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PDAT4 > 10 - T-Cell > Flashcards

10 - T-Cell Flashcards

1
Q

What is found on EVERY surface of
B-Cells / T-cells / pancreatic Cells

A

MHC1 Molecules

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2
Q

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

A

NAIVE LYMPHOCYTE

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3
Q

What type of LYMPHOCYTE?

Activated lymphocyte that performs functions to
ELIMINATE MICROBES

in the Periphery

A

EFFECTOR LYMPHOCYTES

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4
Q

What type of LYMPHOCYTE?

Long-Lived // Functionally SILENT

Mount a RAPID response to Ag challenge
secondary response

A

MEMORY LYMPHOCYTES

Phenotypically different:
Express a HIGH LEVEL of:
INTEGRINS // CHemokine Receptors

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5
Q

MHC General Functions

A

Control POSITIVE / NEGATIVE SELECTION

Present Protein-Ag to T-Lymphocytes

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6
Q

MHC Class 1

Expressed on what?

Gets Antigen from where?

A

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

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7
Q

MHC Class 2

Expressed on what?

Gets Antigen from where?

A

Expressed on:
SPECIALIZED APCs
and interact with CD4+ Helper T-cells

  • *EXTERNAL Problem Alert**
  • *EXOgenous protein Ag** catabolized in ACID DEPARTMENT
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8
Q

APC Functions

A

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

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9
Q

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

A

DENDRITIC CELLS

initiate the adaptive immune response

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10
Q

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

A

MACROPHAGES

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11
Q

Which APC is this?

Have high affinity for Ag & rapidly process AG onto MHC

important for
Immunologic Recall
or
Later on during primary infection

A

B-Cells

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12
Q

Phases of Adaptive Response

A
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13
Q

Lymph Nodes

A

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

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14
Q

Why is
Contact between TCR & APC
NOT SUFFICIENT
in Fully Activating T-Cells?

A

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

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15
Q

What is required for FULL T-cell Activation?
Naive T-Cell –> Effector T-cell

A

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

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16
Q

Costimulatory Pairs

Types

Function

A

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

17
Q

B7 - CD28

A

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

18
Q

CD40 / CD40L

A

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

19
Q

Adhesion Molecules

A

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**
20
Q

ZAP-70

A
  • *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

21
Q

CALCINEURIN

A

ENZYME that activates NFAT

NFAT = transcription factor
that produces IL-2

which is the most important CYTOKINE SIGNAL
for proliferation // self-promoting // more receptors

22
Q
  • *Three Signals Needed for**
  • *T-Cell Proliferation & Differentiation**
A

#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

23
Q

Proliferation
of Naive T-cell

A

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

24
Q

What happens after T-cell Activation ENDS?

A

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

25
Q

Differentiation of T-cell after Activation

A

Occurs after proliferation

Active CD8+ Tcytotoxic cells –> destroy Ag carrying cells

Active CD4+ Thelper cells –> secrete Cytokines
how does it know what cytokines?

Presence of current cytokines at the time of Ag-recognition
holds a key to T-cell differentiation
LIneage-Determining txn factors

26
Q
  • *Th1**
  • *Differentiation / Secreted Cytokines / Function**
A

Naive CD4 + IL-12 (dendritic cell) –> Th1

Secretes:
INF-y** & **IL-2

  • *CELLULAR RESPONSES**
  • *Anti-viral/microbial activity**

Cell-mediated Immunity

Inflammation

27
Q

Th2
Differentiation / Secreted Cytokines / Function

A

Naive T-cell + IL-4 (mast cell)–> Th2
stay in lymph nodes to activate B-cells

Secretes:
IL-4 / IL-5** / **IL-13

  • *ANTIBODy / HUMORAL (b-cell) RESPONSE**
  • *immunity to EXTRAcellular parasites**

ALLERGENS

IgE / IgA / Eosinophil Recruitment / Mast-cell Recruitment

28
Q

INF-y

Which T-cell secretes this & What does it act on/fxn

A

Dendritic Cell –> IL-12 –>
Th-1

INF-y acts on Activated Macrophages
for
Cell-Mediated Immunity
Phagocytosis / Cytotoxicity

29
Q

CD8- Tcytotoxic Cell Activation

A

can NOT directly recognize Ag
VVV
Ag must be processed & presented on MHC1 molecule
VVV
CD8+ cell Recognizes a SPECIFIC MHC-Ag combination

2 activation pathways:
CD4+ Th INDEPENDENT

CD4+ Th Dependent

30
Q

CD4+ Th INDEPENDENT activation pathway

CD8+ Tc Cell Activation

A
  • *DIRECT interaction** w/ MHC1 presenting cell
  • *APC** or virus infected cell

Activation & proliferation of CD8+ Tcells
capable of killing cells that express the activating Ag MHC1

transplant rejection:
CD8+ cell recognizes non-self MHC1 on tissue or dendritic cells

31
Q
  • *CD4+ Th Dependent Activation Pathway**
  • *CD8+ Tc Cell ACtivation**
A

APC/CD4+ interaction produces CYTOKINES (IL-2)
VVV
Induces CD8+ Tc cell activation
VVV
Destruction of target cells w/ MHC1 associated Ag Peptides

32
Q

CD8+ Activation REQUIRES:

A
  • *Tc recognizes a COMBO of Ag + MHC**
  • rather than the Ag alone*
  • *Same MHC1 Protein**
  • *HLA-A** or B or C

Same Ag Epitope

33
Q

CD8+ Cytotoxic T-cell
KILLING MECHANISMS

A

Perforin -> Granzymes (cytotoxins)
Granzyme B can activate initiator caspases

Fas/FasL** –> **CAPSPASE

34
Q

CASPASES

A

CD8+ Cytotoxic T-cell Killing Mechanism

Present initially as Procaspase = Zymogen
NO ACTIVITY until cleaved or activated by:

Granzyme B
activates Initiator Caspases –> effector/excutionor caspsases

  • *Death Receptor = Fas**
  • *directly activate initiator caspases**

VVV
Activation of apoptosis and death of virally infected cell​

35
Q

Production of
CD8+ Memory T-cells

A

After pathogen clearance, the immune response is:
Self-Limiting & most cells die

leaving a
small # of Memory CD8+ T-cells
that are
ONLY generated via Th-DEPENDENT activation
needs the T-helper to activate it

Negative signals from CTLA4 via B7 Protein

36
Q

Functions of
CD8+ Memory T-cells

A

PRODUCED RAPIDLY

Require LESS COSTIMULATION
vs naive cells, activated w/ less antigen

produce GREATER # of CYTOKINES
vs naive cells

37
Q

Negative Regulation

A

Prevents HYPER-activation of immune response

Achived by Negative Signals from:
CTLA4** via **B7 protein
that serves as a
natural inhibitor & leads to memory Cell generation
within 24-48 hours

deregulation of T-cell fxn –> immunodeficiency / Autoimmunity

38
Q

CTLA4

A

CTLA4 via B7 Protein binding serves as a:

NATURAL INHIBITOR of T-cells
&
Leads to MEMORY CELL generation

Necessary for preventing HYPER-activation of immune response:
NEGATIVE REGULATION

  • *B7** normally binds CD28 –> to activate T-cell
  • *CTLA4 production is UP-REGULATED after this**

PDAT4 (34 decks)

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