Toll-like receptors (TLRs) act as receptors for numerous stimuli of immune cells, including bacterial cell wall constituents (lipopolysaccharide [LPS] from Gram-negative bacteria and lipopeptides from Gram-positive species), plasma proteins and extracellular matrix breakdown products. TLR2 and TLR4 bind lipopeptide and LPS respectively, mediating responses of alveolar macrophages and other immune cells to bacterial infection in the lungs. Exposure of lungs to LPS leads to pro-inflammatory responses of a number of cell types, including airway smooth muscle, which secretes a number of cytokines involved in leucocyte recruitment and the Th2 polarization of immune responses. Human airway smooth muscle cells were cultured with LPS in the absence and presence of peripheral blood mononuclear cells to determine direct and leucocyte-dependent TLR-mediated responses. (more…)

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A general pattern of factors influencing development of asthma seems to be emerging, including family allergy history/ asthma genetics, smoking, diet, obesity, and inactivity, all of which seem to influence the development of asthma and disease outcomes (Table bellow).

Many clinical or area studies have reported substantially higher rates of asthma prevalence, hospitalization, and mortality among racial and ethnic minorities. However, asthma is also most common among low socioeconomic groups, regardless of race. While black children have higher rates of asthma than white children, most studies have found that black race is not a significant correlate of asthma after controlling for location of residence and socioeconomic status (SES). The basis for the effects of poverty and urban residence on asthma prevalence is not known. One potential asthma factor is allergen exposure and allergen sensitization are common in urban environments. Black children in inner city Atlanta are exposed to high levels of dust mites and cockroach allergen, and a high proportion of the children with asthma were sensitized to these allergens. Litonjua and colleagues also concluded that a large proportion of racial/ethnic differences in asthma prevalence can be explained by factors related to income, area of residence, and level of education.

Asthma Factors that Influence Disease Development and Severity

Income is a determinant of access to health care, and frequently, the quantity and quality of health care available. Persons who have low income, regardless of race or ethnicity, are more likely to be uninsured, to encounter delays or be denied care, to rely on hospital clinics in emergency departments for health services, and to receive substandard care. The usual socioeconomic indicators, education and personal or household income, serve only as surrogates for more complicated correlates of individuals within populations and multiple asthma factors that can impact both on prevalence of asthma and adverse outcomes from the disease.

Studies from Germany comparing the populations of East and West Germany have shown the prevalence of hay fever and asthma as significantly higher in West German children, suggesting that asthma environmental factors explain the difference in prevalence in these ethnically similar populations. Early exposure to infections (as with being in a day-care environment early in life) or exposure to endotoxin (as with growing up on a farm with close exposure to the farm animals) are associated with a decreased prevalence of asthma. In contrast, growing up in an urban environment or generally with an increased standard of living are associated with an increased prevalence of asthma. Such correlates are also present for atopic disorders other than asthma. In fact, Strachan, who noted that prevalence of hay fever was inversely related to family size, was the first to recognize the importance of early exposures on atopic disease. In the USA, asthma is more prevalent in African-Americans and Puerto Ricans. These findings are not explained by the observations on the role of social class in European studies. Given the ethnic differences between African-Americans and whites, these studies may represent gene-by-environment interaction producing varied phenotypic outcomes.

Exotoxins are secreted products, usually of bacteria but sometimes protozoa and fungi. They can act in a number of ways:

• Inhibition of protein synthesis. Corynebacterium diphtheriae, the cause of diphtheria, produces a toxin that causes ADP-ribosylation elongation factor-2, thereby stopping protein synthesis. It is extremely potent and one molecule of toxin is capable of killing a cell. Escherichia coli, Vibrio cholerae and Bordatella pertussis (the cause of whooping cough) also produce toxins that cause ADP-ribosylation of proteins. (more…)

The final stage of the disease process (although it may not be the final stage of the infection) is the actual production of disease. Many microorganisms live in or on the body without causing disease. These organisms are called commensal organisms and may be beneficial to the host: the production of lactic and lactobacilli proprionic acidophilus in the vagina inhibits the growth of many other bacteria and many commensal organisms compete with pathogens for ‘living space’ in the gut. Microbial pathogens differ in that they cause dis- ease by one or more mechanisms like picture bellow. These include the following: (more…)

CD14 is part of the receptor complex for endotoxin, which is a component of tobacco smoke. The CD14 gene is located on chromosome 5q, a region previously demonstrated to be linked to asthma when stratified for smoke exposure. This study was designed to extend these findings by determining whether polymorphisms in the CD14 gene are related to this gene–environment interaction on asthma. Puerto Rican (n = 362 trios) and Mexican (n = 259 trios) families ascertained through a child with asthma were studied. (more…)

Asthma and allergic diseases are common in both children and adults. Their development depends on an interaction between asthma genetic and asthma environmental risk factors. Genetic manipulation in multi factorial diseases such as asthma is not feasible in the foreseeable future. However, theoretically, environmental exposures can be controlled in an attempt to stem the rising prevalence of these diseases (primary prevention). Environmental exposures may also influence the frequency of symptoms and the requirement for medication in those with established disease. (more…)

There is much controversy as to the role of allergen exposure for the development of atopic sensitization towards this allergen. While in some studies, a clear, almost linear dose-response relation between allergen exposure and sensitization has been found, others described a bell-shaped association with higher levels of exposures relating to lower rates of atopic sensitization. Part of the discrepancy may relate to the type of allergen, since mostly cat but not house dust mite allergy allergen exposure has been shown, in some studies, to exert protective effects at higher levels of exposure. (more…)

Exotoxins are noxious proteins secreted by many bacteria. These toxins are often heat-labile and thus can be heat-inactivated for use as vaccines to prevent toxigenic immunity to bacteria disease. Many bacteria produce more than one protein exotoxin, making vaccine development more difficult. (more…)