Exam 2 - German - T Cell Mediated Immunity Flashcards
Tell me, in general, what CD4 T cells do.
Enhance innate and adaptive immunity
Regulatory T cell arm
Targeted
Direct and indirect effector fxs - one iteration CAN kill directly
*BIND MHC II
Tell me, in general, about CD8 T cells.
Kills infected or diseased cells
Direct effector T cell arm
Targeted
Repeated activity until inhibited
*BINDS MHC 1
_______ ________ are the most common T cell activator.
Dendritic cells
*Must be activated
**Presentation occurs in secondary lymphoid organs - started by macropinocytosis
Tell me about dendritic cell maturation.
Immature DC encounters pathogens and are activated by PAMPs
TLR signals CCR7
CCR7 directs migration into lymphoid tissues - CCR7 binds CCL19 and CCL21
Now mature DC in T cell zone of lymph tissues primes naive T cells
The 3 different presenting cells migrate to different areas of the lymph node. Name them.
Dendritic cells - T cell areas
Macrophages - All over the node
B cells - B cell areas
T/F - DCs present antigen by MHC I and II
True
Cross-presentation is critical for CD8 T cell activation
What are the proteins involved in the immune synapse?
First bound thru low-affinity LFA-1 and ICAM-1 interaction
TCRs send signal to LFA-1
Signal causes a change in LFA-1 and increases affinity to prolong cell-cell contact
T/F - T cell activation req’s 3 signals.
TRUE
What are the 3 signals that T Cell Activation req’s?
T Cell Receptor (TCR)
-Activation signal
Co-Stimulatory molecules
-Survival signal
Cytokines
-Differentiation signal
Tell me about signal 1 - TCR - activation signal.
- Peptide recognition
- MHC I or II
- CD4 or CD8
Tell me about signal 2 - Co-stimulatory molecules - survival signal.
- B7 family (APC)
- CD28 family (T cell)
- B7-CD28 is REQUIRED for T cell activation
What do APCs do?
Deliver the three signals to naive T cells.
Tell me about signal 3 - Cytokines - differentiation signal.
- Paracrine and autocrine
- Propagation (IL-2)
-Differentiation with cytokines
—IL-2,4,6,12
—TGF-beta : T reg cell
—TGF-beta, IL-16,23 : T H 17
Naive T cell TCR activation (signal 1) in the ABSENCE of co-stimulation (signal 2 - B7) leads to _________. This is peripheral tolerance, and cytokine signaling (signal 3) would also be absent in this case. This is a checkpoint that halts auto-immunity.
ANERGY
CD 8 T cells differentiate into 2 things. Name them.
Effector cells or memory cells
CD 4 T cells can differ into 7 things. Name them.
Effector cells
Memory cells
Thelper - 1,2,17
TFH
Treg
After differentiation, what do T cells do?
Clonally expand
Change in surface protein expression
Migrate to target tissues
- Lymph nodes
- Site of infection or damage
Effector fxs
A CD4 T cell will have what two surface proteins always expressed?
CD4
TCR
IL-____ drives clonal expansion.
2
What is CTLA-4 and what does it do?
Cytotoxic T lymphocyte-associated protein 4
It inhibits continued T cell activation and proliferation
-Binds B7 with more avidity than CD28 does and delivers inhibitory signals to T cells
_____ T cells are selective serial killers.
CD8
Tell me about CD8 fxs. 4 of them.
Do NOT die once effector fx is complete
Kill repeatedly
ONLY KILL CELLS EXPRESSING TARGETED PEPTIDE VIA MHC I
Can differ into effector or memory cells
What are the two ways to activate naive CD8 T cells?
Dendritic cells infected with some types of virus can activate a naive virus-specific T cell on their own
—IL-2 is the driver of CD8’s own proliferation and differentiation
Dendritic cells infected with some viruses need help to activate a naive virus-specific CD8 T cell
—IL-2 is that helper from CD4 and that drives proliferation and differentiation of CD8
T/F - CD8 T cells kill repeatedly, but specifically.
TRUE
T/F - There is NO secondary signal necessary for activated T cells to kill.
TRUE
What do CD8 T cells use to kill? 3 things
Perforin
-Aids in delivering contents of granules into cytoplasm of target cell
Granzymes
-Serine proteases - activate apoptosis once in cytoplasm of target cell
Granulysin
-Antimicrobial actions and can induce apoptosis
Thelper 1 is cellular or humoral?
Thelper 2 is cellular or humoral?
TH1 - Cellular
TH2 - Humoral
TH0 is what?
Naive CD4 T cell
What induces CD4 T cell subtype differentiation?
Cytokines
What are the different types of Thelper cells and their fxs? 5
TH1 - Activate MACROPHAGES
TH2 - Activate cellular and antibody response to PARASITES
TH17 - NEUTROPHILS
TFH - B CELL MATURATION
Treg - SUPPRESS EFFECTOR T CELLS
TH1
Cytokines that induce differentiation
Characteristic cytokines
IL-12
IFN-gamma
IL-12
IFN-gamma
TH2
Differentiation cytokines
Characteristic cytokines
IL-4
IL-4
IL-5
TH17
Differentiation cytokines
Characteristic cytokines
IL-16
TGF-beta
IL-23
IL-17
IL-6
TFH cells
Differentiation cytokines
Characteristic cytokines
IL-6
IL-21
IL-21
Treg cells
Differentiation cytokines
Characteristic cytokines
TGF-beta
TGF-beta
IL-10
What TLR responds to bacteria (LPS)?
TLR4 or TLR5
What TLR-like receptor responds to fungi and what TLRs respond to fungi?
Dectin-1
TLR 2/6
What TLR responds to helminths?
TLR 2/1
What TLRs respond to viruses?
TLR 3, 7, 9
Bacteria (LPS) -> TLR 4 or TLR 5 causes release of what IL and causes a naive T cell to differentiate into what?
IL-12
TH1
Fungi -> Dectin-1 causes release of what IL and causes the naive T cell to differentiate into what?
IL-6 and IL-23
TH17
Fungi -> TLR 2/6 causes release of what IL and causes naive T cell to differentiate into what?
IL-10, RA, TGF-beta
Treg
CD8 effector cytokines and cytotoxins?
Cytokines: IFN-gamma, LT, IL-2
Cytotoxins: Perforin, granzymes, granulysin, serglycin
TH1 effector cytokines and fx?
IFN-gamma GM-CSF TNF-alpha LT IL-2
Help macrophages to suppress intracellular infections
TH2 effector cytokines and their fx?
IL-4,5,10,13
TGF-beta
PARASITE assistance
-Basophils, mast cells, eosinophils, B cells
TFH effector cytokines and their fx?
IL-4, 21
IFN-gamma
TH17 effector cytokines and their fx?
IL-17,21,22,26
FUNGAL and BACTERIAL infections
Treg effector cytokines and their fx?
IL-10,35
TGF-beta
Suppress effector T cells
What TH cell activates macrophages?
TH1
What do activated macrophages do?
Express co-signaling ligands
Kill intracellular pathogens
Release cytokines and antimicrobial effectors
Present antigen
What do TH1 cells form when pathogens cannot be cleared?
GRANULOMAS
-A compact aggregate of leukocytes that sequester a pathogen
—Pyogenic granulomas are NOT true granulomas
Which TH cells regulate mucosal inflammation?
TH17 and Treg
What do Treg cells do?
Suppress other T cells
- Stops adaptive immune response
- PREVENTS AUTOIMMUNITY
What TH cells activate B cells and induce class switching?
TFH (Follicular helper T cells)
What TH cell promotes tissue protection and repair?
TH2
-LARGE EXTRAcellular infections
What do TH1 cytokines do, in general?
Enhance the induced innate response
IFN-gamma and CD40 do what?
Activates macrophage to destroy engulfed bacteria
Fas ligand or LT-beta do what?
Kills chronically infected cells
-Release bacteria to be destroyed by fresh macrophages
IL-2 does what?
Induces T cell proliferation which increases numbers of effector cells
IL-3 and GM-CSF do what?
Induces macrophage differentiation in the bone marrow
What do TNF-alpha and LT-alpha do?
Activates endothelium to induce macrophage binding and extravasate
What does CXCL2 do?
Direct macrophages to accumulate at site of infection
Helminth -> TLR 2/1 causes release of what IL and causes naive T cell to differentiate into what?
IL-10
TH2
