what is the most common APCs?
dendritic cells
they must be activated
presentation occurs in secondary lymphoid
how are DCs targeted to lymph nodes?
by CCR7 binding to CCL19 and 21
how do DCs present antigen?
via MHC I and II
why is cross-presentation critical for CD8 T cell activation
so that cells that aren’t infected can still activate T cells by presenting intra celluar antigen
what are the two routes that a naive T cell can enter a draining lymph node?
in the blood
in the afferent lymph coming from an upstream lymph node
why is it important for naive T cells to be in circulation?
because it allows for a high probability of antigen contact
- systemic antigen exposure
- localize activation
what two cells make up the immune synapse?
T cells
DCs
what dictates if a T cell is activated by a DC?
the tightness of binding between the TCR and MHC
T cell activation requires three signals, what are they?
TCR
Co-stimulatory molecules
cytokines
why are the co-stimulatory molecules important?
they signal to the T cell to stay alive
B7 and CD28 are the co-stim signals, which is on the DC and T cell
B7 is on the activated DC
CD28 is on the T cell
what is required for T cell activation?
B7-CD28 bindings
why do the cytokines do to T cells?
propagation and differentiation
IL-2
propagation and differentiation of CD8 and all Th cells
the absence of a co-stimulatory interaction leads to what?
anergy
what are the 5 steps of T cell activation
differentiation clonal expansion changes in surface protein expansion migration to target tissues effector functions
what is an important thing that occurs with T cell activation
up regulation of adhesion molecules
what cytokine drives clonal expansion
IL-2
autocrine signaling
how does IL-2 drive clonal expansion
T cells produce own IL-2, which causes and upregualtion of IL-2 receptor, which then induces proliferation
what inhibits continued T cell activation and proliferation?
CTLA-4
How does CTLA-4 inhibit T cells?
it is expressed on activated T cells
- binds an APC after activation leads to T cell inhibition
- B7 binds CTLA-5 twentyfold stronger than CD28
- *remember T cells DO NOT die after function is performed
what are the two ways to activate naive CD8 T cells?
by autocrine IL-2 or by another CD4 T cell producing IL-2
is there a secondary signal needed for activated T cells to kill and infected cell?
NO
the process is very specific
how to CD8 T cells kill the infected cells?
perforin and granzymes
-causes caspase-mediated apoptosis
why is granzyme important?
activates apoptosis
what is granulysin
has antimicrobial actions and can induce apoptosis
Th1
cellular mediated
Th2
humoral mediated (antibodies)
differentiation of CD4 involves what?
cytokine induction
transcription factor
effector cytokines
cytokines that induce Th1 and function
IL-12 and IFN-gamma
-activate macrophages
cytokines that induce Th17 and function
IL-16
TGF-beta
IL-23
-enhance neutrophil response
cytokines that induce Th2 and function
IL-4
-activate cellular and antibody response
cytokines that induce Tfh and function
IL-6
IL-21
-activate B cells maturation of antibody response
cytokines that induce T reg and function
TGF-beta
-suppress other effector T cells
what cytokines do Th1 cells produce?
IFN-gamma
TNF-alpha
IL-2
-these help macrophages to suppress intracellular infections
what cytokines do Th2 cells produce?
IL-4
TGF-beta
-help basophils, mast cells, eosinophils, and B cells respond to parasite infection
Th1 cells activate macrophages to do what?
express co-signaling ligands kill intra-cellular pathogens release cytokines and antimicrobials present antigen *promotes inflammation
Th1 cells also form granulomas when pathogens cannot be cleared, what is a granuloma
compact aggregate of leukocytes that sequester a pathogen
- chronic inflammation
- infections and non-infectious agents
- several types
- pyogenic granulomas are NOT true granulomas
how can Th1 cells kill infected cells?
via the Fas ligand
Th1 cells promote what?
INFLAMMATION
Th2 cells promote what?
tissue protection and repair
how do Th2 cells promote tissue protection and repair?
respond to prolonged extracelluar infection
- mast cell and eosinophils recruitment and activation
- B cell activation
- cytokine release
Tfh cell activate B cells and do what?
induce class switching
where to Tfh cells activate B cells?
in the lymph nodes
what do T reg cells do?
suppress other T cells by interacting with the same APC
why are T reg cells important?
prevent T cell activation in the lymph node
- stops adaptive immune response
- prevents auto immunity
- TGF-beta differentiation
Th17 cells do what?
- go to mucosal surfaces to release cytokines which bring neutrophils to area, tissue repair, antimicrobial peptide production
- Th17 and T reg cells are enriched in the gut
