Punam Final

8/2/2019 Punam Final

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Genetically EngineeredProduction of Lymphokines.

-By

Gurjar Punam B.Roll No. 11Sem. V

Pharmaceutics.


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Definition:.Lymphokines are a subset of cytokines that

are produced by a type of immune cell. Protein mediators. Roles

- including the attraction of other immune

cells.- including macrophages.

Important lymphokines secreted by the T helpercell include:

Interleukin 2, Interleukin 3, Interleukin 4,Interleukin 5, Interleukin 6


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The cytokine profile of "natural immunity" by different

offending agents in the of different host geneticbackgrounds appears to be a critical factor indetermining the phenotype of the subsequent specificresponse.

Strongly polarized human Th1-type and Th2-typeresponses not only play different roles in protection, they

can also promote different immunopathologicalreactions.


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Th1-type responses appear to be involved in organ

specific autoimmunity, in contact dermatitis, and insome chronic inflammatory disorders of unknownetiology.

In contrast, in genetically predisposed hosts, Th2-typeresponses against common environmental allergens areresponsible for triggering of allergic atopic disorders.

Altered profiles of lymphokine production mayaccount for immune dysfunctions in some primary oracquired immunodeficiency syndromes.


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The role of lymphokines produced by T cells in thepathogenesis of systemic autoimmune disorders is lessclear.

Further work is also required to better clarify the role ofT cell-derived lymphokines in protecting against tumors

or in favoring their development.


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Abnormal lymphokine production:.

-unbalanced cytokine production in Fanconi anemia (FA)cells, i.e., an underproduction of interleukin 6 (IL-6)during growth.

Among a number of cytokines analyzed, the only detectedconcern tumor necrosis factor alpha (TNF alpha).

In comparison to normal cells, this cytokine isoverproduced by FA lymphoblasts from the four geneticcomplementation groups.


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Indeed, up to an eight-fold increase in TNF alpha is observed inthe growth medium of FA cells.

Moreover, addition of anti-TNF alpha antibodies partiallycorrects the FA hypersensitivity to treatment by mitomycin C(MMC).

Treatment of FA cells with IL-6, which partially restored analmost normal sensitivity to MMC of FA cells also reduces theTNF alpha overproduction in FA lymphoblasts.

No anomalies at the molecular level are detected for the TNFalpha gene and its mRNA.

We have investigated the in vivo situation by assaying TNF alphalevels in the serum from FA homozygotes and heterozygotes.


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In contrast to normal healthy donors or to aplasticanemia patients in whom serum TNF alpha is presentonly in trace amounts, all 36 FA patients and 21 FAparents monitored show a significantly higher level of

serum TNF alpha activity.

Consequently, abnormal TNF alpha production seemsto be associated with the FA genetic background.


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Proleukin.Antineoplastic Agents.

Synonym:. IL-2, Interleukin-2 precursor, T-cell growth factor,Aldesleukin.

-Proleukin, a lymphokine, is produced by recombinant DNAtechnology using a genetically engineered E. coli strain containing ananalog of the human interleukin-2 gene.

-Genetic engineering techniques were used to modify the humanIL-2 gene, and the resulting expression clone encodes a modifiedhuman interleukin-2.


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This recombinant form differs from native interleukin-2 in the

following ways:

a) proleukin is not glycosylated because it is derived from E. coli;

b) the molecule has no N-terminal alanine;

c) the molecule has serine substituted for cysteine at amino acid.

-used to treat renal cell carcinoma,

-used in immunotherapy to treat cancer.-enhancement of lymphocyte cytotoxicity.


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Mechanism of action:

Proleukin binds to the IL-2 receptor which leads to

heterodimerization of the cytoplasmic domains of the IL-2R betaand gamma(c) chains, activation of the tyrosine kinase, andphosphorylation of tyrosine residues on the IL-2R beta chain.

These events led to the creation of an activated receptor complex,to which various cytoplasmic signaling molecules are recruitedand become substrates for regulatory enzymes that are associated

with the receptor.

These events stimulate growth and differentiation of T cells.


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