24.3: Humoral Immune Responses

The humoral immune response, also known as the antibody-mediated immune response, targets pathogens circulating in “humors,” or extracellular fluids, such as blood and lymph. Antibodies target invading pathogens for destruction via multiple defense mechanisms, including neutralization, opsonization, and activation of the complement system. Patients that are impaired in the production of antibodies suffer from severe and frequent infections by common pathogens and unusual pathogens.

B Cells Are Produced by the Bone Marrow and Circulate through Body Fluids

B lymphocytes, also called B cells, detect pathogens in the blood or lymph system. Although B cells originate in the bone marrow, their name is derived from a specialized organ in birds in which B cells were first discovered, the bursa of Fabricius. After release from the bone marrow, B cells mature in secondary lymphoid tissues, such as the spleen, lymph nodes, tonsils and mucosa-associated lymphoid tissue throughout the body.

B Cells Differentiate into Antibody Releasing Plasma Cells and Memory B Cells

B cells bind to specific parts of a pathogen, called antigens, via their B cell receptors. In addition to antigen binding, B cells require a second signal for activation. This signal can be provided by helper T cells or, in some cases, by the antigen itself. When both stimuli are present, B cells form germinal centers, where they proliferate into plasma cells and memory B cells. All cells that are derived from a common ancestral B cell (monoclonal) respond to the same antigen. Each plasma cell secretes genetically identical antibodies that circulate in the bloodstream. Memory B cells produce antibodies that are bound to the cell’s surface and are highly specific against the antigen that initially led to the production of the memory B cell. Memory B cells are long-lived and enable the organism to react much faster and stronger upon secondary exposure to the same pathogen.

Antibodies Kill Pathogens in Diverse Ways

Antibodies bind to antigens that they encounter in body fluids. The resulting antibody-antigen complex activates three major defense mechanisms: neutralization, opsonization and the complement system.

Neutralization: Antibodies “neutralize” a pathogen by interfering with its ability to infect host cells. For example, when an antibody binds to the surface of a virus, it may impair the ability of the virus to attach to or gain entry into target cells, effectively inhibiting the infection.

Opsonization: Antibodies function as opsonins, which “tag” pathogens for destruction. Specifically, the formation of the antigen-antibody complex attracts and stimulates phagocytic cells that engulf and destroy the pathogen.

Complement: Antibodies can activate the complement system, which plays a role in both innate and adaptive immunity. The complement system is a sequential cascade of more than 30 proteins. With the help of antibodies, these proteins opsonize pathogens for destruction by macrophages and neutrophils, induce an inflammatory response with the recruitment of additional immune cells, and promote lysis (destruction) of the pathogen.

Disruption of the Humoral Immune System Is Life-Threatening

Humans suffering from humoral immune system disorders are often identified early in life, when the number of antibodies that the infant received from its mother (i.e., passive immunity) decreases. Given the complexity of the humoral immune system, the causes for its malfunction are manifold. However, nearly 80% of patients with a primary immunodeficiency disease involve an antibody disorder. For example, hypogammaglobulinemia is the deficiency, or low number, of all classes of antibodies. Patients have more frequent ear, sinus, and pulmonary infections and suffer from gastrointestinal problems, such as diarrhea, malabsorption, and symptoms of irritable bowel syndrome. In general, the frequency and severity of patient infections increase with age. Infections by unusual pathogens tend to be severe, and infections by common pathogens are often both serious and recurrent.

In the other adaptive immune response, humoral immunity, the immune system targets pathogens circulating in extracellular fluids including blood and lymph.

Invading pathogens such as bacteria are detected by specific white blood cells called B cells which recognize specific antigens on bacterial surfaces.

Once B cells are activated they proliferate and differentiate into plasma cells which secrete millions of antibodies that circulate throughout the body and activate several defense mechanisms.

In one method, antibodies that bind antigens on the surface of a pathogen can inactivate or neutralize it by interfering with its ability to infect the host cell.

They can also opsonize or tag pathogens for engulfment and destruction by phagocytes such as macrophages or neutrophils.

Finally, antibodies can activate the complement system, a complex of proteins that further enhances the opsonization and destruction of pathogens.

Even with the pathogens destroyed some activated B cells differentiate into Memory B cells instead of plasma cells. These Memory B cells continue to produce small amounts of antibody long after an infection has cleared. If the same pathogen reenters the body these circulating antibodies can target it for immediate destruction.