Cytokines

Cytokines

small soluble proteins that regulates the immune system

Cytokines

Chemical messengers that influence innate and adaptive immune responses

Cytokines

Produces in response to a specific stimuli (ex: bacterial products)

Regulation of cell growth

Differentiation of cells

Gene expression on cell membranes

Effects of cytokines

Autocrine stimulation

Affecting same cell which secreted it

Paracrine stimulation

Affecting a target cell in close proximity

Chemokines

Tumor necrosis factors

Interferons

Transforming growth factor

Colony stimulating factors

Interleukins

Major cytokine families (6)

Cytokines (innate immune response)

Responsible for physical symptoms of inflammation: fever, swelling, pain, cellular infiltrates to damaged tissues

IL-1

TNF-a

IL-6

Chemokinss

TGD-B

IFN-a, IFN-B

Cytokines involved in innate immune response

IL-1a

IL-1B

Pro-inflammatory cytokine produced by monocytes and macrophages

IL-1a

remains intracellular within monocytes and macrophages

IL-1a

released after cell death

IL-1a

attracts other inflammatory cell towards the site of tissue injury

IL-1B

Extracellular: secreted by monocytes

IL-1B

responsible for: fever, phagocyte activation, acute phase proteins production

IL-1RA (IL-1 receptor antagonist)

produced by monocytes and macrophages

IL-1RA

Antagonist to IL-1: blocks IL-1 receptor → inhibiting effects of IL-1

IL-1RA

serves as a regulator of physiological response to IL-1 (positive feedback mechanism) and turns off the response when no longer needed (negative feedback mechanism)

IL-1

considered as an endogenous pyrogen (induces fever) during acute phase response through its action on the hypothalamus

Hypothalamus

Body temperature regulator; IL-1 sets body temperature higher (during fever)

Elevated body temperature

It inhibits bacterial and viral growth, increases lymphocyte activity

IL-1

induces production of vascular cell-adhesion molecules and IL-6

IL-6

attracts and assists WBCs towards site of tissue injury (through diapedesis)

IL-1

induces production of CSF in the bone marrow → proliferation of cells

Tumor necrosis factor-a (TNF-a)

first isolated from tumor cells; they induce lysis to tumor cells

TNF-a

most prominent member of TNF superfamily

2 types of TNF-a

Causes vasodilation and increased vasopermeability

membrane-bound (TNF-a)

mediates all the cytotoxic and inflammatory effects of TNF through cell-to-cell contact

Soluble forms (TNF-a)

derived from membrane-bound forms, unstable, shorter half-life

LPS in gram-negative bacteria

main trigger of TNF-a

TNF-a

secreted by activated monocytes and macrophages: T-cell activation

TNF-a

induces MHC class II moleculs, vascular adhesion molecules, chemokines → activation of T-cells to destroy pathogen

TNF → septic shock/septic shock syndrome

decreased BP, reduced tissue perfusion, DIC (leads to uncontrolled bleeding)

IL-6

produced by both lymphoid an non-lymphoid cells

IL-6

responds to LPS

IL-6

affects inflammation, APR, Ig synthesis, activation of B-cells and T-cells

Chemotaxis

enhance motility and promote migration of WBCs towards site of tissu injury

alpha or CXC chemokines

Beta or CC chemokines

C chemokines

CX3C chemokines

4 families: classified based on the position of N-terminal cys residues

alpha or CXC chemokines

has 1 amino acid between 1st and 2nd cys

Beta or CC chemokines

has adjacent cys residues

C chemokines

lacks one of two cys

CX3C chemokines

has 3 amino acids between 1st and 2nd cyst

Transforming growth factor B (TGF-B)

primary regulator of cell growth, differentiation, apoptosis, migration and inflammatory response

TGF-B

controls down-regulation of inflammation (negative fm)

IFN-a and IFN-B

produced by dendritic cells

IFN-a and IFN-B

interferons: interfere with viral replication

IFN-a and IFN-B

induce production of proteins which interferes in viral replication process = limits infection

IFN-a and IFN-B

activates NK cells

IFN-a and IFN-B

enhances expression of MHC class I molecules = enhancing recognition and killing of viral-infected cells

IFN-a and IFN-B

active against malignancies and other inflammatory processes

cytokines (adaptive immune response)

responsible for:

• mainly secreted by T-cells: T-helper cells

• Directly affects T-cells and B-cells functions

IFN-y

IL-2

Th1 cytokines (2)

IFN-y

principal molecule produced by th1 cells

IFN-y

affects RNA expression

IFN-y

stimulated Ag presentation by MHC I and MHC II

IL-2

aka: t-cell growth factor

IL-2

enhances growth and differentiation of T-cells and B-cells

IL-4

IL-10

Th2 cytokines (2)

IL-4

anitbody-mediated immunity

IL-10

anti-inflammatory and suppressive effects on Th1 cells

IL-3

EPO

G-CSF

M-CSF

GM-CSF

colony stimulating factor

EPO & CSF

promote proliferation and differentiation of cells within the bone marrow