Cytotoxic T cells Flashcards
what does CD8+ T bind to on dendritic cells?
peptides on MHC class I molecules on dendritic cells
- usually on Dendritic cells that take up virus (processed by proteasome) and present on MHC class I
AND
CD28 on T cell binds to costimulatory molecule B7 on DC
binding induces clonal expansion of CD8+ T cells
Cytotoxic T lymphocytes or CTLs include … cells which are good at responding to trial infections
CD8+ T cells
Naive CD8+ T cell Differentiates after clonal expansion into CTLs which are also called effector cells
what is cross presentation refer to?
Cross presentation refers to when a dendritic cell presents a viral antigen to a T cell
- it is a crucial role of dendritic cells to present virus
- dendritic cell picks up virus and puts a viral peptide on MHC I
Clonal expansion of CD8+ T cells is WAY larger than for CD4+ T cells
what is the difference between naive CD8+ T cells and CTLs or effector cells?
CTLS have granules impt for killing function of CTL - include perforin and granzymes
Naive CD8+ T cells responses to viral infection involve:
- The cross-presentation of viral antigens by DCs
- clonal selection and expansion of antigen-specific T cells
- differentiation into effector cells called cytotoxic T lymphocytes (CTLs), which have cytotoxic granules called perforin and granzymes that help kill
naive t cells are initially activated in ..
secondary lymphoid organs
this granule perturbs membrane integrity, will insert itself into membrane of epithelial cells and allow entry of granzyme into epithelial
perforin
this granule is a proteolytic enzyme that activates caspases then DNAses in the epithelial cell leading to apoptosis of infected cell
granzymes
In addition to releasing granules (perforin and granzymes) , CTLs also release … that
inflammatory cytokines - such as interferon gamma
when activated native T cells differentiate into CTLs (in lymph nodes) then the activated CTLS:
- mirgrate out of lymph nodes and into infected tissue
- recognize viral peptides displayed on MHC class I molecules on infected cells
- release granzymes and perforin to kill infected cell
- release cytokines to promote inflammation in the infected tissue
After an infection is cleared, these lymphocytes are no longer necessary. Effector T and B cells have functions that promote inflammation and tissue damage, which could make them dangerous. After immune clearance of a microbe, the vast majority of the lymphocytes that expanded to clear the microbe undergo apoptosis. This reduction of lymphocyte numbers is known as …
contraction
A small number of antigen-specific lymphocytes differentiate into … cells. These can persist for many years and are the mediators of immunologic memory.
Memory cells
The first adaptive immune response to a particular type of pathogen is known as the …. immune response. A subsequent response to the same type of pathogen re-activates memory cells and is known as a … immune response.
primary
secondary
…. is a new type of therapy that involves using monoclonal antibodies that bind to and block inhibitory receptors (CTLA-4 & PD-1)
checkpoint blockade
if you wanted, how would you stop T cell expansion?
by using an inhibitory receptor such as CTLA-4 or PD-1 that have higher affinity than CD28 (normal costimulatory) for DCs and lead to slowing down proliferation/expansion of T cells
Using monoclonal antibodies that target CTLA-4 or PD-1, will bind to and block the inhibitory receptors. What is the result?
T cell proliferation - can go and kill tumor or infetion
- one of the therapeis for cancer
CTLA-4 blockade occurs in the …. while PD-1 blockade occurs in the …
lymph nodes
tissue (tumor site)
CD28 binds to B7 molecules, but ____________ binds to B7 with higher affinity. This binding blocks the interaction of CD28 with B7 that is necessary for costimulatory signaling.
CTLA-4
High expression of ____________ by tumor cells could render that tumor resistant to T cell immunity.
PD-L1
PD-1 on T cells can recognize and bind to PD-L1 on tumor cells but becomes exhausted and doesnt work
- PD-1 indicates T cell exhaustion
therapy- monoclonal antibody to block PD-1 so that prevents inhibitory signaling - t cell now reawakened
when t cells and b cells gain immune functions (after naive cell) they become … cells
effector cells
naive CD8+ t Cells becmoe Cytotoxic T cells
naive CD4+ T cells become helper T cells
naive B cells become plasma cells
when t cells and b cells gain immune functions (after naive cell) they become effector cells
naive CD8+ t Cells becmoe … cells
naive CD4+ T cells become …. cells
naive B cells become ….. cells
naive CD8+ t Cells becmoe Cytotoxic T cells
naive CD4+ T cells become helper T cells
naive B cells become plasma cells
B cells coordinate … immunity
Plasma cells make antibodies
function: complement fixation, ADDC, opsonization, neutralization
T cells coordinate … immunity
function: direct killing of infected cells, activation of innate immune cells, activation of B cells
Humoral immunity
cell-mediated adaptive immunity
CTLs can target and kill any cell except what?
RBCs
why?
bc RBCs lack nuclei
only cells that are nucleated will express MHC I on surface and therefore can be targeted by CTLs
what 2 effector cells are major cellular sources that both secrete IFN- γ in the defense against cellular pathogens?
Th1 and CTLs
