Genetic defects can occur in almost any molecule involved in the immune response. These defects give rise to characteristic deficiency diseases, which, although rare, provide much information about the development and functioning of the immune system in normal humans. Inherited immunodeficiencies illustrate the vital role of the adaptive immune response and T cells in particular, without which both cellmediated and humoral immunity fail. They have provided information about the separate roles of B lymphocytes in humoral immunity and of T lymphocytes in cellmediated immunity, the importance of phagocytes and complement in humoral and innate immunity, and the specific functions of a growing number of cellsurface or signaling molecules in the adaptive immune response. There are also some inherited immune disorders whose causes we still do not understand. The study of these diseases will undoubtedly teach us more about the normal immune response and its control. Acquired defects in the immune system, the secondary immunodeficiencies, are much more common than the primary, inherited immunodeficiencies. In the next sections we briefly consider general mechanisms by which successful pathogens evade or subvert immune defenses and then detail how extreme subversion of the immune system by one pathogen, the human immunodeficiency virus (HIV), has created a major pandemic characterized by the acquired immune deficiency syndrome (AIDS) in affected individuals.
Evasion and subversion of immune defenses.
In the previous section, we learned how specific defects in immune pathways lead to infection, often by microbes that would normally be defeated by a healthy immune system. These ‘opportunistic’ infections often dominate the clinical expression of inherited immunodeficiencies because the causative organisms are ubiquitous and abundant in the environment. A minority of microbes are true pathogens that can infect those with normal immune defenses. A defining feature of pathogens is their ability to avoid immune destruction by components of the innate and adaptive immune systems, at least long enough to replicate in the infected host and spread to new hosts. At one end of the spectrum are pathogens that establish an acute infection, replicate quickly, and find a new host before they are cleared by a successful immune response; at the other are pathogens that establish chronic infections, persisting long term in the host while evading elimination by immune defenses. Successful pathogens use different strategies to achieve these ends, and over millions of years of coevolution with their hosts have evolved a remarkable diversity of strategies for avoiding detection and destruction by the immune system, often employing several strategies that subvert immunity at multiple points. The antiimmune strategies employed by pathogens are as sophisticated as the immune system itself. They must be for any pathogens to achieve success against the diverse strategies that vertebrates have evolved to ensure host protection.
Viruses, bacteria, and protozoan (unicellular) or metazoan (multicellular) parasites can all act as pathogens. While fungi and helminthic (metazoan) parasites are major causes of common skin infections and intestinal worm infestation, respectively, they do not typically cause lifethreatening infections in normal people and will not be considered further here. In contrast, a select number of viruses, bacteria, and protozoan parasites are the major causes of morbidity and mortality caused by infectious agents. AIDS, tuberculosis, and malaria, caused by the human immunodeficiency virus (HIV), Mycobacterium tuberculosis, and Plasmodium falciparum, respectively, are the three largest infectious disease threats to humans; each of these pathogens infects over 100 million people worldwide and kills 1 to 2 million people annually. Although the strategies for survival within—and propagation between—hosts differ for each type of pathogen, many of the innate and adaptive immune mechanisms employed to thwart the pathogen are the same. Here we briefly consider the lifestyles of, and the principal immune responses elicited by, different types of pathogens, and the strategies the pathogens employ to evade or subvert the immune system.