The macrophages (Greek-based: macros = big, phagein = eat) are part of the inherent immunity and playing a central role in the defense of microorganisms such as bacteria and viruses. In contrast to the acquired immunity, which is marked by the production of antibodies during specific infections, the macrophages (so-called “phagocytes”) are incorporate and eliminate “foreign invaders” directly by phagocytosis. Very often the elimination of these microorganisms is not effective, because some bacteria are able to inhibit the fusion of the phagosome with the lysosme, the degrading organelle of the cell. Peptides of the deadened pathogens are presented on the cell-surface of the macrophages. These peptides can be recognized by so-called T_H1 cells, which then transform into CD4-T effector cells. These cells are able to eliminate the pathogenic organisms and can increase the fusion frequency between phagosome and lysosome. For the activation of macrophages normally two signals are necessary. In the case of activated  T_H1 cells the release of Interferone-γ (IFN-γ) and the binding of the CD40-ligand to the CD40-receptor of macrophages are these signals, which stimulates their activation. Besides the T_H1 cells cytotoxic T cells, which are presents cytosolic proteins of mostly viruses, are also an important resource of IFN-γ for the activation of macrophages. Furthermore, small amounts of lipopolysaccharide (LPS) which is part of the cell wall of gram-negative bacteria is sufficient to activate macrophages. 

The release of reactive oxygen species from activated macrophages can result in the destruction of healthy host tissue. Besides, the release of different Interleukins causes among others an upper permeability of the vascular endothelium. A systemic effect of these messengers is for example the appearance of fever.

In this process TNF-α plays a special role. During a local infection with gram-negative bacteria the release of TNF-α by macrophages causes a vascular obliteration of small blood vessels and inhibits in this way the release of the pathogens into the blood stream. Accordingly, the infection stays regional. However, in the case of a systemic infection with gram-negative bacteria (sepsis) TNF-α has a negative effect, because it is released by the macrophages e.g. into the spleen, liver and lung. The consequence of which are vascular dilatations and thereby a loss of blood plasma, which results in a septic shock and causes the formation of edema and multiple organ failure and death, respectively.¹