Histamine is a low-molecular-weight monoamine that binds to four different G-protein-coupled receptors, and has recently been demonstrated to regulate several essential events in the immune response. The histamine receptor type 2 (HR2) is coupled to adenylate cyclase and studies in different species and several human cells have demonstrated that inhibition of characteristic features of the cells by primarily cAMP formation dominates in HR2-dependent effects of histamine. (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…)

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.

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…)

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…)

Anti-IgE therapy could be particularly beneficial for patients with concomitant asthma and rhinitis as it targets a common factor in the two diseases. Omalizumab is significantly more efficacious than placebo in preventing asthma exacerbations and in improving disease-related quality of life scores when added to standard asthma and rhinitis therapies. (more…)