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…)

The induction of immune tolerance and specific immune suppression are essential processes in the control of immune responses. Regulatory T cells (Treg) play a central role in immune control in the periphery. Two broad categories of Treg have been described: naturally occurring Treg that are present in all individuals and antigen-induced Treg that secrete inhibitory cytokines such as interleukin (IL)-10 and/or transforming growth factor (TGF)-ß. (more…)

The response to injury usually begins with dilatation of small blood vessels in and around the injured site (figure bellow). This response (called vasodilatation) results from relaxation of smooth muscle in the vascular walls. It can begin within seconds after an acute injury or develop over hours or days of low-grade irritation or infection. Vasodilatation initially results in increased blood flow through arterioles, capillaries, and venules of the affected region, leading to redness (erythema) and warmth. As the vessels dilate, endothelial cells lining some of the vessels actively retract away from one another to create temporary, microscopic gaps in the endothelial lining. Endothelial retraction occurs only in the smallest venules (often called postcapillary venules), which are thin-walled vessels with lumenal diameters of 20 - 60 µm. (more…)

An especially elaborate and important type of innate antimicrobial enzymes defense is provided by a group of serum proteins that together make up the complement cascade pathway. This group comprises more than two dozen different liver-and macrophage-derived proteins, called complement factors or components, most of which normally circulate in the form of proenzymes that have latent protease activity. As a rule, each of the proteases becomes active when proteolytically cleaved and will then catalyze cleavage and activation of a different complement component. (more…)

One especially favored target for immune recognition is bacterial lipopolysaccharide (LPS). This macromolecule is found only in the outer lipid bilayer that surrounds the cell walls of gram-negative bacteria, such as Neisseria, Salmonella, and Escherichia coli. Each molecule of bacterial lipopolysaccharide consists of a core carbohydrate linked on one side to a phospholipid (called lipid A) that is anchored in the bilayer and on the other side to a long polysaccharide chain (called the O sidechain) that extends outward from the bacterial surface (Figure 1 bellow). The sequence of sugars making up the O sidechain is species-specific and highly variable, even within a single bacterial genus: For example, more than 1000 variants in Salmonella are known. (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.

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…)

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…)

Diagnosis of food hypersensitivity is a clinical challenge and the only current definitive test is the Double Blind Placebo-Controlled Food Challenges. Although the Double Blind Placebo-Controlled Food Challenges is the current gold standard, it is difficult to perform and is very time-consuming. Hence, researchers are continually evaluating new tests and assessing the value of the available serum tests. (more…)

The geographical variation in the prevalence of asthma in children does not coincide with variations in air pollution levels. The increase in the prevalence of asthma and allergies seen over the last decades was paralleled by a decrease in emissions of SO2 and particles from coal combustion, and an increase of emissions from motor vehicle traffic. There is a growing number of studies suggesting that increased exposure to traffic exhausts, particularly diesel exhausts, may be a risk factor for the new onset of asthma. (more…)