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PDAT4 > 9 - T-Cell Bio > Flashcards

9 - T-Cell Bio Flashcards

1
Q

What mediates the transcriptional activation of T-lineage genes?

A

CYTOKINES

NOTCH 1

GATA 3

occurs within the THYMUS

Stem Cell = CLP (Common Lymphoid Progenitor)
VVVV
Pro-T Cell

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2
Q

Bone Marrow

A

Site of LYMPHOCYTE GENERATION
Hematopoeitic Stem Cell = HSC
common precursor to ALL lymphocytes + other cells

Generative = Primary = Central
LYMPHOID ORGAN

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3
Q

HSC

A

Hematopoietic Stem Cell
Common Precursor for:
B&T Lymphocytes
dendritic cells / red cells / monocytes / dendritic cells / NK

Pluripotent
single HSC –> generates ALL DIFF TYPES

Self-Renewing = A-symmetric division

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4
Q

What stimulates the PROLIFERATION & MATURATION
of HSC’s?

A

CYTOKINES

In Bone Marrow
HSC + Cytokines
VVVV
Common Lymphoid Progenitor + Common Myeloid Progenitor
CLP –> Tcells / b cells / Nk cells

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5
Q

CLP

A

Common Lymphoid Progenitor

In thymus, HSC + Cytokines –> CLP + CMP

CLP
can become T-cells // B-cells / NK Cells

CLP –> THYMUS to MATURE into a T-CELL

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6
Q

Thymus

A

​Primary / Central Lymphoid Organ

CLP migrates to
THYMUS for T-Cell Maturation

Thymocyte = T-lymphocyte within thymus

Cortex –> Medulla
for maturation

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7
Q

Thymus Cortex

A

OUTER PART

DENSE collection of T-Lymphocytes

Produce IL-7 which is required for
Early T-cell Development

Cortex –> Medulla
for maturation of T-lymphocytes

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8
Q

Thymus Medulla

A

Cortex -> Medulla

T-Lymphocytes –> MATURE-T-Lymphocytes
Consists mainly of Mature ones

Where this occurs:
Epithelial cells present SELF-ANTIGENS to Developing T-cells

Positive & Negative Selection

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9
Q

Overall Picture of T-Cell Maturation

A
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10
Q

TCR Structure

A
  • *Heterodimer**
  • *2 Disulfide** linked with polypeptide chains

Variable Region = AG binding

Constant = ANCHORs receptor to cell surface

Types of Polypetide chains:
aB TCR = MAJORITY

yG TCR

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11
Q

TCR Genes Features

A

Once the

  • *CLP –> Thymus**
  • ALL** of the Genes are THERE, but they are *NOT rearranged yet

Rearrangement by:
Recombinase Enzyme

Significant DIVERSITY in TCR:
VDJGenes withrandom combination

  • *TCR DOES NOT SWITCH AFTER IT IS FORMED**
  • unlike IG’s*
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12
Q

yG TCR

A

Only 1-10% of peripheral T-lymhocytes

  • *INNATE IMMUNE RESPONSE**
  • not Adaptive –>* respond rapidly
  • NO memory response*

found in Mucosal epithelial Sites

does NOT bind aB TCR cites = does not bind to MHC
instead they bind to:
Phospholipids / Phospho-AGs / Heat-shock proteins

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13
Q

aB TCR

A

Expressed on 90% of peripheral T-Lymphocytes

Once COMMITTED to aB –> NO further rearrangements to yG

FXN:
ADAPTIVE Immune response –> Bind to MHC
Shows memory response

ONLY BINDS TO:
MHC1 or MHC2+AG peptide

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14
Q

TCR Complex
Consists of What?

A

TCR PLUS
2 x CD3 + 2 x ZetaChains
bound by a TIGHT NON-Covalent Association

Do NOT bind the Antigen
Simply:
SIGNAL TRANSDUCTION MOLECULES

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15
Q

Co-Receptors

A

Transmembrane Glycoprotein Chain

CD4** or **CD8
Bind MHC2 vs MHC1
does NOT bind Antigen!

STABILIZE TCR Complex’s
interaction with the peptide-MHC complex
VVVV
Enhanced T-Cell Activation** & **Signal Transduction

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16
Q

TCR vs BCR

Comparison Chart

A
17
Q

3 Stages of T-Cell Maturation

A

1 = Double Negative
Pro-T-cell –> Pre-T-cell
Express Beta TCR chain only

  • *2 = Double Positive**
  • *Pre-T Cell** –> Double Positive T-Cell
  • *Alpha+Beta TCR** + BOTH CD4/CD8

3 = Single Positive
DP T-Cell –> Mature T-Cell
loses 1 CD chain & matures to either CD4+ or CD8+

18
Q

Double Negative

Stage 1 of T-Cell Maturation

A

Pro-T cell
CLP has gotten the SIGNAL = Notch 1 + GATA3, so it is COMMITED
has the TCR genes, but does NOT express TCR complex yet

DECISION is made to be aB TCR OR yG TCR
double negative that fail to express = cell death

B-TCR chain ONLY

IL-7 –> mediates thymocytes proliferation in cortex

RAG1 & RAG2 –> trigger TCR gene rearrangement

19
Q

IL-7 Function

A

During Stage 1 of T-Cell Maturation

Mediates the:
Thymocyte Proliferation in CORTEX
vvvvv
Decision to become:
aB TCR or yG TCR

(Pro-Tcell –> Pre-Tcell)

20
Q

RAG1 & RAG2 Function

A

Occurs during
BOTH Stage 1/2 of T-Cell maturation

Triggers the:
REARRANGEMENT of TCR GENES

Double Negative Stage 1 –> B TCR chain only
DP Stage 2 –> A TCR also

21
Q

Double Positive
Stage 2 of T-Cell Maturation

A

Pre-T Cell –> DP T-cell

  • *RAG1/2** trigger the rearrangement
  • *A TCR chain** is expressed

BOTH CD4 & CD8
coreceptors are proliferated & expressed

Expression of productive:
TCR Complex + CD4 AND CD8 (Double Positive)

Positive or Negative Selection
occurs at this stage

22
Q

Single Positive
Stage 3 of T-Cell Maturation

A

Double Positive T-cell –> Naive T-Cell

Undergoes Phenotypic & functional selection processes:
DP cell will LOSE one CD chain and mature to:
EITHER CD4+ or CD8+

Gains ability to perform their respective functions

  • *CD4** –> produce cytokines
  • *CD8** –> secrete molecules to kill cells

Migrates to MEDULLA
while undergoing +/- selection via interaction w/ SELF antigen

23
Q

NAIVE T-Cell

A

INACTIVE T-cell

DP T-Cell –> Single Positive T-Cell
Cortex –> Medulla

NAIVE until it LEAVES THE THYMUS
to circulate through the lymphatic system

24
Q

Positive Selection
Occurs when?

A

Stimulates Survival of T-cells that recognize:
Self Peptide MHC complexes with:
LOW Avidity
(weak recognition)

  • *DP T-cell** + MHC1 becomes = CD8 T-cells
  • *RUNX** = transcription factor that triggers to LOSS of CD4

DP T-Cell + MHC2 becomes = CD4 T-cells
ThPOK = transcription factor that triggers to LOSS of CD8

Results in a:
SELF-MHC RESTRICTED SINGLE POSITIVE T-CELL
can recognize self, SP t-cell

25
Q

Death By Neglect
Occurs When

A

DP T-cell that
does NOT recognize Self-MHC
VVVV
APOTOSIS

26
Q

ThPOK

A
  • no RUNX*
  • *Transcription Factor** that triggers the
  • LOSS* of CD8

DP T-cell
VVVVV
CD4+ T-Cell

27
Q

RUNX

A
  • no ThPOK*
  • *Transcription Factor** that triggers the
  • LOSS of CD4*

DP T-cell
VVVVV
CD8+ T-Cell

28
Q

Negative Selection
Occurs when?

A

Triggers APOPTOSIS of T-cells that:
recognize self-peptide MHC complexes with:
HIGH AVIDITY

Occurs within the cortex & medulla
when DP or SP T-Cells encounter APCs, that display MHC1/2

Eliminates potential of SELF-REACTIVE T-cells
VVV
SELF-TOLERANCE

29
Q

T-Cell Stages DISTRIBUTION

A

80% in the DOUBLE POSITIVE stage 2

Most commonly:
CD4+ & CD4+ in the THYMUS

30
Q

CD4+ T-Helper Cell FUNCTIONS

(or Effector)

A

66% of T-lymphocytes
Interacts with MHC2
many different types: Th1 / Th2 / Th17 / Treg

Functions:
Help B-Lymphocytes develop into plasma cells

Help Activate CD8+ Cytotoxic T-Cell

Help macrophages effect delayed HYPERsensitivity

31
Q

Th1 Function
T-Helper Cell CD4+

A

Th1
Activate CD8+ Cytotoxic T-cells & macrophages
+
initiate delayed HYPERsensitivity reaction

Type of T-Helper cell differentiation is:
made based on signature cytokines secreted

No surface marks differentiate the subsets

32
Q

Th2 Function
T-Helper Cell CD4+

A

Th2

Activate B lymphocytes –> plasma cells = IgE Production

Eosinophil Activation

Type of T-Helper cell differentiation is:
made based on signature cytokines secreted

No surface marks differentiate the subsets

33
Q

Th17 Function
T-Helper Cell CD4+

A

Th17

Pro-Inflammatory

Type of T-Helper cell differentiation is:
made based on signature cytokines secreted

No surface marks differentiate the subsets

34
Q

Treg Function
T-Helper Cell CD4+

A

Treg

Secrete IL-10 & TGF-B

Suppress activity of T/B-cells (other CD4+’s)

SELF-TOLERANCE
involved in auto-reactivity & neg feedback

Type of T-Helper cell differentiation is:
made based on signature cytokines secreted

No surface marks differentiate the subsets

35
Q

Cytotoxic T-Cell FUNCTION
CD8+ T-Cell

A

33% of T-cells
interacts with MHC Class 1

Fxns:

  • *Elimination of Target Cells:**
  • *Virus-infected / Tumor-cells / Foreign Tissue**
36
Q

Cytotoxic CD8+ T-cells

3 MECHANISMS

A
  • *Cytotoxic Granule Proteins**
  • *Perforin** –> holes -> apoptosis

Toxic Cytokines
IFN-y & TNF-A
interact w/ receptor –> apoptosis

Cell Surface Molecule Interaction
FasL - Fas
Fas on cell –> death dopain -> caspase-3

37
Q

Toxic Cytokines
1 of 3 CD8+ T-Cell Mechanisms

A

IFN-y** & **TNF-a

Released directly onto target cell surface
VVVV
interect w/ receptor
VVVV
APOPTOSIS

38
Q

Cytotoxic Granule Proteins
1 of 3 CD8+ T-Cell Mechanisms

A

PERFORIN

Engages target cell
VVVV
lysosomal structures –> release Perforin
VVVVV
forms PORES in membrane
VVVVV
Apoptosis

39
Q

Cell Surface Molecule Interaction
1 of 3 CD8+ T-Cell Mechanisms

A

FasL - Fas

Engages Fas on target cell
VVVV
Triggers intracellular “death” domain
V
activates Caspase -3
V
APOPTOSIS

PDAT4 (34 decks)

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