Lecture 20 Flashcards
Where are Fas and CD40 ligand expressed
Both expressed on surface of effector T cells (NOT on naive T cells)
Crucial for effector T cell function
Transmembrane ligands of TNF family
Which cells express Fas ligand
Fas ligand is expressed on surface of effector CD8+ cells and TH1 cells
What does Fas ligand bind to
Binds to Fas on surface of infected cells in periphery
What cells express CD40 ligand
CD40 ligand is expressed on surface of TH1, TH2, TH17, and TFH cells
What does CD40 ligand bind to
CD40 ligand binds to CD40 on B cells and innate immune cells
Action of CD40 ligand binding
Activate target cells
Allows for dendritic cell licensing and expression of more co-stimulatory molecules
Action of Fas ligand binding
Exert cytotoxic effect when expressed on surface of CD8+ T cells
Naive CD8+ T cell precursors generate
Effector Cytotoxic T lymphocytes (CTL)
Signal 1
TCR binds peptide presented by APC on MHC class 1
Signal 2
Costimulatory signal transmitted by CD28-B7 (CD80/CD86) interaction between the T cell and APC
Signal 3
Provided mainly by IL-2 and other cytokines to some extent (IL-12), inducing proliferation and differentiation into CTL form
How do CTLs recognize and kill infected/tumor cells
Via recognition with their TCR
Specialties of CD8+ T cells
Require help of effector CD4+ T cells
Require more costimulation
Cytokine release (IL-2) can be autocrine and paracrine from TH1 or TH17 cells
Simple and Rarest way CD8+ T cell are activated
By dendritic cells with high co-stimulatory activity
Most common way CD8+ T cells are activated
Help from CD4 effector T cells and licensed cross presenting dendritic cells
Main consequence of CD40 signaling
CD40 signaling leads to dendritic cell licensing and expression of more co-stimulatory molecules
CD8+ T cell activation requires
1) CD4+ T cell to find p:MHC class II match
2) CD4+ to receive all 3 signals
3) CD4+ to express CD40 ligand which binds to CD40 on APC
Pathway for antigen presentation by dendritic cells to BOTH CD4+ and CD8+ T cells
Dendritic cell encounters PAMP–>travels to secondary lymphoid organ (lymph node)–>present antigen on MHC Class II to CD4+ T cell–>get licensed through CD40 binding–>present exogenous antigen on MHC class I to CD8+ T cell
Consequences of CD4+ T cell activation
1) IL-2 secretion
2) CD40L expression
Mechanism if Fas-FasL mediated CTL killing
Effector CTL expresses FasL, infected cells express Fas–>Fas and FasL bind–>signaling cascade–>cleavage of procaspase 3 and 7–>caspase (active) which releases apoptotic enzymes–>apoptosis of target cell
CTL (cytotoxic T lymphocyte) effector functions
1) Induce apoptosis to kill infected cells (through Fas-FasL and Granules)
2) Secrete cytokines to direct immune response
Mechanism of Granule-mediated killing
CTL interacts with target cell via nonspecific adhesion–>specific recognition is by TCR:pMHC–>triggers intracellular signaling–>reorganization of cytoskeleton–>Granules released at point of cell contact–>perforin and granzyme B are released from granules (proteins)–>perforin forms pores–>granzyme B are serine proteases–>granzyme B induces apoptosis directly through procaspases cleavage –>caspases, and perforin (indirectly)
Main action of perforin
Pore-forming protein, makes holes in membrane to help deliver granule contents
Main action of Granzyme B
Serine protease which activate apoptosis once in the target cell’s cytoplasm
