Antibody: Difference between revisions

==Cellular Basis of Antibody Production==

When a foreign antigen binds to a B-lymphocyte ([http://en.wikipedia.org/wiki/B_cell B-cell]), it activates the B-cell, and upon stimulation by [http://en.wikipedia.org/wiki/Helper_t_cell helper T-cells], undergoes clonal proliferation and B-cell maturation into antibody forming [http://en.wikipedia.org/wiki/Plasma_cells plasma cells]. Each plasma cell is programmed to make an antibody of a single specificity, which it releases into the blood. <ref name="Roit"> Roit, I. M. Roit's Essential Immunology. Oxford: Blackwell Science Ltd., 1997.</ref>  Once in the blood, antibodies aid [http://en.wikipedia.org/wiki/Humoral_immune_system the humoral immune system] in three predominant ways: They coat foreign pathogens preventing them from entering healthy cells or disrupting antigen function; they coat pathogens, stimulating their removal via [http://en.wikipedia.org/wiki/Opsonization opsonization] by [http://en.wikipedia.org/wiki/Phagocytes phagocytes]; and they trigger destruction of pathogens by stimulating the [http://en.wikipedia.org/wiki/Complement_system complement pathway] or by [http://en.wikipedia.org/wiki/Antibody-dependent_cellular_cytotoxicity Antibody Dependent Cell-mediated Cytotoxicity], among other immune responses. <ref>PMID:8476565</ref> <ref>PMID:16234578</ref> All of these functions rely heavily on accurate antigen binding and communication with other immune effector cells. The amazing specificity antibodies operate with is made possible by the physical structure of the antibody, which appears simplistic, but contains several levels of additional complexity.  

==Structure of the Immunoglobulin==

The basic functional unit of an antibody is an immunoglobulin monomer, but antibodies secreted from plasma cells are typically dimeric with occasional higher order structures. Typical secreted antibodies have a basic four-peptide structure of two identical <scene name='Antibody/1igt_heavy_chains/1'>heavy chains </scene>and two identical <scene name='Antibody/1igt_light_chains/1'>light chains</scene> joined together by interchain <scene name='Antibody/1igt_disulfide_bonds/2'>disulfide bonds</scene>, forming a “Y” shaped molecule. The disulfide bonds are positioned within a flexible region called the <scene name='Antibody/1igt_hinge_region/1'>hinge region</scene>, which seperates the lobes of the antibody from one another and provides ample flexibility to bind antigens effectively. <ref name="Roit" /> Each domain (2 heavy and 2 light) contain between 70-110 amino acids and are classified into different categories according to size and function. <ref>PMID:10545762</ref> Both domains, heavy and light, contain variable and constant regions that are crucial to antibody function. <ref>PMID:107164</ref>  

[[Image:VDJ recombination.png|400px|left|thumb| Image of V(D)J Recombination]]

Considering the nearly infinite number of possible antigens that can invade the body, the immune system had to develop a method for accurately targeting each one of these compounds, ranging from small molecules, to stray proteins, to viruses capable of infecting cells. The antibody was the immune systems response to this problem. It has been estimated that humans generate about 10^10 different antigens, each capable of binding a unique epitope of an antigen. Since antibodies are proteins, and proteins are controlled by the genes from which they are transcribed, a clever system of gene shuffling and manipulations developed to enable the immune system to create a huge repertoire of antibodies from a limited number of genes. <ref>PMID:8612345</ref> The variable region of each immunoglobulin chain is encoded in several pieces known as gene segments. For heavy chains, these segments are called the variable (V), diversity (D), and joining (J) segments. (Only V and J exist for light chains)  50 V segments, 25 D segments, and 6 J segments exist and are randomly arranged and rearranged in the genome in a process called [http://en.wikipedia.org/wiki/VDJ_recombination V(D)J recombination]. Each B-cell is programmed to produce antibodies of a single V(D)J recombination order.  

[[Image:FluorescentCells.jpg|300px|right|thumb| Direct Immuno fluorescence Antibody labeling]]

==Antibody Applications==

Detection of particular antibodies is very common in medical diagnostic testing. Numerous biochemical assays exist to detect whether antibodies for specific antigens are present in the blood or other bodily fluids such as antibodies against [http://en.wikipedia.org/wiki/Lyme_disease Lyme disease] or [http://en.wikipedia.org/wiki/HIV HIV], etc. Another common medical test involving antibodies is blood type detection in which an individual’s blood is screened against anti-A and anti-B antibodies to determine the identity of that individual’s [http://en.wikipedia.org/wiki/Blood_type blood antigen type]. <ref>PMID:13477267</ref>  

The last two decades have seen a dramatic increase in antibody based technologies both for the lab and medicine thanks to the invention of the monoclonal antiboy, a discovery that won Niels K. Jerne, Georges J.F. Köhler, César Milstein the [http://nobelprize.org/nobel_prizes/medicine/laureates/1984/press.html Nobel Prize in Medicine in 1984]. See: [[Monoclonal Antibody]] for additional information.  

==References==