Cytokines

Cytokines

chemical messengers that regulate the immune system, orchestrating both innate immunity and the adaptive response to infection

Cytokines

they are small proteins produces by several different types of cells that influence the hematopoietic and immune systems through activation of cellbounc receptors

Lymphokines

Cytokines that are produced by the T cells are known as ____

Monokines

Cytokines that are produced by the Monocytes/Macrophages are known as __

autocrine stimulation, paracrine and endocrine activities

Effect of cytokines:

Pleiotropy

A single cytokine that can have many different actions

Redundancy

Different cytokines activate some of the same pathways and genes

Synergistic reaction

Cytokines often act in networks; if the effects complement and enhance each other.

antagonism

A cytokine that may counteract the action of another cytokine

Cytokine Storm

▪ A massive overproduction and dysregulation of cytokines produced by hyperstimulation of the immune response or hypercytokinemia. _____ may lead to shock, multiorgan failure, or even death, thus contributing to pathogenesis

1. Interleukins

2. Chemokines

3. Colony stimulating factors (CSF)

4. Tumor necrosis factor ( TNF)

5. Transforming growth factor (TGF)

6. Interferons

Major classification of cytokines:

Interleukin

• regulate immune cell communication

• growth differentiation

Chemokines

promotes chemotaxis

Colony stimulating factor(CSF)

involves in hematopoiesis and cell proliferation

Tumor necrosis factor (TNF)

• principle mediator of the ACP in gram negative bacteria

Transforming growth factor ( TGF)

• for cell differentiation, immune response, tissue remodeling

• Acts as both pro inflammatory or anti inflammatory agents

Cytokines, Interferon type 1 (IFN-alpha and beta), IL-1, IL-6, IL-10, IL-12, IL-15, IL-18, TNF

Cytokines of the Innate immune response:

Interferon Gamma, IL-2, IL-4, IL-5, IL-13, Lymphotoxin,TGF-Beta

Cytokines of the adaptive immune response

TNF-a, IL-1, IL-6, IFN-Gamma

Major inflammatory cytokines

TGF-BETA, IL-10, IL-13, IL-35

Major anti-inflammatory cytoines:

IL-1α and IL-1β

are pro-inflammatory cytokines produced by monocytes, macrophages, and dendritic cells early on in the immune response

IL-1

acts as an endogenous pyrogen (induces fever) in the acute-phase response through its actions

on the hypothalamus

IL-1β

is responsible for most of the systemic activity attributed to IL-1, including fever, activation of phagocytes, and production of acute-phase proteins

vascular cell-adhesion molecules

chemokines

IL-6

IL-1 induces the production of _____ as well as _____ and _____

diapedesis

These chemokines and cell-adhesion molecules attract and assist leukocytes to enter the inflamed area through a process known as _____

IL-2

T cell and B cell growth factor

IL-2

It drives the growth and differentiation of both T and B cells and induces lytic activity in NK cells

IL-2

____ alone can activate proliferation of Th2 cells and helps to generate IgG1- and IgE-producing cells

Multi-colony stimulating factor

IL-3 Is known as _______

IL-3

It stimulates Myeloid, lymphoid, and erythroid lineage

IL-4

stimulates the production or activation of IgG2, IgG5, and IgA

IL-6

It is a major factor for production of Acute phase reactants

IL-6

Can be used as a Renal stone marker.

cachectin

TNF-a is known as _____

TNF-a

Known as cachectin, produced mainly by the macrophages and NK cells

TNF-a

Lipopolysaccharide found in gram negative bacteria – major stimulus for TNF-a production

septic shock

TNF-a secretion of higher levels will lead to _____

lumphotoxin

TNF-B is known as ___

TNF-B

For killing and endothelia activation

Type 1 IFN

These IFNs are produced by dendritic cells and induce production of proteins and pathways that

directly interfere with viral replication and cell division. -Steven’s 4th edition

leukocyte interferon-secreted by leukocytes fibroblast IFN/Epithelial cell IFN -secreted by fibroblasts

IFN alpha =

IFN beta =

Type I IFN

activates natural killer (NK) cells and enhances the expression of class I MHC proteins, thus increasing the recognition and killing of virus-infected cells

multiple sclerosis

IFN-β is efficacious in treating ___

hepatitis C and Kaposi’s sarcoma

IFN-α has been used to treat ______ , as well as certain leukemias and lymphomas

Type 2 IFN

This is the principal molecule produced by Th1 cells, which affects the RNA expression levels of more than

200 gene

Type 2 IFN

most potent activator of macrophages and boosts their tumoricidal activity.

Type 2 IFN

involved in regulation and activation of CD4+ Th1 cells, CD8+ cytotoxic lymphocytes, and NK cells

Type 2 IFN

Function: Major macrophage activator, and increases expression of MHC class 1 and 2

TGF

was identified as a factor that induces antiproliferative activity in a widevariety of cell types

TGF-β

is primarily a regulator of cell growth, differentiation, apoptosis, migration, and the inflammatory response. Thus, it acts as a control to help down regulate the inflammatory response when no longer needed.

TGF-B

Regulates the expression of CD8 in CD4–CD8– thymocytes and acts as an autocrine inhibitory factor for immature thymocytes.

TGF-B

Blocks the production of IL-12 and strongly inhibits the induction of IFN-gamma

It is recognized as an important factor in the establishment of oral tolerance to bacteria normally found in the mouth

It is recognized as an important factor in the establishment of oral tolerance to bacteria normally found in the mouth