Specific immunotherapy analyzing the current epidemiological studies, it is difficult not to agree that in the near future, there is no prospect to reduce or at least stabilize the rates of incidence of allergic diseases in the population, especially in the pediatric population.
It would seem that we know enough about the etiology, pathogenesis, different flow characteristics of allergy and its diagnosis, but still say that the full control of the symptoms of atopic dermatitis, allergic rhinitis or bronchial asthma, we can not.
In this publication, I wanted to go to a fun, effective and at the same time controversial method of treatment of allergic disease - specific immunotherapy (SIT).
WHO recommends that in addition to the term specific immunotherapy to use the terms specific desensitization, allergen immunotherapy, allergen-specific vaccination, specific allergovaktsinatsiya, allergen vaccine» (WHO Position paper In Allergen Immunotherapy: Therapeutic vaccines for allergic diseases, 1997).
The main purpose of SIT - desensitize the patient to cause significant allergen, to prevent the formation of complexes between fixed on a target cell antibodies and IgE-allergen.
Despite 80 years of experience in the use of this method of treatment, desensitization mechanisms are not fully understood, the original principle - the administration of small doses of the allergen provocation to reduce the risk of anaphylactic-type reactions and increase anti-allergy protection - remains intact.
Beginning with the work of British doctors L.Noon, G.Freeman (1911), SIT is appointed for allergic diseases caused immediate reactions, anaphylactic-type [1].
SIT method took a firm place in the treatment of atopic diseases, which is the etiologic factors of pollen, house dust, certain insect allergens, mold, yeast-like fungi, etc. The use of the ITA provides clinical efficiency.
The rationale for SIT in these cases is to identify patients with specific IgE-response to these allergens.
Another condition for the appointment of SIT in atopic diseases is the inability to eliminate the cause and prevention of significant allergen or contact the patient with an etiological factor of the disease.
Treatment is carried out allergist allergy only in office, hospitals.
Choosing an allergen (allergen) for SIT is based on the data previously held Allergic patient specific diagnostics:
? identification of allergic history;
? production of skin-allergy tests;
? implementation of elimination tests (cessation of contacts the patient to the allergen);
? Allergodiagnostics specific laboratory (in vitro), which is carried out in order to clarify the etiologic factor.
Allergen immunotherapy is assigned only on the basis of specific diagnosis, allowing to identify the cause and significant allergen or allergens, the degree of sensitization to him, the type of allergic reaction to a particular allergen.
According to the allergodiagnostic identify the cause and 1-3 significant allergens, with medical forms which hold the ITA.
The optimal age of the patients, who are encouraged to SIT, ranges from 5 to 50 years. The earlier treatment is started (in the early stages of the disease), the higher the probability of a good effect.
Most natural allergens are proteins having a molecular weight in the range from 10 to 70 kD. The parameters of the molecules determine its ability to easily penetrate through the barriers of the mucous membranes of the airways.
According H.Lowenstein, allergenic properties can be characterized as a glycoprotein with high molecular weight (200 kD). However macromolecular allergens with difficulty or not at all penetrate mucosal barriers. In this case, the action allergenic factors can be realized only when they receive a parenteral and in very small amounts (microgram nano-).
Sensitization possible if the barrier is overcome gistogematologichesky. Allergenic extracts containing from 20 to 50 protein antigens which can be regarded as potential allergens. [3]
Methods of extraction of allergens from natural raw materials include the following steps:
- study of quality allergenic raw materials;
- extraction of raw materials, in which the requirement is met maximum extraction of allergens with a minimum degree of denaturation and destruction;
- highly purified extracts impurities from the ballast;
- the isolation and analysis of the major and minor allergens and their identification;
- Analysis of the functional groups of allergens;
- assessment of specificity and safety allergens.
Pollen allergens - the major allergens of plant origin. Pollen - male germ cells of the plant. Vegetative parts of the plant and the fruit may also have allergenic properties, but in a less pronounced degree.
Pollen is produced in microsporangiums (anthers). Ripe pollen from wind enters the airspace.
The most allergenic pollen is wind-pollinated plants, the size of pollen grains in which are small in size, and quantitative indicators to ten times higher than the same levels of pollen entomophilous plants.
It is known that the structure of the most allergenic pollen grains are exine, mitochondrial, ribosomal structure, the nucleus. Exine surface has a variety of spines, appendages, teeth, etc., which determine the specific structure of the pollen grain.
In central Ukraine, Russia, Europe and in several other countries, the most common allergic reaction to pollen allergens are identified trees (birch, alder, hazel, etc.), cereals (timothy, rye, etc.), weeds (mugwort, quinoa and etc.). The plants that produce pollen, refer to the group Spermatophyta.
House dust is one of the most active inhaled allergens, hypersensitivity to it is detected in the majority of patients with bronchial asthma. According allergenic composition, it is a multiple. Clamp, fungal, epidermal, bacterial, chemical and other components may be determined profile of house dust allergen.
Hypersensitivity patients may be identified as a complex allergen of house dust and to its individual components.
RCPanzani described the process of transition of individual allergens insektnyh human dwellings in aeroallergens. Particles of dead insects, mites and other metabolites of live animals are the source of insektnyh aeroallergens. All of them are of the type taxonomically Arthropoda - the most popular in the fauna of the earth.
The most common allergy to representatives akarofauny home: Dermatophgoides pteronyssinus, Dermatophgoides farinae, Dermatophgoides microceras, Lepidoglyphys destructor, etc.
The problem of hypersensitivity to mite allergens in respiratory allergy remains one of the most important. Despite the fact that an allergy to cockroaches was recorded in the same period as the tick bite, the interest in the problem of the so-called cockroach-allergy manifested itself later. The most active allergens isolated from the body, cockroach feces and dumped them cover (molt).
The capsule, eggs, head were less allergenic.
Extremely important is the analysis of the mechanisms of cross-allergic reactions to allergens of mites, cockroaches, stinging insects (Aedes aegypti, Honey bee, Bumble bee, etc.) [5].
Regulatory T cells in melanoma: the final hurdle towards effective immunotherapy?
Dr. Hans Jacobs and Dr. Stefan Nierkens in a joint collaboration between the Departments of Tumour Immunology, Medical Oncology and Laboratory Medicine have recently published an article in top journal Lancet oncology with new insights into immunoltherapy of melanoma patients.
Immunotherapy studies in patients with melanoma have reported success in the expansion of tumour-specific effector T cells in vivo, but even in the presence of substantial numbers of functional T cells circulating in the blood, favourable clinical outcomes are scarce. This failure to induce robust clinical responses might be related to tumour-induced immune evasion, rendering the host tolerant to melanoma antigens. Immunosuppression in the tumour microenvironment mediated by regulatory T cells (Treg) is a dominant mechanism of tumour immune escape and is a major hurdle for tumour immunotherapy. Accumulation of Treg in melanoma is frequently recorded and the ratio of CD8-positive T cells versus Treg in the tumour microenvironment is predictive for survival of patients with melanoma. Hence, depletion of Treg seems to be a promising strategy for the enhancement of melanoma-specific immunity. Indeed, murine studies have shown that Treg depletion greatly increases the efficacy of immunotherapy. But despite the success of some strategies in depletion of Treg in patients, overall clinical efficacy has been disappointing. The lack of Treg specificity of the Treg depleting strategies applied so far imply that well-designed studies into dosage, timing, and administration regimens with more specific agents are urgently needed. Depletion of functional Treg from the tumour microenvironment as part of multifaceted immunotherapeutic treatments is a major challenge to induce clinically relevant immune responses against melanomas.
Jacobs JF, Nierkens S, Figdor CG, de Vries IJ, Adema GJ. Regulatory T cells in melanoma: the final hurdle towards effective immunotherapy? Lancet Oncol. 2012 Jan;13(1):e32-42.
Photo: Hans Jacobs
