Cytokines and Receptors Overview

Cytokines

Soluble, free or membrane bound, used to communicate in immune cells, assist locomotion, increase or decrease enzyme activity, change transcription, direct cell death

Cytokine affinity

Kd of 10^-8 to 10^-12 to their receptorsq

Affinity/Proximity

Increase effect of small numbers of cytokines

Interleukins

First cytokine to be characterized, named for inter communication between leukocytes

Earliest discovered cytokines

Interleukins, TNF (tumor necrosis factor), and IFN (interferon)

Chemokines

Subpopulation of cytokines, mobilize cells through chemoattraction

Endocrine

Bloodstream, long distance

Paracrine

Cells near the secreting cell, short distance

Autocrine

Cell has receptors for its own cytokine, affects itself

Technical problems of cytokine therapy

Hard to get high concentration in specific area, need to be stabilized before body and destabilize in body, can elicit too much response from leukocytes leaving other body parts vulnerable

Interferon alpha (IFNa) / INF beta

Secreted by macrophages, dendritic cells, virus-infected cells, increase MHC, activate NK cells, induce antiviral state in cells

IFN gamma

Secreted by T-cells and NK cells, activates macrophages, increases MHC and Ag presentation

Pleiotropic cytokines

one cytokine can affect multiple target cells

Redundant cytokines

multiple cytokines have similar functions

Synergy

additive cytokine response

Antagonism

one cytokine response inhibits the effects of another

Cascade induction

cytokine response creates more cytokines creating a positive feedback loop

Interleukin-1 family

Inflammatory mediators

Proinflammatory

Initiates or promote inflammation

IL-1 secretory cells

Innate immune cells (monocytes, dendritic cells, etc.)

IL-1 target cells

Adaptive B and T cells, other non cytokine-secreting cells

Caspase-1

Causes cytokines to be mature and activated

IL-1RI

Receptor for IL-1, causes immune response when bound

IL-1Ra

Mimic ligand of IL-1, binds IL-1RI and IL-1RII receptors but does not cause immune response (inhibitory function)

Class 1 (hematopoietic) cytokine family

Large diversity of function and sequence

Class 1 IL-2

functions in B and T cell proliferation

Class 1 IL-4

targets T-helper cells

Class 1 IL-6

differentiation of plasma B-cells

Class 2 (interferon) cytokine family

Antiviral response and immune response modulation

3 subtypes of Class 2 Cytokines

alpha/beta (type 1), gamma (type 2), lambda (type 3)

Class II type 1

secreted by macrophages and dendritic cells when PRR encounters PAMP, ribonuclease IFNa and IFNB

Class II type 2

ribonucleases, kill RNA and stop viruses (ex. leprosy, toxoplasmosis), secreted by activated T and NK cells (IFN gamma)

Class 2 type 3

secreted plasmacytoid dendritic cells secrete IFN lambda

Tumor necrosis factor family

Involved in inflammation, immune system development, effector function, and homeostasis

TNF secretory cells

activated macrophages, lymphocytes, fibroblasts, and keratinocytes

TNF receptor-1 molecules

when TNF binds, it forms a trimer and causes intracellular response

Decoy receptors

non-membrane bound, soluble TNF receptors that bind ligand to block signal (inhibitory)

Interleukin-17 family

Promote neutrophil accumulation and activation - proinflammatory

IL-17 secretory cells

activated T-helper cells, NK, and NKT cells, named IL-17A through IL-17F

Chemokines

All serve chemoattractant functions