Polyclonal B cell response is a natural mode of immune response exhibited by the adaptive immune system of mammals. It ensures that a single antigen is recognized and attacked through its overlapping parts, called epitopes, by multiple clones of B cell.
In the course of normal immune response, parts of pathogens (e.g. bacteria) 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. The immune system may respond in multiple ways to an antigen; a key feature of this response is the production of antibodies by B cells (or B lymphocytes) involving an arm of the immune system known as humoral immunity. 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. The heterogeneous polyclonal antibodies are distinct from monoclonal antibody 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 diseases, and the causative biological agent involved is known as a pathogen. The process by which the pathogen is introduced into the body is known as inoculation,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—the causative organism for typhoid fever. 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, it can result in an infection, consequently harming the host directly or through the harmful substances called toxins it can produce. This results in the various symptoms and signs characteristic of an infectious disease like pneumonia or diphtheria.
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 cells, tissues and organs that specializes in protecting the body against infections is known as the immune system. The immune system accomplishes this through direct contact of certain white blood cells 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 specificallySpecificity 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. Thus the antibody acts as an opsonin. The process of engulfing is known as phagocytosis (literally, cell eating) Activating the complement system, which most importantly pokes holes into the pathogen's outer covering (its cell membrane), killing it in the process Marking up host cells infected by viruses for destruction in a process known as Antibody-dependent cell-mediated cytotoxicity (ADCC)
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 cells, a type of white blood cell. This production is tightly regulated and requires the activation of B cells by activated T cells (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 macrophages. This activates the B cell only partially. Antigen processing. Antigen presentation. Activation of the T helper cells by antigen-presenting cells. Co-stimulation of the B cell by activated T cell resulting in its complete activation. ProliferationProliferation in this context means multiplication by cell division and differentiation of B cells with resultant production of soluble antibodies.
Recognition of pathogens
Pathogens synthesize proteins 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. The same antibodies can be anchored to the surface of cells of the immune system, in which case they serve as receptors, 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 epitopes, 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 the immune system, membrane-bound antibodies are the B-cell receptor (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 (MHC) molecules.The major histocompatibility complex is a gene region on the DNA 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 (MHC class III). The first two products are important in antigen presentation. MHC-compatibility is a major consideration in organ transplantation, and in humans is also known as the human leukocyte antigen (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 (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 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 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, 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 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 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 receptors (PRRs) like the toll-like receptors (TLRs) expressed by the macrophages. Since the same receptor could bind to a given motif present on surfaces of widely disparate microorganisms, this mode of recognition is relatively nonspecific, and constitutes an innate immune response.
Antigen processing
After recognizing an antigen, an antigen-presenting cell such as the macrophage or B lymphocyte engulfs it completely by a process called phagocytosis. The engulfed particle, along with some material surrounding it, forms the endocytic vesicle (the phagosome), which fuses with lysosomes. Within the lysosome, the antigen is broken down into smaller pieces called peptides by proteases (enzymes that degrade larger proteins). The individual peptides are then complexed with major histocompatibility complex class II (MHC class II) 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 or in a tumor cell) with MHC class I molecules.