Antibodies And Their Role In the Immune Response
The immune response consists of two complementary systems, the humoral and cellular immune systems. The humoral immune system is focused on bacterial infections and extracellular viruses (those found in body fluids), but can also respond to individual foreign proteins. At the heart of the humoral immune response are soluble globular proteins known as antibodies or immunoglobulins, often abbreviated Ig. Immunoglobulin bind foreign bacteria, viruses, and other large molecules and target them for destruction. They are composed of 20% blood protein, and are produced by B lymphocytes, or plasma B cells, named because they complete their development in the Bone marrow.
Each antibody of the immune system specifically binds to a particular chemical structure which distinguishes it from all others. Humans are capable of producing billions of types of antibodies with unique binding specificities. Therefore, any chemical structure on the surface of a virus or invading cell will most likely be recognized and bound by one or more antibodies. This diversity is derived from genetic recombination mechanisms for a set of immunoglobulin gene segments. Any molecule or pathogen capable of eliciting an immune response is called an antigen. Antigens include viruses, bacterial cell walls, or individual proteins or macromolecules. Antigens are of varying complexity, and can be bound by several different antibodies. An individual antibody binds only a particular molecular structure within the antigen, called its antigenic determinant, or epitope.
Immunoglobulin G, or IgG is the major antibody class and one of the most abundant proteins in the blood serum. It is composed of four polypeptide chains: two heavy chains and two light chains, linked by noncovalent and disulfide bonds (yellow bonds above). The heavy chains of an IgG molecule interact at one end, then branch to interact separately with the light chains, forming a Y-shaped molecule. At the “hinges” separating the base of an IgG molecule from its branches, the immunoglobulin can be cleaved with proteases. Cleavage with the protease papain liberates the basal fragment, called Fc because it usually crystallizes readily, and the two branches, called Fab, the antigen binding fragment. Each branch contains a single antigen-binding site. IgG is the major antibody in secondary immune responses, which are initiated by a class of B cells called memory B cells. As part of ongoing immunity to antigens already encountered and dealt with, IgG is the most abundant immunoglobulin in the blood.
IgG is one of five classes of immunoglobulins found in vertebrates. Each class has a characteristic type of heavy chain, denoted by the greek letters alpha, delta, epsilon, gamma, and mu for IgA, IgD, IgE, IgG, and IgM, respectively.
- IgG makes up 75% of plasma antibody in adults because they are produced in secondary immune responses. Maternal IgG crosses the placental membrane and gives infants immunity in the first few months of life. IgG also activates the complement system.
- IgA antibodies are found in external secretions, such as saliva, tears, intestinal and bronchial mucus, and breast milk, where they disable pathogens before they reach the internal environment.
- **IgE is associated with allergic responses. When mast cell receptors bind with IgE and antigen, the mast cells degranulate and release chemical mediators, such as histamine.
- IgM antibodies are associated with primary immune responses and with the antibodies that react to blood group antigens. IgM also activates the complement system.
- IgD antibody proteins appear on the surface of B lymphocytes along with IgM, but the physiological role of IgD is unclear.
Immunoglobulins have several immune mechanisms (denoted by numbers above):
Making antigens more visible to the immune system:
- (2) Acting as opsonins (opsonization) - Soluble antibodies coat antigens to facilitate recognition and phagocytosis by immune cells such as leukocytes (white blood cells).
- (3) Agglutination (clumping of antigens) - binding of pathogens causing their immobilization and clumping them together to enhance phagocytosis
- (3) Inactivating bacterial toxins - binding and neutralizing toxins produced by bacteria
- (6) Activating the complement system - Antigen-bound antibodies use the Fc end of the antibody molecule to activate complement, part of the innate immune system that involves cleavage of small proteins which release cytokines that amplify the response and activation of cell killing membrane attack complex.
- (5) Activating mast cells - Mast cells have IgE antibodies attached to their surface. When antigens or complement proteins bind to IgE, the mast cells degranulate, releasing chemicals that mediate the inflammatory response. Mast cells contain histamine and heparin, and are involved in allergic response. Antihistamines stabilize mast cells and prevent degranulation.
Activating immune cells:
- (1) Activating immune cells - Phagocytic and some cytotoxic cells have membrane receptors that attract the Fc region of antigen-bound antibodies. The presence of a single Fc receptor eliminates the need to have millions of different receptors to recognize different antigens. Instead, with one type of receptor the immune cells are activated by any antibody-bound antigen. If the immune cell is a phagocyte, Fc binding initiates phagocytosis (3). If the immune cell is cytotoxic (eosinophils and natural killer cells), Fc binding initiates respones that kill the antibody-bound cell (4). In the case of B lymphocytes, the antibodies are already an integral part of the lymphocyte (1). In this case, antigen binding plus cytokines from other immune cells activate the cell to produce memory and plasma B cells.
**IgE plays an important role in the allergic response, interacting with basophils (phagocytic white blood cells) in the blood and with histamine-secreting cells called mast cells, which are widely distributed in tissues. This antibody binds through its Fc region, to special Fc receptors on the basophils or mast cells. In this form, IgE serves as a receptor for antigen. If antigen is bound, the cells are induced to secrete histamine and other biologically active amines that cause dilation and increased permeability of blood vessels. These effects on the blood vessels facilitate the movement of immune system ells and proteins to sites of inflammation. They also produce the symptoms associated with allergies. Pollen or other allergens are recognized as foreign, triggering an immune response normally reserved for pathogens. Specifically, IgE plays a large role in Type 1 hypersensitivity, which involves several diseases such as allergic asthma, allergic rhinitis (inflammation of nasal passages), food allergies, anaphylaxis, and eosiniophilia.
Lehninger’s Principles of BIochemistry, 5th edition, David Nelson, Michael Cox
Human Physiology, An Integrated Approach, 5th edition, Dee Silverthorn