Immunoglobulin preparations

Biotechnologies and Drug Immunotherapy

Modern immunology actively utilizes advanced biotechnological developments. Today, physicians have monoclonal antibodies, recombinant cytokines, genetically engineered molecules, and cloned cells at their disposal.

The need for pharmacological intervention is dictated by the nature of immunological disorders:

• Immune stimulation is required for patients suffering from various forms of immunodeficiencies.
• Immunosuppression (artificial suppression of host defenses) is vital in conditions associated with hypersensitivity, as well as to prevent rejection in organ and tissue allotransplantation.

Classification of Immunomodulators

According to the modified B.V. Pinegin scheme, all immunomodulators are divided into two large groups.

I. Preparations based on natural factors:

1. Derived from humans and higher vertebrates:
2. Immunoglobulin preparations.
3. Peptide agents (thymus peptides, their analogues, and peptides of other origins).
4. Cytokines and their receptors (including interferons, interleukins, and soluble receptor forms).
5. Of bacterial origin:
6. Agents based on bacterial cell wall components.
7. Preparations based on nucleic acids.
8. Other agents of microbial origin.

II. Synthetic preparations: This group includes cyclic compounds, polyelectrolytes, synthetic analogues of natural immunomodulators, and a number of other artificially synthesized substances.

Features of Immunoglobulin Preparations

Immunoglobulin preparations are produced from a pool of sera collected from a vast number of donors — at least 5,000 individuals. This ensures the presence of the widest possible spectrum of natural antibodies against most known pathogens in the final product.

There are two main approaches to their production:

• Historical method: Cohn ethanol fractionation, which yields fraction II.
• Modern method: a sophisticated, advanced purification procedure for intravenous formulations. Sometimes the manufacturing process includes partial proteolytic cleavage of molecules.

Safety requirements for intravenous formulations are extremely strict: molecular aggregates must be completely absent in them. The entry of such complexes into the bloodstream can trigger complement system activation, initiate intravascular blood coagulation, and lead to severe complications.

Preparations are used to increase resistance to infections (especially against the background of immunodeficiencies) and possess regulatory activity, which is, however, difficult to predict precisely. If targeted protection against a specific pathogen is required, specialized forms enriched with corresponding antibodies are used.

Peptide Immunomodulators: Thymus Preparations

Historically, physicians attempted to treat immunodeficiencies by thymus transplantation, but as the T-lymphocyte population recovered, graft rejection inevitably occurred. This stimulated the search for alternatives — extracts and peptide preparations.

A. Goldstein became a pioneer by creating the first preparation in the 1960s — calf thymosin fraction V. Later in the USSR, complex agents were developed:

• Thymalin (creators V.G. Morozov, V.Kh. Khavinson) — produced by acetic acid extraction.
• Thymosin (creator V.Ya. Arion) — synthesized using a modified thymosin V production technology.

Synthetic Analogues of Thymus Peptides

Chemical synthesis made it possible to recreate the structure of thymus hormones and their active fragments. Among them are:

• Thymogen: dipeptide L-Glu-L-Trp (alpha-glutamyl-tryptophan), first found in the thymus extract.
• Thymodepressin: dimer of D-isomers of the same amino acids (gamma-glutamyl-tryptophan).
• Bestim: dimer of D-Glu and L-Trp linked via a γ-bond, which cardinally increases its biological activity.
• Neogen: trimer in which a leucine residue is attached to the N-terminus of the L-dimer (thymogen analogue).
• Imunofan: complex peptide (arginyl-alpha-aspartyl-lysyl-valyl-tyrosyl-arginine) developed by V.V. Lebedev based on thymopentin (fragment 32–36 of thymopoietins). The order of two amino acids is changed and a terminal arginine is added in it.

Mechanism of Action of Peptides

Despite the general similarity in the action of natural and synthetic thymus preparations, there are no clear boundaries in their indications for use.

Their exact mechanism remains to be fully elucidated. It has been experimentally proven that they stimulate the production of Th1 cytokines (including IL-2 and IFNγ). There is an unconfirmed hypothesis that peptides promote the "maturation" of T lymphocytes in the periphery. It is important to note that their effects are not strictly specific exclusively to T cells. The main indication for prescribing such agents is mild immunodeficiencies, since they are incapable of completely taking over the function of the thymus and ensuring the differentiation of T lymphocyte precursors.

Briefly: answers to topical questions

Class and exam questions

What else to study on this topic

• Monoclonal antibodies in modern immunotherapy
• Recombinant cytokines: types and applications
• Bacterial immunomodulators
• Mechanisms of rejection in allogeneic transplantation
• Immunostimulation in various types of immunodeficiencies

Other topics in the section "Immunity in defense and damage of the organism. Pathology of immunity"

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