Cell mediated/ T cells Flashcards
During anitgen recognition and T cell activation:
When a T cell recognizes an antiG displayed, it will increase integrin_________ to help keep it locked in place with APC
LFA-1
What two recognitions need to happen between the TCR and the APC for our first signal during AntG recognition and T cell activaiton
- TCR recognizes MHC
2. TCR’s CD4 or CD8 needs to recognize and bind to MHC
CD4 or CD8 recognize the MHC protein ______ of the andtiG presented
independent
How many TCR co-receptors need to be engaged with the APC to active a naive T cell
2 or more
—thus T cell only responds if it encounters an array of MHC:antiG complexes
Alpha/betta TCR recognize what kind of antiG
Gamma/delta TCR recognize what kind of antiG
peptides
lipids
2 signals to activate a T cell
1st: TCR interacts with _____
2nd: T cell CD28 interacts with ______
MHC/antigen
B7
Once Tcell has it’s 2 signals during activation of naive T lymphocytes, it releases this cytokine
IL-2
IL-2 released during activation by T cell promotes
clonal expansion and proliferation and differentiation to effector cells
A T cell TRC binds to MHC with antiG but the T cells’ CD28 has NO B7 to bind to from APC… what happens?
Anergy or tolerance by T cell
CD28 on T cell will bind to ______ on APC along with TCR:MHC binding and the T cell will release this cytokine ____
CD28: B7
releases IL-2
CD3 is a signaling receptor expressed on
all T cells
When CTLA-4 on T regs bind to B7 what happends
negative regulation
CTLA-4 binding to B7 induceds ITAM or ITIM
ITIM
To anchor naive T cells during antiG presentation, LFA-1 on the Tcell anchors to ______ on the APC
ICAM
bindting of LFA-1 on Tcells to ICAM on APC causes APC to release what? and why?
releases chemokines to the Tcell… the chemokines will tell the TCell to put the LFA-1 into high affnity statte and bind that ICAM super tight
Once and APC engulfs an antiG it will:
- upregulate expression of ____ on it’s cell surface
- Will increase production of ______ to present antiG
- Will release this cytokine _____
Co-stimulators (B7)
MHC production increases
IL-12
A B cell can act as a _______ for a T cell
professional APC
If a B cell is acting as a Professional APC, what does it do to the antiG that bind to it’s BCR on the cell surface?
will internalize it and process it to present at MHC II to a T cell
This is a T cell proliferation cytokine T cells release to act on themselves
IL-2
T cell proliferation by IL-2 occurs during what days?
day 1-2 after activation
Daughter T cells of proliferating cells are ______ thus express identical TCR and co-recpetor (CD4 or CD8) and recognize same antigen as naive T cell
CLONES
Which expands more, CD4+ or CD8+ T cells after activation and expansion
CD8+
Once a T cell begins to secreate IL-2 (recogniztion of MHC and co-stim molecule happened), what does the T cell need to upregulate?
upregulates expression of IL-2-alpha chain for a high affinity IL-2 recetpors
this is the high affinity part of the IL-2 receptors
IL-2alpha
Why do T cells want to upregulate expression of IL-2 alpha receptor on cell surface?
creates high affnity binding for IL-2 and IL-2 is a proliferation signal for T cells… they have recieved all proper signals that their antiG is out there, now we want them to expand
During differentiation, progeny of our original activated T cells become:
effector T cells or memory T cells
How do T cells determine if they will be memory or effector cell?
they express dif genes driven by transcription factors
Once T cell is activated to effector function in the _______ it migrates out to the ________
peripheral lymphoid
site of infection (via chemokine signal)
CD4+ effector T cells respond to antiG by making surface molecules and cytokines… the function of these molecules and cytokines is to activate: ______ and _____
macrophages and B lymphocytes
_____on CD4+T cells binding to _______ on APC provides amplification signal APC to maintain it’s awesome immune resonspe
CD40L on CD4+ binding to CD40 on APC
INF-gamma and IL-12 cause Tsubset to turn into:
Th1 cells
Th1 cells release
INF-gamma
INF-gamma released by TH1 cells has these three functions
- stimulates anitB production to bind APC Fc receptors
- activates complment
- stimulates co-stim expression
This subset does phagocyte mediated killing of intracellular microbes
Th1
IL-4 drives expression of this Th subset
Th2
Th2 will release these cytokines
IL-4, IL-5 and IL-10
this T sub functions to promote isotype switching and allergies
Th2
TGF-B, IL6 and IL-23 promote this Thsub
Th17
Th17 releaesse
IL-17
this T sub does neutrophil inflmation, phagocyte killing of extracellular bacteria and fungi
Th17
Memory T cells do not produce cytokines or infected cells BUT
maintain ability to do so once exposed to their antiG
resolution of immune response occurs w/in ______ after eradication of infection
1-2 weeks
Antigen from intracell microbes is recognized twice:
- In peripheral lymphoid and we _______ require co stimulation
- In site of infection and we ________ require co stim
DO require
DON”T require
Once a CD4+ cell recognizes an APC presenting antiG in the periphery… how does it cause fight the infection?
it will release cytokines to cause inflammation or will send cytokine to tell APC (macrophage) to activate and kill the ingested microbe
Once a CD8+ cell recognizes and infected cell with microbe in periphery it will
kill the infected cell
Th1 will activate a macrophage to–>
kill intracellular bacteria
Th2 will activate B cells to—>
secreate antiB to parasites or allergens
Th17 will activate PMNs to —->
kill bacteria and fungi involved in autoimmune resonse
CD8+ can be activated by:
Direct=
Indirect =
direct = anitgien + APC Indirect = antigen + Th1 help
Endothelial cells that have infection will increase expression of _____ and ____ as a function of innate immunity
TNF and IL-1
Effector T cells ready to patrol the periphery for infection will decrease expression of ______ and increase expression of ______ to inhibit trafficking back to lymph node
L-selectin (lose this)
E and P selecting (will express this
T cells that are activated will express high levels of LFA-1 and VLA-4, why?
helps with tight adhesion to endothelium at sight of infection
This is a complex reaction of many parts of the innate immune system in vascularlized tissues and involves:
- recruiting phagos and granulos to site of infection
- initiated by change in blood vessels to promote leukocyte recruitement
Inflammation
A phagocyte engults a macrophage in epithelium… the phagoctye releases ____ and _____ to change structure of epithelium to make is leaky
TNF and IL-1
Inflammatory cells such as ____, _____ and _____ migrate through leaky epithelium to site of inflamation
monocytes, lymphocytes and neutrophils
T cell homing is ________ of antiG recognition
INDEPENDENT
—-all T cells recognize this chemokine signal sent by damaged tissue to maximize effectiveness of cell mediated immune response
An effector T cell gets to sight of inflammation and reconiizes IT’s own antiG… as a result the T cell will increase expression of:
VLA4 integrins so it can bind to VCAM1 on site of infection
What is our chemokine receptor that homes T cells to the lymph nodes
CCR7 and L-selectin
What is our chemokine receptor that homes T cells to teh periphery?
CXCR10 or e/p selecting
If a T cells is expressing CCR7 and L selecting we know it’s located in
lymph node
if a T cell is expressinc CXCR10 or E/P selectin we know it’s in the:
periphery or tissues
CD4+ can work with macrophages that are APC’s by:
CD4+ can work with B cells presenting antiG by:
- activating the macrophage to kill phagocytized microbe
- activate APC B cell to secreate antiB with enhanced abilities to neutralize and eliminate anitGs
INF-gamma released by Th1 on APC B cells will cause B cells to
go complement binding and opsoinizing via IgG antibodies
what is a macrophage’s response to Th1 that releases IFN-gamma
- produce reactive oxygen species, NO, lyososomal enz
- will secreate TNF, IL1 and IL-12
- increase expression of MHC and co-stimulators
What is the special feedback loop between macrophages and Th1?
Th1 releases IFN-gamma to macrophages….
….macrophages get activated + release IL-12 as a response—- the IL-12 causes more Thsub to turn into Th1 and over/over/ove
TH2 cells releasing IL-4 causes
B cell to isotype switch to IgG (antiB production) or release IgE for mast cell degranulation
Th2 releasing IL-5 causes
eosinophil activation against helminths
Th2 releaing IL-4 with IL-13 can promote a macrophage
to undergo ALTERNATE macrophage acitvation so more about tissue repair and fibrosis)
this subset pushes macrophages to be activated while this Th subset pushes for inactivation of macrphages
Th1==activation
Th2 for inactiation
IL-17 released from Th17 will cause:
inflammation and neutorphil release
this Th will increase recruitment of PMNs and maintain epithelial barrier integrity
Th17
How do CTL’s kill?
they secreate proteins that create pores in infected cell membrane :perforins and GranZ and express FasL that incduces apoptosis
CTL’s express this ligand that can induce apoptosis
Fas Ligand
binds to Fas receptor on target cells
Activated CTL’s make _____ to drive it’s own proliferation and differentiation
IL-2
If a CTL recognizes an APC that has a weak co-stimulatory signal…. who can help it out so that it can still this APC
CD4+ will release IFN-gamma that will bind to the APC and cause the APC to express more co=stimulatory signals to the CTL can kill it
These guys x-link many different clones of T cells with MHC II class expressing APCs
superantiG
IL-1 and TNF are responsible for
acute phase protein release from liver and changes vascular permeability
IL2 causes
T cell proliefation
Because the super antiG binds outside of recognition cleft to many different TCR’s we get what kind of expansion
NON-clonal expansion
End resultiof superantiG is this:
cytokine storm
