Group 1: Antibody Structure
– Antibodies are heavy proteins of about 150kDa in size.
– They are arranged in three globular regions forming a Y shape.
– An antibody unit consists of four polypeptide chains: two identical heavy chains and two identical light chains.
– The chains are connected by disulfide bonds.
– Each chain is a series of domains.
– Variable domains are referred to as the F region.
– Each variable domain contains three hypervariable regions.
– Complementarity-determining regions (CDRs) form the antibody-binding site.
– The Fc region is composed of constant domains from the heavy chains.
– Antibodies have glycosylation sites in the Fc region.
– Each chain has an N-terminus at the tip.
– Immunoglobulin domains have a similar structure in the immunoglobulin superfamily.
– Immunoglobulin fold is composed of beta strands forming beta sheets.
– Immunoglobulin domains are held together by disulfide bonds.
– Variable domains have more beta strands than constant domains.
Group 2: Antibody Function
– Antibodies are used by the immune system to identify and neutralize foreign objects.
– They can tag microbes or infected cells for attack by other parts of the immune system.
– Antibodies can neutralize pathogens directly by blocking essential parts.
– The antigen-binding sites on antibodies come in a wide variety to recognize diverse antigens.
– Humoral immunity is often synonymous with the antibody response.
– Antibodies are considered part of the adaptive immune system.
– Antibodies play a central role in immune protection from vaccines and infections.
– Durable protection from infections relies on sustained production of antibodies.
– Antibodies bind to pathogens in different formations like opsonization and neutralization.
– Activated B cells differentiate into plasma cells that secrete soluble antibodies or memory cells.
– Antibodies contribute to immunity by preventing pathogen entry, stimulating pathogen removal, and triggering destruction of pathogens.
– Main categories of antibody action include neutralization, agglutination, and complement activation.
– IgA is found in mucosal areas and prevents colonization by pathogens.
– IgD functions mainly as an antigen receptor on B cells.
– IgE triggers histamine release from mast cells and basophils.
– IgG provides the majority of antibody-based immunity against pathogens.
– IgM eliminates pathogens in the early stages of B cell-mediated immunity.
Group 3: Immune Response and Antibody Production
– Plasmablasts are rapidly proliferating, short-lived cells.
– Plasma cells do not divide and rely on survival niches to persist.
– Plasma cells secrete large quantities of antibodies.
– Long-lived plasma cells can reside in the bone marrow or mucosal tissues.
– Memory B cells persist for decades and can be recalled in a secondary immune response.
– B cells can differentiate into antibody-secreting cells or memory B cells.
– Long-lived plasma cells can live potentially for the entire lifetime of an organism.
– Effective vaccines elicit persistent high levels of antibodies.
– Microbes can mutate to escape antibodies, countered by memory B cells.
– Long-lived plasma cells contribute to sustained antibody production.
Group 4: Antibody Classes and Diversity
– Humans have five classes of antibodies: IgA, IgD, IgE, IgG, and IgM.
– Antibody classes are further subdivided into subclasses.
– The prefix Ig stands for immunoglobulin.
– Each antibody class is determined by the heavy chain type within the hinge and Fc region.
– Mammals have lambda (λ) and kappa (κ) types of light chains.
– Both λ and κ light chains can occur with any of the five major types of heavy chains.
– Each antibody contains two identical light chains: both κ or both λ.
– Proportions of κ and λ types vary by species.
– Humans generate about 10 billion different antibodies.
– Diversity among antibodies is crucial for recognizing and eradicating various microbes.
– Genetic mechanisms allow B cells to generate a diverse pool of antibodies.
– Antibodies have variable amino acid compositions to interact with different antigens.
Group 5: Antibody-Antigen Interactions and Immunoglobulin Function
– Antibody complexes can form by binding to multiple antigen molecules.
– Some antibodies form complexes binding to multiple antigen molecules.
– Antibodies can occur as monomers, dimers, tetramers, or pentamers.
– B cell receptors (BCRs) are composed of surface-bound IgD or IgM antibodies.
– Antibodies bind to pathogens to agglutinate them.
– Antibodies stimulate effector functions in cells with Fc receptors.
– Different effector functions include phagocytosis, degranulation, and cytokine release.
– Antibody-dependent cell-mediated cytotoxicity (ADCC) is initiated by natural killer cells.
– The antibody’s paratope interacts with the antigen’s epitope.
– Antibody and antigen interact by spatial complementarity.
– Molecular forces involved in the Fab-epitope interaction are weak and non-specific.
– Antibody-antigen binding is reversible, and the antibody’s affinity towards an antigen is relative.
An antibody (Ab) is the secreted form of a B cell receptor; the term immunoglobulin (Ig) can refer to either the membrane-bound form or the secreted form of the B cell receptor, but they are, broadly speaking, the same protein, and so the terms are often treated as synonymous. Antibodies are large, Y-shaped proteins belonging to the immunoglobulin superfamily which are used by the immune system to identify and neutralize foreign objects such as bacteria and viruses, including those that cause disease. Antibodies can recognize virtually any size antigen with diverse chemical compositions from molecules. Each antibody recognizes one or more specific antigens. This term literally means "antibody generator", as it is the presence of an antigen that drives the formation of an antigen-specific antibody. Each tip of the "Y" of an antibody contains a paratope that specifically binds to one particular epitope on an antigen, allowing the two molecules to bind together with precision. Using this mechanism, antibodies can effectively "tag" a microbe or an infected cell for attack by other parts of the immune system, or can neutralize it directly (for example, by blocking a part of a virus that is essential for its invasion).
To allow the immune system to recognize millions of different antigens, the antigen-binding sites at both tips of the antibody come in an equally wide variety. The rest of the antibody structure is relatively generic. In humans, antibodies occur in five classes, sometimes called isotypes: IgA, IgD, IgE, IgG, and IgM. Human IgG and IgA antibodies are also divided into discrete subclasses (IgG1, IgG2, IgG3, IgG4; IgA1 and IgA2). The class refers to the functions triggered by the antibody (also known as effector functions), in addition to some other structural features. Antibodies from different classes also differ in where they are released in the body and at what stage of an immune response. Importantly, while classes and subclasses of antibodies may be shared between species (at least in name), their functions and distribution throughout the body may be different. For example, mouse IgG1 is closer to human IgG2 than human IgG1 in terms of its function.
The term humoral immunity is often treated as synonymous with the antibody response, describing the function of the immune system that exists in the body's humors (fluids) in the form of soluble proteins, as distinct from cell-mediated immunity, which generally describes the responses of T cells (especially cytotoxic T cells). In general, antibodies are considered part of the adaptive immune system, though this classification can become complicated. For example, natural IgM, which are made by B-1 lineage cells that have properties more similar to innate immune cells than adaptive, refers to IgM antibodies made independently of an immune response that demonstrate polyreactivity- they recognize multiple distinct (unrelated) antigens. These can work with the complement system in the earliest phases of an immune response to help facilitate clearance of the offending antigen and delivery of the resulting immune complexes to the lymph nodes or spleen for initiation of an immune response. Hence in this capacity, the function of antibodies is more akin to that of innate immunity than adaptive. Nonetheless, in general antibodies are regarded as part of the adaptive immune system because they demonstrate exceptional specificity (with some exception), are produced through genetic rearrangements (rather than being encoded directly in germline), and are a manifestation of immunological memory.
In the course of an immune response, B cells can progressively differentiate into antibody-secreting cells (B cells themselves do not secrete antibody; B cells do, however, express B cell receptors, the membrane-bound form of the antibody, on their surface) or memory B cells. Antibody-secreting cells comprise plasmablasts and plasma cells, which differ mainly in the degree to which they secrete antibody, their lifespan, metabolic adaptations, and surface markers. Plasmablasts are rapidly proliferating, short-lived cells produced in the early phases of the immune response (classically described as arising extrafollicularly rather than from the germinal center) which have the potential to differentiate further into plasma cells. The literature is sloppy at times and often describes plasmablasts as just short-lived plasma cells- formally this is incorrect. Plasma cells, in contrast, do not divide (they are terminally differentiated), and rely on survival niches comprising specific cell types and cytokines to persist. Plasma cells will secrete huge quantities of antibody regardless of whether or not their cognate antigen is present, ensuring that antibody levels to the antigen in question do not fall to 0, provided the plasma cell stays alive. The rate of antibody secretion, however, can be regulated, for example, by the presence of adjuvant molecules that stimulate the immune response such as TLR ligands. Long-lived plasma cells can live for potentially the entire lifetime of the organism. Classically, the survival niches that house long-lived plasma cells reside in the bone marrow, though it cannot be assumed that any given plasma cell in the bone marrow will be long-lived. However, other work indicates that survival niches can readily be established within the mucosal tissues- though the classes of antibodies involved show a different hierarchy from those in the bone marrow. B cells can also differentiate into memory B cells which can persist for decades similarly to long-lived plasma cells. These cells can be rapidly recalled in a secondary immune response, undergoing class switching, affinity maturation, and differentiating into antibody-secreting cells.
Antibodies are central to the immune protection elicited by most vaccines and infections (although other components of the immune system certainly participate and for some diseases are considerably more important than antibodies in generating an immune response, e.g. herpes zoster). Durable protection from infections caused by a given microbe – that is, the ability of the microbe to enter the body and begin to replicate (not necessarily to cause disease) – depends on sustained production of large quantities of antibodies, meaning that effective vaccines ideally elicit persistent high levels of antibody, which relies on long-lived plasma cells. At the same time, many microbes of medical importance have the ability to mutate to escape antibodies elicited by prior infections, and long-lived plasma cells cannot undergo affinity maturation or class switching. This is compensated for through memory B cells: novel variants of a microbe that still retain structural features of previously encountered antigens can elicit memory B cell responses that adapt to those changes. It has been suggested that long-lived plasma cells secrete B cell receptors with higher affinity than those on the surfaces of memory B cells, but findings are not entirely consistent on this point.
