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Polyclonal B cell response is a natural mode of immune response exhibited by the
adaptive immune system The adaptive immune system (AIS), also known as the acquired immune system, or specific immune system is a subsystem of the immune system that is composed of specialized cells, organs, and processes that eliminate pathogens specifically. The ac ...
of
mammals A mammal () is a vertebrate animal of the class Mammalia (). Mammals are characterised by the presence of milk-producing mammary glands for feeding their young, a broad neocortex region of the brain, fur or hair, and three middle e ...
. It ensures that a single
antigen In immunology, an antigen (Ag) is a molecule, moiety, foreign particulate matter, or an allergen, such as pollen, that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...
is recognized and attacked through its overlapping parts, called
epitope An epitope, also known as antigenic determinant, is the part of an antigen that is recognized by the immune system, specifically by antibodies, B cells, or T cells. The part of an antibody that binds to the epitope is called a paratope. Although e ...
s, by multiple clones of
B cell B cells, also known as B lymphocytes, are a type of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted or inserted into the plasm ...
. In the course of normal immune response, parts of
pathogen In biology, a pathogen (, "suffering", "passion" and , "producer of"), in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a Germ theory of d ...
s (e.g.
bacteria Bacteria (; : bacterium) are ubiquitous, mostly free-living organisms often consisting of one Cell (biology), biological cell. They constitute a large domain (biology), domain of Prokaryote, prokaryotic microorganisms. Typically a few micr ...
) are recognized by the immune system as foreign (non-self), and eliminated or effectively neutralized to reduce their potential damage. Such a recognizable substance is called an
antigen In immunology, an antigen (Ag) is a molecule, moiety, foreign particulate matter, or an allergen, such as pollen, that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...
. The immune system may respond in multiple ways to an antigen; a key feature of this response is the production of
antibodies An antibody (Ab) or immunoglobulin (Ig) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as bacteria and viruses, including those that caus ...
by B cells (or B lymphocytes) involving an arm of the immune system known as
humoral immunity Humoral immunity is the aspect of immunity (medical), immunity that is mediated by macromolecules – including secreted antibodies, complement proteins, and certain antimicrobial peptides – located in extracellular fluids. Humoral immunity is ...
. The antibodies are soluble and do not require direct cell-to-cell contact between the pathogen and the B-cell to function. Antigens can be large and complex substances, and any single antibody can only bind to a small, specific area on the antigen. Consequently, an effective immune response often involves the production of many different antibodies by many different B cells against the ''same'' antigen. Hence the term "polyclonal", which derives from the words ''poly'', meaning many, and ''clones'' from Greek ''klōn'', meaning sprout or twig; a clone is a group of cells arising from a common "mother" cell. The antibodies thus produced in a polyclonal response are known as
polyclonal antibodies Polyclonal antibodies (pAbs) are antibodies that are secreted by different B cell lineages within the body (whereas monoclonal antibodies come from a single cell lineage). They are a collection of immunoglobulin molecules that react against a s ...
. The
heterogeneous Homogeneity and heterogeneity are concepts relating to the uniformity of a substance, process or image. A homogeneous feature is uniform in composition or character (i.e., color, shape, size, weight, height, distribution, texture, language, i ...
polyclonal antibodies are distinct from
monoclonal antibody A monoclonal antibody (mAb, more rarely called moAb) is an antibody produced from a cell lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell. Monoclonal antibodie ...
molecules, which are identical and react against a single epitope only, i.e., are more specific. Although the polyclonal response confers advantages on the immune system, in particular, greater probability of reacting against pathogens, it also increases chances of developing certain autoimmune diseases resulting from the reaction of the immune system against native molecules produced within the host.


Humoral response to infection

Diseases which can be transmitted from one organism to another are known as
infectious disease An infection is the invasion of tissue (biology), tissues by pathogens, their multiplication, and the reaction of host (biology), host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmis ...
s, and the causative biological agent involved is known as a
pathogen In biology, a pathogen (, "suffering", "passion" and , "producer of"), in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a Germ theory of d ...
. The process by which the pathogen is introduced into the body is known as
inoculation Inoculation is the act of implanting a pathogen or other microbe or virus into a person or other organism. It is a method of artificially inducing immunity against various infectious diseases. The term "inoculation" is also used more generally ...
,The term ''"inoculation"'' is usually used in context of active immunization, i.e., deliberately introducing the antigenic substance into the host's body. But in many discussions of infectious diseases, it is not uncommon to use the term to imply a spontaneous (that is, without human intervention) event resulting in introduction of the causative organism into the body, say ingesting water contaminated with
Salmonella typhi ''Salmonella enterica'' subsp. ''enterica'' is a subspecies of ''Salmonella enterica'', the rod-shaped, flagellated, aerobic, Gram-negative bacterium. Many of the pathogenic serovars of the ''S. enterica'' species are in this subspecies, includin ...
—the causative organism for
typhoid fever Typhoid fever, also known simply as typhoid, is a disease caused by '' Salmonella enterica'' serotype Typhi bacteria, also called ''Salmonella'' Typhi. Symptoms vary from mild to severe, and usually begin six to 30 days after exposure. Often th ...
. In such cases the causative organism itself is known as the ''inoculum'', and the number of organisms introduced as the "dose of inoculum". and the organism it affects is known as a biological host. When the pathogen establishes itself in a step known as
colonization 475px, Map of the year each country achieved List of sovereign states by date of formation, independence. Colonization (British English: colonisation) is a process of establishing occupation of or control over foreign territories or peoples f ...
, it can result in an
infection An infection is the invasion of tissue (biology), tissues by pathogens, their multiplication, and the reaction of host (biology), host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmis ...
, consequently harming the host directly or through the harmful substances called
toxin A toxin is a naturally occurring poison produced by metabolic activities of living cells or organisms. They occur especially as proteins, often conjugated. The term was first used by organic chemist Ludwig Brieger (1849–1919), derived ...
s it can produce. This results in the various
symptom Signs and symptoms are diagnostic indications of an illness, injury, or condition. Signs are objective and externally observable; symptoms are a person's reported subjective experiences. A sign for example may be a higher or lower temperature ...
s and signs characteristic of an infectious disease like
pneumonia Pneumonia is an Inflammation, inflammatory condition of the lung primarily affecting the small air sacs known as Pulmonary alveolus, alveoli. Symptoms typically include some combination of Cough#Classification, productive or dry cough, ches ...
or
diphtheria Diphtheria is an infection caused by the bacteria, bacterium ''Corynebacterium diphtheriae''. Most infections are asymptomatic or have a mild Course (medicine), clinical course, but in some outbreaks, the mortality rate approaches 10%. Signs a ...
. Countering the various infectious diseases is very important for the survival of the susceptible organism, in particular, and the species, in general. This is achieved by the host by eliminating the pathogen and its toxins or rendering them nonfunctional. The collection of various
cell Cell most often refers to: * Cell (biology), the functional basic unit of life * Cellphone, a phone connected to a cellular network * Clandestine cell, a penetration-resistant form of a secret or outlawed organization * Electrochemical cell, a de ...
s, tissues and
organ Organ and organs may refer to: Biology * Organ (biology), a group of tissues organized to serve a common function * Organ system, a collection of organs that function together to carry out specific functions within the body. Musical instruments ...
s that specializes in protecting the body against infections is known as the
immune system The immune system is a network of biological systems that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to bacteria, as well as Tumor immunology, cancer cells, Parasitic worm, parasitic ...
. The immune system accomplishes this through direct contact of certain
white blood cell White blood cells (scientific name leukocytes), also called immune cells or immunocytes, are cells of the immune system that are involved in protecting the body against both infectious disease and foreign entities. White blood cells are genera ...
s with the invading pathogen involving an arm of the immune system known as the cell-mediated immunity, or by producing substances that move to sites ''distant'' from where they are produced, "seek" the disease-causing cells and toxins by specifically''Specificity'' implies that two different pathogens will be actually viewed as two distinct entities, and countered by different antibody molecules. binding with them, and neutralize them in the process–known as the humoral arm of the immune system. Such substances are known as soluble antibodies and perform important functions in countering infections.Actions of antibodies: * Coating the pathogen, preventing it from adhering to the host cell, and thus preventing colonization * Precipitating (making the particles "sink" by attaching to them) the soluble antigens and promoting their clearance by other cells of immune system from the various tissues and blood * Coating the microorganisms to attract cells that can engulf the pathogen. This is known as
opsonization Opsonins are extracellular proteins that, when bound to substances or cells, induce phagocytes to phagocytose the substances or cells with the opsonins bound. Thus, opsonins act as tags to label things in the body that should be phagocytosed (i.e. ...
. Thus the antibody acts as an ''opsonin''. The process of engulfing is known as
phagocytosis Phagocytosis () is the process by which a cell (biology), cell uses its plasma membrane to engulf a large particle (≥ 0.5 μm), giving rise to an internal compartment called the phagosome. It is one type of endocytosis. A cell that performs ph ...
(literally, ''cell eating'') * Activating the
complement system The complement system, also known as complement cascade, is a part of the humoral, innate immune system and enhances (complements) the ability of antibodies and phagocytic cells to clear microbes and damaged cells from an organism, promote inf ...
, which most importantly pokes holes into the pathogen's outer covering (its
cell membrane The cell membrane (also known as the plasma membrane or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of a cell from the outside environment (the extr ...
), killing it in the process * Marking up host cells infected by viruses for destruction in a process known as
Antibody-dependent cell-mediated cytotoxicity Antibody-dependent cellular cytotoxicity (ADCC), also referred to as antibody-dependent cell-mediated cytotoxicity, is a mechanism of Cell-mediated immunity, cell-mediated immune defense whereby an effector cell of the immune system kills a target ...
(ADCC) White blood cell White blood cells (scientific name leukocytes), also called immune cells or immunocytes, are cells of the immune system that are involved in protecting the body against both infectious disease and foreign entities. White blood cells are genera ...
s (WBCs)" widths="80px" heights="50px" perrow="6"> Image:Neutrophil.png,
Neutrophil Neutrophils are a type of phagocytic white blood cell and part of innate immunity. More specifically, they form the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. Their functions vary in differe ...
Image:Eosinophil2.png,
Eosinophil Eosinophils, sometimes called eosinophiles or, less commonly, acidophils, are a variety of white blood cells and one of the immune system components responsible for combating multicellular parasites and certain infections in vertebrates. Along wi ...
Image:Basophil.png,
Basophil Basophils are a type of white blood cell White blood cells (scientific name leukocytes), also called immune cells or immunocytes, are cells of the immune system that are involved in protecting the body against both infectious disease and f ...
Image:Lymphocyte.png,
Lymphocyte A lymphocyte is a type of white blood cell (leukocyte) in the immune system of most vertebrates. Lymphocytes include T cells (for cell-mediated and cytotoxic adaptive immunity), B cells (for humoral, antibody-driven adaptive immunity), an ...
Image:Monocyte.png,
Monocyte Monocytes are a type of leukocyte or white blood cell. They are the largest type of leukocyte in blood and can differentiate into macrophages and monocyte-derived dendritic cells. As a part of the vertebrate innate immune system monocytes also ...
Image:Macrophage.png,
Macrophage Macrophages (; abbreviated MPhi, φ, MΦ or MP) are a type of white blood cell of the innate immune system that engulf and digest pathogens, such as cancer cells, microbes, cellular debris and foreign substances, which do not have proteins that ...


B cell response

Antibodies serve various functions in protecting the host against the pathogen. Their soluble forms which carry out these functions are produced by
plasma B cell Plasma cells, also called plasma B cells or effector B cells, are white blood cells that originate in the lymphoid organs as B cells and secrete large quantities of proteins called antibodies in response to being presented specific substances c ...
s, a type of white blood cell. This production is tightly regulated and requires the activation of B cells by activated
T cell T cells (also known as T lymphocytes) are an important part of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell receptor (TCR) on their cell ...
s (another type of white blood cell), which is a sequential procedure. The major steps involved are: *Specific or nonspecific recognition of the pathogen (because of its antigens) with its subsequent engulfing by B cells or
macrophage Macrophages (; abbreviated MPhi, φ, MΦ or MP) are a type of white blood cell of the innate immune system that engulf and digest pathogens, such as cancer cells, microbes, cellular debris and foreign substances, which do not have proteins that ...
s. This activates the B cell only ''partially''. * Antigen processing. *
Antigen presentation Antigen presentation is a vital immune process that is essential for T cell immune response triggering. Because T cells recognize only fragmented antigens displayed on cell surfaces, antigen processing must occur before the antigen fragment can ...
. *Activation of the
T helper cell The T helper cells (Th cells), also known as CD4+ cells or CD4-positive cells, are a type of T cell that play an important role in the adaptive immune system. They aid the activity of other immune cells by releasing cytokines. They are considere ...
s by
antigen-presenting cell An antigen-presenting cell (APC) or accessory cell is a Cell (biology), cell that displays an antigen bound by major histocompatibility complex (MHC) proteins on its surface; this process is known as antigen presentation. T cells may recognize the ...
s. *
Co-stimulation Co-stimulation is a secondary signal which immune cells rely on to activate an immune response in the presence of an antigen-presenting cell. In the case of T cells, two stimuli are required to fully activate their immune response. During the activa ...
of the B cell by ''activated'' T cell resulting in its ''complete'' activation. * ProliferationProliferation in this context means multiplication by
cell division Cell division is the process by which a parent cell (biology), cell divides into two daughter cells. Cell division usually occurs as part of a larger cell cycle in which the cell grows and replicates its chromosome(s) before dividing. In eukar ...
and differentiation of B cells with resultant production of soluble antibodies.


Recognition of pathogens

Pathogens synthesize
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
s that can serve as ''" recognizable"'' antigens; they may express the molecules on their surface or release them into the surroundings (body fluids). What makes these substances recognizable is that they bind very specifically and somewhat strongly to certain host proteins called ''
antibodies An antibody (Ab) or immunoglobulin (Ig) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as bacteria and viruses, including those that caus ...
''. The same antibodies can be anchored to the surface of cells of the immune system, in which case they serve as
receptors Receptor may refer to: *Sensory receptor, in physiology, any neurite structure that, on receiving environmental stimuli, produces an informative nerve impulse *Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds ...
, or they can be secreted in the blood, known as soluble antibodies. On a molecular scale, the proteins are relatively large, so they cannot be recognized as a whole; instead, their segments, called
epitope An epitope, also known as antigenic determinant, is the part of an antigen that is recognized by the immune system, specifically by antibodies, B cells, or T cells. The part of an antibody that binds to the epitope is called a paratope. Although e ...
s, can be recognized. An epitope comes in contact with a very small region (of 15–22 amino acids) of the antibody molecule; this region is known as the
paratope In immunology, a paratope, also known as an antigen-binding site, is the part of an antibody which recognizes and binds to an antigen. It is a small region at the tip of the antibody's antigen-binding fragment and contains parts of the antibody' ...
. In the immune system, membrane-bound antibodies are the
B-cell receptor The B-cell receptor (BCR) is a transmembrane protein on the surface of a B cell. A B-cell receptor is composed of a membrane-bound immunoglobulin molecule and a signal transduction moiety. The former forms a type 1 Transmembrane protein, transmemb ...
(BCR). Also, while the T-cell receptor is not biochemically classified as an antibody, it serves a similar function in that it specifically binds to epitopes complexed with
major histocompatibility complex The major histocompatibility complex (MHC) is a large Locus (genetics), locus on vertebrate DNA containing a set of closely linked polymorphic genes that code for Cell (biology), cell surface proteins essential for the adaptive immune system. The ...
(MHC) molecules.The
major histocompatibility complex The major histocompatibility complex (MHC) is a large Locus (genetics), locus on vertebrate DNA containing a set of closely linked polymorphic genes that code for Cell (biology), cell surface proteins essential for the adaptive immune system. The ...
is a gene region on the
DNA Deoxyribonucleic acid (; DNA) is a polymer composed of two polynucleotide chains that coil around each other to form a double helix. The polymer carries genetic instructions for the development, functioning, growth and reproduction of al ...
that codes for the synthesis of Major histocompatibility class I molecule, Major histocompatibility class II molecule and other proteins involved in the function of
complement system The complement system, also known as complement cascade, is a part of the humoral, innate immune system and enhances (complements) the ability of antibodies and phagocytic cells to clear microbes and damaged cells from an organism, promote inf ...
(MHC class III). The first two products are important in
antigen presentation Antigen presentation is a vital immune process that is essential for T cell immune response triggering. Because T cells recognize only fragmented antigens displayed on cell surfaces, antigen processing must occur before the antigen fragment can ...
. MHC-compatibility is a major consideration in
organ transplantation Organ transplantation is a medical procedure in which an organ is removed from one body and placed in the body of a recipient, to replace a damaged or missing organ. The donor and recipient may be at the same location, or organs may be trans ...
, and in humans is also known as the
human leukocyte antigen The human leukocyte antigen (HLA) system is a complex of genes on chromosome 6 in humans that encode cell-surface proteins responsible for regulation of the immune system. The HLA system is also known as the human version of the major histo ...
(HLA). The binding between a paratope and its corresponding antigen is very specific, owing to its structure, and is guided by various noncovalent bonds, not unlike the pairing of other types of
ligands In coordination chemistry, a ligand is an ion or molecule with a functional group that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's ...
(any atom, ion or molecule that binds with any receptor with at least some degree of ''specificity'' and ''strength''). The specificity of binding does not arise out of a rigid
lock and key A lock is a mechanical or electronic fastening device that is released by a physical object (such as a key, keycard, fingerprint, RFID card, security token or coin), by supplying secret information (such as a number or letter permutation or p ...
type of interaction, but rather requires both the paratope and the epitope to undergo slight conformational changes in each other's presence.


Specific recognition of epitope by B cells

In figure at left, the various segments that form the epitope have been shown to be continuously collinear, meaning that they have been shown as sequential; however, for the situation being discussed here (i.e., the antigen recognition by the B cell), this explanation is too simplistic. Such epitopes are known as ''sequential'' or '' linear epitopes'', as all the amino acids on them are in the same sequence (line). This mode of recognition is possible only when the peptide is small (about six to eight amino acids long), and is employed by the T cells (T lymphocytes). However, the B memory/naive cells recognize intact proteins present on the pathogen surface.Here, ''intact'' implies that the undigested protein is recognized, and ''not'' that the paratope on B cell receptor comes in contact with the ''whole'' protein structure at the same time; the paratope will still contact only a restricted portion of the antigen exposed on its surface. In this situation, the protein in its
tertiary structure Protein tertiary structure is the three-dimensional shape of a protein. The tertiary structure will have a single polypeptide chain "backbone" with one or more protein secondary structures, the protein domains. Amino acid side chains and the ...
is so greatly folded that some loops of amino acids come to lie in the interior of the protein, and the segments that flank them may lie on the surface. The paratope on the B cell receptor comes in contact only with those amino acids that lie on the ''surface'' of the protein. The surface amino acids may actually be discontinuous in the protein's
primary structure Protein primary structure is the linear sequence of amino acids in a peptide or protein. By convention, the primary structure of a protein is reported starting from the amino-terminal (N) end to the carboxyl-terminal (C) end. Protein biosynthe ...
, but get juxtaposed owing to the complex protein folding patterns (as in the adjoining figure). Such epitopes are known as ''conformational'' epitopes and tend to be longer (15–22 amino acid residues) than the linear epitopes. Likewise, the antibodies produced by the plasma cells belonging to the same clone would bind to the same conformational epitopes on the pathogen proteins. The binding of a specific antigen with corresponding BCR molecules results in increased production of the MHC-II molecules. This assumes significance as the same does not happen when the same antigen would be internalized by a relatively nonspecific process called
pinocytosis In cellular biology, pinocytosis, otherwise known as fluid endocytosis and bulk-phase pinocytosis, is a mode of endocytosis in which small molecules dissolved in extracellular fluid are brought into the cell through an invagination of the cell me ...
, in which the antigen with the surrounding fluid is "drunk" as a small vesicle by the B cell. Hence, such an antigen is known as a ''nonspecific antigen'' and does not lead to activation of the B cell, or subsequent production of antibodies against it.


Nonspecific recognition by macrophages

Macrophages Macrophages (; abbreviated MPhi, φ, MΦ or MP) are a type of white blood cell of the innate immune system that engulf and digest pathogens, such as cancer cells, microbes, cellular debris and foreign substances, which do not have proteins that ...
and related cells employ a different mechanism to recognize the pathogen. Their receptors recognize certain motifs present on the invading pathogen that are very ''unlikely'' to be present on a host cell. Such repeating motifs are recognized by
pattern recognition receptor Pattern recognition receptors (PRRs) play a crucial role in the proper function of the innate immune system. PRRs are germline-encoded host sensors, which detect molecules typical for the pathogens. They are proteins expressed mainly by cells of th ...
s (PRRs) like the
toll-like receptor Toll-like receptors (TLRs) are a class of proteins that play a key role in the innate immune system. They are single-pass membrane protein, single-spanning receptor (biochemistry), receptors usually expressed on sentinel cells such as macrophages ...
s (TLRs) expressed by the macrophages. Since the same receptor could bind to a given motif present on surfaces of widely disparate
microorganism A microorganism, or microbe, is an organism of microscopic scale, microscopic size, which may exist in its unicellular organism, single-celled form or as a Colony (biology)#Microbial colonies, colony of cells. The possible existence of unseen ...
s, this mode of recognition is relatively nonspecific, and constitutes an
innate immune response The innate immune system or nonspecific immune system is one of the two main immunity strategies in vertebrates (the other being the adaptive immune system). The innate immune system is an alternate defense strategy and is the dominant immune s ...
.


Antigen processing

After recognizing an antigen, an
antigen-presenting cell An antigen-presenting cell (APC) or accessory cell is a Cell (biology), cell that displays an antigen bound by major histocompatibility complex (MHC) proteins on its surface; this process is known as antigen presentation. T cells may recognize the ...
such as the
macrophage Macrophages (; abbreviated MPhi, φ, MΦ or MP) are a type of white blood cell of the innate immune system that engulf and digest pathogens, such as cancer cells, microbes, cellular debris and foreign substances, which do not have proteins that ...
or B lymphocyte engulfs it completely by a process called
phagocytosis Phagocytosis () is the process by which a cell (biology), cell uses its plasma membrane to engulf a large particle (≥ 0.5 μm), giving rise to an internal compartment called the phagosome. It is one type of endocytosis. A cell that performs ph ...
. The engulfed particle, along with some material surrounding it, forms the endocytic vesicle (the
phagosome In cell biology, a phagosome is a vesicle formed around a particle engulfed by a phagocyte via phagocytosis. Professional phagocytes include macrophages, neutrophils, and dendritic cells (DCs). A phagosome is formed by the fusion of the cel ...
), which fuses with
lysosomes A lysosome () is a membrane-bound organelle that is found in all mammalian cells, with the exception of red blood cells (erythrocytes). There are normally hundreds of lysosomes in the cytosol, where they function as the cell’s degradation cent ...
. Within the lysosome, the antigen is broken down into smaller pieces called
peptides Peptides are short chains of amino acids linked by peptide bonds. A polypeptide is a longer, continuous, unbranched peptide chain. Polypeptides that have a molecular mass of 10,000 Dalton (unit), Da or more are called proteins. Chains of fewer t ...
by
protease A protease (also called a peptidase, proteinase, or proteolytic enzyme) is an enzyme that catalysis, catalyzes proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the formation of new protein products ...
s (
enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...
s that degrade larger proteins). The individual peptides are then complexed with major histocompatibility complex class II (
MHC class II MHC Class II molecules are a class of major histocompatibility complex (MHC) molecules normally found only on professional antigen-presenting cells such as dendritic cells, macrophages, some endothelial cells, thymic epithelial cells, and B cell ...
) molecules located in the lysosome – this method of "handling" the antigen is known as the exogenous or endocytic pathway of antigen processing in contrast to the ''endogenous or cytosolic pathway'', which complexes the ''abnormal'' proteins produced within the cell (e.g. under the influence of a
viral infection A viral disease (or viral infection) occurs when an organism's body is invaded by pathogenic viruses, and infectious virus particles (virions) attach to and enter susceptible cells. Examples include the common cold, gastroenteritis, COVID-19, t ...
or in a
tumor A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...
cell) with
MHC class I MHC class I molecules are one of two primary classes of major histocompatibility complex (MHC) molecules (the other being MHC class II) and are found on the cell surface of all nucleated cells in the bodies of vertebrates. They also occur on ...
molecules. An alternate pathway of endocytic processing had also been demonstrated wherein certain proteins like
fibrinogen Fibrinogen (coagulation factor I) is a glycoprotein protein complex, complex, produced in the liver, that circulates in the blood of all vertebrates. During tissue and vascular injury, it is converted Enzyme, enzymatically by thrombin to fibrin ...
and
myoglobin Myoglobin (symbol Mb or MB) is an iron- and oxygen-binding protein found in the cardiac and skeletal muscle, skeletal Muscle, muscle tissue of vertebrates in general and in almost all mammals. Myoglobin is distantly related to hemoglobin. Compar ...
can bind as a whole to MHC-II molecules after they are denatured and their
disulfide bond In chemistry, a disulfide (or disulphide in British English) is a compound containing a functional group or the anion. The linkage is also called an SS-bond or sometimes a disulfide bridge and usually derived from two thiol groups. In inor ...
s are reduced (breaking the bond by adding
hydrogen Hydrogen is a chemical element; it has chemical symbol, symbol H and atomic number 1. It is the lightest and abundance of the chemical elements, most abundant chemical element in the universe, constituting about 75% of all baryon, normal matter ...
atom Atoms are the basic particles of the chemical elements. An atom consists of a atomic nucleus, nucleus of protons and generally neutrons, surrounded by an electromagnetically bound swarm of electrons. The chemical elements are distinguished fr ...
s across it). The proteases then degrade the exposed regions of the protein-MHC II-complex.


Antigen presentation

After the processed antigen (peptide) is complexed to the MHC molecule, they both migrate together to the
cell membrane The cell membrane (also known as the plasma membrane or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of a cell from the outside environment (the extr ...
, where they are exhibited (elaborated) as a complex that can be recognized by the CD 4+ (T helper cell) – a type of white blood cell.There are many types of white blood cells. The common way of classifying them is according to their appearance under the
light microscope The optical microscope, also referred to as a light microscope, is a type of microscope that commonly uses visible spectrum, visible light and a system of lens (optics), lenses to generate magnified images of small objects. Optical microscopes ...
after they are stained by chemical dyes. But with advancing technology newer methods of classification has emerged. One of the methods employs the use of
monoclonal antibodies A monoclonal antibody (mAb, more rarely called moAb) is an antibody produced from a Lineage (evolution), cell lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell. Mon ...
, which can bind specifically to each type of cell. Moreover, the same type of white blood cell would express molecules typical to it on its cell membrane at various stages of development. The monoclonal antibodies that can specifically bind with a particular surface molecule would be regarded as ''one''
cluster of differentiation The cluster of differentiation (also known as cluster of designation or classification determinant and often abbreviated as CD) is a protocol used for the identification and investigation of cell surface molecules providing targets for immunophe ...
(CD). Any monoclonal antibody or group of monoclonal antibodies that does not react with known surface molecules of lymphocytes, but rather to a yet-unrecognized surface molecule would be clubbed as a ''new'' cluster of differentiation and numbered accordingly. Each cluster of differentiation is abbreviated as "CD", and followed by a number (usually indicating the order of discovery). So, a cell possessing a surface molecule (called
ligand In coordination chemistry, a ligand is an ion or molecule with a functional group that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's el ...
) that binds specifically to cluster of differentiation ''4'' would be known as ''CD4+ cell''. Likewise, a ''CD8+ cell'' is one that would possess the CD8 ligand and bind to CD8 monoclonal antibodies. This is known as ''antigen presentation.'' However, the epitopes (conformational epitopes) that are recognized by the B cell prior to their digestion may not be the same as that presented to the T helper cell. Additionally, a B cell may present different peptides complexed to different MHC-II molecules.


T helper cell stimulation

The CD 4+ cells through their T cell receptor- CD3 complex recognize the epitope-bound MHC II molecules on the surface of the antigen presenting cells, and get 'activated'. Upon this activation, these T cells proliferate and differentiate into Th1 or Th2 cells. This makes them produce soluble chemical signals that promote their own survival. However, another important function that they carry out is the stimulation of B cell by establishing ''direct'' physical contact with them.


Co-stimulation of B cell by activated T helper cell

Complete stimulation of T helper cells requires the B7 molecule present on the antigen presenting cell to bind with
CD28 CD28 (Cluster of Differentiation 28) is a protein expressed on T cells that provides essential co-stimulation, co-stimulatory signals required for T cell activation and survival. When T cells are stimulated through CD28 in conjunction with the T- ...
molecule present on the T cell surface (in close proximity with the T cell receptor). Likewise, a second interaction between the CD40 ligand or CD154 (
CD40L CD154, also called CD40 ligand or CD40L, is a protein that is primarily expressed on activated T cells and is a member of the TNF superfamily of molecules. It binds to CD40 (protein), CD40 on antigen-presenting cells (APC), which leads to many e ...
) present on T cell surface and
CD40 Cluster of differentiation 40, CD40 is a type I transmembrane protein found on antigen-presenting cells and is required for their activation. The binding of CD154 (CD40L) on T helper cell, TH cells to CD40 activates antigen presenting cells and i ...
present on B cell surface, is also necessary. The same interactions that stimulate the T helper cell also stimulate the B cell, hence the term ''costimulation''. The entire mechanism ensures that an activated T cell only stimulates a B cell that recognizes the antigen containing the ''same'' epitope as recognized by the T cell receptor of the "costimulating" T helper cell. The B cell gets stimulated, apart from the direct costimulation, by certain growth factors, viz.,
interleukins Interleukins (ILs) are a group of cytokines (secreted proteins and signal molecules) that are expressed and secreted by white blood cells (leukocytes) as well as some other body cells. The human genome encodes more than 50 interleukins and related ...
2, 4, 5, and 6 in a
paracrine In cellular biology, paracrine signaling is a form of cell signaling, a type of cellular communication (biology), cellular communication in which a Cell (biology), cell produces a signal to induce changes in nearby cells, altering the behaviour of ...
fashion. These factors are usually produced by the newly activated T helper cell. However, this activation occurs only after the B cell receptor present on a
memory Memory is the faculty of the mind by which data or information is encoded, stored, and retrieved when needed. It is the retention of information over time for the purpose of influencing future action. If past events could not be remembe ...
or a
naive Naivety (also spelled naïvety), naiveness, or naïveté is the state of being naive. It refers to an apparent or actual lack of experience and sophistication, often describing a neglect of pragmatism in favor of moral idealism. A ''naïve'' may b ...
B cell itself would have bound to the corresponding epitope, without which the initiating steps of phagocytosis and antigen processing would not have occurred.


Proliferation and differentiation of B cell

A naive (or ''inexperienced'') B cell is one which belongs to a clone which has never encountered the epitope to which it is specific. In contrast, a memory B cell is one which derives from an activated naive or memory B cell. The activation of a naive or a memory B cell is followed by a manifold proliferation of that particular B cell, most of the progeny of which terminally differentiate into
plasma B cell Plasma cells, also called plasma B cells or effector B cells, are white blood cells that originate in the lymphoid organs as B cells and secrete large quantities of proteins called antibodies in response to being presented specific substances c ...
s;The plasma cells secrete antibodies that bind to the ''same'' structure that had stimulated the B cell in the first place by binding to its B cell receptor. the rest survive as memory B cells. So, when the naive cells belonging to a particular clone encounter their specific antigen to give rise to the plasma cells, and also leave a few memory cells, this is known as the ''primary immune response''. In the course of proliferation of this clone, the B cell receptor
gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
s can undergo frequent (one in every ''two'' cell divisions)
mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, ...
s in the genes coding for paratopes of antibodies. These frequent mutations are termed
somatic hypermutation Somatic hypermutation (or SHM) is a cellular mechanism by which the immune system adapts to the new foreign elements that confront it (e.g. microbes). A major component of the process of affinity maturation, SHM diversifies B cell receptors used t ...
. Each such mutation alters the epitope-binding ability of the paratope slightly, creating new clones of B cells in the process. Some of the newly created paratopes bind ''more strongly'' to the same epitope (leading to the
selection Selection may refer to: Science * Selection (biology), also called natural selection, selection in evolution ** Sex selection, in genetics ** Mate selection, in mating ** Sexual selection in humans, in human sexuality ** Human mating strat ...
of the clones possessing them), which is known as ''
affinity maturation In immunology, affinity maturation is the process by which TFH cell-activated B cells produce antibodies with increased affinity for antigen during the course of an immune response. With repeated exposures to the same antigen, a host will produce ...
''.Affinity roughly translates as ''attraction'' from Latin. See also
Definition of ''Affinity'' from Online Etymology Dictionary
an
Definition of ''Affinity'' from TheFreeDictionary by Farlex
/ref> Other paratopes bind better to epitopes that are ''slightly'' different from the original epitope that had stimulated proliferation. Variations in the epitope structure are also usually produced by mutations in the genes of pathogen coding for their antigen. Somatic hypermutation, thus, makes the B cell receptors and the soluble antibodies in subsequent encounters with antigens, more inclusive in their antigen recognition potential of ''altered'' epitopes, apart from bestowing greater specificity for the antigen that induced proliferation in the first place. When the memory cells get stimulated by the antigen to produce plasma cells (just like in the clone's primary response), and leave even more memory cells in the process, this is known as a '' secondary immune response,'' which translates into greater numbers of plasma cells and faster rate of antibody production lasting for longer periods. The memory B cells produced as a part of secondary response recognize the corresponding antigen faster and bind more strongly with it (i.e., greater affinity of binding) owing to affinity maturation. The soluble antibodies produced by the clone show a similar enhancement in antigen binding.


Basis of polyclonality

Responses are polyclonal in nature as each clone somewhat specializes in producing antibodies against a given epitope, and because, each antigen contains multiple epitopes, each of which in turn can be recognized by more than one clone of B cells. To be able to react to innumerable antigens, as well as multiple constituent epitopes, the immune system requires the ability to recognize a very great number of epitopes in all, i.e., there should be a great diversity of B cell clones.


Clonality of B cells

Memory Memory is the faculty of the mind by which data or information is encoded, stored, and retrieved when needed. It is the retention of information over time for the purpose of influencing future action. If past events could not be remembe ...
and naïve B cells normally exist in relatively small numbers. As the body needs to be able to respond to a large number of potential pathogens, it maintains a pool of B cells with a wide range of specificities. Consequently, while there is almost always at least one B (naive or memory) cell capable of responding to any given epitope (of all that the immune system can react against), there are very few exact duplicates. However, when a single B cell encounters an antigen to which it can bind, it can proliferate very rapidly. Such a group of cells with identical specificity towards the epitope is known as a '' clone'', and is derived from a common "mother" cell. All the "daughter" B cells match the original "mother" cell in their epitope specificity, and they secrete antibodies with identical paratopes. These antibodies are
monoclonal antibodies A monoclonal antibody (mAb, more rarely called moAb) is an antibody produced from a Lineage (evolution), cell lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell. Mon ...
, since they derive from clones of the same parent cell. A polyclonal response is one in which clones of multiple B cells react to the same antigen.


Single antigen contains multiple overlapping epitopes

A single antigen can be thought of as a sequence of multiple overlapping epitopes. Many unique B cell clones may be able to bind to the individual epitopes. This imparts even greater multiplicity to the overall response. All of these B cells can become activated and produce large colonies of plasma cell clones, each of which can secrete up to 1000 antibody molecules against each epitope per second.


Multiple clones recognize single epitope

In addition to different B cells reacting to ''different'' epitopes on the same antigen, B cells belonging to different clones may also be able to react to the ''same'' epitope. An epitope that can be attacked by many different B cells is said to be highly ''immunogenic''. In these cases, the ''binding affinities'' for respective epitope-paratope pairs vary, with some B cell clones producing antibodies that bind strongly to the epitope, and others producing antibodies that bind weakly.


Clonal selection

The clones that bind to a particular epitope with greater strength are more likely to be ''selected'' for further proliferation in the germinal centers of the follicles in various lymphoid tissues like the
lymph nodes A lymph node, or lymph gland, is a kidney-shaped Organ (anatomy), organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphoc ...
. This is not unlike
natural selection Natural selection is the differential survival and reproduction of individuals due to differences in phenotype. It is a key mechanism of evolution, the change in the Heredity, heritable traits characteristic of a population over generation ...
: clones are selected for their fitness to attack the epitopes (strength of binding) on the encountered pathogen. What makes the analogy even stronger is that the B lymphocytes have to compete with each other for signals that promote their survival in the germinal centers.


Diversity of B cell clones

Although there are many diverse pathogens, many of which are constantly mutating, it is a surprise that a majority of individuals remain free of infections. Thus, maintenance of health requires the body to recognize all pathogens (antigens they present or produce) likely to exist. This is achieved by maintaining a pool of immensely large (about 109) clones of B cells, each of which reacts against a specific epitope by recognizing and producing antibodies against it. However, at any given time very few clones actually remain receptive to their specific epitope. Thus, approximately 107 different epitopes can be recognized by all the B cell clones combined. Moreover, in a lifetime, an individual usually requires the generation of antibodies against very few antigens in comparison with the number that the body can recognize and respond against.


Significance of the phenomenon


Increased probability of recognizing any antigen

If an antigen can be recognized by more than one component of its structure, it is less likely to be "missed" by the immune system.Analogically, if in a crowded place, one is supposed to recognize a person, it is better to know as many physical features as possible. If you know the person only by the hairstyle, there is a chance of overlooking the person if that changes. Whereas, if apart from the hairstyle, if you also happen to know the facial features and what the person will wear on a particular day, it becomes much more unlikely that you will miss that person. Mutation of pathogenic organisms can result in modification of antigen—and, hence, epitope—structure. If the immune system "remembers" what the other epitopes look like, the antigen, and the organism, will still be recognized and subjected to the body's immune response. Thus, the polyclonal response widens the range of pathogens that can be recognized.


Limitation of immune system against rapidly mutating viruses

Many viruses undergo frequent
mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, ...
s that result in changes in amino acid composition of their important proteins. Epitopes located on the protein may also undergo alterations in the process. Such an altered epitope binds less strongly with the antibodies specific to the unaltered epitope that would have stimulated the immune system. This is unfortunate because somatic hypermutation does give rise to clones capable of producing soluble antibodies that would have bound the altered epitope avidly enough to neutralize it. But these clones would consist of naive cells which are not allowed to proliferate by the weakly binding antibodies produced by the priorly stimulated clone. This doctrine is known as the ''
original antigenic sin Original antigenic sin, also known as antigenic imprinting, the Hoskins effect, immunological imprinting, or primary addiction is the propensity of the immune system to preferentially use immunological memory based on a previous infection when a ...
''. This phenomenon comes into play particularly in immune responses against
influenza Influenza, commonly known as the flu, is an infectious disease caused by influenza viruses. Symptoms range from mild to severe and often include fever, runny nose, sore throat, muscle pain, headache, coughing, and fatigue. These sympto ...
,
dengue Dengue fever is a mosquito-borne disease caused by dengue virus, prevalent in tropical and subtropical areas. Asymptomatic infections are uncommon, mild cases happen frequently; if symptoms appear, they typically begin 3 to 14 days after ...
and
HIV The human immunodeficiency viruses (HIV) are two species of '' Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the im ...
viruses. This limitation, however, is not imposed ''by'' the phenomenon of polyclonal response, but rather, ''against it'' by an immune response that is biased in favor of experienced memory cells against the "novice" naive cells.


Increased chances of autoimmune reactions

In
autoimmunity In immunology, autoimmunity is the system of immune responses of an organism against its own healthy cells, tissues and other normal body constituents. Any disease resulting from this type of immune response is termed an " autoimmune disease ...
the immune system wrongly recognizes certain native molecules in the body as foreign (''self-antigen''), and mounts an immune response against them. Since these native molecules, as normal parts of the body, will naturally always exist in the body, the attacks against them can get stronger over time (akin to secondary immune response). Moreover, many organisms exhibit
molecular mimicry Molecular mimicry is the theoretical possibility that sequence similarities between foreign and self-peptides are enough to result in the cross-activation of autoreactive T or B cells by pathogen-derived peptides. Despite the prevalence of sever ...
, which involves showing those antigens on their surface that are antigenically similar to the host proteins. This has two possible consequences: first, either the organism will be spared as a self antigen; or secondly, that the antibodies produced against it will also bind to the mimicked native proteins. The antibodies will attack the self-antigens and the tissues harboring them by activating various mechanisms like the complement activation and
antibody-dependent cell-mediated cytotoxicity Antibody-dependent cellular cytotoxicity (ADCC), also referred to as antibody-dependent cell-mediated cytotoxicity, is a mechanism of Cell-mediated immunity, cell-mediated immune defense whereby an effector cell of the immune system kills a target ...
. Hence, wider the range of antibody-specificities, greater the chance that one or the other will react against self-antigens (native molecules of the body).


Difficulty in producing monoclonal antibodies

Monoclonal antibodies A monoclonal antibody (mAb, more rarely called moAb) is an antibody produced from a Lineage (evolution), cell lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell. Mon ...
are structurally identical immunoglobulin molecules with identical epitope-specificity (all of them bind with the same epitope with same affinity) as against their polyclonal counterparts which have varying affinities for the same epitope. They are usually not produced in a natural immune response, but only in diseased states like
multiple myeloma Multiple myeloma (MM), also known as plasma cell myeloma and simply myeloma, is a cancer of plasma cells, a type of white blood cell that normally produces antibody, antibodies. Often, no symptoms are noticed initially. As it progresses, bone ...
, or through specialized laboratory techniques. Because of their specificity, monoclonal antibodies are used in certain applications to quantify or detect the presence of substances (which act as antigen for the monoclonal antibodies), and for targeting individual cells (e.g. cancer cells). Monoclonal antibodies find use in various diagnostic modalities (see:
western blot The western blot (sometimes called the protein immunoblot), or western blotting, is a widely used analytical technique in molecular biology and immunogenetics to detect specific proteins in a sample of tissue homogenate or extract. Besides detect ...
and
immunofluorescence Immunofluorescence (IF) is a light microscopy-based technique that allows detection and localization of a wide variety of target biomolecules within a cell or tissue at a quantitative level. The technique utilizes the binding specificity of anti ...
) and
therapies A therapy or medical treatment is the attempted remediation of a health problem, usually following a medical diagnosis. Both words, ''treatment'' and ''therapy'', are often abbreviated tx, Tx, or Tx. As a rule, each therapy has indications an ...
—particularly of cancer and diseases with autoimmune component. But, since virtually all responses in nature are polyclonal, it makes production of immensely useful monoclonal antibodies less straightforward.


History

The first evidence of presence of a neutralizing substance in the blood that could counter infections came when
Emil von Behring Emil von Behring (; Emil Adolf von Behring: born Emil Adolf Behring; 15 March 1854 – 31 March 1917), was a German physiologist who received the 1901 Nobel Prize in Physiology or Medicine, the first one awarded in that field, for his discovery ...
along with
Kitasato Shibasaburō Baron was a Japanese physician and bacteriologist. He is remembered as the co-discoverer of the infectious agent of bubonic plague in Hong Kong during an outbreak in 1894, almost simultaneously with Alexandre Yersin. Kitasato was nomin ...
in 1890 developed effective serum against diphtheria. This they did by transferring serum produced from animals immunized against diphtheria to animals suffering from it. Transferring the serum thus could cure the infected animals. Behring was awarded the
Nobel Prize The Nobel Prizes ( ; ; ) are awards administered by the Nobel Foundation and granted in accordance with the principle of "for the greatest benefit to humankind". The prizes were first awarded in 1901, marking the fifth anniversary of Alfred N ...
for this work in 1901. At this time though the chemical nature of what exactly in the blood conferred this protection was not known. In a few decades to follow, it was shown that the protective serum could neutralize and precipitate toxins, and clump bacteria. All these functions were attributed to different substances in the serum, and named accordingly as ''antitoxin'', ''precipitin'' and ''agglutinin''. That all the three substances were one entity (
gamma globulin Gamma globulins are a class of globulins, identified by their position after serum protein electrophoresis. The most significant gamma globulins are immunoglobulins (antibodies), although some immunoglobulins are not gamma globulins, and some ...
s) was demonstrated by Elvin A. Kabat in 1939. In the preceding year Kabat had demonstrated the heterogeneity of antibodies through ultracentrifugation studies of horses' sera. Until this time, cell-mediated immunity and humoral immunity were considered to be contending theories to explain effective immune response, but the former lagged behind owing to lack of advanced techniques. Cell-mediated immunity got an impetus in its recognition and study when in 1942,
Merrill Chase Merrill W. Chase (September 17, 1905 – January 5, 2004) was an immunologist working at Rockefeller University in New York City who is credited with discovering cell-mediated immunology in the early 1940s. While working with Dr. Karl Landsteine ...
successfully transferred immunity against
tuberculosis Tuberculosis (TB), also known colloquially as the "white death", or historically as consumption, is a contagious disease usually caused by ''Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can al ...
between pigs by transferring white blood cells. It was later shown in 1948 by Astrid Fagraeus in her doctoral thesis that the plasma B cells are specifically involved in antibody production. The role of lymphocytes in mediating both cell-mediated and humoral responses was demonstrated by James Gowans in 1959. In order to account for the wide range of antigens the immune system can recognize,
Paul Ehrlich Paul Ehrlich (; 14 March 1854 – 20 August 1915) was a Nobel Prize-winning German physician and scientist who worked in the fields of hematology, immunology and antimicrobial chemotherapy. Among his foremost achievements were finding a cure fo ...
in 1900 had hypothesized that preexisting ''"side chain receptors"'' bind a given pathogen, and that this interaction induces the cell exhibiting the receptor to multiply and produce more copies of the same receptor. This theory, called ''the selective theory'' was not proven for next five decades, and had been challenged by several ''instructional theories'' which were based on the notion that an antibody would assume its effective structure by folding around the antigen. In the late 1950s however, the works of three scientists— Jerne, Talmage and Burnet (who largely modified the theory)—gave rise to the
clonal selection theory In immunology, clonal selection theory explains the functions of cells of the immune system (lymphocytes) in response to specific antigens invading the body. The concept was introduced by Australian doctor Frank Macfarlane Burnet in 1957, in an ...
, which proved all the elements of Ehrlich's hypothesis except that the specific receptors that could neutralize the agent were soluble and not membrane-bound. The clonal selection theory was proved correct when Sir
Gustav Nossal Sir Gustav Victor Joseph Nossal (born 4 June 1931) is an Austrian-born Australian research biologist. He is famous for his contributions to the fields of antibody formation and immunological tolerance. Early life and education Nossal's family w ...
showed that each B cell always produces only one antibody. In 1974, the role of MHC in antigen presentation was demonstrated by
Rolf Zinkernagel Rolf Martin Zinkernagel AC (born 6 January 1944) is a professor of experimental immunology at the University of Zurich. Along with Peter C. Doherty, he shared the 1996 Nobel Prize in Physiology or Medicine for the discovery of how t ...
and
Peter C. Doherty Peter Charles Doherty (born 15 October 1940) is an Australian immunologist and Nobel laureate. Doherty received the Albert Lasker Award for Basic Medical Research in 1995, the Nobel Prize in Physiology or Medicine jointly with Rolf M. Zink ...
.


See also

*
Polyclonal antibodies Polyclonal antibodies (pAbs) are antibodies that are secreted by different B cell lineages within the body (whereas monoclonal antibodies come from a single cell lineage). They are a collection of immunoglobulin molecules that react against a s ...
* Antigen processing *
Antiserum In immunology, antiserum is a blood serum containing antibodies (either monoclonal or polyclonal) that is used to spread passive immunity to many diseases via blood donation ( plasmapheresis). For example, convalescent serum, or passive ant ...
, a polyclonal antibody preparation used to treat envenomation


Notes


References


Further reading

* * *


External links


An Introduction to the Immune system
{{DEFAULTSORT:Polyclonal B Cell Response Immune system Immunology Cell biology