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…)

Allergen-specific immunotherapy is highly effective in the treatment of IgE-mediated allergy diseases such as rhinitis, conjunctivitis, asthma, and venom allergy hypersensitivity. It is the only treatment that leads to lifelong tolerance against previously disease-causing allergens due to restoration of the normal immunity. (more…)

Regulatory T cells Treg (picture above) is the existence of suppressor cells, which limit ongoing immune responses and prevent autoimmune disease, was postulated over 30 years ago. The recent phenotypic and functional characterization of these cells has led to a resurgence of interest in their therapeutic application in a number of immune-mediated diseases. Two broad subsets of CD3+CD4+ suppressive or Treg cells have been described: constitutive or naturally occurring versus adaptive or inducible Treg. (more…)

With the exception of complement protein C3, most soluble mediators of innate immunity are found in relatively small amounts in the serum under normal conditions. The concentrations of several of these proteins, however, can increase as much as 1000-fold during serious infections or other crises, as part of a coordinated protective reaction called the acute-phase response. In this response, the liver temporarily increases its synthesis of more than 30 different serum proteins, often called acute-phase proteins (Table bellow). Many of these, such as complement factors C3 and B, MBL, LBP, C-reactive protein, and serum amyloid protein P, participate in antimicrobial defense. (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…)

Other humoral effectors and humoral factors have the ability to lyse microorganisms directly. The best studied of these are a class of small peptide antibiotics known as defensins, which in their active forms are all roughly 30 amino acids long (3,5 kilodaltons), positively charged, and protease-resistant. Each also has three internal disulfide bonds. They are classified as either α or β defensins based on the arrangement of the disulfides, but both classes have nearly the same compact, folded structure consisting of three strands of antiparallel β-pleated sheets. (more…)

A few of the best known humoral effectors of innate immunity are listed in Table 1 bellow, along with the types of target molecules they recognize. Some are enzymes that can directly injure or kill microbial pathogens. An example is lysozyme, an endoglycosidase found in human saliva, mucus, tears, and other secretions, which attacks the protective cell wall encasing every bacterial cell. Lysozyme acts by digesting the peptidoglycan meshwork formed by long carbohydrate chains of alternating N-acetylmuramic acid and N-acetylglucosamine residues, crosslinked covalently by short oligopeptide sidechains which is a major constituent of all bacterial cell walls but is not found in mammalian tissues. (more…)

The body’s innate resistance to many pathogens is provided by enzymes and other proteins in the blood and tissue fluids. These proteins are the effectors (ie, the active agents) of humoral innate immunity, and they have features in common with one another that are also characteristics of the innate immune system as a whole. First, these proteins are continually expressed throughout life, regardless of whether or not their protective effects are needed at a given moment. Second, although many of these proteins can be produced in higher quantities in times of need, their intrinsic properties (eg, substrate specificity and ige binding affinity) never change: The characteristics of these proteins have been shaped by evolution, are genetically determined, and are fixed at birth, so that they do not vary during an individual’s lifetime. (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…)