Chemical immunology and allergy最新文献

In 1846, T. Wharton-Jones described a coarsely granular stage in the development of granulocytic cells in animal and human blood. Shortly thereafter, Max Schultze redefined the coarsely granular cells as a type distinct from finely granular cells, rather than just a developmental stage. It was, however, not until 1879, when Paul Ehrlich introduced a method to distinguish granular cells by the staining properties of their granules, that a classification became possible. An intensive staining for eosin, among other aniline dyes, was eponymous for the coarsely granular cell type, which thereupon became referred to as eosinophil granulocyte. Eosinophilia had already been described in many diseases by the late 19th century. The role of these cells, however, today remains a matter of continuing speculation and investigation. Many functions have been attributed to the eosinophil over the years, often linked to increasing knowledge about the granular and cytoplasmatic contents. A better understanding of the regulatory mechanisms of eosinopoiesis has led to the development of knock-out mice strains as well as therapeutic strategies for reducing the eosinophil load in patients. The effect of these therapeutics and the characterization of the knock-out phenotypes have led to a great increase in the knowledge of the role of the eosinophil in disease. Today we think of the eosinophil as a multifunctional cell involved in host defense, tissue damage and remodeling, as well as immunomodulation.

This paper summarizes the development of the extraction and characterization of allergens responsible for the induction of immunoglobulin (lg) E-induced allergies from the beginning of the 20th century, including the nomenclature of allergens. The majority of papers characterizing allergens and allergen extracts state that the lack of standardization of allergen extracts is the reason for the paper, and so it has been for more than 100 years. A natural part of that process might be the isolation of an allergen molecule and this starts the speculation of 'what makes that allergen an allergen?' To achieve the perfect standardization is a desirable end that is still awaited. So far none of these problems have been finally solved. I started in allergy shortly after the discovery of IgE in 1967. Since that time the history as I remember it is based on the literature, my interpretation of it, and of course may be a little biased due to personal prejudice! The history of the last 10-15 years has still not matured and it might be a little early to draw conclusions. However, at the end of this chapter I do dare to make a few conclusions after having followed the development in this field for 40 years. As this is history it is not meant to be either comprehensive or technically and scientifically precise in all aspects, but rather draws on some thoughts as to what in my mind have been important developments until now. Specific techniques are only mentioned by name and not intended to be discussed in depth. This activity has, however, pushed me to reflect on my hopes and speculations at the time of my introduction to the field of allergen chemistry. To my surprise I realize that far more than I ever expected at that time has been fulfilled. It has been extremely exciting to be a part of that development.

Angiogenesis and lymphangiogenesis are distinct and complex processes requiring a finely tuned balance between stimulatory and inhibitory signals. Immune and inflammatory cells can contribute to these processes by multiple mechanisms: directly by producing a broad array of angiogenic growth factors, and indirectly by secreting several cytokines, chemokines and other mediators able to coordinate the cell-cell interactions. Immune cells can stimulate or inhibit angiogenesis/lymphangiogenesis, depending on their activation status and subset specificity. We summarize recent findings reporting the expression and activity of angiogenic and lymphangiogenic factors and their receptors and coreceptors in immune cells. It is evident that modulation of angiogenesis and lymphangiogenesis by the innate and adaptive immune cells (mast cells, macrophages, dendritic cells, basophils, eosinophils, and some subsets of T cells) is a highly complex process not yet completely understood.

Prostate cancer is the most common cancer in men in the United States and is the second most common cause of death. While treatment options in early stage disease are curative in intent, treatment of metastatic prostate cancer remains challenging. Although, several new and promising treatment options exploiting novel targets have permeated the therapeutic landscape in recent years, another viable target for therapy is tumor angiogenesis. Many antiangiogenic agents are under development and some are currently under investigation in clinical trials.

The milky sap of the rubber tree Hevea brasiliensis is the source of the commercial production of natural rubber latex (NRL) devices, and also represents a source of potent allergenic proteins. NRL materials were introduced in the health care field in about 1840 with the advent of technical abilities to produce suitable and flexible NRL materials for medical products, especially gloves. In the late 1980s, with the increase of transmittable diseases, particularly HIV infection, the use of NRL gloves increased dramatically. During the 1990s, NRL emerged as a major cause of clinically relevant allergy in health care workers using NRL gloves and spina bifida patients with operation on the first day. The increased recognition of NRL allergies, the enhanced research on allergen characterization and sensitization mechanisms, and education about this allergy in health care facilities combined with the introduction of powder-free gloves with reduced protein levels are all factors associated with a decline in the number of suspected cases of NRL allergies in the late 1990s. NRL allergy is a very good example of a 'new allergy' that suddenly arises with tremendous health and economic implications, and also of an allergy which becomes history in a relatively short period of time based on successful primary prevention strategies by strict allergen avoidance.

The role of allergen-specific CD4+ effector type 2 helper (Th2) cells in the pathogenesis of allergic disorders is an established fact. Th2 cells produce interleukin (IL)-4 and IL-13, which induce immunoglobulin E production by B cells, and IL-5 that allows recruitment of eosinophils. Two main mechanisms control the Th2-mediated allergic inflammation: immune deviation (or Th1 redirection) and immune regulation. Regulatory T (Treg) cells exhibit a CD4+ phenotype and include Foxp3-positive thymic and induced Tregs, as well as Foxp3-negative IL-10-producing cells. Both immune deviation and immune regulation evoked by the maternal and newborn microbial environment probably operate in preventing allergen-specific Th2 responses. However, microbe-related protection from allergy seems to mainly depend on epigenetically controlled acetylation of the IFNG promoter of CD4+ T cells. Even Th17 and Th9 cells, as well as invariant NKT cells, have been implicated in the pathogenesis of allergic disorders, but their role is certainly more limited. Recently, innate lymphoid type 2 cells (ILC2) have been found to be able to produce high amounts of IL-5 and IL-13 in response to stimulation with IL-25 and IL-33 produced by non-immune cells. Together with Th2 cells, ILC2 may contribute to the induction and maintenance of allergic inflammation.

Blood vessels connect all districts of the body and allow blood oxygen and nutrients to reach every cell in the organism. Dysregulation of blood vessel formation or functionality is the origin of a large number of diseases. During new vessel formation, endothelial cells degrade their basement membrane, migrate into the interstitial matrix and proliferate. Migrating endothelial cells need to be polarized, to focus at their leading edge the proteolytic machinery, which is essential for extracellular matrix degradation; thus, proteases and their receptors play a crucial role in angiogenesis. The urokinase-mediated plasminogen activation system is a complex system of serine proteases strongly involved in angiogenesis. The plasminogen activation system includes plasminogen/plasmin, activators, inhibitors and cell receptors. In the last decades, a large body of evidence has clearly indicated that the role of this system is not limited to extracellular matrix proteolysis but can contribute to all phases of the angiogenic process.

Specific immunotherapy was introduced for the treatment of grass pollen-induced hay fever in 1911. The treatment was soon extended to other pollens as well as perennial allergens, and to the treatment of bronchial asthma. Definitive studies of its efficacy for both rhinitis and asthma came only many decades later. Understanding gradually emerged of the underlying immunologic mechanisms that include the generation of regulatory T lymphocytes, immune deviation from allergen-specific Th2 to Th1 responses, and a shift in allergen-specific antibody production from immunoglobulin (Ig) E to IgG4. Along with understanding of the immune basis came an appreciation that immunotherapy modifies allergic disease expression, producing protection against disease progression and symptomatic improvement that persists for years after the treatment is discontinued. Recent new directions for immunotherapy include sublingual administration of inhalant allergens and use of the oral route to treat food allergy.