Natural and acquired immunity

Every animal species possesses some natural resistance to disease. Humans have a high degree of resistance to foot-and-mouth disease, for example, while the cattle and sheep with which they may be in close contact suffer in the thousands from it. Rats are highly resistant to diphtheria, whereas unimmunized children readily contract the disease.

What such resistance depends on is not always well understood. In the case of many viruses, resistance is related to the presence on the cell surface of protein receptors that bind to the virus, allowing it to gain entry into the cell and thus cause infection. Presumably, most causes of absolute resistance are genetically determined; it is possible, for example, to produce by selective breeding two strains of rabbits, one highly susceptible to tuberculosis, the other highly resistant. In humans there may be apparent racial differences, but it is always important to disentangle such factors as climate, nutrition, and economics from those that might be genetically determined. In some tropical and subtropical countries, for example, polio is a rare clinical disease, though a common infection, but unimmunized visitors to such countries often contract serious clinical forms of the disease. The absence of serious disease in the residents is due not to natural resistance, however, but to resistance acquired after repeated exposure to poliovirus from infancy onward. Unimmunized visitors from other countries, with perhaps stricter standards of hygiene, are protected from such immunizing exposures and have no acquired resistance to the virus when they encounter it as adults.

Natural resistance, in contrast to acquired immunity, does not depend upon such exposures. The human skin obviously has great inherent powers of resistance to infection, for most cuts and abrasions heal quickly, though often they are smothered with potentially pathogenic microorganisms. If an equal number of typhoid bacteria are spread on a person’s skin and on a glass plate, those on the skin die much more quickly than do those on the plate, suggesting that the skin has some bactericidal property against typhoid germs. The skin also varies in its resistance to infectious organisms at different ages: impetigo is a common bacterial infection of children’s skin but is rarer in adults, and acne is a common infection of the skin of adolescents but is uncommon in childhood or in older adults. The phenomenon of natural immunity can be illustrated equally well with examples from the respiratory, intestinal, or genital tracts, where large surface areas are exposed to potentially infective agents and yet infection does not occur.

If an organism causes local infection or gains entry into the bloodstream, a complicated series of events ensues. These events are described in detail in the article immune system, but they can be summarized as follows: special types of white blood cells called polymorphonuclear leukocytes or granulocytes, which are normally manufactured in the bone marrow and which circulate in the blood, move to the site of the infection. Some of these cells reach the site by chance, in a process called random migration, since almost every body site is supplied constantly with the blood in which these cells circulate. Additional granulocytes are attracted and directed to the sites of infection in a process called directed migration, or chemotaxis.

When a granulocyte reaches the invading organism, it attempts to ingest the invader. Ingestion of bacteria may require the help of still other components of the blood, called opsonins, which act to coat the bacterial cell wall and prepare it for ingestion. An opsonin generally is a protein substance, such as one of the circulating immunoglobulins or complement components.

Once a prepared bacterium has been taken inside the white blood cell, a complex series of biochemical events occurs. A bacterium-containing vacuole (phagosome) may combine with another vacuole that contains bacterial-degrading proteins (lysozymes). The bacterium may be killed, but its products pass into the bloodstream, where they come in contact with other circulating white blood cells called lymphocytes. Two general types of lymphocytes—T cells and B cells—are of great importance in protecting the human host. When a T cell encounters bacterial products, either directly or via presentation by a special antigen-presenting cell, it is sensitized to recognize the material as foreign, and, once sensitized, it possesses an immunologic memory. If the T cell encounters the same bacterial product again, it immediately recognizes it and sets up an appropriate defense more rapidly than it did on the first encounter. The ability of a T cell to function normally, providing what is generally referred to as cellular immunity, is dependent on the thymus gland. The lack of a thymus, therefore, impairs the body’s ability to defend itself against various types of infections.

After a T cell has encountered and responded to a foreign bacterium, it interacts with B cells, which are responsible for producing circulating proteins called immunoglobulins or antibodies. There are various types of B cells, each of which can produce only one of the five known forms of immunoglobulin (Ig). The first immunoglobulin to be produced is IgM. Later, during recovery from infection, the immunoglobulin IgG, which can specifically kill the invading microorganism, is produced. If the same microorganism invades the host again, the B cell immediately responds with a dramatic production of IgG specific for that organism, rapidly killing it and preventing disease.

In many cases, acquired immunity is lifelong, as with measles or rubella. In other instances, it can be short-lived, lasting not more than a few months. The persistence of acquired immunity is related not only to the level of circulating antibody but also to sensitized T cells (cell-mediated immunity). Although both cell-mediated immunity and humoral (B-cell) immunity are important, their relative significance in protecting a person against disease varies with particular microorganisms. For example, antibody is of great importance in protection against common bacterial infections such as pneumococcal pneumonia or streptococcal disease and against bacterial toxins, whereas cell-mediated immunity is of greater importance in protection against viruses such as measles or against the bacteria that cause tuberculosis.