Treg cells or regulatory T cells constitute a large population of cellular infiltrate in atopic/allergic inflammation and a dysregulated immune response appears to be an important pathogenetic factor. Cardinal events during allergic inflammation can be classified as activation, organ-selective homing, survival and reactivation, and effector functions of immune system cells. T cells are activated by aeroallergens, food antigens, autoantigens, and bacterial exotoxins superantigens in allergic inflammation. They are under the influence of the skin, lung, or nose-related chemokine network and show organ-selective homing. (more…)

Routes by which infectious organisms gain entry into the body include the skin, respiratory tract, gastro-intestinal (GI) tract and GU tract. There are fundamentally two ways in which infectious agents cross the physical and chemical barriers: either they are able to penetrate the intact barriers at one or more anatomical sites, or the physical barriers are damaged and breached, allowing entry of the organism.

Bellow are some possibles pathogens entry into human body:

Penetration of intact skin or mucosa

• Skin. Few organisms are able to penetrate intact skin. However, some parasites (e.g. hookworm) or their larvae (e.g. schistosoma) can do this. Other agents, such as wart viruses, set up infection in the skin and do not enter further into the body.

• Mucosa. Mucosa, being softer and damper than skin, are much more frequent sites of entry and all intact mucosa can be penetrated by some organisms. Examples are shown in table bellow. Pathogens can cross epithelia by passing through epithelial cells, as in the case of the meningococcus (a bacteria causing meningitis), or by passing between the epithelial cells, seen with Haemophilus influenzae.

Mucosal Sites of Entry for Pathogens

Penetration of damaged skin or mucosa

There are many ways in which skin or mucosa can be damaged, allowing entry of infectious organisms that could not cross intact skin or mucosa. Damage to skin is a particularly important route of infection and can occur in a number of ways:

• Burns. Burns, especially severe ones, pose a major risk for infection, particularly with Staphylococcus, Streptococcus, Pseudomonas and Clostridium tetanus.

• Cuts and wounds. These can allow entry of similar organisms to those seen after burns.

• Insect bites. Numerous infections pathogenesis are transmitted via insect bites. These include malaria, typhus and plague.

• Animal bites. Animal bites can provide direct transmission of infection, such as in rabies. Because they cause significant damage to the skin, bites can allow the entry of the same environmental pathogens as burns, cuts and wounds (see above).

• Human behaviour. Various aspects of uniquely human behaviour can result in the skin being penetrated. Sharing of syringes by intravenous (IV) drug users exposes them to risk of hepatitis and human immunodeficiency virus (HIV). A number of viral infections (hepatitis, HIV) have been transmitted by blood transfusion and blood products (e.g. factor VIII for haemophiliacs) before appropriate screening procedures were developed. Transplantation has also resulted in transmission of infection before the introduction of appropriate donor screening.

Damage to mucosa may not increase the likelihood of infection to the same extent as damage to the skin. However, physical or chemical damage may allow entry of some organisms (e.g. smoking increases the risk of respiratory bacterial infections or respiratory allergies). Furthermore, infection of the mucosa with a virus may cause damage and facilitate the entry of bacterial pathogens spread.

Our understanding of hematopoiesis has advanced greatly in recent years with the isolation and characterization of hematopoietic stem cells (HSCs) and the identification of many of the factors that influence the production and differentiation of lineage-committed progenitors (Figure 1 bellow). HSCs are defined by their abilities to self-renew throughout life and to give rise to committed progenitors that can differentiate along all of the possible hematopoietic lineages. They were first purified from mice as a tiny sub-population of marrow cells that could completely reconstitute the hematopoietic systems of other mice, whose own marrows had been destroyed by inherited mutations or by radiation. (more…)

Normally present at very low levels in plasma, antibodies of the immunoglobulin E (IgE) isotype were first discovered in 1967, decades after the description of IgA, IgG, and IM. IgE antibodies are produced primarily by plasma cells in mucosal-associated lymphoid tissue and their levels are uniformly elevated in patients suffering from atopic conditions like allergic rhinitis, asthma and atopic dermatitis. Production of allergen-specific IgE in atopic individuals is driven both by a genetic predisposition to the synthesis of this isotype as well as by environmental factors, including chronic allergen exposure. (more…)

CD14 is part of the receptor complex for endotoxin, which is a component of tobacco smoke. The CD14 gene is located on chromosome 5q, a region previously demonstrated to be linked to asthma when stratified for smoke exposure. This study was designed to extend these findings by determining whether polymorphisms in the CD14 gene are related to this gene–environment interaction on asthma. Puerto Rican (n = 362 trios) and Mexican (n = 259 trios) families ascertained through a child with asthma were studied. (more…)

Asthma is characterized by Th2-dominant cytokine profiles. The risk of developing asthma is lower in children attending day care in the first year of life. Therefore, this study was conducted to assess the interaction between day-care attendance, T-cell cytokine profiles and atopic phenotypes in early childhood. Children (n = 208) in the Childhood Onset of Asthma (COAST) study were genotyped for 72 polymorphisms in 45 immune response genes. The COAST cohort was selected on the basis of a high risk of asthma. Measurements of IFN-y (Th1), IL-5 and IL-13 (Th2), and IL-10 (Treg) were made at birth and at age 1 year and the children were stratified by day-care attendance. Wheeze and atopic dermatitis phenotypes were documented in the first year. (more…)

The Tcell Ig domain and mucin domain (TIM) proteins, the genes for which are located on chromosome 5q, have been suggested to be involved in allergic disease. This study examined allergies genetic association of sequence variants of the TIM1 and TIM3 genes in an African-American population. Case–control and family based association analyses were performed for three SNPs each in the TIM1 and TIM3 genes, and an insertion/deletion polymorphism in Tcell Ig domain and mucin domain 1. (more…)

Atopic dermatitis is a chronic inflammatory condition of the skin which usually starts in infancy. It is sometimes called ‘atopic eczema’ or even simply ‘eczema’. Recently, the term ‘atopic eczema dermatitis syndrome’ or eczema symptoms or infantile eczema has also been proposed to indicate the varied nature of this disease. The diagnosis is based on clinical features of a chronic itchy dermatitis with typical morphology and distribution and a relapsing and remitting course. (more…)

The genetics of asthma will be discussed only in the context of environmental exposures. In general, the identification of novel genes for asthma suggests that many genes with small effects, rather than a few genes with strong effects, contribute to the development of asthma. These genetic effects may, in part, differ with respect to a subject’s environmental exposures, although some genes may also exert their effect independently of the environment. (more…)

It is clear from the results of large epidemiologic studies that while atopy is a major risk factor for asthma, it is usually not sufficient by itself to drive the disease process to chronicity, as less than 25% of atopics develop persistent asthma. The situation in childhood is further complicated by an additional series of development factors, related to postnatal maturation of respiratory function. (more…)