The immune system has evolved to protect the host from a universe of pathogenic microbes that are themselves constantly evolving. The immune system also helps the host eliminate toxic or allergenic substances that enter through mucosal surfaces. Central to the immune system’s ability to mobilize a response to an invading pathogen, toxin or allergen is its ability to distinguish self from non-self. The host uses both innate and adaptive mechanisms to detect and eliminate pathogenic microbes. Both of these mechanisms include self-nonself discrimination. This overview identifies key mechanisms used by the immune system to respond to invading microbes and other exogenous threats and identifies settings in which disturbed immune function exacerbates tissue injury.
Introduction
Humans and other mammals live in a world that is heavily populated by both pathogenic and non-pathogenic microbes, and that contains a vast array of toxic or allergenic substances that threaten normal homeostasis. The community of microbes includes both obligate pathogens, and beneficial, commensal organisms, which the host must tolerate and hold in check in order to support normal tissue and organ function. Pathogenic microbes possess a diverse collection of mechanisms by which they replicate, spread and threaten normal host functions. At the same time that the immune system is eliminating pathological microbes and toxic or allergenic proteins, it must avoid responses that produce excessive damage of self-tissues or that might eliminate beneficial, commensal microbes. Our environment contains a huge range of pathogenic microbes and toxic substances that challenge the host by a very broad selection of pathogenic mechanisms. It is not surprising, therefore, that the immune system uses a complex array of protective mechanisms to control and usually eliminate these organisms and toxins. A general feature of the immune system is that these mechanisms rely on detecting structural features of the pathogen or toxin that mark it as distinct from host cells. Such host-pathogen or host-toxin discrimination is essential to permit the host to eliminate the threat without damaging its own tissues.
The mechanisms permitting recognition of microbial, toxic, or allergenic structures can be broken down into two general categories: i) hard-wired responses that are encoded by genes in the host’s germ line and that recognize molecular patterns shared both by many microbes and toxins that are not present in the mammalian host; and ii) responses that are encoded by gene elements that somatically rearrange to assemble antigen-binding molecules with exquisite specificity for individual unique foreign structures. The first set of responses constitutes the innate immune response. Because the recognition molecules used by the innate system are expressed broadly on a large number of cells, this system is poised to act rapidly after an invading pathogen or toxin is encountered and thus constitutes the initial host response. The second set of responses constitutes the adaptive immune response. Because the adaptive system is composed of small numbers of cells with specificity for any individual pathogen, toxin or allergen, the responding cells must proliferate after encountering the antigen in order to attain sufficient numbers to mount an effective response against the microbe or the toxin. Thus, the adaptive response generally expresses itself temporally after the innate response in host defense. A key feature of the adaptive response is that it produces long-lived cells that persist in an apparently dormant state, but that can re-express effector functions rapidly after another encounter with their specific antigen. This provides the adaptive response with the ability to manifest immune memory, permitting it to contribute prominently to a more effective host response against specific pathogens or toxins when they are encountered a second time, even decades after the initial