HEALTH ISSUES FOR EVERY DAY

HELICOBACTER PYLORI : VIRULENCE FACTORS 

Helicobacter pylori virulence factors and the host immune response: implications for therapeutic vaccination.

Prinz C, Hafsi N, Voland P.

Source

Department of Medicine II, Technical University, Ismaningerstr. 22, 81675 Munich, Germany. christian.prinz@lrz.tum.edu

Abstract

Helicobacter pylori colonizes the human gastric mucosa and is associated with specific gastric disease. Virulence factors, such as urease, the vacuolating toxin (VacA), the cytotoxin-associated antigen CagA or blood-group-antigen-binding adhesin (BabA), an adherence factor, might account for the development of different diseases. Vaccination trials exploiting the antigenic properties of some of these proteins have not been successful in preventing infection in humans. A more in-depth understanding of the immune response to H. pylori infection as well as additional information on suitable epitopes and adjuvants will be required before a successful vaccine can be developed.

Among people infected with Helicobacter pylori, the virulence of the infecting strain is a major determinant of who develops disease. Strains producing vacuolating cytotoxin activity are more commonly isolated from people with peptic ulcers than without. The gene encoding the toxin, vacA, varies between strains, especially in its signal sequence and mid regions. vacA genotype influences cytotoxin activity, and signal sequence type correlates closely with peptic ulceration. Infection with strains possessing cag>4 (cytotoxin associated gene A) is more common among people with peptic ulceration or gastric adenocarcinoma than without. cagA is a marker for the cag pathogenicity island, which includes genes necessary for the enhanced inflammation induced by pathogenic strains. Serological detection of infection with cagA* strains is at present the best practical test for virulence. However, before a strategy of screening and selective treatment can be considered, it is important to assess whether cagA- strains are entirely non-pathogenic.

Helicobacter pylori infection is the main cause of duodenal and gastric ulceration and a major risk factor for gastric adenocarcinoma and lymphoma. However, these diseases only occur in about 15% of infected persons1. Of those infected, who will develop disease is influenced by the virulence of the infecting H. pylori strain, the genetic susceptibility of the host and environmental co-factors. Of these, bacterial virulence factors are the most studied2 . Bacterial virulence factors are characteristics present in some bacteria which enable them, rather than others, to cause disease. For H. pylori, it is still unclear whether all or only some strains are pathogenic. All strains cause a long-lasting histological gastritis characterised by lymphocytic and some degree of neutrophilic infiltration, although this gastritis per se is clinically silent. Whether all strains can potentially cause peptic ulceration or gastric carcinoma is unclear, although the risks associated with some are certainly much greater than those associated with others. Certain characteristics are present in only some strains and have been linked with disease. These are, firstly, vacuolating cytotoxin production and certain types of vacA (vacuolating cytotoxin gene A) alleles; secondly, CagA (cytotoxin associated gene product A) and genes in the cag (cytotoxin associated gene) pathogenicity island; and thirdly, the ability to strongly and rapidly stimulate neutrophils to degranulate. Host susceptibility may be relevant both in determining who becomes infected with H. pylori and who amongst those infected develops disease3 . There is growing evidence that the host's HLA type4 , and blood group antigen type and expression5  are important, at least as genetic markers of susceptibility. Important environmental factors include childhood living conditions (the strongest environmental correlate of who becomes infected6 ), smoking (a major risk factor for duodenal ulceration amongst H. pylori-infected persons7 ) and dietary factors (important risk factors for gastric adenocarcinoma8 ).

Many characteristics of H. pylori are necessary for disease and thus are potential therapeutic targets and important subjects for research. Gastric colonisation is a prerequisite for H. pylori-associated disease, and for this both motility (derived from flagella) and urease have been shown to be important: mutant strains lacking these features cannot establish infection in animal models9 -10. Following colonisation, H.pylori must acquire nutrients in the gastric mucus niche, and as for all bacterial parasites, acquisition of iron from the host is a particular challenge11. Infection is virtually lifelong in the absence of treatment, implying that evasion of the host response is efficient, and this is discussed in the accompanying paper on inflammation and autoimmunity. Adhesion is important for the enhanced inflammatory response seen for some pathogenic strains: for example, these strains only stimulate cultured epithelial cells to produce the pro-inflammatory cytokine interleukin 8 if they are allowed to adhere12. Other H. pylori components are also pro-inflammatory: urease is an important stimulant of both local and systemic immunity as are many other surface expressed and cytoplasmic proteins13 . However, none of these shared factors can explain differences in disease outcome unless they differ qualitatively or quantitively between strains, and in the rare instances where differences have been shown13 , these have not correlated with disease. 

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10 Kebiasaan yang dapat Merusak Otak

Ternyata otak bisa rusak karena hal-hal berikut ini..

1. Tidak Sarapan Pagi
Mereka yang tidak mengkonsumsi sarapan pagi memiliki kadar gula darah yang rendah, yang akibatnya suplai nutrisi ke otak menjadi kurang.

2. Makan Terlalu BanyakTerlalu banyak makan, apalagi yang kadar lemaknya tinggi, dapat berakibat mengerasnya pembuluh darah otak karena penimbunan lemak pada dinding dalam pembuluh darah. Akibatnya kemampuan kerja otak akan menurun.

3. MerokokZat dalam rokok yang terhisap akan mengakibatkan penyusutan otak secara cepat, serta dapat mengakibatkan penyakit Alzheimer.

4. Mengkonsumsi gula terlalu banyakKonsumsi gula yang terlalu banyak akan menyebabkan terganggunya penyerapan protein dan nutrisi, sehingga terjadi ketidakseimbangan gizi yang akan mengganggu perkembangan otak

5. Polusi UdaraOtak adalah konsumen oksigen terbesar dalam tubuh manusia. Menghirup udara yang berpolusi menurunkan suplai oksigen ke otak sehingga dapat menurunkan efisiensi otak.
Baca Selengkapnya " 5 Kebiasaan yang Dapat Merusak Otak" di Unik dan Keren

See Translation

Jangan terperangkap dengan 'tipu daya' bantuan tambahan susu. Dapatkan bantuan jika anda merasakan susu anda seolah-olah tidak mencukupi. Dalam kebanyakan kes, perasaan ragu-ragu ini timbul akibat tekanan daripada orang sekeliling dan bukan tanda sebenar bayi tidak mendapat cukup susu.