PHSC1312 Microbiology/Immunology Lecture 5 Immune Cell Communication: Cytokines & Chemokines

cytokines

small soluble proteins that mediate immune cell communication

immune cell communication

What is mediated through cytokines?

autocrine

when a cell makes a communication substance like cytokines and also has the receptors sensitive to that cytokine

paracrine

when a cell has cytokines diffused to nearby cells as they are communicating

small soluble proteins

What are cytokines?

downstream of PRR ligation

Where are cytokines produced in relation to a receptor ligand interaction?

innate immune cytokines

cytokines that induce inflammation, inhibit viral replication, promote T cell response, limit innate immune response

induce inflammation, inhibit viral replication, promote T cell response, limit innate immune response

innate immune cytokine functions

adaptive immune cytokines

cytokines that promote effector cytokine production, inhibit viral replication, induce MHC and innate cell activity, promote homeostasis and limit damage

promote effector cytokine production, inhibit viral replication, induce MHC and innate cell activity, promote homeostasis and limit damage

adaptive immune cytokine functions

effector cytokines

cytokines produced by helper T cells

glycoprotein receptors on cell membranes

What do cytokines bind to?

intracellular signaling pathway propagated through kinase mediated phosphorylation

What is induced from the receptor ligation of cytokines binding to glycoprotein receptors on cell membranes?

kinase

enzyme used to mediate phosphorylation

TNF alpha, IL1, IL6

three main pro-inflammatory cytokines; always made in an acute inflammatory response

pro-inflammatory

What type of cytokines are TNF alpha, IL1, IL6?

TGF beta, IL10

two main anti inflammatory cytokines

anti-inflammatory

What type of cytokines are TGF beta and IL10?

interferons

antiviral pro-inflammatory cytokines that are immunoregulatory and antiproliferative

alpha, beta, gamma

three types of interferons

innate

What part of the immune system are alpha and beta interferons?

adaptive

What part of the immune system are gamma interferons?

leukocytes

primary cell type of alpha interferons

MHC I class and NK cell activity

What do alpha and beta interferons enhance as an immunoregulatory feature?

fibroblasts, epithelial cells

primary cell types of beta interferons

T cells, NK cells, ILC1 cells

primary cell types of gamma interferons

MHC I and II classes and macrophage activation

What do gamma interferons enhance as an immunoregulatory feature?

tumor necrosis factor

What does TNF stand for?

alpha and beta

two types of TNF cytokines

alpha

What is the super important pro-inflammatory TNF cytokine? (doesn't need TNF in front of it)

macrophages, lymphocytes

primary cell types for TNF-alpha cytokines

macrophages and cytotoxic cells

What does TNF alpha activate?

cachexia, acute phase proteins, cytokines IL1 and IL6

What does TNF alpha induce?

cachexia

a condition of physical wasting away due to the loss of weight and muscle mass that occurs in patients with diseases

interleukin

What does IL stand for?

IL1 and IL6

two important pro-inflammatory interleukin cytokines

most cells, macrophages, dendritic cells

primary cell types for IL-1 cytokines

induce inflammation, fever, sepsis, activate TNF alpha

IL-1 cytokine functions

fever

major function of IL-1

stored in proform in mast cells

important feature of IL-1 cytokines

IL2

adaptive immune cell cytokine and T cell growth factor

T cells

IL2 primary cell type

proliferation and maturation of T cells

functions of IL-2 cytokines

most cells

primary cell type for IL-6 cytokines

causes liver to produce soluble proteins

important function of IL-6

complement and acute phase proteins

What type of proteins does IL-6 cause the liver to produce?

IL10

important anti-inflammatory interleukin cytokine

T cells, monocytes/macrophages

primary cell types for IL-10 cytokines

inhibits production of proinflammatory cytokines

IL-10 cytokine function

promote certain immune cell growth

growth factor cytokine function

bone marrow

What do growth factors communicate to in order to stimulate leukocyte production?

M-CSF

stimulated monocytes, which are macrophage precursors

monocytes

What cell type do M-CSF cytokines stimulate?

macrophage precursor proliferation

function of M-CSF cytokines

macrophages

primary cell type of G-CSF cytokines

proliferation, differentiation, and activation of neutrophils

G-CSF cytokine functions

granulocytes

What does the G in G-CSF stand for?

T cells, macrophages

primary cell types for GM-CSF cytokines

granulocyte and macrophage precursor proliferation

GM-CSF cytokine functions

TGF beta

super important growth factor anti-inflammatory cytokine found in most cells

VEGF-A

growth factor cytokine in most cells that stimulates vasculogenesis and angiogenesis

vasculogenesis and angiogenesis

stimulated by VEGF-A

tumor structure

Where would VEGF-A be highly expressed due to its vascularization promotion?

endothelial

What type of cell growth does VEGF-A promote?

chemokines

subtype of cytokines that promote movement of cells

CC and CXC

two structural types of chemokines

CC

structural type of chemokine with two adjacent cysteine residues

CXC

structural type of chemokine with cysteine residues separated by 1 amino acid

CXC chemokines

Which chemokines recruit neutrophils? (include the word chemokines)

CC chemokines

Which chemokines recruit monocytes? (include the word chemokines)

CXC and CC

Which chemokines recruit lymphocytes? (don't include the word chemokines)

IL8 or CXCL8

specific chemokine that causes neutrophil activation and chemotaxis

RANTES or CCL5

specific chemokine chemotactic for T cells, monocytes, eosinophils, and basophils

T cells, monocytes, eosinophils, basophils

What is RANTES or CCL5 chemotactic for?

adhesion molecules

used by immune cells following cytokine signals to interact with the environment at the site of infection or accute inflammation

ICAM1, VCAM1, E selectin

three types of adhesion molecules

endothelial cells

primary cell type for adhesion molecules ICAM-1 and E-selectin

adhesion and migration

simplified function of adhesion molecules

inflammatory cytokines

What makes the endothelium lining of blood vessels get sticky to rolling neutrophils?

selectin

protein on the endothelium that increases affinity for the ligands on PMN

LFA integrin expression

What does PMN increase on its cell surface to bind to ICAM?

ICAM surface protein

What expression does the endothelium increase to bind to the LFA on the PMN?