The intracellular forkhead winged transcription factor Foxp3 (forkhead box P3) appears to be specifically expressed by naturally occurring Treg cells, particularly in mice, although in humans there is evidence of upregulation of Foxp3 in all T cells on activation. Foxp3 is required for the development and function of naturally occurring regulatory t cells (treg) and expression is sufficient to convert non-regulatory CD4+CD25T cells into cells with regulatory activity. Conversion of peripheral CD4+CD25 naive T cells to Foxp3+CD4+CD25 foxp3+ Treg cells can be induced by TGF-ß. In a murine asthma model, these TGF-ß-induced Treg prevented house-dust mite-induced allergic pathogenesis or infection pathogenesis in lungs. A single independent report has suggested that IL-4 and IL-13 also induce Foxp3+CD25+ Treg from CD4+CD25precursors. (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…)

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.

There are thousands of components to the immune system, and during the course of learning about some of these it can appear that the immune system is far more complex and complicated than necessary for achieving what is, on the surface, the simple task of eliminating an infectious organism. There are a number of reasons why the immune system is complex. The first of these is the desirability of eliminating pathogens without causing damage to the host. Getting rid of a pathogen is theoretically easy. If you had an infection in your liver you could produce a nasty toxin that would kill the pathogen; unfortunately it would also destroy your liver. Killing pathogens is not difficult, but getting rid of pathogens without damaging the host is much more complicated. (more…)

The immune system consists of proteins, cells and organs that are concerned with defense of the individual, primarily against the threat of disease caused by infectious organisms. An infectious organism that causes disease is called a pathogen and the individual (person or animal) that is infected by a pathogen is called the host. Not all infectious organisms cause disease and some are actually beneficial, for example bacteria living in the gut help to digest certain foods. Infectious organisms that help the host are called commensalism organisms. (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…)

Tumour Necrosis Factor is a pro-inflammatory cytokine implicated in the pathogenesis of asthmatic airway inflammation, hyper-reactivity and remodelling. The primary aim of the trial was to assess whether TNF antagonism, using a soluble Tumour Necrosis Factor receptor (TNFR:Fc etanercept, Enbrel ® ), can attenuate eosinophilic airway inflammation in patients with mild to moderate allergic asthma. (more…)

Interleukin-5 is the key cytokine in eosinophil differentiation and growth in the bone marrow and stimulates the release of eosinophils into the peripheral circulation. Thus, it is thought that IL-5 may be involved in the pathogenesis of hypereosinophilic syndromes (HES), a diverse group of poorly treated disorders characterized by sustained peripheral blood and/or tissue eosinophilia. Mepolizumab is a humanized monoclonal antibody to IL-5, and its safety and efficacy were assessed in this open-labelled trial. (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 symptoms of asthma occur together with variations in the diameter of medium- size airways such that it is increasingly difficult to exhale. Narrowing of the airways can occur because of smooth muscle contraction, edema or swelling of the wall, or increased mucus in the airways. However, it is increasingly clear that the pathologic event underlying most cases of asthma is acute inflammation of the airway walls. (more…)