The brief outline of basic immunology presented here provides a foundation for considering the diseases of the immune system. We first discuss the immune reactions that cause injury, called hypersensitivity reactions, and then disorders caused by the failure of tolerance to self antigens, called autoimmune disorders, and the rejection of transplants. This is followed by diseases caused by a defective immune system, called immunodeficiency diseases. We close with a consideration of amyloidosis, a disorder that is often associated with immune and inflammatory diseases.
HYPERSENSITIVITY:IMMUNOLOGICALLYMEDIATEDTISSUEINJURY
Immune responses that normally are protective also are capable of causing tissue injury. Injurious immune reactions are grouped under hypersensitivity, and the resulting diseases are called hypersensitivity diseases. This term originated from the idea that persons who mount immune responses against an antigen are sensitized to that antigen, so pathologic or excessive reactions represent manifestations of a hypersensitive state. Normally, an exquisite system of checks and balances optimizes the eradication of infecting organisms without serious injury to host tissues. However, immune responses may be inadequately controlled or directed against normally harmless antigens or inappropriately targeted to host tissues, and in such situations, the normally beneficial response is the cause of disease. In this section, we describe the causes and general mechanisms of hypersensitivity diseases and then discuss specific situations in which the immune response is responsible for the disease.
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Pathologic immune responses may be directed against different types of antigens and may result from various underlying abnormalities.
Autoimmunity: reactions against self antigens. Normally, the immune system does not react against one’s own antigens. This phenomenon is called self tolerance, implying that the body “tolerates” its own antigens. On occasion, self-tolerance fails, resulting in reactions against one’s own cells and tissues. Collectively, such reactions constitute autoimmunity, and diseases caused by autoimmunity are referred to as autoimmune diseases. We will return to the mechanisms of self-tolerance and autoimmunity later in this chapter.
Reactions against microbes. There are many types of reactions against microbial antigens that may cause disease. In some cases, the reaction appears to be excessive or the microbial antigen is unusually persistent. If antibodies are produced against such antigens, the antibodies may bind to the microbial antigens to produce immune complexes, which deposit in tissues and trigger inflammation; this is the underlying mechanism of post-streptococcal glomerulonephritis (Chapter 14). T-cell responses against persistent microbes may give rise to severe inflammation, sometimes with the formation of granulomas (Chapter 3); this is the cause of tissue injury in tuberculosis and other infections. Rarely, antibodies or T cells reactive with a microbe cross-react with a host tissue; such cross-reactivity is believed to be the basis for rheumatic heart disease (Chapter 11). In some instances, the disease-causing immune response may be entirely normal, but in the process of eradicating the infection, host tissues are injured. In viral hepatitis, the virus that infects liver cells is not cytopathic, but it is recognized as foreign by the immune system. Cytotoxic
Table 5.2 Mechanisms of Hypersensitivity Reactions
T cells try to eliminate infected cells, and this normal immune response damages liver cells.
• Reactions against environmental antigens. Almost 20% of the population is allergic to common environmental substances (e.g., pollens, animal danders, and dust mites), as well as some metal ions and therapeutic drugs. Such individuals are genetically predisposed to make unusual immune responses to noninfectious, typically harmless antigens to which all persons are exposed but against which only some react.