12.2B: Antibody Functions - Biology

12.2B: Antibody Functions - Biology

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Antibodies, part of the humoral immune response, are involved in pathogen detection and neutralization.

Learning Objectives

  • Differentiate among affinity, avidity, and cross-reactivity in antibodies

Key Points

  • Antibodies are produced by plasma cells, but, once secreted, can act independently against extracellular pathogen and toxins.
  • Antibodies bind to specific antigens on pathogens; this binding can inhibit pathogen infectivity by blocking key extracellular sites, such as receptors involved in host cell entry.
  • Antibodies can also induce the innate immune response to destroy a pathogen, by activating phagocytes such as macrophages or neutrophils, which are attracted to antibody-bound cells.
  • Affinity describes how strongly a single antibody binds a given antigen, while avidity describes the binding of a multimeric antibody to multiple antigens.
  • A multimeric antibody may have individual arms with low affinity, but have high overall avidity due to synergistic effects between binding sites.
  • Cross reactivity occurs when an antibody binds to a different-but-similar antigen than the one for which it was raised; this can increase pathogen resistance or result in an autoimmune reaction.

Key Terms

  • avidity: the measure of the synergism of the strength individual interactions between proteins
  • affinity: the attraction between an antibody and an antigen

Antibody Functions

Differentiated plasma cells are crucial players in the humoral immunity response. The antibodies they secrete are particularly significant against extracellular pathogens and toxins. Once secreted, antibodies circulate freely and act independently of plasma cells. Sometimes, antibodies can be transferred from one individual to another. For instance, a person who has recently produced a successful immune response against a particular disease agent can donate blood to a non-immune recipient, confering temporary immunity through antibodies in the donor’s blood serum. This phenomenon, called passive immunity, also occurs naturally during breastfeeding, which makes breastfed infants highly resistant to infections during the first few months of life.

Antibodies coat extracellular pathogens and neutralize them by blocking key sites on the pathogen that enhance their infectivity, such as receptors that “dock” pathogens on host cells. Antibody neutralization can prevent pathogens from entering and infecting host cells, as opposed to the cytotoxic T-cell-mediated approach of killing cells that are already infected to prevent progression of an established infection. The neutralized antibody-coated pathogens can then be filtered by the spleen and eliminated in urine or feces.

Antibodies also mark pathogens for destruction by phagocytic cells, such as macrophages or neutrophils, because they are highly attracted to macromolecules complexed with antibodies. Phagocytic enhancement by antibodies is called opsonization. In another process, complement fixation, IgM and IgG in serum bind to antigens, providing docking sites onto which sequential complement proteins can bind. The combination of antibodies and complement enhances opsonization even further, promoting rapid clearing of pathogens.

Affinity, avidity, and cross reactivity

Not all antibodies bind with the same strength, specificity, and stability. In fact, antibodies exhibit different affinities (attraction) depending on the molecular complementarity between antigen and antibody molecules. An antibody with a higher affinity for a particular antigen would bind more strongly and stably. It would be expected to present a more challenging defense against the pathogen corresponding to the specific antigen.

The term avidity describes binding by antibody classes that are secreted as joined, multivalent structures (such as IgM and IgA). Although avidity measures the strength of binding, just as affinity does, the avidity is not simply the sum of the affinities of the antibodies in a multimeric structure. The avidity depends on the number of identical binding sites on the antigen being detected, as well as other physical and chemical factors. Typically, multimeric antibodies, such as pentameric IgM, are classified as having lower affinity than monomeric antibodies, but high avidity. Essentially, the fact that multimeric antibodies can bind many antigens simultaneously balances their slightly-lower-binding strength for each antibody/antigen interaction.

Antibodies secreted after binding to one epitope on an antigen may exhibit cross reactivity for the same or similar epitopes on different antigens. Cross reactivity occurs when an antibody binds not to the antigen that elicited its synthesis and secretion, but to a different antigen. Because an epitope corresponds to such a small region (the surface area of about four to six amino acids), it is possible for different macromolecules to exhibit the same molecular identities and orientations over short regions.

Cross reactivity can be beneficial if an individual develops immunity to several related pathogens despite having been exposed to or vaccinated against only one of them. For instance, antibody cross reactivity may occur against the similar surface structures of various Gram-negative bacteria. Conversely, antibodies raised against pathogenic molecular components that resemble self molecules may incorrectly mark host cells for destruction, causing autoimmune damage. Patients who develop systemic lupus erythematosus (SLE) commonly exhibit antibodies that react with their own DNA. These antibodies may have been initially raised against the nucleic acid of microorganisms, but later cross-reacted with self-antigens. This phenomenon is also called molecular mimicry.

The biological function of antibodies

Antibody is an immunoglobulin produced by the body’s immune system and stimulated by antigen to proliferate and differentiate from B lymphocytes or memory cells and specifically bind to the corresponding antigen. So what are the major biological functions of antibodies?

1. Specific binding of the corresponding antigen

Antibody hypervariable region and antigenic determinants of the three-dimensional structure must be consistent in order to bind the antibody and the antigen binding is highly specific. Antibody molecules that specifically bind antigen can mediate a variety of physiological and pathological effects in vivo.

Antibody and antigen binding by non-covalent bond is reversible, and electrolyte concentration, PH, temperature and the integrity of the antibody structure can affect the ability of antibodies and antigen binding. The binding valence of IgG is bivalent the binding valence of IgM is theoretically deca-valent but is practically pentavalent due to steric hindrance and the dimeric IgA is tetravalent.

2. Activation of complement

When the IgG1, IgG2, IgG3 and IgM antibody molecules specifically bind to the corresponding antigen, their conformation changes. The complement of the complement binding site, CH2 of IgM or CH2 of IgG is bound to Clq and the complement system is activated by the traditional pathway. For IgG, at least two closely adjacent IgG molecules are needed to activate complement when they are bound to the corresponding antigen. Aggregates of other Ig molecules, such as IgG4 and IgA, activate complement by alternative pathways. Human natural anti-A and anti-B blood group antibody is IgM, and when blood group does not meet the blood transfusion, the antigen-antibody reaction activates complement hemolysis, causing rapid and serious transfusion reactions.

3. Binding Fc receptors

After binding the corresponding antigen through the V region, Ig can bind trough Fc segment to a variety of cell surface Fc receptors, and stimulate different effector functions.

3.1 Opsonization promotes phagocytosis

IgG molecules binds to bacteria and other particulate antigen, then pass through the Fc segment and mononuclear phagocytes and neutrophils corresponding receptors (FcγR), and thus promotes its phagocytosis called opsonization. Complement and antibody play the role of conditioning phagocytosis, known as the joint conditioning effect. Neutrophils, monocytes and macrophages have high affinity or low affinity for FcγRI (CD64) and FcrRII (CD32), and IgG, particularly human IgGl and IgG3 subclasses, plays major roles in opsonophagocytosis. Eosinophils have affinity FcyRII, and IgE and the corresponding antigen can promote phagocytosis of eosinophils.

3.2 Mediated allergic reactions

Fc fragments of IgE, upon binding to the corresponding receptors on the surface of mast cells and basophils (FcεR), sensitize these cells and under the action of allergens, degranulate these cells to release bioactive substances such as Histamine, bradykinin, causing local telangiectasia, increased permeability, stimulate type I hypersensitivity.

3.3 Antibody-dependent cellular cytotoxicity, ADCC effect

IgG binds to corresponding target cells, such as virus-infected cells and tumor cells, and exerts an ADCC effect by binding its Fc fragment to the corresponding receptor (FcγR) on NK cells. Mononuclear phagocytes and neutrophils, which have IgG Fc receptors on the surface, also produce ADCC effects on target cells that bind to IgG as described above.

4. Through the placenta

Among the five types of Ig, IgG is the only Ig that can be transferred from the mother to the fetus through the placenta, and the immunity obtained by the fetus in this manner is called natural passive immunity. Studies have shown that maternal IgG may be transported to the fetus by binding to the corresponding receptor on the surface of the placental trophoblast—FcγR.

5. Immune regulation

Antibodies have a positive and a negative regulatory effect on immune response, and through the unique and anti-unique type of network involve in the body’s immune regulation. The above briefly described the five biological functions of antibodies, which are a specific function with the antigen, activation of complement, binding of Fc receptors and transplacental and immunoregulation. Resulting from a single B cell clone, monoclonal antibody is highly uniform and only binds to specific antigenic epitopes and polyclonal antibodies are hybrid antibodies that stimulate various types of monoclonal antibodies produced by various epitopes. All of these antibodies have the basic biological function of antibodies and are widely used in many types of research and diagnosis.

Structure of Antibody Molecule (With Diagram)

Antibody is a type of protein molecule produced by B-lymphocytes in response to pathogens. T-cells do not secrete antibodies directly however, they help B-cells to produce them. Each antibody molecule has four peptide chains.

Out of the four chains are:

(i) Two small chains called Light (L) chains.

(ii) Two large chains called Heavy (H) chains.

An antibody is represented as H2L2 molecule. In our body, different types of antibodies are produced such as IgA, IgM, IgE, IgG.

Response via antibodies is also called as humoral immune response. These antibodies are found in blood.

1. Most Prevent class of antibody 75-80% of total antibody.

2. Protects against fungi , bacteria, toxins, etc.

3. It can cross placenta from mother to child and provides immune protection to new born.

4. Responsible for RH factors in blood.

1. Third most common antibody. Constitutes 5-10% of total antibodies.

2. They are first to be produced in responses to encounter with a pathogen.

3. Responsible for blood transfusion reaction in ABO blood system.

1. Second most prevent antibody.

2. It is 15% of the total antibodies.

3. Secreted through parts lined by mucous system.

4. Found in secretions from nose, eyes , lungs and digestive tract , saliva , tears ,etc.

5. Also found in colostrum i.e breasts milk for newborns immune protection.

1. The least common antibody.

2. It make up to only 0.002% of total antibodies and is involved in allergic reactions.

PreciAb™ Platform

Computer science and technology has made tremendous progress in the past decade, and it has influenced every aspect of our life. Since the late 1990s, computational biology has become an important part of emerging technologies in the field of biology. Benefit from the advancement in the development of computer hardware, such as the advent of supercomputer, and the programming language for computational biology, scientists are able to achieve structural information with more details, which is not only necessary to understand the various function and mechanism of biological molecules, but also, more importantly, the key to the design of molecules with new or improved functions.

Creative Biolabs is a leading biotech company focused on antibody engineering in all fields, covering research, diagnosis, and therapy. To follow the trend of immunotherapy, our scientists have established a series of platforms for antibody development and services, our featured antibody-based services include Phage Display & Antibody Library Services, Single Domain Antibody Services, Magic™ Membrane Protein Antibody Discovery, Human or Humanized Antibody Services, etc. With years of experience in computational structural biology and antibody engineering, we develop a comprehensive computer-aided antibody development platform, named PreciAb™, which comprise a full set of technologies and proprietary algorithms for designing antibodies with defined formats and functions.

Antibodies are binding proteins produced by B lymphocytes to defend an organism against pathogens and foreign macromolecules. They are widely used as a research tool, in diagnostics, and also as therapeutic agents. Antibody molecules are characterized by their enormous diversity and specificity of recognition. Although the development of phage display technology has enabled the selection of antibodies to any antigen with acceptable binding affinity, properties of the antibody need to be further optimized for their application, especially for therapy. When available, refined antibody structure and even structure of antibody-antigen complex are very useful in antibody molecular design and engineering. In our PreciAb™ platform, key steps of antibody development are described as follow,

  • Antibody structure construction through combining structure- and homology-based modeling methods
  • Structure optimization by dynamics simulation, rotamer library, loop modeling, and etc.
  • Complementarity-determining region (CDR) identification on the basis of tertiary structure of the antibody
  • Antibody-antigen complex modeling and interaction analysis
  • Paratope and epitope identification and key residues analysis
  • Computer-aided antibody affinity maturation and function modification
  • Global analysis and optimization of antibody biophysical properties (thermodynamic stability, aggregation propensity, immunogenicity)

Up to now, the major challenge in antibody modeling remains to be the prediction of the conformations of the CDR loops and modification of antibody affinity and function by computer-aided design coupled with knowledge-based design, our scientists at Creative Biolabs will keep striving on improving our loop modeling techniques. In addition to computer-based analysis, we can offer knowledge-based analysis and advice on in silico antibody engineering for various downstream applications.

The Need for Better Protection Against Influenza Virus

Seasonal influenza vaccines are reformulated and administered yearly, but influenza epidemics still cause 290 000–650 000 deaths annually. 10 The protection afforded by influenza vaccination is limited by several factors including antigenic drift, antigenic shift and suboptimal responsiveness in high-risk groups. Avian-origin influenza viruses (H5N1 and H7N9) also pose a significant threat to global health, particularly if they acquire the ability to transmit efficiently from human-to-human.

Influenza vaccination and infection primarily generate antibodies targeting the major envelope glycoprotein hemagglutinin (HA), which is required for influenza virus attachment and entry into cells. The classical hemagglutination inhibition (HAI) assay is frequently used to assess protection following influenza vaccination. 11 HAI assays detect a subset of NAbs that block influenza virus attachment by binding to epitopes surrounding the receptor-binding site in the HA head domain. A serum HAI titer of 40 correlates with a ≈50% reduction in the rate of influenza virus infection. 12 However, HAI antibodies that bind in the hypervariable HA head are typically strain-specific and are not protective against drifted or emerging influenza viruses with pandemic potential.

The development of a universally protective influenza vaccine is a global priority. Influenza-specific antibodies that protect through Fc-mediated functions preferentially target conserved epitopes on the HA molecule, including the highly conserved HA stem domain. 9, 13 Antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent phagocytosis (ADP) and antibody-dependent complement activation are increasingly recognized as mediators of influenza immunity and may inform the development of more universal influenza vaccines and immunotherapies.

Structure of Antibodies

The antibody recognizes a unique part of an antigen (foreign object). Each tip of the &ldquoY&rdquo of an antibody contains a paratope (a structure analogous to a lock) that is specific for one particular epitope (similarly analogous to a key) on an antigen, allowing these two structures to bind together with precision. Using this binding mechanism, an antibody can neutralize its target directly or tag it for attack by other parts of the immune system.

Antibody: Each antibody binds to a specific antigen, an interaction similar to a lock and key.

Antibodies are glycoproteins belonging to the immunoglobulin superfamily, typically made of basic structural units each with two large heavy chains and two small light chains. Most antibodies exist as a monomer, in which they have a single &ldquoY&rdquo shaped sub-unit, but some antibodies can exist as dimers (two subunits) or pentamers (five subunits). The paratope is considered a hypervariable region and has the same specificity and antigen-binding affinity as the B cell receptor of the B cell that created the antibody. In some isotypes, the tail end of the antibody is called the constant region and faces away from the &ldquoY-shaped&rdquo paratobe ends, functioning as an Fc tail to which phagocytes can bind.

Subclasses of immunoglobulins

In addition to the major immunoglobulin classes, several Ig subclasses exist in all members of a particular animal species. Antibodies are classified into subclasses based on minor differences in the heavy chain type of each Ig class. In humans there are four subclasses of IgG: IgG1, IgG2, IgG3 and IgG4 (numbered in order of decreasing concentration in serum).

Variance among different subclasses is less than the variance among different classes. For example, IgG1 is more closely related to IgG2, IgG3 and IgG4 than to IgA, IgM, IgD or IgE. Consequently, antibody-binding proteins (e.g., Protein A or Protein G) and most secondary antibodies used in immunodetection methods cross-react with multiple subclasses but usually not multiple classes of Ig.

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Immune Tolerance

The immune system has to be regulated to prevent wasteful, unnecessary responses to harmless substances, and more importantly, so that it does not attack “self.” The acquired ability to prevent an unnecessary or harmful immune response to a detected foreign substance known not to cause disease, or self-antigens, is described as immune tolerance . The primary mechanism for developing immune tolerance to self-antigens occurs during the selection for weakly self-binding cells during T and B lymphocyte maturation. There are populations of T cells that suppress the immune response to self-antigens and that suppress the immune response after the infection has cleared to minimize host cell damage induced by inflammation and cell lysis. Immune tolerance is especially well developed in the mucosa of the upper digestive system because of the tremendous number of foreign substances (such as food proteins) that APCs of the oral cavity, pharynx, and gastrointestinal mucosa encounter. Immune tolerance is brought about by specialized APCs in the liver, lymph nodes, small intestine, and lung that present harmless antigens to a diverse population of regulatory T (Treg) cells, specialized lymphocytes that suppress local inflammation and inhibit the secretion of stimulatory immune factors. The combined result of Treg cells is to prevent immunologic activation and inflammation in undesired tissue compartments and to allow the immune system to focus on pathogens instead.

The functions of SARS-CoV-2 neutralizing and infection-enhancing antibodies in vitro and in mice and nonhuman primates

SARS-CoV-2 neutralizing antibodies (NAbs) protect against COVID-19. A concern regarding SARS-CoV-2 antibodies is whether they mediate disease enhancement. Here, we isolated NAbs against the receptor-binding domain (RBD) and the N-terminal domain (NTD) of SARS-CoV-2 spike from individuals with acute or convalescent SARS-CoV-2 or a history of SARS-CoV-1 infection. Cryo-electron microscopy of RBD and NTD antibodies demonstrated function-specific modes of binding. Select RBD NAbs also demonstrated Fc receptor-γ (FcγR)-mediated enhancement of virus infection in vitro, while five non-neutralizing NTD antibodies mediated FcγR-independent in vitro infection enhancement. However, both types of infection-enhancing antibodies protected from SARS-CoV-2 replication in monkeys and mice. Nonetheless, three of 31 monkeys infused with enhancing antibodies had higher lung inflammation scores compared to controls. One monkey had alveolar edema and elevated bronchoalveolar lavage inflammatory cytokines. Thus, while in vitro antibody-enhanced infection does not necessarily herald enhanced infection in vivo, increased lung inflammation can occur in SARS-CoV-2 antibody-infused macaques.

Difference between T cells and Antibodies?


T cells are a type of white blood cell called a T lymphocyte. An antibody is a protein called an immunoglobulin, which binds to antigens or helps stop functions of pathogens through disrupting certain processes.


T cells are produced from stem cells in the bone marrow which later differentiate in the thymus. Antibodies are chemicals that are formed and released from specific B cells in response to a signal from a T cell.


A T cell is a type of lymphocyte that has T cell-type receptors on the plasma membrane of the cell. An antibody is a protein that has various chains, some of which are modified for attachment to antigens.


There are two major types of T cells, namely, helper T cells and cytotoxic T cells. There are five main types of antibodies, namely, IgA, IgM, IgG, IgE, and IgD.


The function of T cells is to help with the cellular-response of the immune system, and in fact, helper T cells activate B cells to release antibodies cytotoxic T cells directly kill pathogens. The function of antibodies is to attach to antigens of pathogens, but some can also inhibit movement of pathogens, or paralyze or inhibit protein synthesis in viruses.