B and T Cells

Lymphocytes, which are white blood cells, are formed with other blood cells in the red bone marrow found in many flat bones, such as the shoulder or pelvic bones. The two types of lymphocytes of the adaptive immune response are B and T cells (Figure). Whether an immature lymphocyte becomes a B cell or T cell depends on where in the body it matures. The B cells remain in the bone marrow to mature (hence the name “B” for “bone marrow”), while T cells migrate to the thymus (located above the heart), where they mature (hence the name “T” for “thymus”).

Maturation of a B or T cell involves becoming immunocompetent, meaning that it can recognize, by binding, a specific molecule or antigen (discussed below). During the maturation process, B and T cells that bind too strongly to the body’s own cells are eliminated in order to minimize an immune response against the body’s own tissues. Those cells that react weakly to the body’s own cells, but have highly specific receptors on their cell surfaces that allow them to recognize a foreign molecule, or antigen, remain. This process occurs during fetal development and continues throughout life. The specificity of this receptor is determined by the genetics of the individual and is present before a foreign molecule is introduced to the body or encountered. Thus, it is genetics and not experience that initially provides a vast array of cells, each capable of binding to a different specific foreign molecule. Once they are immunocompetent, the T and B cells will migrate to the spleen and lymph nodes where they will remain until they are called on during an infection. B cells are involved in the humoral immune response (humor is the old term for body fluid), which targets pathogens loose in body fluids (blood and lymph), and T cells (Figure 23.6) are involved in the cell-mediated immune response, which targets infected cells and cancer cells.

Humoral (or Antibody)-Mediated Immune Response

As mentioned, an antigen is a molecule that stimulates a response in the immune system. Not every molecule is antigenic. B cells participate in a chemical response to antigens present in the body by producing specific antibodies that circulate throughout the body in the body fluids and bind with the antigen whenever it is encountered. This is known as the humoral immune response. As discussed, during maturation of B cells, many different highly specific B cells are produced that each recognize a different antigen with the receptor molecules in their membrane (Figure 23.7).

Each B cell has only one kind of antigen receptor, which makes every B cell different. Once the B cells mature in the bone marrow, they migrate to lymph nodes or other lymphatic organs. When a B cell encounters the antigen that binds to its receptor, the antigen molecule is brought into the cell by endocytosis and reappears on the surface of the cell bound to an MHC class II molecule. When this process is complete, the B cell is sensitized. In most cases, the sensitized B cell must then encounter a specific kind of T cell, called a helper T cell, before it is activated. The helper T cell must already have been activated through an encounter with the antigen (discussed below).

The helper T cell binds to the antigen-MHC class II complex and is stimulated to release cytokines that cause the B cell to divide rapidly, which makes thousands of identical (clonal) cells via mitosis. This process is called clonal expansion. These daughter cells become either plasma cells or memory B cells. The memory B cells remain inactive at this point until another later encounter with the antigen caused by a reinfection by the same bacteria or virus results in them dividing into a new population of plasma cells. The plasma cells, on the other hand, produce and secrete large quantities, up to 100 million molecules per hour, of antibody molecules. An antibody, also known as an immunoglobulin (Ig), is a protein that is produced by plasma cells after stimulation by an antigen. Antibodies are the agents of humoral immunity. Antibodies occur in the blood, in gastric and mucus secretions, and in breast milk. Antibodies in these bodily fluids can bind pathogens and mark them for destruction by phagocytes and make it easier for the phagocytes to ingest them (called opsonization) before they can infect cells. Antibodies can also neutralize the pathogen by blocking it from binding to our cells (called neutralization). And finally, antibodies can activate the complement system, which will get rid of the pathogen (see Figure 23.8).

Figure 23.8 Antibodies may inhibit infection by (a) preventing the antigen from binding its target, (b) tagging a pathogen for destruction by macrophages or neutrophils, or (c) activating the complement cascade. (credit: Openstax Human Biology)

The production of antibodies by plasma cells in response to an antigen is called active immunity and describes the host’s active response of the immune system to an infection or to a vaccination. In passive immunity, antibodies come from an outside source, instead of the individual’s own plasma cells, and are introduced into the host. For example, antibodies circulating in a pregnant woman’s body move across the placenta into the developing fetus. Mom’s antibodies are also passed to the baby after birth in the colostrum, the first milk. The child benefits from the presence of these antibodies for up to several months after birth. Another example of passive immunity is injecting antibodies into an individual in the form of an antivenom to a snake-bite toxin or antibodies in blood serum to help fight a hepatitis infection. This gives immediate protection since the body does not need the time required to mount its own response.

Cell-Mediated Immunity

Unlike B cells, T lymphocytes are unable to recognize pathogens without assistance. Instead, dendritic cells (a type of white blood cell found in the tissues) and macrophages first engulf and digest pathogens into hundreds or thousands of antigens. These two cell types are called antigen-presenting cells (APCs) because they then put the antigen fragments bound to MHC class II molecules on their surface and present the antigen to helper T cells (Figure 23.9). Helper T cells cannot properly respond to an antigen unless it is processed and embedded in an MHC class II molecule.

There are two main types of T cells: helper T lymphocytes (T_H) and the cytotoxic T lymphocytes (T_C). The T_H lymphocytes function indirectly and help activate B cells and cytotoxic T cells to go after the pathogen that they recognize (Figure 23.10).

Figure 23.10 A helper T cell becomes activated by binding to an antigen presented by an APC via the MHC II receptor, causing it to release cytokines. Depending on the cytokines released, this activates either the humoral or the cell-mediated immune response. (credit: Openstax Human Biology)

Cytotoxic T cells (T_C) are the key component of the cell-mediated part of the adaptive immune system and attack and destroy infected cells and cancer cells. T_C cells are particularly important in protecting against viral infections; this is because viruses replicate within cells where they are shielded from contact with circulating antibodies outside of the cells. Once activated, the T_C creates a large clone of cells with one specific set of cell-surface receptors, as in the case with clonal expansion of activated B cells. As with B cells, the clone includes active T_C cells and inactive memory T_C cells. The resulting active T_C cells then identify infected host cells and kill them. Because of the time required to generate a population of clonal T and B cells, there is a delay in the adaptive immune response compared to the innate immune response.

Plasma cells (activated B cells that produce antibodies) and T_C cells are collectively called effector cells because they are involved in “effecting” (bringing about) the immune response of killing pathogens and infected host cells.

Immunological Memory

The adaptive immune response has a memory component that allows for a rapid and large response upon re-invasion of the same pathogen. During the adaptive immune response to a pathogen that has not been encountered before, known as the primary immune response, plasma cells secreting antibodies and differentiated T cells increase, then plateau over time. As B and T cells mature into effector cells, a subset of the naïve populations differentiates into B and T memory cells with the same antigen specificities (Figure 23.11). A memory cell is an antigen-specific B or T lymphocyte that does not differentiate into an effector cell during the primary immune response, but that can immediately become an effector cell on re-exposure to the same pathogen. As the infection is cleared and pathogenic stimuli subside, the effectors are no longer needed and they die off. In contrast, the memory cells persist in the circulation.

If the pathogen is never encountered again during the individual’s lifetime, B and T memory cells will circulate for a few years or even several decades and will gradually die off, having never functioned as effector cells. However, if the host is re-exposed to the same pathogen type, circulating memory cells will immediately differentiate into plasma cells and T_C cells without input from APCs or T_H cells. This is known as the secondary immune response. One reason why the adaptive immune response is delayed is because it takes time for naïve B and T cells with the appropriate antigen specificities to be identified, activated, and proliferate. On reinfection, this step is skipped, and the result is a more rapid production of immune defenses. Memory B cells that differentiate into plasma cells output tens to hundreds-fold greater antibody amounts than were secreted during the primary response (Figure 3.12). This rapid and dramatic antibody response may stop the infection before it can even become established, and the individual may not realize they had been exposed.

Vaccination is based on the knowledge that exposure to noninfectious antigens, derived from known pathogens, generates a mild primary immune response. The immune response to vaccination may not be perceived by the host as illness but still confers immune memory. When exposed to the corresponding pathogen to which an individual was vaccinated, the reaction is similar to a secondary exposure. Because each re-infection generates more memory cells and increased resistance to the pathogen, some vaccine courses involve one or more booster vaccinations to mimic repeat exposures.

Section Summary

The adaptive immune response is a slower-acting, longer-lasting, and more specific response than the innate response. However, the adaptive response requires information from the innate immune system to function. APCs display antigens on MHC molecules to naïve helper T cells. In response, the helper T cells activate the B cells and cytotoxic T cells that recognize that pathogen. B cells differentiate into plasma cells that secrete antibodies, whereas T_C cells destroy infected or cancerous cells. Memory cells are produced by activated and proliferating B and T cells and persist after a primary exposure to a pathogen. If re-exposure occurs, memory cells differentiate into effector cells without input from the innate immune system.

23.4 The Lymphatic System

The immune system is closely tied to the lymphatic system because white blood cells are made in the bone marrow of the lymphatic system and travel through lymphatic vessels and hang out in lymph nodes and other lymphoid organs. The lymphatic system is made up of lymphatic vessels, lymph nodes, and organs, such as tonsils, adenoids, thymus, and spleen. Lymph is the watery fluid that bathes tissues and organs and travels through the lymphatic vessels. It contains protective white blood cells but does not contain red blood cells.

Recall that cells of the immune system originate from stem cells in the bone marrow. B cell maturation occurs in the bone marrow, whereas T cells mature in the thymus.

On maturation, T and B lymphocytes circulate to various destinations through the blood vessels and lymphatic vessels. Lymph nodes scattered throughout the body house large populations of T and B cells, dendritic cells, and macrophages (Figure 23.13). As lymph drains from tissues, it also carries any antigens from pathogens with it. These antigens then are filtered through lymph nodes before the lymph is returned to circulation. APCs in the lymph nodes capture and process antigens and inform nearby helper T lymphocytes about potential pathogens.

The spleen also houses B and T cells along, macrophages, dendritic cells, and NK cells (Figure 23.14). The spleen filters the blood, and these white blood cells look for pathogens in the blood and respond if they find any.

This section is about how the immune system goes wrong. When it goes haywire and becomes too weak or too strong, it leads to a state of disease. The factors that maintain immunological homeostasis are complex and incompletely understood.

Overactive Immune Responses

The immune system can also cause problems by overreacting and responding to the wrong things or by reacting too strongly. We will look at two examples of this: allergies and autoimmune diseases.

Allergies

In allergies, the immune system reacts to substances that are not pathogens and are not harmful to us. Antigens that cause allergic responses are often referred to as allergens. Examples of allergens include pollen, grasses, foods, insect stings, latex, and medications (ex- penicillin). Exposure to the allergen causes certain white blood cells to release the chemical, histamine. Histamine causes the symptoms of allergies. Symptoms of an allergic response include hay fever, asthma, eczema, hives, GI upset, and in severe cases, anaphylactic shock, which can be fatal if not treated. Anaphylactic shock can kill a person because the blood pressure drops (shock) and the airways constrict, making it difficult to breathe. Epinephrine is given to treat anaphylactic shock because it raises blood pressure and opens the airways. Patients with known severe allergies are encouraged to keep automatic epinephrine injectors with them at all times, especially when away from easy access to hospitals.

Allergists use skin testing to identify allergens. In skin testing, allergen extracts are injected into the epidermis, and a positive result of a soft, pale swelling at the site surrounded by a red zone (called the wheal and flare response), caused by the release of histamine, usually occurs within 30 minutes.

Autoimmune Diseases

In people with an autoimmune disease, the immune system overreacts and attacks their own bodies, causing significant damage. The trigger for these diseases is, more often than not, unknown, and the treatments are usually based on resolving the symptoms using immunosuppressive and anti-inflammatory drugs such as steroids. These diseases can be localized and crippling, as in rheumatoid arthritis, or diffuse in the body with multiple symptoms that differ in different individuals, as is the case with systemic lupus erythematosus (Figure 23.16).

Figure 23.16 Autoimmune Disorders: Rheumatoid Arthritis and Lupus (a) Extensive damage to the right hand of a rheumatoid arthritis sufferer is shown in the x-ray. (b) The diagram shows a variety of possible symptoms of systemic lupus erythematosus.