| Themes > Science > Life Sciences > General Biology > Immunology > Immunity to Infection > The Immediate defence systems |
The immediate defence of the body against an invasion must be in the hands of preformed molecules, already present constitutively. Unless the specific microorganism has been encountered previously (of which more later) these molecules must be part of the innate immune system. The very earliest events of host defence against a new pathogen are those of acute inflammation. Complement The most important immediate defender is the C3 component of complement. The alternative pathway initiator is spontaneously activated C3, which is continually generated at a low rate (C3 'tickover'). Normally this reactive species is shortlived but it can covalently attach to a protein or carbohydrate surface, recruit the serum factor B which is a substrate for the protease factor D, generating the active C3 convertase (C3*Bb). If this is a host cell, then regulators of the complement system rapidly inactivate the convertase. However a pathogen lacks the host regulatory proteins and thus the C3 convertase rapidly amplifies itself. In addition some microbes catalyse the binding of another serum component, P (properdin) which significantly stabilises the convertase and prevents its' inactivation by the soluble inhibitor factor H. The conditions which favour properdin binding are not fully understood - possibly low sialic acid (=less -ve charge). Complement alone is able to destroy some pathogens, primarily gram +ve bacteria by activation of the terminal complement components and assembly of the membrane attack complex. Complement also serves to activate the acute inflammatory response. The C5a fragment is a potent chaemoattractant for neutrophils and activates vascular endothelium directly, furthermore C5a also activates mast cells which amplify the inflammatory signals by releasing their preformed vasoactive mediators. Phagocytes Macrophages are resident in almost all tissues and are found in particularly large numbers in mucosal tissues. Neutrophils are present in the blood in very large numbers, they can be rapidly recruited to any site which activates complement (see above). Both types of phagocyte possess receptors which enable them to bind and phagocytose microbial organisms. These receptors recognise carbohydrate structures which are not present on host cells including certain mannose linkages (Mannose-fucose receptor) and lipopolysaccharide on gram -ve bacteria (CD14). Both type of phagocyte also possess receptors for iC3b which potently stimulate phagocytosis. Once organisms are engulfed, they are subject to a battery of chemical and enzymatic attacks which in many cases destroys them. 'Natural' antibody Even when an organism is encountered for the first time there may be some IgM antibody which may bind to its' surface structures. This is called 'natural' antibody. It is a matter of some dispute what role environmental stimuli play in the development of this normal serum antibody. However it should be recognised that even very low affinity reactions with IgM can produce binding and classical pathway complement activation when the target is a bacterial carbohydrate due to the density of epitopes on the microbial surface. Click here to see how IgM activates complement The Host-Pathogen Interplay Despite this armoury of ready-made weapons, the fact that specific immune antibody is required to prevent some infections shows that they are not always sufficient . Often this is because the invading organism has evolved some mechanisms for escaping destruction; examples of this include the capsule of certain bacteria which prevents innate recognition. Some species of bacteria and protozoa actually welcome phagocytosis, having devised means of surviving inside the phagosome or cytoplasm of the cell, phagocytosis helps hide them from other immune mechanisms. Because of their short generation times pathogens will always hold an advantage in the cat and mouse game of immunity. |
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