Innate And Adaptive Immunity

Without an immune system we would quickly fall prey to the plethora of viruses, bacteria, and parasites that live within and around us. The immune system is a multi-layered defense system. In its broadest sense, it includes physical barriers, such as the skin and the lining of the gastrointestinal tract; chemical barriers, such as stomach acid; microbial barriers, such as beneficial intestinal microflora; and the immune system proper (immune cells, antibodies, and so forth). This chapter focuses on the immune system proper.

The cells of the immune system are called white blood cells (leukocytes) that, like red blood cells (erythrocytes), are derived from stem cells in the bone marrow. The production of the different types of cells from the bone marrow is shown in Figure 11.1 (adapted from reference 1). Other cells important in the immune response but not shown in the figure (e.g., natural killer cells and dendritic cells) are discussed below.

As Figure 11.1 shows, leukocytes can be classified into two categories: those that derive from myeloid stem cells (macrophages and granulocytes) and those from lymphoid stem cells (the lymphocytes). Macrophages and granulocytes are involved with innate immunity, and lymphocytes are involved with adaptive immunity. Innate immunity provides the first line of defense against newly encountered pathogens.a It limits the initial progression of the pathogens and activates the adaptive immune system. Unlike the innate system, the adaptive system has the ability to remember previous pathogens and thereby mount a fast attack if the pathogen is encountered more than once.

The two systems function together to keep out foreign organisms, which are recognized as such by their foreign proteins or their lack of "self-proteins." In a simple analogy, the two systems can be likened to the security system at an international airport. A small group of se-

a The immune system protects against four classes of pathogens: extracellular bacteria, parasites, and fungi; intracellular bacteria and parasites; intracellular viruses; and extracellular parasitic worms.

Figure 11.1 Origins of Blood Cells

Figure 11.1 Origins of Blood Cells

red platelets monocyte eosinophil basophil neutrophil B cell blood cell

T cell red platelets monocyte eosinophil basophil neutrophil B cell blood cell

T cell

CTC = cytotoxic T cells Th = helper T cells macrophage mast cell plasma activated cell T cells (Th1, TH2, ctc)

macrophage mast cell plasma activated cell T cells (Th1, TH2, ctc)

CTC = cytotoxic T cells Th = helper T cells




gregate formed by the MHC and antigen then rests at the surface of the innate immune cell, waiting for a cell from the adaptive system to come sample it. Cells of the adaptive system could not recognize the antigen as foreign if it were not presented to them in an MHC-antigen aggregate.

As the analogy illustrates, cells of the innate immune system handle the initial response to a pathogen. They attempt to clear the pathogen from the body, and if they are successful, the immune response ends. If unsuccessful and the amount of antigen reaches a threshold concentration, the adaptive immune system is stimulated. The cells of the adaptive immune system then help those of the innate system to destroy the pathogen. Furthermore, some of the B cells of the adaptive system form memory B cells that remember the specific antigen if it is encountered again. Other B cells differentiate to form plasma cells, which produce antibodies specific to the new foreign antigens. On reinfection with the same pathogen, the memory B cells quickly produce antibodies and engage the adaptive immune system.

curity guards—the cells of the innate system—are on guard at the security checkpoint to screen all incoming passengers, looking for "undesirable foreign elements." These guards have a rather nonspecific way of identifying suspects. Possibly they look for an absence of ordinary characteristics (a lack of self-proteins), or they look for generalized suspicious characteristics. If they spot suspects, they obtain their ID and call nearby guards— also cells of the innate system—for assistance. If there is trouble these guards can't handle, they call the state police—the adaptive immune system—who might take some time to arrive. Once they do, the guards present the suspect's IDs and the police take the suspects into custody. Importantly, the police also remember the suspect's IDs so that next time they come through the airport they can quickly be recognized.

The method that cells of the innate immune system use to "obtain" the IDs of foreign organisms and "present" them to the cells of the adaptive system is fascinating. Cells of the innate system ingest the foreign pathogens and, after digesting them a bit, "burp up" their protein fragments (called antigens) in a carrier molecule, called the major histocompatibility complex (MHC). The ag

The different cell types of the innate and adaptive immune system are listed in Table 11.1, along with a description of what activates them, what their function is, and what cells assist them (accessory cells). Two cell types, natural killer (NK) cells and dendritic cells, not shown in Figure 11.1, are also listed. NK cells are a type of specialized lymphocyte that destroy foreign cells. The main function of dendritic cells is to present antigens to T cells. Each of these cell types are described later in this chapter.

In Table 11.1, T cells are categorized by their CD (cluster of differentiation) number. TH1 and TH2 cells are CD4 cells, and cytotoxic T cells are CD8 cells. The CD number is simply a way to identify cells by their prominent surface proteins. Recall from Chapter 9 that the CD44 protein is a cell adhesion molecule that binds to components of the extracellular matrix. Similarly, both CD4 and CD8 are proteins that assist T cells in the final phase of docking with antigen-presenting cells. The first phase is accomplished by ICAMs, which are surface proteins that allow cells to stick together (see Chapter 6).

The primary molecule that allows a CD4 or a CD8 T cell to dock with antigen-presenting cells is called the T-




Activated by

Activated function


general microbial constituents (but not antigens)

Eat (phagocytose) pathogens and tumor cells. Macrophages are the primary phagocytic cells of tissues outside the blood vessels; their name literally means "big eaters." They also present antigens from the pathogens they ingest to T cells.

Natural killer (NK) cells

uncertain, but may recognize a lack of MHC molecules on the surface of foreign cells

Release compounds that destroy some virus-infected cells; they can also kill tumor cells.



Activated function

Neutrophils, eosinophils, basophils, and mast cells

Granulocytes are so named because of their densely staining intracellular granules. Neutrophils phagocytose pathogens and are the primary phagocytic cells of the blood. Eosinophils destroy antibody-coated parasites. Basophils release granules containing histamine and other inflammatory agents (see Chapter 8); those that reside in tissues are called mast cells. Granulocytes do not play as large a role in destroying cancer cells as macrophages and NK cells.




Activated by

Activated Function

CD4 T Cells

Th1 cells: (helper T cells): a T lymphocyte that expresses the CD4 surface protein

antigen-MHC class II aggregate on infected macrophage

Activate macrophages to kill bacteria that lie within them. Release cytokines that attract macrophages.

Th2 cells (helper T cells): a T lymphocyte that expresses the CD4 surface protein

antigen-MHC class II aggregate on B cells

stimulate B cells to produce antibodies

CD8 T Cells

cytotoxic T cells: a T lymphocyte that expresses the CD8 surface protein

antigen-MHC class I aggregate on infected cell

destroy infected cells

B Cells

B lymphocytes

contact with antigen

present antigens to T cells and produce antibodies

Accessory Cells


Activated By

Activated Function

Antigen-presenting cells (APCs)

dendritic cells, macrophages, and B cells

contact with antigen or by viral infection

Present antigens to T cells. Dendritic cells are the most important of the three types of antigen-presenting cells.

cell receptor. The T-cell receptor actually docks directly to the antigen-MHC aggregate, and in this way the antigen is presented to the T cell. CD4 and D8 proteins are called co-receptor molecules, since they assist the T-cell receptor molecule to dock.

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