The effector molecules of Innate

response
Macrophage effectors molecules
 Macrophage effectors molecules: Cytokines and their receptors
Cytokine Cytokines Functions Receptors
family
IL-1 family 11 members Produced by IL-1 family receptors:,
Eg. IL-1a, IL-1b, IL-18 macrophages in heterodimeric,
Mostly produced as inactive pro- response to TLR Extracellular Ig domains,
proteins that need to be cleaved /NLRP activation, cytoplasmic TIR domains
to produce mature cytokine signals via NF-kB associates with IL-1
pathway receptor accessory
proteins, signals through
MyD88

Hematopoeitin Erythropoitein, GM-CSF, Production of Heterodimeric

superfamily IL-6 monocytes and receptor with
granulocytes in common chain (bind
bone marrow to closely related
(GM-CSF); IL-6: receptors sharing a
lymphocyte common b chain or g
activation, Ab chain *
production

* Common g chain of the IL-2 receptor, inactivation of which leads to SCID, due to
inactivation of several cytokines and signaling pathways
 Macrophage effectors molecules: Cytokines and their receptors
Cytokine Cytokines Functions Receptors
family
TNF family TNF is the prototype, more than Activates Two receptors: TNFR 1
17 members with important endothelium, (expressed on
functions in both innate and increases vascular endothelial cells and
adaptive immunity. Many permeability macrophages) and
members are transmembrane TNFR-II (Expressed on
proteins and homotrimers; some lymphocytes). Receptors
are released from membranes also cluster for
activation

Chemokines CXC chemokines 1. Act on different leukocytes to induce

CC chemokines, CX3C stable binding with activated
chemokines endothelial cells for the leukocytes to
squeeze through
2. Directs migration of the leukocytes
along a gradient of the chemokine
molecules
Eg. CXCL8 (attracts neutrophils and T
cells); CCL2 (attracts monocytes to
become tissue macrophages);
 Cell-adhesion molecules: recruitment of cells during inflammation
Macrophage

TNF

Endothelial activation

Sulfated sialyl-Lewis x (a carbohydrate on glycoproteins

1. P-selectin expression of circulating leukocytes
CXCL8
2. Intercellular adhesion
molecules on endothelium Heterotrimeric integrins on leukocytes: tighter adhesion
(ICAMs)
Endothelial Activation: Neutrophil recruitment
Systemic effects of Effectors
Systemic effects of Effectors: Sepsis