-CYTOKINES IN THE ADAPTIVE IMMUNE RESPONSE

- ERYTHROPOIETIN AND COLONY STIMULATING FACTORS

CYTOKINES IN THE ADAPTIVE IMMUNE RESPONSE•Mainly secreted by T cells

▫By T helper (Th) cells•Affect T and B cell function more directly.• Three main subclasses of T cells

Th 1 Th 2 Treg (T regulatory cells)

Each has a specific function and produces a different set of cytokines

•Development of T helper and T regulatory cells

Naive

Naive

Th1

Th2

Treg

IL-12

IL-4

IL-10

IFN-γ

IL-4

IL -10

Cell mediated immunity

Antibody mediated immunity

Regulate Th1 and Th2 activities

CYTOKINES IN THE ADAPTIVE IMMUNE RESPONSE•Th1 cytokines

▫IL-12 Produced by dentritic cells in damaged

tissues, macrophages and B cells. Causes expression of a new set of genes on

naïve T cells which determine its maturation into Th1 cell.

Increases the cytolytic ability of NK cells

CYTOKINES IN THE ADAPTIVE IMMUNE RESPONSE•Th1 cytokines

▫Activation of Th1 cells Induces high-level of expression of IFN-γ.

▫IFN γ Principal molecule produced by Th1 cells Affects the RNA expression levels of more

than 200 genes Genes involved in regulation and activation by

IFN-γ▫CD4+ Th1 cells, CD8+ cytotoxic lymphocytes, Nk

cells, bactericidal activities, IL-12 and IL-18R.

CYTOKINES IN THE ADAPTIVE IMMUNE RESPONSE•Th1 cytokines

▫IFN-γ Stimulates antigen presentation by MHC I

and MHC II molecules Increased expression of MHC class I and II

molecules on antigen presenting cells increases the likelihood of antigen capture and involvement of additional lymphocytes.

Enhances immune response Being a strong stimulator of macrophages

which boosts their tumoricidal activity.

CYTOKINES IN THE ADAPTIVE IMMUNE RESPONSE•Th1 cytokines

▫IL-2 Produced by Th1 cells Known as the T-cell growth factor Drives the growth and differentiation of both

T and B cells Induces lytic activity in NK cells Activate proliferation of Th2 cells and helps

to generate IgG1 and IgE producing cells.

CYTOKINES IN THE ADAPTIVE IMMUNE RESPONSE•Th2 cytokines

▫IL-4 Regulates Th2 immune activities and helps

drive antibody responses in a variety of diseases

Its activity on naïve T cells turns on the genes that generate Th2 cells and turns off the genes that promote Th1 cells.

Production was enhanced by the chemokine MCP-1 which directs the naïve T cells to develop into a Th2 cell.

CYTOKINES IN THE ADAPTIVE IMMUNE RESPONSE

• Th2 cytokines▫ IL-4

Induced genes are: MHC-I IL-5 IL-13 Co-stimulatory molecules

▫B7.1▫B7.2

Promotes production of IgG2a and IgE Along with IL-5, drives the differentiation and

activation of eusinophils in both allergic and immune responses and response to parasitic infections

CYTOKINES IN THE ADAPTIVE IMMUNE RESPONSE•Th2 cell

▫Responsible for regulating many aspects of the immune response Related to allergies Autoimmune diseases Fighting off parasites

CYTOKINES IN THE ADAPTIVE IMMUNE RESPONSE• Th2 cytokines

▫ IL-10 Has anti-inflammatory and suppressive effects on

Th1 cells. Produced by monocytes, macrophages, CD8+ T

cells, and Th2 CD4+ T cells. Inhibits antigen presentation by macrophages and

dendritic cells and stimulate CD8+ T cells. Induces the production of MHC-II on B cells. One of the major effects is the inhibition of IFN-γ

production via suppression of IL-12 synthesis by accessory cells and the promotion of a Th2 cytokine pattern.

CYTOKINES IN THE ADAPTIVE IMMUNE RESPONSE•Cytokines associated with T Regulatory

cells▫T regulatory cells (Treg)

CD4+ CD25 + T cell that are selected in the thymus.

Play a key role in establishing peripheral tolerance to a wide variety of self antigens, and infectious antigens.

Affect T cell activity through the actions of TGF-β

Induce IL-10 and TGF-β expression in adaptive T regulatory 1 (Tr1) cells in the peripheral circulation

ERYTHROPOIETIN AND COLONY STIMULATING FACTORS

▫Colony stimulating factors IL-3, erythropoietin (EPO), granulocyte,

macrophage, and granulocyte-macrophage colony stimulating factors. In response to IL-1, they act on bone marrow

cells at the different developmental stages and promote specific colony formation for various cell lineages

IL-3 Multilineage colony stimulating factor Induces CD34+ bone marrow stem cells to

develop into RBCs, platelets, and various types of WBCs.

ERYTHROPOIETIN AND COLONY STIMULATING FACTORS

▫IL-3 Acts on bone marrow stem cells to begin the

differentiation cycle Alone drives the stem cells into the

lymphocyte differentiation pathway.▫Granulocyte-macrophage colony

stimulating factors (GM-CSF) Act to drive differentiation toward other

white cell types

ERYTHROPOIETIN AND COLONY STIMULATING FACTORS

▫Macrophage-colony stimulating factors If activated, the cells become macrophages Increases phagocytosis, chemotaxis, and

additional cytokine production in monocytes and macrophages.

▫Granulocyte-colony stimulating factors If activated, the cell become neutrophils Enhances the function of mature neutrophils

and affect the survival, proliferation, and differentiation of all cell types in the neutrophil lineage.

ERYTHROPOIETIN AND COLONY STIMULATING FACTORS

▫Granulocyte-colony stimulating factors Decreases IFN-γ production and Increases

IL-4 production in T cells Mobilizes multipotential stem cells from the

bone marrow These stem cells are utilized to repair damaged

tissues and create new vasculature

ERYTHROPOIETIN AND COLONY STIMULATING FACTORS

▫Erythropoietin (EPO) Regulates RBC production in the bone

marrow Primarily produced in the kidneys Protein with high carbohydrate content and

has a molecular mass of 34 kD Two structures: EPO-α and EPO-β EPO-α is often prescribed to improve RBCs

counts for individuals with anemia and cancer.