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Untitled - D Ank Unlimited

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clonal selection theory 179 Clostridium immunity<br />

Antigen<br />

B cells<br />

Production/<br />

maturation<br />

clonal selection theory<br />

A selective theory of antibody formation proposed by<br />

F.M. Burnett, who postulated the presence of numerous<br />

antibody-forming cells, each capable of synthesizing its<br />

own predetermined antibody. One of the cells, after having<br />

been selected by the best-fitting antigen, multiplies<br />

and forms a clone of cells that continue to synthesize the<br />

same antibody. Considering the existence of many different<br />

cells, each capable of synthesizing an antibody of a<br />

different specificity, all known facts of antibody formation<br />

are easily accounted for. An important element of the<br />

clonal selection theory was the hypothesis that many cells<br />

with different antibody specificities arise through random<br />

somatic mutations during a period of hypermutability<br />

early in life. Also early in life, the “forbidden” clones of<br />

antibody-forming cells (i.e., the cells that make antibody<br />

to the animal’s own antigen) are still destroyed after<br />

encountering these autoantigens. This process accounts for<br />

an animal’s tolerance of its own antigens. Antigen would<br />

have no effect on most lymphoid cells, but it would selectively<br />

stimulate those cells already synthesizing the corresponding<br />

antibody at a low rate. The cell surface antibody<br />

would serve as receptor for antigen and proliferate into<br />

a clone of cells, producing antibody of that specificity.<br />

Burnett introduced the forbidden clone concept to explain<br />

autoimmunity. Cells capable of forming antibody against a<br />

normal self antigen were “forbidden” and eliminated during<br />

embryonic life. During fetal development, clones that<br />

react with self antigens are destroyed or suppressed. The<br />

subsequent activation of suppressed clones reactive with<br />

self antigens in later life may induce autoimmune disease.<br />

D.W. Talmage proposed a cell selection theory of antibody<br />

formation that was the basis for Burnett’s clonal selection<br />

theory.<br />

clone<br />

A cell or organism that develops from a single progenitor<br />

cell and has exactly the same genotype and phenotype of<br />

the parent cell. Malignant proliferation of a clone of plasma<br />

cells in multiple myeloma represents a type of monoclonal<br />

gammopathy. The fusion of an antibody-producing B cell<br />

with a mutant myeloma cell in vitro by the action of polyethylene<br />

glycol to form a hybridoma that is immortal and<br />

Clonal selection theory.<br />

Memory cells<br />

Production<br />

of AB3<br />

produces monoclonal antibody is an example of the in vitro<br />

production of a clone.<br />

cloned DNA<br />

A DNA fragment or gene introduced into a vector and replicated<br />

in eukaryotic cells or bacteria.<br />

cloned enzyme donor immunoassay<br />

A homogeneous enzyme immunoassay (EIA) based on<br />

the modulation of enzyme activity by bound fragments<br />

of β-galactosidase.<br />

cloned T cell line<br />

A lineage of T lymphocytes that grow continuously from a<br />

single progenitor cell. Stimulation with antigen from time to<br />

time is necessary to maintain their growth. They are used<br />

in experimental immunology to investigate T cell function<br />

and specificity.<br />

clonotypic<br />

An adjective that defines the features of a specific B cell<br />

population’s receptors for antigen that are products of a single<br />

B lymphocyte clone. Following release from the B cells,<br />

these antibodies should be very specific for antigen, have<br />

a restricted spectrotype, and possess at least one unique<br />

private idiotypic determinant. Clonotypic may also describe<br />

the features of a particular clone of T lymphocytes’ specific<br />

receptor for antigen with respect to idiotypic determinants,<br />

specificity for antigen, and receptor similarity from one<br />

daughter cell of the clone to another.<br />

Clostridium immunity<br />

Clostridia produce disease by releasing exotoxins. They<br />

may produce more than one toxin, and each one is immunologically<br />

unique. For example, each of the five types<br />

of Clostridium perfringens produces a different toxin.<br />

Clostridia enter the host by many routes to produce disease.<br />

C. perfringens gains access through traumatic or surgical<br />

wounds to produce gas gangrene and wound infections.<br />

The microorganism is aided by a poor blood supply in the<br />

area of the wound. Clostridia divide and produce toxins<br />

that cause disease. When antibiotics upset the normal bowel<br />

flora, C. difficile may multiply and induce colitis. The toxins<br />

released from this organism act on intestinal epithelial<br />

cells and produce diarrhea and chronic inflammation. C.<br />

botulinum does not grow in the host but forms toxins in<br />

contaminated food that when ingested leads to disease.<br />

C

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