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The Immune System: Friend and Foe—The 1996 Webcast Lectures

Presented by HHMI investigators:
John W. Kappler, Ph.D, and Philippa Marrack, Ph.D.

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Lecture One—How Immune Cells Create Trillions of Receptors from a Few hundred Parts by John W. Kappler.

White blood cells of the type called lymphocytes are able to recognize almost any kind of foreign material that enters the body—including bacteria, viruses (such as HIV), and man-made chemicals that did not exist when the immune system was evolving. Lymphocytes are divided into two principal groups, termed B cells and T cells. Both have the ability to identify a wide array of intruders because each bears on its surface a unique receptor, one created by random combinations of relatively few components. Much as random choices from a restaurant menu can lead to meals with a huge number of variations, random combinations of components can lead, to trillions of different receptors. The human body therefore has at least a trillion ways of recognizing that something foreign has invaded.

Lecture Two—How the Immune System Detects Invaders— by Philippa Marrack.

The immune system recognizes invaders in a complex way. The two lymphocyte groups use different strategies. B cells can attack the intruder directly. T cells require assistance from B cells or other white blood cells that ingest and digest foreign invaders. Protein fragments from the processed invader reappear on the surface of these cells, bound in specialized grooves of a complex of proteins. This complex, known as MHC (major histocompatibility complex) proteins, presents the invader fragments to T cells. The T cell receptors recognize the bound protein complex and initiate a cascade of events, enlisting the B cell army as well as other T cells. This system allows lymphocytes to identify and destroy cells in which viruses or bacteria are hidden and multiplying.

Lecture Three—How the Host Avoids 'Friendly Fire' by John W. Kappler.

Normally the trillion of lymphocytes do not attack their host. To prevent such attacks, lymphocytes bearing receptors that might react with host tissues are selectively destroyed during their development. Cells that escape this screen treat host molecules as invaders, causing serious autoimmune (self-destructive) diseases such as juvenile diabetes, rheumatoid arthritis, and lupus erythematosis.

Lecture Four—Stalking the Elusive Pathogen by Philippa Marrack.

Some organisms have evolved ways of evading or subverting the body's defenses. The malaria parasite, for example, changes its coat proteins to stay one step ahead of the host's immune cells. Herpes viruses become almost undetectable to lymphocytes. The AIDS virus destroys a subset of T cells that are essential for a successful immune response. Thus the immune system fights off many but not all infections. By learning more about how such pathogens work, new ways may be found to thwart them.

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