8/13/2019 Lecture 4 t Cells

1/26

ADAPTIVE IMMUNITY.

T CELLS

8/13/2019 Lecture 4 t Cells

2/26

Adaptive immunity

IMMUNOLOGY

8/13/2019 Lecture 4 t Cells

3/26

Classification of lymphocytes

IMMUNOLOGY

T lymphocytesB lymphocytesNK cellsNKT cellsImmatureMatureResting (nave)ActivatedEffectorMemory cellsRegulatory

Antigen receptors

Competence

Function

8/13/2019 Lecture 4 t Cells

4/26

Cell count 20-40% of WBC 1000-4800 Ly/uL

IMMUNOLOGY

CD4% = 32.14 - 59.30%

CD8% = 15.05 - 36.11%

CD4 Abs# = 522-1594/uLCD 8 Abs# = 135 1047/uLCD4/CD8 Ratio = 0.67 - 3.11

8/13/2019 Lecture 4 t Cells

5/26

Immunophenotyping

IMMUNOLOGY

8/13/2019 Lecture 4 t Cells

6/26

T and B cells

IMMUNOLOGY

8/13/2019 Lecture 4 t Cells

7/26

T lymphocytes Effectors of cell mediated immunity Functions:

Activate phagocytes (Th1)Kill infected cells (CTLs)

Stimulate production of antibodies (Th2)

T cell receptor recognition (TCR) MHC-restricted

IMMUNOLOGY

8/13/2019 Lecture 4 t Cells

8/26

Lymphocyte development Developmentand maturation

occurs in the central lymphoid

organs Commitmentof progenitor cells to

the T or B lineage Proliferationof progenitor cells

driven by IL-7 Rearrangementof antigen receptor

genes Selectionof lymphocytes with the

correct immune repertoire Differentiationof B and T cell

subpopulations

8/13/2019 Lecture 4 t Cells

9/26

Transcriptional regulation T-cells: Notch-1, GATA-3 B-cells: EBF, E2A, Pax-5

8/13/2019 Lecture 4 t Cells

10/26

T-cell development Cell-surface markersAg receptor - TCR Thymus= major site of maturation. Thymocytes..

8/13/2019 Lecture 4 t Cells

11/26

T cell maturation Sub-capsular sinus cortex medulla

Interaction with thethymic environment

8/13/2019 Lecture 4 t Cells

12/26

Selection checkpoints

Pre-antigen receptorFunctional antigen receptorPositive selectionNegative selection

8/13/2019 Lecture 4 t Cells

13/26

Positive/Negative selection in the

thymus

8/13/2019 Lecture 4 t Cells

14/26

T cell markers

8/13/2019 Lecture 4 t Cells

15/26

T cell subsets Tc (cytotoxic) - CD8+ Th (helper) - CD4+ NKT cells (CD1d restricted)

8/13/2019 Lecture 4 t Cells

16/26

T helper subpopulations

8/13/2019 Lecture 4 t Cells

17/26

TCR TCR recognizes peptide bound to a MHC

molecule expressed on the cell surface

8/13/2019 Lecture 4 t Cells

18/26

TCR types Heterodimer, 2 polypeptide chains

!"T cells (95 % peripheral T cells)#$T cells (epithelia)

8/13/2019 Lecture 4 t Cells

19/26

TCR complex

8/13/2019 Lecture 4 t Cells

20/26

TCR complex CD3 protein (#, $, %) &chain CD4 and CD8 coreceptorsAccessory molecules:

CD2, LFA-1, CD28, CD45R

8/13/2019 Lecture 4 t Cells

21/26

Antigen receptor gene rearrangement Functional Ag receptor genes

in immature B and T cells V(D)J recombination Germline organization - all cell

types

8/13/2019 Lecture 4 t Cells

22/26

8/13/2019 Lecture 4 t Cells

23/26

T cell activation

IMUNOLOGIE

Signal 1:Interaction betweenTCRand MHC/antigen complex

Signal 2:Co-stimulatory interactionsbetween CD28molecules on

the T cell and B7molecules

on the APC

8/13/2019 Lecture 4 t Cells

24/26

Tc response

8/13/2019 Lecture 4 t Cells

25/26

Th regulation

8/13/2019 Lecture 4 t Cells

26/26

SummaryWhat happens during the adaptive immune response Classification of lymphocytes T cell development T cell markers T cell subsets TCR T cell functions T cell activation