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Generation of Diversity

A) Why could gene arrangement be detrimental to lymphocyte survival but indispensable for host integrity?

b) Explain the roles of promotors, enhancers, and silencers as they pertain to immunoglobulin gene expression.

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Biology, Immunology
Generation of Diversity

Hello, this is a two part question. This is for an immunology class for graduate school. Thank you.

a) Why could gene arrangement be detrimental to lymphocyte survival but indispensable for host integrity?

Lymphocyte Development
As described in Part 1, lymphocytes are generated in the bone marrow from a single progenitor cell line. These progenitor cells differentiate into the various myeloid cells, including B cells, that when activated develop into antibody- producing plasma cells and T cells of which there are 2 primary classes in the adaptive immune system. One class of T cells upon activation differentiates into cytotoxic T cells (CTLs), whereas the second class of T cells is known as helper T cells (Th) and differentiate into cells that activate other cells such as B cells, macrophages and CTLs. The B lymphocytes mature in the bone marrow, while T lymphocytes migrate to the thymus to mature. Thus, the bone marrow and thymus are considered primary lymphoid organs, in contrast to the secondary lymphoid organs where the adaptive immune responses are initiated and maintained.

In contrast to the cells of the innate immune system, which recognize similar molecular patterns and structures present on the surface of many micro-organisms, lymphocytes have antigen receptors with a single specificity. This specificity is determined by the re-arrangement and recombination of DNA during lymphocyte development in the bone marrow or thymus. This process results in the production of lymphocytes with millions of different variants of the genes coding the receptor molecules. Each individual lymphocyte has a unique specificity, resulting in a repertoire of millions of lymphocytes with millions of different antigen receptors with differing specificity. However, as with every other aspect of the immune system, this repertoire of antigen receptors is tightly controlled and only those lymphocytes that encounter their specific antigen and do not recognize "self" are allowed to become activated and proliferate into armed effector cells. All others are doomed to failure and death.

Each naive lymphocyte undergoes clonal expansion following recognition and activation by their antigen. Clonal expansion and selection is one of the most important concepts of the immune system. This explains how, upon activation, a single lymphocyte divides to produce many identical progeny responding to a single antigen, known as clones. In the case of B cells, all clones produce identical antibodies resulting in the antibody response to an antigen veterinarians commonly measure to assess exposure to pathogens. The T cell progeny upon clonal expansion each have identical T cell receptors that recognize the identical antigen in an identical fashion. In a similar fashion, all lymphocytes originating from a clone considered to be dangerous to the host are eliminated by clonal deletion. Clonal expansion allows a single lymphocyte to produce the majority of lymphocytes that respond specifically to a pathogen, a fascinating and yet intimidating concept in terms of disease control.

Lymphocyte Survival
Once the lymphocytes have left the central lymphoid tissues and migrate into the periphery, their organization and survival is determined by interactions between lymphocytes and other cells within the secondary lymphoid organs. A lymphocyte circulates throughout the blood, lymph, and various secondary lymphoid organs until either it ...

Solution Summary

The solution discusses the generation of diversity.