The immune system has evolved to protect the host from a wide variety of pathogenic microbes that are constantly changing. It also helps the host eliminate toxic or allergenic substances that enter through mucosal surfaces. The immune system's ability to distinguish self from non-self is crucial for mobilizing a response to invading pathogens, toxins, or allergens. The immune system uses both innate and adaptive mechanisms to detect and eliminate pathogenic microbes. 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. The immune system distinguishes between self and non-self through two general categories of responses: innate responses, which are encoded by genes in the host's germ line and recognize molecular patterns shared by many microbes and toxins not present in the mammalian host; and adaptive responses, which are encoded by gene elements that somatically rearrange to assemble antigen-binding molecules with specificity for individual foreign structures. The innate immune response is the first line of defense and is rapid in response to invading pathogens or toxins. The adaptive immune response, which is composed of small numbers of cells with specificity for any individual pathogen, toxin, or allergen, requires proliferation after encountering the antigen to mount an effective response. The immune system employs many potent effector mechanisms that can destroy a broad range of microbial cells and clear a broad range of toxic and allergenic substances. It is critical that the immune response avoids damaging the host's own tissues. The ability of the immune response to avoid damaging self-tissues is referred to as self-tolerance. Failure of self-tolerance underlies autoimmune diseases, and mechanisms to avoid reaction against self-antigens are expressed in many parts of both the innate and adaptive immune response. The innate immune system includes physical barriers, secreted mucus layers, and soluble proteins and bioactive small molecules. The adaptive immune system is characterized by antigen-specific receptors expressed on T- and B-lymphocytes. These receptors are encoded by genes that are assembled by somatic rearrangement of germ-line gene elements. The adaptive immune system has the ability to manifest immune memory, allowing it to contribute to a more effective host response against specific pathogens or toxins when they are encountered a second time. The innate and adaptive immune systems are often described as contrasting, separate arms of the host response, but they usually act together. The innate response represents the first line of host defense, and the adaptive response becomes prominent after several days. Components of the innate system contribute to activation of antigen-specific cells, and antigen-specific cells amplify their responses by recruiting innate effector mechanisms to control invading microbes. The immune response includes contributions from many subsets of leukocytes, which can be discriminated morphologically and by analysis of glycoprotein differentiation antigens. These antigens are detected by their binding of specific monoclonal antibodies. These cell phenotype-determining antigens are assigned cluster of differentiationThe immune system has evolved to protect the host from a wide variety of pathogenic microbes that are constantly changing. It also helps the host eliminate toxic or allergenic substances that enter through mucosal surfaces. The immune system's ability to distinguish self from non-self is crucial for mobilizing a response to invading pathogens, toxins, or allergens. The immune system uses both innate and adaptive mechanisms to detect and eliminate pathogenic microbes. 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. The immune system distinguishes between self and non-self through two general categories of responses: innate responses, which are encoded by genes in the host's germ line and recognize molecular patterns shared by many microbes and toxins not present in the mammalian host; and adaptive responses, which are encoded by gene elements that somatically rearrange to assemble antigen-binding molecules with specificity for individual foreign structures. The innate immune response is the first line of defense and is rapid in response to invading pathogens or toxins. The adaptive immune response, which is composed of small numbers of cells with specificity for any individual pathogen, toxin, or allergen, requires proliferation after encountering the antigen to mount an effective response. The immune system employs many potent effector mechanisms that can destroy a broad range of microbial cells and clear a broad range of toxic and allergenic substances. It is critical that the immune response avoids damaging the host's own tissues. The ability of the immune response to avoid damaging self-tissues is referred to as self-tolerance. Failure of self-tolerance underlies autoimmune diseases, and mechanisms to avoid reaction against self-antigens are expressed in many parts of both the innate and adaptive immune response. The innate immune system includes physical barriers, secreted mucus layers, and soluble proteins and bioactive small molecules. The adaptive immune system is characterized by antigen-specific receptors expressed on T- and B-lymphocytes. These receptors are encoded by genes that are assembled by somatic rearrangement of germ-line gene elements. The adaptive immune system has the ability to manifest immune memory, allowing it to contribute to a more effective host response against specific pathogens or toxins when they are encountered a second time. The innate and adaptive immune systems are often described as contrasting, separate arms of the host response, but they usually act together. The innate response represents the first line of host defense, and the adaptive response becomes prominent after several days. Components of the innate system contribute to activation of antigen-specific cells, and antigen-specific cells amplify their responses by recruiting innate effector mechanisms to control invading microbes. The immune response includes contributions from many subsets of leukocytes, which can be discriminated morphologically and by analysis of glycoprotein differentiation antigens. These antigens are detected by their binding of specific monoclonal antibodies. These cell phenotype-determining antigens are assigned cluster of differentiation