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 APC T h cytokines

CD4+ T cells interact with APC and other cells by releasing cytokines. APC also release cytokines. APC T h cytokines The type of cytokines that are released are crucial to the type of immune response which results

Cytokine products of cells APC T h IL-1 IL-2 CD28 B7

Cytokine product of cells APC T h IL-1 IL-2 Cells interact through the production and release of cytokines - these bind to cells and affect their function CD28 B7

Cytokine products of cells APC T 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 APC T h IL-1 produced by 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 APC T h CD4 T cell receptor binding to antigen = signal 1 CD28 B7 CD28 binds to B7 = signal 2

Stimulated T cell - IL-2 produced APC T 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 APC T h IL-2 CD28 B7

CTLA-4 - negative signal APC T 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 all involved in B cell stimulation and Ig production

Lymph node - cartoon Alberts et al. T cell activation takes place in lymph node tissue T cell help for B cells takes place in lymph. follicles

Lymph node - histology Lymphoid follicles

Interferon gamma helps kill intracellular infections MO T h TB Interferon - gamma IFN-  IFN-  activates macrophage killing mechanisms

T cytotoxic cell - recognition of antigen, role of CD8 APC T 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 APC T cytx TARGET CELL CD8 perforin enzymes

T cytotoxic cell - cytolytic mechanism APC T cytx Target cell virus Lytic granules perforin Enzymes, water, salts Granules - content perforin, enzymes

Pattern recognition receptors Various stimuli bind to receptors on APC and influence APC reaction APC TOLL Stimulus

Pattern recognition receptors Various stimuli bind to receptors on APC and influence APC reaction Different cytokines APC B7 Toll-like receptors Stimulus

APC –effect on T cell response APC Stimulus TH 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 constant region

T cell receptor structure Alberts et al.

TCR - gamma, delta chains gamma chain delta chain 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 Alberts et al.