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Failures of Host Defense Mechanisms
In the normal course of an infection, the infectious agent first triggers an innate immune response. The foreign antigens of the infectious agent, enhanced by signals from innate immune cells, then induce an adaptive immune response that ultimately clears the infection and establishes a state of protective immunity. This does not always happen, however. In this chapter we examine circumstances in which there are failures of host defense against infectious agents, whether due to immune defects in an abnormal host, as occurs in immunodeficiency, or to the evasion or subversion of immune defenses in normal hosts by pathogens. Finally, we will consider the special case in which the immune defenses of a normal host are impaired by one infectious agent that leads to more generalized susceptibility to infection, as occurs in the acquired immune deficiency syndrome (AIDS) caused by human immunodeficiency virus (HIV).
In the first part of the chapter, we examine primary, or inherited, immunodeficiency diseases, in which host defense fails due to an inherited defect in a gene that results in the elimination or impaired function of one or more components of the immune system, leading to heightened susceptibility to infection with particular classes of pathogens. Immunodeficiency diseases caused by defects in T or Blymphocyte development, phagocyte function, and complement components have all been discovered. In the second part of the chapter, we briefly consider mechanisms by which pathogens evade or subvert specific components of the immune response to avoid elimination, socalled immune evasion. In the last part of the chapter, we consider how persistent infection by HIV leads to AIDS, an example of secondary, or acquired, immunodeficiency. The study of circumstances and mechanisms by which the immune system can fail has already contributed greatly to our understanding of host defense mechanisms and, in the longer term, might help to provide new methods of controlling or preventing infectious diseases, including AIDS.
immunodeficiency diseases.
evasion and subversion of immune defenses.
acquired immune deficiency syndrome.
Immunodeficiency diseases.
Immunodeficiencies occur when one or more components of the immune system are defective; immunodeficiencies are classified as primary (inherited, or congenital) or secondary (acquired). Primary immunodeficiencies are caused by inherited mutations in any of a large number of genes that are involved in or control immune responses. Well over 150 primary immunodeficiencies have now been described that affect the development of immune cells, their function, or both. Clinical features of these disorders are therefore highly variable, although a common feature is recurrent and often overwhelming infections in very young children. In contrast, secondary immunodeficiencies are acquired as a consequence of other diseases, or are secondary to environmental factors such as starvation, or are an adverse consequence of medical intervention. Some forms of immunodeficiency principally affect immuneregulatory pathways. Defects of this type can lead to allergy, abnormal proliferation of lymphocytes, autoimmunity, and certain types of cancer, and will be discussed in other chapters. Here, we will mainly focus on those immunodeficiencies that predispose to infection.