Cytokine Principal Cell Source Principal cellular targets and biologic effects Ligand L on

Innate Immune System

TNF Macrophage, T Cells Endothelial cells: inflammation, coagulation.
Neutrophils: activation. Hypothalamus: fever, Liver:
synthesis of actue phase proteins. Muscle, fat:
catabolism. Many Cell types: apoptosis
IL-1 Macrophages, endothelial cells, Endoth. Activation. Hypothalamus: fever. Liver:
some epithelial cells synthesis of actue phase proteins
Chemokines Macrophages, endothelial cells, t- Chemitaxis and activation of leukocytes
lymphocytes, fibroblasts,
platelets.
IL-12 Macrophages, dentritic Cells Nk cells and T Cells: IFNg synthesis, increased
cytosolic activity. T cells: th1 differentiation
IFN-gamma NK cells, T lymphocytes (Th1) Activation of Macrophages, stimulates AB
production to bind APC Fc receptors, activates
complement production, stimulates co stimulatory
molecule expression
Type 1 IFNs IFNalpha: macrophages. All cells: antiviral state, increased class I MHC
IFNbeta: fibroblasts expression. NK cells: activation
IL-10 Macrophages, T cells (TH2) Macrophages: inhibition of Il-12 production, reduced
exression of costimulators and class II MHC
molecules. Enhance b-cell production
IL-6 Macrophages, endothelial cells, t Liver: synthesis of acute phase proteins. B cells:
cells proliferation of anibody-production cells
IL-15 Macrophages, others NK cells: proliferation. T cells: proliferation
IL-18 Macrophages Nk cells and T Cells: IFNg synthesis,
IL-2 T-cells Stimulates t-cells
IL-13 TH2 Stimulates class swithing to make IgE
TGFbetta Mucosal surfaces Stimulates IgA isotype switching
T-Lymphocytess
CCL17 vascular Endothelium near skin Homes leukocytes to skin
cells
CCL27 Kerotinocytes Binds CCR10 on effector T-Cell, homes t-cell to skin

MadCam-1 Binds T-cell to endo near gut Homes T cells to gut

CCl25 Epithelium of SI Homes t cell to SI
CCL28 Epithelium of LI Homes t cell to LI
CD3 T-cells Signal Transduction
CD4 T-cells Adhesion and signal transduction. MHC II
APC
CD8 T-cells Adhesion and Signal Transduction MHC IAPC
CD28 T-cells Signal Transduction (costimulation) B7 APC
CTLA-4 T-cells Signal Transduction (negative regulation) B7 APC
LFA-1 T-cells Adhesion ICAM-1
APC
Enth
VLA-4 T-cells Adhesion VCAM Enth
CCR7 Dendritic cell Distinct to Activated Dentritic cell
When bound to CD40, amplifies signal to maintain
immune response. Activates macrophages and B cell
CD40L T/B-cells isotype switching CD40 APC
Stimulates Eosinophils, + LKT production and
IL-5 Th2, Mast Cells cytotoxcity for parasites (in vitro)
IL-3, GM-CSF Mast Cells Promotes survival and activation of eosinophils
Stimulates Neutralizing IgG Ab (IgG4) production,
TH2 differentiation. Inhibits Th1 response.
IL-4 Th2 Stimulates IgE production
IL-12 Act. Macrophages/Dendritic TH1 Differentiation
FasL CTLs Induces apoptosis by binding FasR on target cell
L-Selectin High endothelial venule in Low affinity binding of T-cell
Ligand Lypmh node
E/P Selectin Binds E/P selectin on activated Hgh affinity binding on endothelium
Ligand endothelium and platelets (for P)
CD31 Leukocytes binds to PECAM which is on activated leukocytes,
endothelial cell-cell jxns.
cd3 Bound to microbe Cd3 binds CR2 on b cell which leads to b cell
activation via complement system
FC Receptors
FcƔRI Macrophages, neutrophils, Phagocytosis, activation of phagocytes
eosinophils
FCƔRIIIA Nk cells AB dependent cellular cytotoxicity
FC€RI Mast cells, basophils, binds IgE and causes degranulation
esosinophils
PolyIgR Mucosal surfaces Binds IgA and transports it into lumen of GI
FCRn Lumen of GI tract, Placenta Transfers mother's IgG into neonate via placenta or
mother's milk
Plasma
Proteins
C1 inhibitor Plasma inhibits C1 protease activity
Factor I Plasma Cleaves c3b and c4b
Membrane
Proteins
DAF Blood cells, endo/epi causes dissociation of c3 convertase
CR1 Monnuclar phags, PMR's, B/T, Cissoc. Of c3 convertase. Cofactor for factor I
RBC, Eosiniphills, FDCs
Hypersensitivit Mast cells and Basophils Increases vasc. Permeability, causes sm contraction. H1R, H2R
y Toxic to parasites
Histamine Mast cells and Basophils Increases vasc. Permeability, causes sm contraction. H1R, H2R
(heparin is Toxic to parasites
similar)
Histamine 1 Mast cells and Basophils Smooth muscle contraction, vasc. Permeability
Histamine 2 Mast cells and Basophils Vascular Permeability
Mast Cell
Chemokines
CCL3 Mast Cells chemotactic for CCR3
monocytes/macrophages/neutrophils/tcells/eosinophil
s
CCL5 Mast Cells Chmotactic for T cells and Eosinophils CCR3
CCL11 Mast Cells Eotaxin, found at sites of inflammation
Mast Cell
Lipid
Mediators
Leukotrienes Mast Cells Eosinophil migration, smc contraction, vasc.
C4, D4, E4 Permeability, musucs hyperscecretion
Leukotrienes Mast Cells Sm. Muscle Contraction, Increased permeability
Eosinophil
products
MBP Eosinophil Mast cell activation, helminthotoxic
ECP Eosinophil Sames as MBP plus neurtoxic
PAF Eosinophil Bronchoconstriction and activates platelets
LTC4 Eosinophil Bronchoconstriction, mucus hypersecretion, edema