Perspective on Immunity and Immunology
F. How Are Adaptive and Innate Immunity Related?
The innate immune response is crucial to the immunity of the host organism because it takes effect immediately and provides an early defense until the activated lymphocytes of the adaptive immune response can play their role. The usefulness of the innate system is not, however, limited to “playing for time” to allow the adaptive immune response to gear up. In many cases, an infection is completely controlled by innate mechanisms before adaptive immunity is even triggered. Furthermore, molecules essential for the induction of the adaptive response, such as messenger molecules called cytokines (see Ch.2), are synthesized by cells of the innate system.
In fact, one can think of the adaptive response as being a more sophisticated (and more recently evolved) extension of the innate system, in that the complex recognition and memory cascades of the adaptive system trigger many of the same effector cells employed by the innate system to remove pathogens. Cells of the innate system recognize certain conserved antigens on a wide variety of pathogens and work to lyse these invaders, but can do so only in limited numbers and in limited ways. The evolution of the adaptive response has meant that the recognition of a pathogen can trigger the specific proliferation of lymphocytes directed against that particular pathogen.
These activated lymphocytes not only undergo differentiation into effector lymphocytes capable of destroying the pathogen, but also secrete products that activate large numbers of innate response cells. To illustrate the overall need for an adaptive immune system, consider that humans lacking normal lymphocyte function are left defenseless against opportunistic infections and are very ill indeed, as in cases of severe combined immunodeficiency disease (SCID; no normal B or T cell functions) and acquired immunodeficiency syndrome (AIDS; the HIV virus destroys T cells) (see Ch.25).
G. Leukocytes: Cellular Mediators of Immunity
Those cells mediating the innate and adaptive responses are collectively called leukocytes (“leuko,” white; “cyte,” small body, i.e., a cell), or white blood cells, as they can be found in the blood, but are distinct from red blood cells. However, “blood cell” is a bit of a misnomer, since a majority of leukocytes reside in tissues and specialized organs, and move around the body through both the blood circulation and a system of vessels called the lymphatic system (see later). A key type of leukocyte important in the innate immune response is the neutrophil (Fig. 1-4).
Figure 1-4 | Some Important Cells of the Immune System
Neutrophils use phagocytosis to non-specifically engulf and destroy bacteria and other pathogens. Another type of leukocyte is the macrophage. These cells are also powerful phagocytes, engulfing not only pathogens but also dead host cells, cellular debris and macromolecules.
Macrophages also secrete a vast array of proteases, cytokines, and growth factors, including many molecules crucial for the activation of cells in the adaptive immune response. Indeed, after phagocytosing foreign material, macrophages play a key role in presenting this material so that it can be recognized by cells of the adaptive immune response. In this way, macrophages can be said to be cells “bridging” the innate and adaptive responses.
Dendritic cells are leukocytes that also engulf foreign material and play a key role in activating the adaptive immune response. B and T lymphocytes are the leukocytes responsible for adaptive immune responses.
The adaptive response was originally named the “specific response” because each B or T cell bears on its cell surface thousands of copies of a single type of specialized receptor that recognizes only one antigen (or occasionally a few very closely related antigens). The antigen receptors on the surface of a B cell are called B cell receptors (BCR), whereas those on the T cell surface are called T cell receptors (TCR).
In each case, the antigen receptor is a complex of several proteins. Some of these proteins interact directly and specifically with antigen, and others allow the binding of the antigen to send activation signals into the lymphocyte. The engagement of lymphocyte antigen receptors by molecules of specific antigen is critical for triggering the activation of the lymphocyte and the generation of a particular effector response that eliminates the antigen.
H. Where Do Immune Responses Occur?
Innate immune responses occur all over the body, primarily at its outer surfaces and on its mucous membrane interfaces, the places where microbes attempt to enter the body. Wherever infection or injury to a tissue occurs, an inflammatory response is mounted. An inflammatory response is an influx into the site of attack or injury of innate response leukocytes which fight infections using broadly specific recognition mechanisms (see Ch.4).
Those foreign entities evading these innate measures will be handled by different components of the adaptive response, depending on the chemical nature or route of entry of the incoming threat. The vertebrate immune system includes specialized tissues and organs collectively called the lymphoid tissues (Fig. 1-5).
Figure 1-5 | Principal Organs and Tissues of the Immune System
Primary lymphoid organs are shown in blue (bone marrow and thymus). Although only a femur is shown here, other bones in the body also contain bone marrow. Secondary lymphoid tissues are shown in gray (spleen, lymph nodes, and tonsils). Not all lymph nodes or tonsils are shown. Locations where pathogens commonly enter the body and where diffuse collections of lymphoid cells are present are noted in italics.
The cells of both the innate and adaptive immune responses are generated in the primary lymphoid tissues. In mammals, these are the bone marrow and the thymus. The secondary lymphoid tissues include the tonsils, lymph nodes, and spleen, and are the sites where leukocytes commonly encounter foreign entities and in which a vast majority of adaptive immune responses occur. The secondary lymphoid tissues also contain the accessory cells, which assist lymphocytes during an immune response.
The function of the accessory cells is to collect and trap antigens and to display them for recognition by lymphocytes. Host defense mediated by the secondary lymphoid tissues starts with the diffuse collections of lymphocytes that are located in common areas of antigen penetration, normally under the skin and adjacent to the mucous membranes lining the respiratory and gastrointestinal tracts.
Antigens that are not eliminated here may penetrate further into the tissues and enter the lymphatic system, a system of vessels that drains excess fluid from the tissues and in so doing, conveys antigens to the lymph nodes. The lymph nodes are organized cellular structures filled with T and B lymphocytes and are the most important sites of adaptive immune response action. The spleen is another organ composed to a large extent of lymphocytes. It functions in the elimination of antigens that have gained access to the blood circulation either by direct introduction (such as by an insect bite) or by “spillover” into the blood (such as in a case of overwhelming systemic infection).