immunology molecular medicine 3 conleth feighery

Immunology molecular medicine 3

Conleth Feighery

Learning objectives

• T cell binding to APC essential for T cell stimulation

• T cell cytokines – determine their effect

• APC use pattern recognition receptors

• The structure of the T cell receptor

CYTOKINES

Cells of the immune system ‘talk’ to each other by producing cytokines - like ‘text messages’ informing cells

what their function should be!

CD4+ T cells - MHC II interaction

APCT h

cytokines

CD4+ T cells interact with APC and other cells by releasing cytokines. APC also release cytokines.

APCT h

cytokines

The type of cytokines that are released are crucial to the type of immune response which results

Cytokine products of cells

APCT h

IL-1IL-2

CD28 B7

Cytokine product of cells

APCT h

IL-1IL-2

Cells interact through the productionand release of cytokines - these bind to cells and affect their function

CD28 B7

Cytokine products of cells

APCT h

IL-1

IL-2 Receptors - cytokines bind to specific cell receptors

Cytokines

• Small protein molecules c. 20,000 aa

• Specific types produced by different cells

• Bind to cells and affect cell function

• Some are called “interleukins” or IL

IL-1 helps T cell activation

APCT h

IL-1 producedby APC

T cell co-stimulation

Essential to T cell activation, division and replication

Activation of T cells

• Requires 2 signals

• Signal 1 - TCR, MHC, antigen

• Signal 2 - CD28 binding to B7

• Both signals must be from the same APC

• ONLY now can T cell proliferation start

CD4+ T cells - activation requires 2 signals

APCT h

CD4

T cell receptor binding to antigen = signal 1

CD28 B7

CD28 binds to B7 = signal 2

Stimulated T cell - IL-2 produced

APCT h

CD4

CD28 B7

IL-2

IL-2 receptor

IL-2 binds to receptor on cell - causes cell growth, division

IL-2 required for T cell growth

APCT h

IL-2

CD28 B7

CTLA-4 - negative signal

APCT h

CD4

T cell receptor binding to antigen = signal 1

CTLA-4 B7

CTLA-4 binds to B7 - inhibits stimulation

T cell cytokines affect B cells

T h B

IL-4,5,6

T cell cytokines affect B cells

T h B

IL-4, IL-5, IL-6

IL-4, 5 and 6 allinvolved in B cellstimulation and Igproduction

Lymph node - cartoon

Alberts et al.

T cell activation takes place in lymph node tissueT cell help for B cells takes place in lymph. follicles

Lymph node - histology

Lymphoid follicles

Interferon gamma helps kill intracellular infections

MOT h

TBInterferon - gamma

IFN-

IFN- activates macrophage killingmechanisms

T cytotoxic cell - recognition of antigen, role of CD8

APCT cytx

T cytotoxic cell reacting with virus antigen presented by MHC class I molecule

CD8

MHC I

Target cell

virus

CD8+ T cells can kill target cells by inserting a ‘perforating hole’ in the cell, through which enzymes enter, damaging the cell

APCT cytxTARGET

CELL

CD8

• perforin• enzymes

T cytotoxic cell - cytolytic mechanism

APCT cytxTarget cell

virusLytic granules

perforinEnzymes, water, salts

Granules - contentperforin,enzymes

Pattern recognition receptors

Various stimulibind to receptorson APC and influence APC reaction

APC

TOLL Stimulus

Pattern recognition receptors

Various stimulibind to receptorson APC and influence APC reaction

Different cytokinesAPC

B7

Toll-like receptors

Stimulus

APC –effect on T cell response

APC

StimulusTH 1

TH 2

T reg

IFN-

IL-4

IL-10

APC - effect on T cell response

TH 1

TH 2

T reg

IFN-

IL-4

IL-10

APC

Stimulus

Cytokines and T cells

• Depending on the antigen, APC may produce different sets of cytokines

• These cytokines determine the type of T cell that proliferates

• Different types of T cells produce specific sets of cytokines

Structure of molecules of IS

• T cell receptor or TCR• MHC class I• MHC class II• Antibody molecules

Knowledge of these structures is helpful in understanding how immune system functions

TCR - alpha, beta chains

alpha chain

beta chain

variable region

variable region

constant region

T cell receptor structure

Alberts et al.

TCR - gamma, delta chains

gamma chain

delta chain

variable region

variable region

constant region

Immunoglobulin super-family

Many molecules in the immune system have an Ig-like structure and hence, belong to the “Ig superfamily”.

Alberts et al.

MHC I and II structure

Albertset al.