Immune response basophils

Type I allergic reactions are inappropriate immune responses to an allergen with preferential synthesis of immunoglobulin E (IgE), a special antibody class, which binds to mast cells and basophilic granulocytes via Fee receptors. Binding of the allergen to the cell-bound IgE initiates the rapid release of allergic mediators, most prominently histamine, and the de novo synthesis of arachidonic acid metabolites and cytokines, which are responsible for the clinical symptoms. 

The clinical relevance of this finding was suggested by the observation that mice were more susceptible to sepsis following infection with Streptococcus pneumoniae when basophils were depleted before the second vaccination with pneumoccocal antigen [22]. Antigen-specific IgG antibodies produced after the second vaccination were significantly lower in the basophil-depleted mice than in control mice. Thus, basophils are important contributors to humoral memory immune responses. 

Immune responses are mediated through the lymphocytes called B cells and T cells. Lymphocytes are a particular type of white blood cell. White blood cells (leukocytes) are divided into granulocytes (neutrophils, 55-70% eosinophils, 1-3% and basophils, 0.5-1%) and agranulocytes (lymphocytes [B and T cells], 20-40% and monocytes, 1-6%). There are 5000-10,000 white blood cells per milliliter of blood, compared with five million red blood cells in the same volume. 

Basophils and Eosinophils. These two types of granulocyte represent only a small proportion of the circulating leukocytes. The basophil possesses receptors specific for the Fc portion of IgE molecules. It is involved in allergic reactions and can play a role in the clinical state of anaphylaxis, which is a life-threatening allergic response. Eosinophils are involved with the immune reactivity of drug allergies and with the body s immune response to parasitic infestations such as worms (see chapter 9). 

Endogenous histamine has a modulating role in a variety of inflammatory and immune responses. Upon injury to a tissue, released histamine causes local vasodilation and leakage of plasma-containing mediators of acute inflammation (complement, C-reactive protein) and antibodies. Histamine has an active chemotactic attraction for inflammatory cells (neutrophils, eosinophils, basophils, monocytes, and lymphocytes). Histamine inhibits the release of lysosome contents and several T- and B-lymphocyte functions. Most of these actions are mediated by H2 or H4 receptors. Release of peptides from nerves in response to inflammation is also probably modulated by histamine, in this case acting through presynaptic H3 receptors. 

As previously indicated, the primary cells involved in the immune response are lymphocytes which have a centrally located round nucleus, lack specific granules, and have a basophilic cytoplasm containing free ribosomes. The (thymus-dependent) T-lyniphocytes are involved in cell mediated reactions and also interact with B-Iymphocytes (see later) to regulate the production of antibody, The B cells differentiate into the antibody-producing plasma cells. There is growing evidence that neither T... 

Type I, or immediate immune, response involves the body s production of immunoglobulin E (IgE) antibodies in lymphatic tissue that bind to the surface of mast cells and basophils and prime them for action. The antibodies are produced in B lymphocytes during the period of sensitization. Sensitization occurs as the result of exposure to appropriate antigens through the respiratory tract, dermally, or by exposure via the gastrointestinal tract. Subsequent cross-linking of the antibodies... 

The pathophysiology of VKC is derived from a combination of type I and IV hypersensitivity reactions.This allergic response involves IgE,Th-2 lymphocytes, eosinophils, mast cells, basophils, neutrophils, macrophages, proin-flammatory cytokines, interleukins, histamine, and other associated mediators. Also involved in this immune response are hormonal and neuroendocrine influences. This immune response results in the clinical manifestations of photophobia, itching, redness, tearing, papillae, corneal vascularization, mucous discharge, and plaque formation. 

The adrenal corticosteroids have been extensively used to suppress many different aspects of the immune response. AU of the corticosteroids have similar mechanisms of action. They bind to specific corticosteroid binding proteins in the cytoplasm. These complexes are then transported into the nucleus where they bind to discrete portions of the cell s DNA. This binding results in derepression of regulatory genes and the subsequent transcription of new mRNA (Rhen and Cidlowski, 2005). Steroids inhibit the consequences of the immune response. They have several different actions in this regard. One of their most important effects is to transiently alter the number of circulating leukocytes. There is a rapid increase in the number of neutrophils and a concomitant decrease in the number of lymphocytes, monocytes, eosinophils and basophils (Krensky et al, 2005). 

Inhibition of the normal immune response results from a gradual destruction of lymphoid tissue, followed by a decline in antibody production and a decrease in the numbers of eosinophils, basophils, and lymphocytes. The reduction in T-lymphocyte counts by glucocorticoids can occur acutely as a result of the redistribution of these cells from the intravascular space to the spleen, lymph nodes, and bone marrow. Thus an increase in the neutrophil count is commonly observed after glucocorticoid administration. The major suppressive effects of glucocorticoids on the inflamniatory response and the immune system appear to be through the modulation of cytokine production via an inhibition of nuclear factor kappa B (NF-kB) expression and nuclear translocation. Cytoldnes released from immunocompetent cells mediate both the acute and chronic phases of inflammation and participate in the control of the immune response (see Chapter 22). 

Falcone FH, Haas H, Gibbs BF. The human basophil A new appreciation of its role in immune responses. Blood 2000 96 4028-4038. 

Topical tacrolimus suppresses cytokine and costimulatory molecule expression in epidermal and local draining lymph node cells during the initial skin immune response [97]. The inhibitojy effect of tacrolimus on the production of cytokines in T cells has been demonstrated in both Thl and Th2 cells [98]. This is coincident with reports that the transcription factor NEAT, a target for the calcium-regulated phosphatase calcineurin, mediates transcription of both Thl- and Th2-derived cytokines [99]. The effects of tacrolimus on other inflammatory cells such as skin mast cells, basophils, eosinophils, and Langerhans cells have also been studied extensively. Tacrolimus has been shown to inhibit histamine release and cytokine production from human skin, lung, and cord blood-derived cultured mast cells [100-102]. Tacrolimus has also been reported to have a direct inhibitory activity on eosinophil activation [103,104]. 

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