Non-Specific Effector Cells The most famous immune cell is certainly the macrophage; known to many by the simple moniker, "white cell." This cell type and a number of closely related monocytic and granulocytic cells act in two ways. First,they are major killers of invaders. This is accomplished both by the phagocytosis of microorganisms, and the release of high concentrations of chemicals (like NO) which are able to destroy adjacent cells. While these activities seems rather crude compared to the acquired immune system, it is probably the most important antimicrobial activity of any immune cell. The second role of such cells is that of chemical factories. In addition to being critical in the destruction of dangerous organisms and cancerous tissues, these cells are key facilitators of communication between immune elements. They are responsible for a host of chemicals important in the proper communication between immune cells. Not all non-specific effector cells are related to macrophages. The null lymphocytic cell, or Natural Killer (NK) cell is one such cell. As its name suggests, it is derived from a lymphocytic lineage. However, it lacks some of the surface molecules necessary for specific recognition of antigens, and is therefor considered part of the innate immune system. Like monocytic and granulocytic cells, the NK cell produces chemicals involved in the activation and regulation of other immune tissues. In addition,these cells are involved in the destruction of invaders and tumor cells. They appear to use a chemical arsenal composed of complement-like molecules which punch holes in undesired cells. Acquired Immunity Acquired immunity has only begun to be understood in the past few decades. Though the specificity of the acquired immune system makes it the focus of more research than its innate counterpart, it must be remembered that these two arms of the immune system are interrelated and dependent upon one another for proper function. The two features which define the acquired immune system are its specificity and its memory. It is able to distinguish foreign cells from self, and can distinguish one foreign antigen from another. While a macrophage will engulf any foreign (and many self) cells, acquired immune cells have mechanisms for selecting a precisely defined target. It is for this reason that the acquired immune system is also often called the specific immune system (and the innate the non-specific). The second feature of the specific immune system, memory, is what allows immunization and resistance to reinfection with the same microorganism. Once acquired immune cells have encountered particular organism, they are able to persist and convey resistance to that organism for an extended period of time. For this reason, if the acquired immune system has fought off an infection once, it will rapidly be able to do so again since it will"remember" the organism. The cells which are responsible for these remarkable traits are lymphocytes, of which there are two sub-populations: B and T cells. B cells are responsible for the rapid response to extracellular and mucosal microorganisms (including viruses and parasites if they spend part of their life cycle in extracellular fluid), against which they produce soluble factors known as antibodies, orimmunoglobulins. T cells serve two roles. The first is as the coordinator of other acquired immune responses, a task accomplished by their production of a wide variety of cytokines and surface cell signals. The second is as the primary responder to long term intracellular infections. T Cells T cells are responsible for destroying infected or cancerous cells, and for coordinating all acquired immune responses. For this reason T cell immunity is generally called cellular immunity. There are two sub-types of T cell which are responsible for these functions, the Killer or Cytotoxic T cell (CTL cell) and the Helper T cell (Th cell) respectively. Each CTL (cytotoxic T lymphocyte) has a unique surface molecule much like an immunoglobulin, called a T cell receptor (TCR). However, where Ig's can recognize any type of molecule, the TCR is restricted to only being able to recognize shortamino acid chains which are displayed on the surface of cells in conjunction with a molecule known as the Major Histocompatibility Complex molecule (MHC). Almost all the cells in one's body are constantly producing MHC and attaching small internal proteins to it for expression on their surface. CTLs probe the surface of cells for MHC-small protein complexes.In most cases, as with B cells, the CTL never finds a complex which its unique TCR recognizes. However, in the event that it does, it grows and divides into mature CTLs and memory CTLs. The mature CTLs move though the body The Helper T cell is probably the most important immune cell, despite the fact that by definition it does not directly destroy any diseased cells or microorganisms. Rather, it produces a plethora of chemical factors, and expresses many surface elements,thereby regulating all other aspects of the immune system. It too acts by recognizing MHC-small protein complexes with its TCR. However, it recognizes a special type of MHC (MHC class II) which is only found on certain other immune cells(APCs). These cells, whether they be B cells or macrophages, or some other lineage, consume foreign proteins (specifically or randomly), and present small portions of them in conjunction with this special MHC. If the complex they present is recognizedby an Helper T cell, that cell will produce chemicals which effect the cell which presented the MHC complex, as well as otherimmune cells. The Helper T cell will go on to divide and mature, producing more chemicals to activate other cells, and memorycells which function as with CTLs and B cells. No acquired immune response could take place without the chemicals that a Helper T cell produces, and their absence, as in the case of individuals with AIDS, results in a collapse of the immune system. B Cells B cells are the generators of humoral immunity, so called because its product consists of soluble proteins found in the "humors," (blood,etc.). Every B cell has an immunoglobulin molecule on its surface, and due to genetic events, each of those immunoglobulins recognizes a unique three-dimensional epitope. In the bone marrow, millions of different B cells are created, and proceed to circulate throughout the body. Since each one has a different immunoglobulin, each will bind to a different substrate. It is most often the case that a B cell will find nothing to bind to in its short lifespan, and rapidly be replaced by a new B cell. In the event that a B cell's immunoglobulin does find a substrate, the B cell will clonally expand, resulting in many B cells which recognize the same target. Over time, the clones' immunoglobulin genes will mutate to improve the affinity for the target even more. The B cell will also differentiate into two other cell types, plasma cells, and memory cells. The plasma cells will proceed to secrete vast quantities of immunoglobulin which will be identical to that found on their surface. These immunoglobulins (or Ig's) will pass throughout the blood and attach to the foreign object, either disabling it themselves or summoning a non-specific effector cell. Memory cells by contrast are much smaller than plasma cells and don't immediately secrete anything. Instead they persist in the body for long periods, perhaps never becoming activated. However, in the event that the same foreign organism returns, they will develop into plasma cells much more rapidly than the original B cells and proceed to secrete their Ig.searching for cells possessing complexes to which the TCR will bind and proceeding to destroy those cells. Memory CTLs function as do memory B cells, they persist and will multiply and mature if they are re-exposed to the same MHC-small protein complex. Innate/Acquired Interphase As the Helper T cell illustrates, no matter how important any single arm of the immune system may be, none is effective if it is unable to communicate with the whole. It is the synergy of the combined immune system, not the potency of any one element, which makes it so capable a defender. This fact has lead to the study of the various ways in which the immune system interacts with itself and its environment. Although an enormous amount of work remains in this area, we already have learned a great deal. First, it appears that a number of chemicals produced by damaged cells - and destroyed microorganisms - known as heat shock proteins, are responsible for activating the immune system. This fact has been crucial to the development of the theory of the immune system as being able to respond to "danger" as well as "foreign." Heat shock proteins appear to activate both innateand specific cells resulting in increased activity in an area of infection. Second, cytokines produced by non-specific cells clearly affect the activities of the acquired immune system and vice versa.The cytokine environment is very important in determining what kind of response is made, and its effectiveness. Many parasitic diseases owe their success to their ability to induce the production of cytokines which lead to a response which is not harmful to the parasite. It also seems that the initial cells to respond to an infection determine the future course of the response. Natural Killer cells may respond to an infection by producing one cytokine while macrophages would produce another. The knowledgethat the initial site of infection is critical has lead to the development of more effective vaccine adjuvants and inoculationmethods. Third, the acquired immune system appears to be able to impart a degree of specificity upon its innate brethren through the useof a specific surface receptor for immunoglobulins. This receptor enables macrophages and NK cells to use Ig's secreted by B cells to recognize specific foreign factors. The "network" theory of immune regulation postulates an even larger role forimmunoglobulins - suggesting that antibodies to antibodies (etc.) are responsible for the activation and suppression of certainresponses. In short, while it is convenient for descriptive purposes to break the immune system into innate and acquired branches, which themselves can be further sub-divided, this is a somewhat artificial division. Both branches influence each other greatly, and are in turn shaped by their environment.