T Cells 2 Flashcards
What type of cells express Fas and CD40 ligands?
CTLs, some effector CD4+ cells, and B cells
are Fas and CD40 ligands expressed on naive T cells?
no
when are Fas and CD40 ligand genes induced?
genes included in the group of genes that are induced after signals 1,2,3
what type of ligands are Fas and CD40?
transmembrane
what type of cytokines are Fas and CD40?
TNF
what type of interaction are Fas and CD40 ligands involved in?
cell-to-cell
what type of cells is Fas ligand expressed on and where on the cell?
expressed on the surface of effector CD8+ cells and TH1 cells
how is Fas ligand used by CD8+ T cells?
to exert cytotoxic effect and kill infected cells
where does Fas ligand bind?
binds Fas on surface of infected cells in the periphery/site of infection
when do cells express Fas?
when they are stressed/damaged
what type of cells express CD40 ligand?
TH1, TH2, TH17, TFH cells
where does CD40 ligand bind?
binds CD40 on B cells and innate immune cells
what is the role of CD40 ligand binding to CD40?
activates target cells –> allows for DC licensing (cross-presentation) and expression of more co-stimulatory molecules
what are the 3 signals for generating CTLs?
- TCR binds MHC I
- co-stimulatory signal transmitted by CD28-B7
- IL-2 induces proliferation and differentiation into CTL
why don’t CD8+ T cells require polarizing cytokines?
there is only 1 type of effector CD8+ T cell so don’t need to be directed to specific types
what are 3 CD8+ specific considerations?
- CD8+ T cells require more co-stimulation than CD4
- IL-2 can be autocrine AND paracrine (from neighbouring TH1 or TH17)
- Requires help of effector CD4+ T cells
how do CTLs recognize and kill infected/tumour cells?
using their TCR
what is the simplest and most rare method for CD8+ cell activation?
DCs present antigen on MHC I with co-stimulatory molecules
what is the most common method for CD8+ T cell activation?
CROSS-PRESENTATION –> licensed by CD4+ effector T cells
what are the general steps leading to cross-presentation?
PRR on DC recognizes viral PAMP as exogenous peptide –> MHC II –> cross presented to MHC I –> CD8+ T cell activated
what are the 2 types of cross-presentation for CD8+ T cell activation?
- sequential
- simultaneous
describe SEQUENTIAL cross-presentation
- CD40 on APC interacts with CD40 ligand on CD4+ T cell
- APC is licensed
- CD4+ T cell leaves, CD8+ T cell comes
- CD8+ T cell activated
- CD8+ T cell produces IL-2 for proliferation then differentiation
describe SIMULTANEOUS cross-presentation
- CD40 on APC APC interacts with CD40 ligand on CD4+ T cell
- APC is licensed
- CD8+ T cell is already there and interacts with APC before CD4+ T cell can leave
- CD8+ T cell activated
- CD4+ and CD8+ both produce IL-2 to induce proliferation
what is the role of CD40 signaling?
causes DC licensing and expression of more co-stimulatory molecules for cross- presentation
what 3 things need to happen to CD4+ T cells in order for CD8+ T cell activation to occur?
- find peptide - MHC II match
- receive all 3 signals
- expression of CD40 ligand that binds to CD40 on APC
what 5 things need to happen to DCs to allow them to present antigen to both CD4+ and CD8+ T cells?
- encounters a PAMP
- travels to secondary lymphoid organ (lymph node)
- presents antigen on MHC II to CD4+ T cell
- licensed thru CD40 binding
- presents exogenous antigen on MHC I to CD8+ T cell
what occurs during activation of CD4+ T cell?
- IL-2 secretion
- CD40 ligand expression
what 2 things does APC licensing by CD40 cause?
- increased expression of co-stimulatory ligands CD80/86
- induction of 4-1BBL
what is the role of 4-1BBL?
provides co-stimulatory molecules (along with CD80/86) to further activate CD8+ T cells
Assistance by CD4+ T cells is critical for _____
Assistance by CD4+ T cells is critical for generating memory CD8+ T cells
what is required for producing memory CD8+ T cells?
cross-presentation
how do CTLs kill infected cells in the periphery?
thru interaction of TCR with pMHC I and presence of CD8 co-receptor
why are CTLs able to kill periphery cells?
all nucleated cells have MHC I and CTLs kill via TCR interaction with MHC I
what are the 2 effector functions of CTL?
- induces apoptosis to kill infected cells
- secrete cytokines to direct the immune response
what are the 2 ways that CTLs induce apoptosis?
- Fas-Fas ligand
- granules
how do CTLs target infected cells?
Initial interaction is via non-specific adhesion molecules to anchor itself
- if pMHC isn’t a match –> CTL moves on
- if CTL recognizes pMHC –> cell has been infected
then infected cell is killed
describe Fas-FasL mediated killing
- effector CTL expresses Fas ligand
- infected cell expresses Fas
- Fas binds FasL and induces signaling cascade
- procaspases cleaved to caspases
- target cell undergoes apoptosis
describe granule-mediated killing
- specific recognition via TCR:pMHC
- reorganization of cytoskeleton and cytoplasmic contents so that granules get closer to infected cell
- granules released at point of cell contact
what are the 2 types of proteins in CTL granules?
- perforin
- granzymes B
what are CTL granules?
cytotoxins
what does perforin do?
helps to deliver contents of granules into cytoplasm of target cell by making pores
what does granzyme B do?
it is a serine protease that cleaves things to activate apoptosis once in the cytoplasm of the target cell
describe granzyme/perforin-mediated cytolysis
- TCR on CTL binds pMHC
- intracellular signaling is triggered
- leads to reorganization of cytoplasm and cytoskeleton
- PERFORIN punches holes in the membrane
- GRANZYME B enters cytoplasm and causes proteolytic cleavage of procaspases
- leads to cell fragmentation and cell death
what is membrane blebbing?
cytoskeleton breaks and membrane bulges outward, a sign of apoptosis
besides infected cells, what other type of cells can CTLs kill?
tumour cells
what are the 2 types of CTL pathways and where do they converge?
- Perforin/granzyme pathway
- Fas/FasL pathway
both converge on CASPASE 3 activation, leading to apoptosis
how does CTL kill cells that are close to one that it has already killed?
- CTL killing does not affect neighbouring cells, so it must undergo the exact same process for the next cell
kills 1 cell, dissociates, then restart by looking at other cells via non-specific binding
