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Even before the concept of immunity (from immunis, Latin for "exempt") was developed, numerous early physicians characterised organs that would later prove to be part of the immune system. The key organs of the immune system are thymus, spleen, bone marrow, lymph vessels, lymph nodes and secondary lymphatic tissues such as tonsils, adenoids, and skin. Two major organs, the thymus and spleen, are examined histologically only post-mortem during autopsy. However some lymph nodes and secondary lymphatic tissues can be surgically excised for examination while patients are still alive.

Many components of the immune system are actually cellular in nature and not associated with any specific organ but rather are embedded or circulating in various tissues located throughout the body.

Classical immunology ties in with the fields of epidemiology and medicine. It studies the relationship between the body systems, pathogens, and immunity. The earliest written mention of immunity can be traced back to the plague of Athens in 430 BCE. Thucydides noted that people who had recovered from a previous bout of the disease could nurse the sick without contracting the illness a second time. Many other ancient societies have references to this phenomenon, but it was not until the 19th and 20th centuries before the concept developed into scientific theory.

The humoral (antibody) response is defined as the interaction between antibodies and antigens. Antibodies are specific proteins released from a certain class of immune cells (B lymphocytes). Antigens are defined as anything that elicits generation of antibodies, hence they are Antibody Generators. Immunology itself rests on an understanding of the properties of these two biological entities. However, equally important is the cellular response, which can not only kill infected cells in its own right, but is also crucial in controlling the antibody response. Put simply, both systems are highly interdependent.

In the 21st century, immunology has broadened its horizons with much research being performed in the more specialized niches of immunology. This includes the immunological function of cells, organs and systems not normally associated with the immune system, as well as the function of the immune system outside classical models of immunity.

The most well-known disease that affects the immune system itself is AIDS, caused by the HIV virus. AIDS is an immunodeficiency characterized by the lack of CD4+ ("helper") T cells and macrophages, which are destroyed by the HIV virus.

The use of immune system components to treat a disease or disorder is known as immunotherapy. Immunotherapy is most commonly used in the context of the treatment of cancers together with chemotherapy (drugs) and radiotherapy (radiation). However, immunotherapy is also often used in the immunosuppressed (such as HIV patients) and people suffering from other immune deficiencies or autoimmune diseases.

The specificity of the bond between antibody and antigen has made it an excellent tool in the detection of substances in a variety of diagnostic techniques. Antibodies specific for a desired antigen can be conjugated with a radiolabel, fluorescent label, or color-forming enzyme and are used as a "probe" to detect it.

Well known applications of this include immunoblotting, ELISA and immunohistochemical staining of microscope slides. The speed, accuracy and simplicity of such tests has led to the development of rapid techniques for the diagnosis of disease, microbes and even illegal drugs in vivo (of course tests conducted in a closed environment have a higher degree of accuracy). Such testing is also used to distinguish compatible blood types.

Study of the immune system in extant and extinct species is capable of giving us a key understanding of the evolution of species and the immune system.

A development of complexity of the immune system can be seen from simple phagocytotic protection of single celled organisms, to circulating antimicrobial peptides in insects to lymphoid organs in vertebrates. Of course, like much of evolutionary observation, these physical properties are often seen from the anthropocentric aspect. It should be recognised, that every organism living today has an immune system absolutely capable of protecting it from most forms of harm; those organisms that did not adapt their immune systems to external threats are no longer around to be observed.

Insects and other arthropods, while not possessing true adaptive immunity, show highly evolved systems of innate immunity, and are additionally protected from external injury (and exposure to pathogens) by their chitinous shells.