Neutrophils make up an army of more-or-less identical circulating phagocytes that are poised to respond quickly and in vast numbers wherever tissue injury has occurred. The mature cells, which are also known as segmented neutrophils (segs) or polymorphonuclear leukocytes (polys, or PMNs), can easily be identified by their characteristic multilobed nucleus and by the abundant storage granules in their cytoplasm (Figure bellow). (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…)

Once it is tethered onto the venule wall, the neutrophil or other leukocyte comes into contact with a wide variety of inflammatory mediators that may either be expressed by the activated endothelium or simply diffuse into the blood from the injured tissue. Among these mediators are a diverse subset of intermediaries known as leukocyte chemotactic factors which bind to receptors on the leukocyte surface and trigger the second, activation phase of margination. (more…)

Some of the immediate sequelae of injury are uncomfortably familiar: Soon after an injury occurs, the affected site and its surrounding tissues become reddened, warm, swollen, and painful. These four signs which are probably the most useful and ubiquitous diagnostic clues in all of clinical medicine are hallmarks of acute inflammation, the body’s initial physiologic reaction to tissue distress. In its simplest form, inflammation is a response carried out by blood vessels and by the endothelial cells that line them. (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…)

Genome-wide scans have pointed to a number of genomic regions implicated in asthma. This study used an elegant scheme to investigate chromosome 7p, which had been previously identified as containing susceptibility loci for asthma-related phenotypes. Positional cloning of asthma susceptibility genes was undertaken in the Kainuu subpopulation from Finland and two additional population samples from Quebec, Canada. A hierarchical gene mapping strategy was followed by identification of specific genes on the implicated DNA segment of chromosome 7. (more…)

The mediators released by mast cells and basophils can be grouped into two categories:
(1) preformed substances contained within granules and
(2) newly generated chemicals synthesized following cellular activation.

These mediators comprise the effector function of the mast cell. Together they are able to increase vascular permeability, dilate vessels, cause bronchospasm, contract smooth muscle, and summon inflammatory cells. Few cells in the body produce compounds with such a large and varied spectrum of activity. (more…)

Being an immunological disease, the characteristics of allergy are those of specificity and memory. Regardless of whether the clinical manifestation is rhinoconjunctivitis, rhinitis, or asthma, the underlying immunological response disorder is based on the adverse reactions of cells in the immune system upon contact with allergens. These cells are specific for epitopes that are structural parts of allergens present in the allergenic source material. Two types of cells (i.e., T cells and B-cells) produce receptor molecules (i.e., T-cell receptors and immunoglobulin [IgE] antibodies) that, through high-affinity interactions with the allergen, efficiently catalyze the presence of even minute amounts of allergens into clinical symptoms, the extreme consequence of which may be life-threatening to the patient. (more…)