signal 3 induces differentiation into a Th2 cell
IL-4
what signal 3 induces differentiation into a Th17 cell
TGF-beta, IL-1 & IL-6
what signal 3 induces differentiation into a regulatory T cell
TGF-beta & IL-2
deficiency in Th1 cells leads to
susceptibility to mycobacterial disease
deficiency in Th17 cells leads to
hyper-IgE syndrome
deficiency in regulatory T cells leads to
IPEX (autoimmunity)
cytokine profile of Th1 cells
- IL-2: T cell proliferation
- IFN-gamma and TNF-alpha: macrophage activation; increased HLA expression
cytokine profile of Th2 cells
- IL-4: B cell activation; class-switching to IgG1 and IgE
- IL-5: B cell activation; eosinophil growth and differentiation
- IL-6: B cell activation; enhances Th2 cell development
- IL-10: inhibits the generation of Th1 cells
- IL-13: B cell activation; class switching to IgG1 and IgE
what guides T cells to site of infection
expression of chemokine receptors and adhesion molecules
