Introduction
Humoral immunity, also referred to as the antibody-mediated system, is a form of immunity that depends on macromolecules discovered in extracellular fluids. It differs from cell-mediated immunity and includes secreted antibodies, complement proteins, and specific antimicrobial peptides. The term “humoral” is utilized because it describes substances existing in body fluids, which are also known as humours.
The study of immunology encompasses the examination of the immune system’s molecular and cellular constituents, along with their functionalities and interactions. In vertebrates, there exist two key systems: the innate immune system, which is less complex, and the acquired or adaptive immune system. Both of these systems incorporate components that contribute to humoral (pertaining to bodily fluids) and cellular mechanisms.
Humoral immunity encompasses various processes that occur alongside antibody production. These processes include Th2 activation and cytokine production, germinal center formation and isotype switching, affinity maturation, and the generation of memory cells. Additionally, humoral immunity involves the effector functions of antibodies such as neutralizing pathogens and toxins, activating classical complement, and promoting phagocytosis and elimination of pathogens.
History
The theory of humoral immunity emerged from studying the antibacterial properties of serum components. Hans Buchner is recognized for his establishment of the humoral theory. In 1890, he introduced the term “alexins” to describe these “protective substances” found in bodily fluids, including serum, which could effectively eliminate microorganisms. Later on, Paul Ehrlich redefined alexins as “complement” and revealed their role as soluble components in the innate immune response. Complement, therefore, serves as a link between cellular and humoral immunity, encompassing features from both innate and acquired immunity.
Following the 1888 discovery of diphtheria and tetanus, Emil von Behring and Kitasato Shibasaburō demonstrated that disease can be caused by substances other than microorganisms themselves. They found that filtrates without cells were enough to induce illness. In 1890, they used filtrates from diphtheria (later known as diphtheria toxins) to immunize animals. Their goal was to prove that immunized serum contained an antitoxin capable of neutralizing the toxin’s effects and transferring immunity to non-immune animals.
Paul Ehrlich demonstrated in 1897 that antibodies are produced as a response to the toxins ricin and abrin from plants. He hypothesized that these antibodies confer immunity. Working with Emil von Behring, Ehrlich further advanced immunotherapy by creating the diphtheria antitoxin, marking a significant breakthrough. The detection and specificity of compatibility antibodies became crucial in measuring immunity levels and detecting prior infections.
Complement system
The complement system is a biochemical cascade of the innate immune system that aids in removing pathogens from an organism. It is composed of numerous small plasma proteins that collaborate to disrupt the plasma membrane of the target cell, ultimately resulting in cell cytolysis. In total, the complement system is comprised of over 35 soluble and cell-bound proteins, with 12 being directly engaged in the complement pathways.
The complement system plays a role in both innate immunity and acquired immunity, as it is responsible for several functions. These include cytolysis, chemotaxis, opsonization, immune clearance, inflammation, and marking pathogens for phagocytosis.
Around 5% of the proteins found in the serum globulin fraction are zymogens, needing proteolytic cleavage for activation. The complement system can be activated through three biochemical pathways: classical, alternate, and mannose-binding lectin. Activation of the classical pathway is antibody-dependent and a targeted immune response. On the other hand, activation of the alternate pathway is antibody-independent and considered a non-specific immune response. Furthermore, antibodies belonging to the IgG1 class are capable of “fixing” complement.
Antibody
Immunoglobulins, also known as antibodies, are a type of glycoproteins that belong to the immunoglobulin superfamily. The terms “antibody” and “immunoglobulin” are often used interchangeably. These glycoproteins can be found in the blood, tissue fluids, and various secretions. In terms of their structure, they are large proteins with a Y-shaped globular shape. Among mammals, there exist five distinct types of antibodies: IgA, IgD, IgE, IgG, and IgM. Each type of immunoglobulin has unique biological characteristics and is specialized in combatting different antigens.
Plasma cells, derived from B cells in the immune system, release antibodies. These antibodies are used by the acquired immune system to identify and fight foreign substances such as bacteria and viruses. Each antibody can recognize a specific antigen for its target. When they bind with their corresponding antigens, antibodies cause agglutination and precipitation of antibody-antigen compounds. This aids phagocytosis by macrophages and other cells, blocks viral receptors, and triggers additional immune responses like the complement pathway.
An incompatible blood transfusion can cause a transfusion reaction, which is mediated by the humoral immune response. This reaction, called an acute hemolytic reaction, leads to the rapid destruction (hemolysis) of donor red blood cells by antibodies from the recipient. Usually, this happens due to a mistake in paperwork, specifically when the wrong unit of blood is given to the wrong patient. Symptoms of this reaction include fever and chills, sometimes accompanied by back pain and pink or red urine (hemoglobinuria). The main complication linked with this condition is the potential development of acute renal failure because of hemoglobin released during the destruction of red blood cells.
B cell
The main role of B cells is to produce antibodies against soluble antigens. However, B cell activation, which involves clonal proliferation and differentiation into plasma cells, requires more than just recognition of antigens. Naïve B cells can be activated either by T-cell dependence or independently, but in both cases, two signals are needed to initiate activation.
B cell activation relies on three mechanisms for activation: Type 1 T cell-independent activation, Type 2 T cell-independent activation, and T cell-dependent activation. In Type 1 T cell-independent activation, polyclonal activation occurs. In Type 2 T cell-independent activation, mature B cells respond to repetitive structures, which leads to cross-linking of the B cell receptors on the surface of B cells. In T cell-dependent activation, an antigen presenting cell (APC) presents a processed antigen to a helper T (Th) cell, leading to its priming. Afterwards, when a B cell presents the same antigen to the primed Th cell, the released cytokines from the T cell activate the B cell.
Cell-mediated immunity is an immune response that does not rely on antibodies. It activates phagocytes, cytotoxic T-lymphocytes specific to the antigen, and releases cytokines upon encountering an antigen. Initially, the immune system was categorized into humoral immunity, which found protective functions in bodily fluids or serum, and cellular immunity, which linked immunization’s protection with cells. CD4 cells or helper T cells offer defense against different pathogens. In cell-mediated immunity, cytotoxic T cells can induce apoptosis without depending on cytokines; thus their presence may not always be required.
The body is protected by cellular immunity.
- activating antigen-specific cytotoxic T-lymphocytes that are able to induce apoptosis in body cells displaying epitopes of foreign antigen on their surface, such as virus-infected cells, cells with intracellular bacteria, and cancer cells displaying tumor antigens;
- activating macrophages and natural killer cells, enabling them to destroy pathogens;
- stimulating cells to secrete a variety of cytokines that influence the function of other cells involved in adaptive immune responses and innate immune responses.
The main focus of cell-mediated immunity is on microbes that stay within phagocytes and those that invade non-phagocytic cells. Its primary purpose is to remove virus-infected cells and offer protection against fungi, protozoans, cancers, intracellular bacteria, and rejection of transplants.
