An alternative, and still experimental, immunotherapy approach is a vaccination strategy using allergen coupled to oligodeoxynucleotides rich in unmethylated CpG. The oligonucleotide mimics the CpG motifs in bacterial DNA and strongly promotes TH1 responses while suppressing TH2 responses. This appears to be useful for chronic treatment of an antigen-specific allergic response, but is not effective for acute desensitization.
A further approach to the treatment of allergic disease may be to block the recruitment of eosinophils to sites of allergic inflammation. The eotaxin receptor CCR3 is a potential target in this context. In experimental animals, the production of eosinophils in bone marrow and their exit into the circulation is reduced by blocking IL-5 action. Anti-IL-5 antibody (mepolizumab) is of benefit in treating human patients with the hypereosinophilic syndrome, in which chronic overproduction of eosinophils causes severe organ damage. Clinical trials of anti-IL-5 treatment of asthma, however, show that, in practice, any beneficial effect is likely to be limited to a small subset of asthma patients with prednisone-dependent eosinophilic asthma; in these patients, IL-5 blockade seems to reduce the number of asthma attacks when the corticosteroid dose is reduced.
Summary.
The allergic response to innocuous antigens reflects the pathophysiological aspects of a defensive immune response whose physiological role is to protect against helminth parasites. It is triggered by the binding of antigen to IgE antibodies bound to the high-affinity IgE receptor FcεRI on mast cells and basophils. Mast cells are strategically distributed beneath the mucosal surfaces of the body and in connective tissue. Antigen cross-linking the IgE on the surface of mast cells causes them to release large amounts of inflammatory mediators. The resulting inflammation can be divided into early events that are characterized by short-lived mediators such as histamine, and later events that involve leukotrienes, cytokines, and chemokines, which recruit and activate eosinophils, basophils, and other leukocytes. This response can evolve into chronic inflammation, which is characterized by the presence of effector T cells and eosinophils, and is most clearly seen in chronic allergic asthma.
Non-IgE-mediated allergic diseases.
In this part of the chapter we focus on immunological hypersensitivity responses involving IgG antibodies and type 1 or type 3 immune responses that involve antigen-specific TH1 or TH17 cells or CD8 T cells. These effector arms of the immune response occasionally react with noninfectious antigens to produce acute or chronic allergic reactions. Although the mechanisms initiating the various forms of hypersensitivity are different, much of the pathology is due to the same immunological effector mechanisms.
in susceptible individuals occur by binding of the drug to the surface of circulating blood cells.
Antibody-mediated destruction of red blood cells (hemolytic anemia) or platelets (thrombocytopenia) can be caused by some drugs, including the β-lactam antibiotics penicillin and cephalosporin. In these reactions, the drug binds covalently to the cell surface and is a target for anti-drug IgG antibodies that cause destruction of the cell. The anti-drug antibodies are made in only a minority of people, and it is not clear why these individuals make them. The cell-bound antibody triggers the clearance of the cell from the circulation, predominantly by tissue macrophages in the spleen, which bear Fcγ receptors.
can follow the administration of large quantities of poorly catabolized antigens.