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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