10 - T-Cell Flashcards
What is found on EVERY surface of
B-Cells / T-cells / pancreatic Cells
MHC1 Molecules
What type of Lymphocyte?
Mature lymphocyte that resides in lymph nodes
Fxn = Ag Recognition, has NOT encountered AG yet
T-Cell
protein Ag ONLY // require Ag Presentation
B-Cell
any organic molecule // can recognize Ag on their own
NAIVE LYMPHOCYTE
What type of LYMPHOCYTE?
Activated lymphocyte that performs functions to
ELIMINATE MICROBES
in the Periphery
EFFECTOR LYMPHOCYTES
What type of LYMPHOCYTE?
Long-Lived // Functionally SILENT
Mount a RAPID response to Ag challenge
secondary response
MEMORY LYMPHOCYTES
Phenotypically different:
Express a HIGH LEVEL of:
INTEGRINS // CHemokine Receptors
MHC General Functions
Control POSITIVE / NEGATIVE SELECTION
Present Protein-Ag to T-Lymphocytes
MHC Class 1
Expressed on what?
Gets Antigen from where?
Expressed by:
nearly ALL NUCLEATED CELLS
and interacts with CD8+ Cytotoxic T-cells
- *INTERNAL Defect Alert**
- *EndoGenous** protein Ag is catobilized in the CYTOPLASM
Good for detecting:
VIRUS / CANCER
MHC Class 2
Expressed on what?
Gets Antigen from where?
Expressed on:
SPECIALIZED APCs
and interact with CD4+ Helper T-cells
- *EXTERNAL Problem Alert**
- *EXOgenous protein Ag** catabolized in ACID DEPARTMENT
APC Functions
Process & Present Ag –> T-cells
Provide Secondary Stimuli to the T-cell, required for:
achievement of Full-Tcell response
Nearly ALL nucleated cells express MHC1
for interaction with CD8+ Cytotoxic T-cells
These Express MHC2 proteins for CD4T-cells, but ALSO MHC1
Dendritic > Macrophages > B-cells
Which APC is this?
Most efficient in INITIATING the Adaptive immune response
Travel from periphery (site of infxn) –> lymph nodes
to activate Naive T-cells
Have the broadest range of Ag presentation
high levels of these molecules:
MHC + Costimulatory + Adhesion
DENDRITIC CELLS
initiate the adaptive immune response
Which APC is this?
Provide CONTINUOUS stimuli to keep T-cells going
Located in the periphery (site of infection)
Baseline MHC2 is low
VVVVVV
Cytokine stimulation –> MHC2 increase
MACROPHAGES
Which APC is this?
Have high affinity for Ag & rapidly process AG onto MHC
important for
Immunologic Recall
or
Later on during primary infection
B-Cells
Phases of Adaptive Response
Lymph Nodes
Lymph Nodes
Collection points where APCs interact with NAIVE T-Cells
dendritic cell –> 500 t-cells/hr, 8-10 hours after exposure
APC-MHC-Ag interacts with the Specific TCR complex
on T-cell
VVVV
CD4 = Coreceptor that:
Stabilizes Interaction & Enhances Signaling Potential
but this is NOT ENOUGH FOR ACTIVATION
Why is
Contact between TCR & APC
NOT SUFFICIENT
in Fully Activating T-Cells?
Few IDENTICAL MHC/Ag complexes
on surface of 1 APC
*Low AFFINITY* of interaction
cells are always moving / dissociating
SHORT Cytoplasmic Tails
CD3 / Zeta molecules with TCR are not strong enough to propagate the AG signal
What is required for FULL T-cell Activation?
Naive T-Cell –> Effector T-cell
TCR-APC-Ag
Complexing / contact, required but NOT SUFFICIENT
- *Co-Receptor**
- *CD4** or CD8
CoStimulatory Pairs
B7-CD28 // CD40-CD40L
ESSENTIAL
ADHESION MOLECULES
Stabilize T-cell + APC contact
Assist in migration of T-cell –> site of inflammation+infxn
Costimulatory Pairs
Types
Function
B7 + CD28
CD40 + CD40L
ESSENTIAL for activation of Naive T-cells
Inhibition of this pair binding –> IMPAIRED t-cell response
how we KNOW this is needed for activation
Effector / Memory T-cells require LESS costimulation
vs NAIVE T-cell
B7 - CD28
Costimulatory Pairs necessary for Naive T-cell maturation
Fxns:
Mobilizes kinases around TCR
Increases HALF LIFE of cytokine mRNA
Increases T-Cell Proliferation
PREVENTS induction of Anergy & Cell death
induces expressio of ANTI-apoptotic proteins
CD40 / CD40L
Costimulatory Pairs
On APC:
Promote UP-Regulation of MHC + other costim molecueles
&
Promotes LONGEVITY of Dendritic cell by
increasing IL2 production
Important for B-cell Activation, promotes:
B-cell proliferation // Ig Class switching
Adhesion Molecules
NOT specific to T-cells or APC
- *TCR-Ag engagement
- ->**UPREGULATE expression of Adhesion molecules
These form an outer ring,
STABILIZING T-Cell + APC contact
and assist in the MIGRATION of t-cells –> inflammation/infxn site
- *LFA-1 Integrin + CD54**
- *LFA-3 Integrin + CD2**
ZAP-70
- *KINASE** involved in T-cell+APC SIGNAL TRANSDUCTION
- absense of ZAP-70 –> severe immunodeficiency*
PLC-y activation -> PIP1 -> IP3 -> ^Ca2+^
VV
CALCINEURIN (enzyme)
there is also PKC // ERK+JNK
VV
NFAT (transcription factor)
V
IL-2 Cytokine Production
most important cytokine signal for Proliferation / more Receptors
CALCINEURIN
ENZYME that activates NFAT
NFAT = transcription factor
that produces IL-2
which is the most important CYTOKINE SIGNAL
for proliferation // self-promoting // more receptors
- *Three Signals Needed for**
- *T-Cell Proliferation & Differentiation**
#1 Antigenic Signal
TCR+MHC2-Ag
#2 Costimulatory Signal
Costim Pairs = B7/CD28 + CD40/CD40L
Adhesion Molecules
#3 Cytokine Signal
ZAP-70 -> Calcineurin -> NFAT -> IL-2 Production
Proliferation
of Naive T-cell
After the 3 signals, the T-cell secretes its own:
IL-2 = Growth Promoting Cytokine
&
Expresses Cell surface receptor for that Cytokine (IL2 receptor)
Obey the principle of clonal expansion:
Active cell PROLIFERATES to build up clones w/ same Ag specificity
T-cell doubles its # q6 hours for 3-4 days
VVV
DIFFERENTIATION occurs
What happens after T-cell Activation ENDS?
APC - Naive T-cell –> DISENGAGE
APC goes on to activate other Naive T-cells
Activated T-cell:
DOWN REGULATES expression of homing molecules
&
Up Regulates expression of
chemokine receptors + adhesion molecules
allowing it to migrate OUT of lymph node –> affected tissue
