Summary

We have looked at the seven major cells involved in the innate immune response: mast cells, macrophages, neutrophils, dendritic cells, basophils, eosinophils and natural killer cells. There are two useful classifications we can use when discussing these cells: granulocyte and phagocyte. Some of the cells are both. A granulocyte is a cell which contains granules of molecules which aid the immune response. Some of these molecules are involved in signalling and chemotaxis of immunocompetent cells, some are involved in directly damaging the pathogen and generally they initiate and/or mediate the immune response. Phagocytes stretch themselves around pathogens, engulf them, destroy them and may then recover antigens, which they present to cells of the adaptive immune system.

Mast cells are phagocytes and granulocytes. Their primary function is to degranulate, when stimulated to do so, and thereby instigate the inflammatory response. This may be achieved by damage to the mast cell, by activation by complement and by means of antibodies. These antibodies will be produced in response to particular pathogens and will bind to mast cells. Should the relevant pathogen then bind to two or more receptors (via the antibodies), a signalling cascade will be initiated leading to the degranulation of the mast cell. Degranulation is achieved by transporting the granule to the cell membrane, where it fuses with the membrane and so expels its contents.

Macrophages are large phagocytes. They mature from monocytes and are involved in the release of cytokines, in cleaning up debris left by neutrophils and in tissue repair. Also, of course, they phagocytose. So-called M1 macrophages are particularly aggressive hunters of pathogens, while M2 macrophages are more focused on cleaning up and repair.

Neutrophils are highly effective phagocytes and are also granulocytes and are responsible, in part, for releasing inflammatory cytokines. As well as this, they form neutrophil extracellular traps (NETs), which trap invading pathogens and destroy them by means of the proteins which make up the NETs.

Dendritic cells are "sentinels." They are prolific phagocytes and even "nibble" on perfectly healthy host cells when looking for pathogens. When they find one they phagocytose it and present antigens from it to cells of the adaptive immune system. Dendritic cells are perhaps the most effective antigen presenting cells.

Basophils are useful granulocytes. Their granules contain a number of important molecules, including histamine and heparin, as well as IL-4. Notably, basophil degranulation can be mediated by IgE antibodies.

Eosinophils are also granulocytes but, as well as inflammatory mediators, eosinophils are particularly noteworthy for releasing highly destructive chemicals. Eosinophils, then, are particularly involved with the actual killing.

Natural killer cells attack cells which have been infected by viruses, or which are otherwise "stressed" or damaged in some way. They "select" their target using stimulatory and inhibitory receptors. Inhibitory ligands - particularly MHC I - on healthy cells prevent NK cells from attacking. Thus NK cells do not harm the body they're supposed to be defending - this is self-tolerance. However, on damaged cells MHC I is often under expressed. Damaged cells are also likely to express increased levels of stimulatory ligands (or they may have expressed these when they were healthy as well, but the MHC I levels counterbalanced them). Thus, NK cells "recognise" a lack of MHC I (missing self recognition) and can then be stimulated to attack the cell by the stimulatory ligands. Put more briefly (and more accurately): NK cells attack only if the stimulatory signal is stronger than the inhibitory signal. This is the means by which NK cells select the right target and kill damaged and infected cells, without harming healthy cells. If the NK cell is activated it can release IFNγ and TNFα. The most prominent method of attack, though, is the release of granules. These contain perforin, which forms a pore in the target cell, which allows other substances in the granules to enter the cell and kill it by lysis or apoptosis. NK cells are additionally stimulated by cytokines and can be activated with the help of antibodies.