Clonal selection theory

CLONAL SELECTION THEORY IS AN SCIENTIFIC THEORY IN IMMUNOLOGY THAT EXPALINS THE FUNCTION OF CELLS OF THE IMMUNE SYSTEM IN RESPONSE TO SPECIFIC ANTIGEN INVADING THE BODY.

1. Prepared By: Vipin Kr Shukla Assistant Lecturer . CLONAL SELECTION THEORY

2. Introduction: Clonal   selection  theory is a scientific theory in immunology that explains the functions of cells (lymphocytes) of the immune system in response to specific antigens invading the body. The concept was introduced by an Australian doctor Frank Macfarlane Burnet in 1957 in an attempt to explain the formation of a diversity of antibodies during initiation of the immune response .

3. History: In 1900, Paul Ehrlich proposed the so-called side chain theory of antibody production. In 1955, Danish immunologist Niels Jerne put forward a hypothesis that there is already a vast array of soluble antibodies in the serum prior to any infection. The entrance of an antigen into the body results in the selection of only one type of antibody to match it. In 1957, Frank Macfarlane Burnet published a paper titled ‘A modification of Jerne's theory of antibody production using the concept of Clonal selection’ in a rather obscure Australian Journal of Science. In it Burnet expanded the ideas of Talmage and named it "Clonal selection theory

4. Continued……. B lymphocytes (b cells): Lymphocytes respond specifically to antigens on foreign cells, cells infected by pathogens and toxins released by pathogens. AN ANTIGEN IS A COMPLEX MOLECULE RECOGNISABLE AS SELF OR FOREIGN/ NON-SELF ANTIGEN TRIGGERS PRODUCTION OF ANTIBODIES ANTIBODY IS A Y-SHAPED MOLECULE WITH A SPECIFIC RECEPTOR (BINDING SITE)

5. Memory B cells : ( MBCs ) are a B-cell sub-type that are formed within germinal centers following primary infection. Memory B cells can survive for decades and repeatedly generate an accelerated and robust antibody-mediated immune response in the case of re-infection (also known as a secondary immune response).

6. Production of antibodies from B Cell: B cells develop from stem cells in the bone marrow of adults (liver of fetuses). After maturation B cells migrate to lymphoid organs (lymph node or spleen). Clonal Selection: When a B cell encounters an antigen it recognizes, it is stimulated and divides into many clones called plasma cells, which actively secrete antibodies. Each B cell produces antibodies that will recognize only one antigenic determinant.

7. Clonal selection of B Cell is done by antigenic stimulation:

8. Cloning: Cloning is the process of creating an identical copy of an original organism or thing. Cloning in the biological sense results in a molecule, single cell (for example: bacteria, lymphocytes, etc.) or multi-cellular organism that has been directly copied from and is therefore genetically identical to the molecule, cells or organism being cloned. Sometimes this term can refer to "natural" clones, which may arise when an organism reproduces asexually by chance (as with identical twins), but in common parlance, a clone is an identical copy created intentionally.

9. Molecular Cloning: Molecular cloning refers to the procedure of isolating a DNA sequence of interest and obtaining multiple copies of it in an organism. Cloning is frequently employed to amplify DNA fragments containing genes, an essential step in their subsequent analysis. Frequently, the term cloning is misleadingly used to refer to the identification of the chromosomal location of a gene associated with a particular phenotype of interest, such as in positional cloning. In practice, localization of the gene to a chromosome or genomic region does not necessarily enable one to isolate or amplify the relevant genomic sequence.

10. New organisms creation by cloning: Cloning means to create a new organism with the same genetic information as a cell from an existing one(identical). It is an asexual method of reproduction, where fertilization or inter-gamete contact does not take place. Asexual reproduction (also known as agamogenesis) is a form of reproduction which does not involve meiosis, gamete formation, or fertilization. In laymen's terms, there is only one "parent“ involved. This form of reproduction is common among simple organisms such as amoeba and other single-celled organisms, although most plants reproduce asexually as well

11. Species cloned so far: The modern cloning techniques involving nuclear transfer have been successfully performed on several species. Landmark experiments in chronological order: Tadpole: (1952) Many scientists questioned whether cloning had actually occurred and unpublished experiments by other labs were not able to reproduce the reported results. Carp: (1963) In China, embryologist Tong Dizhou cloned a fish. He published the findings in an obscure Chinese science journal which was never translated into English.

12. Continued…… Mice: (1986) was the first successfully cloned mammal; Soviet scientists Chaylakhyan, Veprencev, Sviridova, Nikitin had mice "Marsha" cloned. Research was published in the magazine "Biofizika“ Sheep: (1996) From early embryonic cells by Steen Willadsen. Megan and Morag cloned from differentiated embryonic cells in June 1995 and Dolly the sheep in 1997. Rhesus Monkey: Tetra (female, January 2000) from embryo splitting Cattle: Alpha and Beta (males, 2001) and (2005) Brazil.

13. Continued….. Cat: CopyCat "CC" (female, late 2001), Little Nicky, 2004, was the first cat cloned for commercial reasons Mule: Idaho Gem, a john mule born 2003-05-04, was the first horse-family clone. Horse: Prometea, a Haflinger female born 2003-05-28, was the first horse clone.

14. Clonal selection theory: It is one of the theory of Immune Response. This theory explains how our immune system recognize Antigen, or how our immune responds against any Antigen. It is one of the relevant and most widely accepted theory. It was proposed by scientist named as “ Burnet”. According to this theory cell capable of recognizing or responding against any antigen during embryonic period. In this theory , the cells are formed by somatic mutation. The cells that react with self antigens are eliminated and called as forbidden cells. Their persistence in later life leads to Autoimmune process.

15. Continued……. During encounter of Antigen these Immunocompetent cells proliferate and they synthesize Antibodies. Later these Antibodies going to interact with the Antigen in blood stream were Antigen & Antibody Interactions takes place.

16. Theories supported by Clonal selection: Burnet and Peter Medawar worked together on understanding immunological tolerance, a phenomenon also explained by Clonal selection. This is the organism’s ability to tolerate the introduction of cells prior to the development of an immune response as long as it occurs early in the organism’s development.

17. Continued…… There are a vast number of lymphocytes occurring in the immune system, ranging from cells that tolerate self tissue to cells that do not . However, only cells tolerant of self tissue survive the embryonic stage. If non-self tissue is introduced, lymphocytes that develop are the ones that include the non-self tissues as self tissue.

18. Continued…… In 1959, Burnet proposed that under certain circumstances, tissues could be successfully transplanted into foreign recipients. This work has led to a much greater understanding of the immune system and also great advances in tissue transplantation. Burnet and Medawar shared the Nobel Prize in Physiology or Medicine  in 1960.

19. Continued…… In 1974, Niels Kaj Jerne  proposed that the immune system functions as a network that is regulated via interactions between the variable parts of lymphocytes and their secreted molecules.  Immune network theory is firmly based on the concept of Clonal selection. Jerne won the Nobel Prize in Physiology or Medicine in 1984, largely for his contributions to immune network theory.