CYTOKINES TNF and TNF share similar activities

- Stimulate the recruitment of

Small soluble proteins that regulate the
immune system, orchestrating both innate
immunity and the adaptive response to
infection
Chemical messengers that influence the
activities of other cells.
Lymphocytes Lymphokines
o Primarily produced cytokines
Monocytes Monokines
Chemotactic factor Chemokines
neutrophils and monocytes to sites of
infection
- Activate these cells to eradicate
microbes
Chemokines
Stimulate trans-endothelial leukocyte
movement from the blood to the tissue site of
infection and regulate the migration of PMNs
and mononuclear leukocytes within tissues

ACTIONS OF CYTOKINES Interleukins

1. Autocrine affecting the same cell that Modulate inflammation and immunity by
secreted it regulating growth, mobility and differentiation
2. Paracrine affecting a target cell in close of lymphoid cells
proximity Each interleukin functions through a separate
3. Endocrine systemic receptor system and a distinct molecule by
gene cloning and sequencing
FEATURES OF CYTOKINES
Interferons
Pleotropism
Discovered in virally infected cultured cells
- single cytokine has many different
Enhances expression of specific genes,
actions
inhibiting cell proliferation, and augmenting
Redundancy
immune effector cells
- different cytokines often have very similar Antiviral agents, immunomodulators,
effects
antineoplastic agents
Act in networks
Ex. Drugs for anticancer
- stimulate the release of other cytokines
Act as growth factors for hematopoietic cells
Hematopoietic Factors
- modulate the number and composition of
Stem cell Factor
cells
- it acts on immature stem cells, needed
to make Bone Marrow stem cells
ROLES OF CYTOKINES
responsive to other CSFs
Innate immunity Colony-stimulating Factors
Adaptive immunity - Stimulate hematopoietic progenitor
Growth and differentiation of immature cells to form colonies (G-CSF, GM-CSF)
leukocytes Transforming Growth Factors
- Products of virally transformed cells
CYTOKINES CATEGORIES/ FAMILIES - Induce phenotypic transformation in
Tumor Necrosis Factor non-neoplastic cells
Chemokines
Interleukins
Interferons CYTOKINES IN INNATE IMMUNITY
Hematopoietic Factors 1. Non-immune (Type 1) Interferons
IFN-, IFN-
Tumor Necrosis Factor 2. Tumor Necrosis factor
Principal mediator of the acute inflammatory 3. Interleukins
response to gram-negative bacteria and other IL-1, IL-6, IL-10 , IL-12, IL-15
infectious microbes 4. Chemokines
Stimulates gene transcription or induces C-X-C, C-C, C subgroup
apoptosis
Type 1 Interferons Interleukin-10
IFN- Inhibits production of pro-inflammatory
- Produced by mononuclear phagocytes cytokines by mononuclear phagocytes
IFN- Inhibits the accessory functions of mononuclear
- Produced by fibroblasts phagocytes for T-cell activation
* Viral infection may produce these molecules Antagonist of IL-1

Induce expression of proteins that inhibit viral Interleukin-12

replication Triggers secretion of IFN- by T-cells and NK
Inhibits cell proliferation cells
They bind to same receptor Promotes differentiation of T-helper1 to secrete
They increase the ability of NK cells to kill virally IFN-
infected c ells Enhances the cytotoxic function of NK cells
Enhance expression of MHC class I molecules CD8+ T cells

Tumor Necrosis Factor Interleukin-15

Triggered by the lipopolysaccharide from gram- Release occurs in response to viral, LPS, or
negative bacteria other pathogens
Bound by a specific LPS-binding protein that Supports the development of NK cells
binds to a receptor on mononuclear phagocytes
CD14 Chemokines
o IL-1, IL-6 CC chemokine
In low concentration it acts on leukocytes and - Attract mononuclear cells to sites of
endothelium to induce acute inflammation chronic inflammation (MCP-1)
At moderate concentrations it mediates the CXC chemokine
systemic effects of inflammation - Attracts PMNs to sites of inflammation,
o IL-1, IL-6, IL-8 activates monocytes and may direct the
High concentrations leads to metabolic recruitment of these cells to vascular
alterations and shock lesions (CXCL8)
CX3 chemokine
Interleukin-1 - Forms a cell-adhesion receptor capable
Produced by macrophages and monocytes in of arresting cells under physiologic flow
response to bacterial LPS and TNF conditions
Pro-inflammatory cytokine
Induces IL-2 and IL-2 receptor(CD25) in T-cells,
proliferation and differentiation of B-cells CYTOKINES IN SPECIFIC IMMUNITY
Enhancement of cytotoxicity of NK cells 1. Th1 cytokines
Two types (,) IL-2, IFN-, TNF
o type possesses activity without 2. Th2 cytokines
further processing IL-4, IL-5, IL-10, IL-13
o type require cleavage before its
functional Interleukin-2
T-cell growth factor
Interleukin-6 drives the growth and differentiation of both T
Appears after IL-1 has been triggered and B cells and induces lytic activity in NK cells
Primary mediator of acute phase response
Signal for enhanced fibrinogen synthesis IFN-
Growth factor to activated B-cell and plasma stimulates antigen presentation by MHC I and
cell MHC II molecules
Synergist with IL-3 to promote growth of Strong stimulator of macrophages and boosts
hematopoietic progenitor cells and activation their tumoricidal activity
and generation of T-cytotoxic cells
Tumor Necrosis Factor
Formerly called as lymphotoxin
Binds to a specific receptor and triggers
apoptosis of the target cell
Short-lived and localized

Interleukin-4
Triggers activation, proliferation and
differentiation of B-cells
Responsible in allergic reactions, parasitic
infections and autoimmune diseases

Cytokine Antagonists
Antagonists Exist In 2 Forms
o Receptor Antagonists (Bind Receptor, No
Activation)
o Bind Cytokine (Prevent Cytokine From
Binding Receptor)
Well Studied Example: IL1Ra
In Many Cases Antagonist Is A Soluble Receptor
o Derived From Proteolytic Cleavage Of
Extracellular Domain Of Particular
Receptor
o IL-2, IL-4, IFN, IFN
Viruses Produce Cytokine Mimics Or Cytokine
Binding Proteins
o Ex. Poxviruses Produce IL-1-Binding
Protein And TNF-binding-protein
o These Agents Offer Viruses An
Advantage
Regulate the function of cytokines