Immune Response to Infection
Many innate defenses protect us from potential pathogens, including structural barriers and cells and molecules of the innate immune system such as phagocytes and acute phase proteins (also called inflammation). The adap-tive immune response of vertebrates differs from these in that it is a specific, inducible,and anticipatory defense mechanism that allows the discrimination between self and non-self. The concept of immunity on which the science of immunology is built begins with ancient observations, such as Thucydides’ description of the plague of Athens in 430 BC in which individuals who were infected and survived were not susceptible to infection by the same pathogen. A specific contemporary definition of the immune response is that it is a complex and precisely regulated inducible defense mechanism that allows the specific discrimination between self and nonself. The immune system requires for its function the presence of antigen-specific lymphocytes of two major types, thymus-derived lympho-cytes (T cells) and bone marrow – derived lymphocytes (B cells), and it builds on the more primitive defense mechanisms of the innate immune system such as phagocytosis, while using mediators of cell communication termed cytokines to facilitate regulation of the complex system. Another characteristic that defines the immune response of mam-mals is that it is anticipatory; a process of combinatorial gene rearrangement generates an array of T and B cells with the aggregate populations comprising hundreds of millions of individual lymphocytes, each expressing a different receptor specificity in advance of any challenge. This preexisting readiness allows the production of circulating antibodies to the foreign challenge as well as the generation of the T-cell receptors that initiates the specific immune process leading to the elaboration of specific effector T lymphocytes (eg, helpers or killers).
One of the major recent successes of immunology has been eradication by vaccina-tion of historic scourges such as smallpox. In addition to defense against infection, the immune system is important in normal developmental processes, aging, maintenance of internal homeostasis, and surveillance against neoplasms.
The adaptive immune response differs from the innate or constitutive mechanisms in two major respects. The first is that the response is inducible; that is, the challenge to a healthy individual by a bacterium, virus, or other foreign (nonself) matter initiates a process leading to the production of circulating proteins called antibodies that recognize and bind the invading pathogen in a specific manner.
A second challenge by the same pathogen results in an accelerated immune response (secondary or anamnestic) that can confer greater protection on the host in a manner specific for that pathogen (eg, vaccination against measles protects against measles but not against polio).
The second major definitive characteristic of the human immune response is that it is anticipatory; that is, because of the combinatorial generation of the recognition repertoire, it has the potential to respond to pathogens not yet encountered in evolutionary history. This striking feature of the immune response results from the large number of genes specifying individual antibody combining sites for antigen and from a genetic recombination mecha-nism that allows us to form millions of potential antibody combining sites. Each antigen-specific lymphocyte (T or B) expresses a single receptor, and the cells are thus clonally restricted. In 1959, Sir MacFarlane Burnet predicted clonal restriction and selection by antigen, thus providing the intellectual foundation of modern immunology. The system is also endowed with the property of memory, so that reexposure to the inciting agent in the future usually brings about an enhanced response. Another crucial property of the combina-tional system is that it can be come tolerant or nonreactive to self based on contact during early development. Immune defenses against infectious organisms involve both the innate and adaptive systems, with emphasis on different aspects for individual pathogens.
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