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UCSF Magazine, August 2002, © UCSF patterns that immunologists have The Immune System learned to recognize. Full-scale immune system The Body’s Armed mobilization requires the manufac- Services ture of more ammunition and weaponry. Most resource-intensive Military metaphors used to of all, soldier cells of the immune describe the immune system are system must enhance their often apt. The immune system numbers when an invader strikes. does indeed comprise the body’s This requires massive amounts of armed services. Different branches Ph a g o c y t e protein, which in turn requires fulfill different roles in defending that genes within leukocytes be the body against bacteria, viruses, that fails to wind down once the switched on to direct this protein fungi and parasites. Immune enemy is vanquished. When the production. system success in the battle immune system targets harmless against these pathogens, like that particles, the result may be allergy of any fighting force, depends on or asthma; when the immune getting enough of the right troops system targets our own tissues, First Line of Defense the result is autoimmune disease. in the right place at the right time. The Innate Immune As befits these needs, immune cell soldiers are mobile. To reach The Battle Plan Response embattled tissue, they deploy As a group, immune cells are Those immune cells that are ready through the bloodstream or via often called white blood cells, to fight as soon as bacteria, fungi, their own system of canals, called although immunologists prefer the viruses or parasites infect us are lymphatic vessels. The leukocyte term leukocytes. A small number part of what is called the “innate” cells and organs of the immune of constantly dividing stem immune system. The innate system are small and spread cells in the bone marrow, called immune system often ends the throughout the body. But taken “hematopoietic” stem cells, threat without our ever becoming together, the components of the generates all blood cells, including aware of the danger, thanks to immune system are as massive as leukocytes. (This is why bone sentinel cells that patrol the outer the brain or liver. During infection, marrow transplants, or transplants borders of our body. Phagocytes the immune system gets even of the stem cells themselves, can — cell eaters — are concentrated bigger, and its soldier cells be used to reconstitute immune near the surfaces of nearly all expand their numbers with a systems.) tissues. One of their major tasks is speed unrivaled by other cells in Most immune cells mature in to gobble up invading microbes the adult organism. the bone marrow where they first that get through barriers along We might fail to appreciate arise. Each type has different these outer borders — the skin or the resources the body dedicates duties to perform and, depending the mucus-covered linings of the to the immune system if we upon the nature of the threat, a respiratory and gastrointestinal were not sometimes reminded by different battlefield scenario in tracts, for example. swollen tissue, aches, fever, which to act. It is clear that a func- Phagocytes known as fatigue and inflammation — the tioning immune system depends neutrophils, which patrol the blood byproducts of a vigorous immune on the orderly, coordinated stream, are the first to arrive. response and the evidence of a deployment of its various com- Other phagocyte troops geared struggle. ponents. But, surprisingly, there is toward rapid response are the To limit the resources spent on no apparent commander in chief. macrophages — “big eaters,” warfare — and our own aches and Instead, signals and status reports which are stationed in all tissues. pains — the cells of the immune from cells within the immune Macrophages increase their system work together, exchanging system help in the shape and numbers in response to invasion feedback and mustering just the execution of a battle plan. The and begin to hit the battlefield level of response needed to signals sent between leukocytes, en masse shortly after the counter only real threats. Once a as well as the character of the neutrophils. Natural killer cells, threat is eliminated, leukocyte cell immune response that unfolds as another component of the innate populations and immune tissues a result, depend largely on the immune system, knock off infected return to normal size. Failure to nature of the pathogen and the cells that harbor invading viruses. mount an adequate immune site of invasion. Within these Even more abundant are response to infection can be parameters, the mobilization and dendritic cells. Dendritic cells deadly, but so too can an immune demobilization of immune forces quickly ferry captured foreign response that is too vigorous, or normally unfold according to molecules to nearby lymph nodes, 14 (Italicized words are also defined in the glossary on page 20.) where other immune cells, particu- Signal transduction involves spe- moment. Among the cytokines, larly those known as lymphocytes, cialized proteins inside the cell that a special class called chemokine garrison themselves. The dendritic integrate incoming signals from guides soldier cells to their cells sound the alert, put the cell-surface receptors and transmit fighting destinations via chemo- enemy target on display and gene-switching orders to the attractant signals. rouse the garrisoned cells to the nucleus. Failures in signal trans- The innate immune response, challenge. duction have been implicated in with its engulf-and-destroy These brothers-in-arms are certain im m u n o d e fi ciency diseases, tactics, is a primitive but still called to the fray because in which the immune system is vital throwback. Although it leukocytes exchange information weakened, and also may play a quickly responds to pathogens and send orders to each other by role in some autoimmune disorde r s . that breach the borders, the secreting specialized chemical Different cytokines carry weaponry used by its forces is signals, called cytokines. The different messages, resulting in a generic — some is anti-viral, process of getting the message different mix of specially trained some is anti-bacterial, and from a cell-surface receptor to the immune-cell fighting forces. some works especially well on cell nucleus, where it can be acted This makes the forces well-suited parasitic worms. It is not tailored upon, is called signal transduction. to fighting the pathogen of the to particular enemy species. Two Kinds of Immune Response The immune response has two mechanisms. The innate response involves phagocytes (cell-eaters) and natural killer cells, which patrol the pathogen’s normal points of entry and gobble up invaders or cripple cells harboring viruses. The innate response is generic, immediate and often successful. Should the infectious agent get past this first line of defense, the adaptive immune response — which arises anywhere from three to seven days after the initial infection — sets in motion a different set of fighting forces with weaponry aimed at specific targets. One key feature of the adaptive immune response is that it remembers the enemy (see “All-Out War ,” page 17). MM E D I AT E 3 –7 DAYS Invading pathogens First line of defense Second line of defense Natural killer cells B cells An t i b o d i e s Ph a g o c y t e s T cells 15 Even after the pathogen is All-Out War The Adaptive Immune Response defeated, some specialized T cells, called memory Increasing the Ranks; Ma t u r e activated helper T cells, remain. Memory T Aiming at Specific Targets T cells can in turn activate cells can get the immune While our pre-human ancestors T cell proliferation their brothers-in-arms, response rolling much retained an innate immune system the B lymphocytes, or mo r e quickly and effectively during their evolutionary journey, If the T cell is presented with the pathogen marker B cells. B cells make free - if the same pathogen should they added additional layers of it can recognize by one of the immune system’s floating antibodies that ever be encountered again. defense along the way. In the antigen presenting cells, and if it receives additional target the same antigen in same way that the brain’s primitive “co-stimulatory” signals req u i r ed for activation, the blood stream or on the the T cell will expand its numbers. The resultant M e m o ry T cells cerebellum, sitting atop the brain surfaces of infected cells. T cells will mature into fighting forces capable of stem, is in communication with fulfilling many functions. the overlying, highly evolved Helper T cell cerebral cortex, the dendritic cells, phagocytes and natural killers of the innate immune system are in communication with cells from the more evolutionarily advanced branches of the immune system. These more evolved branches, T cell found in almost all vertebrates, are collectively known as the adaptive immune system. Antigen-presenting cell From the time sentinel cells of (Dendritic cell) the innate immune system first detect an infectious threat, full activation of the adaptive immune B cell response takes from three to Antibody production seven days. An adaptive response involves more fighting forces and weaponry aimed at specific targets. An extremely important aspect Macrophage stimulation of the adaptive immune system Cytokine is that it remembers the enemy. The immune response is When the war is over, a few characterized by feedback. p r o d u c t i o n veteran soldiers of the adaptive For instance, the macrophages immune system stick around. T cells release a variety of that help trigger T cell C y t o t o x i c Their presence ensures a faster activation by engulfing signaling molecules, such as T cells cytokines.

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