IMMUNOLOGY SEROLOGY CYTOKINES ADAPTIVE IMMUNE RESPONSE

1. -CYTOKINES IN THE ADAPTIVE
IMMUNE RESPONSE
- ERYTHROPOIETIN AND COLONY
STIMULATING FACTORS

2. 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

3. • Development of T helper and T regulatory cells
Naiv
e
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

4. 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

6. 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.

7. 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.

8. 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.

9. 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.

10. 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

11. 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

12. 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.

13. 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

14. 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.

15. 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

16. 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.

17. 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

18. 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.