Polyclonal B cell response
Polyclonal response is a natural mode of response exhibited by the adaptive immune system. It ensures that a single antigen is recognized through its multiple overlapping parts (epitopes) by multiple clones of B lymphocytes.[1][2]
B cell response
An antigen is any substance (usually a protein) that can be ‘recognized’ by the host organism. As the proteins are relatively large, they cannot be recognized as a whole; instead, certain portions on it--the epitopes—-are recognized. So, when an antigen is phagocytosed by an antigen presenting cell (APC) like the macrophage or the B lymphocyte, it is broken down into various peptides in its lysosomes.
The individual peptides are then complexed with major histocompatibility class II (MHC class II) molecules located in the lysosome—exogenous pathway of antigen processing. From here the complex migrates to the plasma membrane, and is elaborated as a complex that can be recognized by the CD 4+ (T helper cells).
Whatever the cell type, recognizing an antigen or a segment thereof (epitope) requires binding of the antigen with the corresponding paratope present on the receptor present on the surface of the recognizing cell. In the immune system, these are the T (TCR) and the B (BCR) cell receptors. The binding between a paratope and its corresponding antigen is very specific owing to their structures and is guided by various noncovalent bonds not unlike pairing of other types of ligands and their corresponding receptors.
The CD 4+ cells through their TCR recognize the epitope-bound MHC II molecules on the surface of the APCs, and get 'activated'. However, complete stimulation requires the B7 molecule present on the APC to bind with CD28 molecule present on the T cell surface close to the TCR. When this activated T cell encounters a B cell with the paratope that recognizes the same epitope as recognized by TCR's paratope, the latter (B cell) gets stimulated because of secretion of certain growth factors, viz., interleukins 2, 4, 5, and 6 in a paracrine fashion.[3] However, this activation occurs only when the BCR present on a memory or a naive B cell itself is bound to the corresponding epitope.
This is followed by a manifold proliferation of that particular B lymphocyte, most of the progenies of which terminally differentiate into Plasma (or B effector) cells, which secrete the antibodies (first IgM, and then IgG, in that sequence) that have the same paratope as that present on the B and the T cells that had got stimulated initially.
In the course of this proliferation, the BCR genes can undergo somatic hypermutation, making the subsequent encounters with antigens more inclusive in their antigen recognition potential.
Basis of polyclonal response
Polyclonal derives from the words poly, meaning many, and clones. A clone is a group of cells with common ancestry (mother cell).
In natural immune response the memory or naïve B cells exist in only small numbers, which can proliferate upon encountering an antigen to which they are specific. Each such group of cells with identical specificity towards the epitope is known as a colony or a clone, and is essentially derived from a common mother cell. Also, the paratopes contained on the antibodies secreted by the derivatives (plasma cells) will be the same.
However, the same epitope can be recognized by naïve/memory cells belonging to different clones. The binding affinities for respective epitope-paratope pairs are varying, with certain epitopes being more "immunogenic" than others. This bonding requires both the paratope and the epitope to undergo slight conformational changes in each others' presence.[4] The clones that bind to a particular epitope with sufficient strength are selected for further proliferation in the germinal centers of the follicles in various lymphoid tissues like the lymph nodes. This is not very different from Darwinian concept of natural selection—a clone that gets selected in one of the encounters stands lesser chance of getting selected if the epitope structure changes somewhat.
Moreover, if the same epitope can elicit response from multiple clones, a single antigen can be broken down into multiple peptides, which in turn contain overlapping epitopes (see the schematic above), imparting even greater multiplicity to the overall response.[5]
Significance
Greatest probability of recognizing antigen
This is because, if an antigen can be recognized by more than one components of its structure, it is less likely to be "missed" by the immune system. An analogy could be helpful: 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 unlikelier that you will miss the person. Here the concept of mutation of pathogenic organisms is being explained, which can result in modification of antigen (and, hence, epitope-) structure. Now, if the immune system "remembers" what the other epitopes look like, the antigen, and the organism will still be recognized and subjected to body's immune response.
Increased chances of autoimmune reactions
The phenomenon of autoimmunity can be most simply explained in terms of immune system mistaking certain native molecules in the body to be foreign, and in turn mounting an immune response against them. Since these native molecules will not be eliminated in course of time, the responses against them get stronger with time resulting in worsening of the situation. Moreover, many organisms exhibit molecular mimicry, whereby, they elaborate those antigens on their surface, which are antigenically similar to the host proteins with two possible consequences that either the organism will be "spared" as a self antigen, or the antibodies produced against it will also bind to the proteins that the organism would have "mimicked", and the the harboring tissue will come under attack by various mechanisms like the complement activation and Antibody-dependent cell-mediated cytotoxicity. Hence, if the body produces more varieties (differing specificities as a result of polyclonal response) of the antibodies, greater the chance that one or the other will react against self-antigens (native molecules of the body).[6],[7]
Monoclonal antibodies have to be produced by specialized techniques
Monoclonal antibodies are structurally identical immunoglobulin molecules with identical epitope-specificity (all of them bind with the same epitope with same strength [avidity]) as against their polyclonal counterparts which have varying affinities for the same epitope. Monoclonal antibodies find use in various diagnostic modalities (see: western blot and immunofluorescence) and therapies--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.
See also
References
- ^ Goldsby RA, Kindt TK, Osborne BA and Kuby J (2003) Immunology, 5th Edition, W.H. Freeman and Company, New York, New York, ISBN 0-7167-4947-5
- ^ http://www.medterms.com/script/main/art.asp?articlekey=20127
- ^ McPhee, Stephen; Ganong, William (2006). . "Pathophysiology of Disease: An Introduction to Clinical Medicine". Lange Medical Books/McGraw-Hill. p. 39. ISBN 0-07-110523-9.
- ^ Nair, Deepak; Singh, Kavita; Siddiqui, Zaved; Nayak, Bishnu; Rao, Kanury; Salunke, Dinakar (2001-09-24), "Epitope Recognition by Diverse Antibodies Suggests Conformational Convergence in an Antibody Response" (PDF), vol. 168, The American Association of Immunologists (published 2002-01-09), pp. 2371–2382, retrieved 2008-05-03
{{citation}}: Check date values in:|year=/|date=mismatch (help) - ^ http://www.microbiologybytes.com/iandi/3b.html/
- ^ Granholm, Norman (1992). ""Autoimmunity, Polyclonal B-Cell Activation and Infection"(abstract)". Lupus. 1 (2). SAGE Publications: 63-74. doi:<font>10.1177/096120339200100203</font>. Retrieved 2008-05-4.
{{cite journal}}: Check|doi=value (help); Check date values in:|accessdate=(help); Unknown parameter|coauthors=ignored (|author=suggested) (help) - ^ Montes, Carolina. "Polyclonal B cell activation in infections: infectious agents' devilry or defense mechanism of the host? (abstract)". Journal of Leukocyte Biology. 82: 1027–1032. doi:<font>10.1189/jlb.0407214</font>.
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