MUDr. Dana Maňasková


Vyhledávání na medicinman.cz
 

Popis, patofyziologie

Gastric microbiota

  • Highly heterogeneous results for gastric microbial composition
  • 266 bacterial genera identified
    • 57 were more frequently reported in the normal acidic stomach
      • Proteobacteria, Firmicutes, Bacteroidetes, Actinobacteria, Fusobacteria
      • The most abundant genera: Helicobacter, Streptococcus, and Prevotella
  • Regarding the gastric microbiota in subjects with gastric cancer
    • Most studies have shown that it seems to be characterized by an enrichment of bacterial diversity due to the additional colonization of the gastric environment by oral taxa such as:
      • Streptococcus, Staphylococcus,
      • Lactococcus, Bacillus,
      • Prevotella, Veillonella, and Leptotrichia
    • Intestinal taxa such as
      • Lactobacillus
      • Clostridium
      • Fusobacterium
        • With a contemporary decreased presence of Hp
  • Individuals with this condition, who are predisposed to gastric cancer
    • The largest proportion of Streptococci was found
      • These microbes notably belong to the oral microbiota and, probably, the non-acidic gastric environment due to the fact that hypochlorhydria offers an acceptable habitat
        • Making this oral commensal intriguing because plays a potential role in gastric carcinogenesis
    • But in Portuguese studies a decrease in Streptococcus in individuals with gastric cancer was reported
  • www.mdpi.com/2076-2607/8/11/1827

Autoimunitní gastritis a perniciozní anemie

  • Imunitní systém útočí na buňky v žaludku, které jsou zodpovědné za tvorbu vnitřního faktoru.
  • Vnitřní faktor je bílkovina, která je nezbytná pro vstřebávání vitamínu B12 z potravy. Nedostatek vitamínu B12 vede k perniciózní anémii.
  • Triggery autoimunitní perniciózní anémie jsou tedy spojeny s narušením tvorby vnitřního faktoru v těle.

Both immune responses

  • It is typical that:
  • Anti-bacterial immune response
    • Promotes differentiation of CD4+ T cells into Th1 cells that produce IFN-gamma and TNFalpha
  • Parasitic infection or allergy
    • Th2 cells that produce IL-4 and IL-13
  • Hp-specific CD4+ T cells
    • Are predominantly differentiated into Th1 cells
      • In response to Hp antigens (e.g., CagA, FlaA, VacA, UreB)
  • IFN-gamma, but not IL-4
    • Important for promoting gastric inflammation (Nurgalieva et al., 2005; Smythies et al., 2000; D'Elios et al., 1997).
  • Early parasitic infection skews an individual’s immune response toward Th2
    • Decreasing the risk of Hp associated gastric cancer
  • Increased levels of the type 2 cytokine, IL-13, in chronically Hp infected individuals
    • To be associated with enhanced disease progression beyond inflammation (Holcombe, 1992; Marotti et al., 2008)
  • Both Th1 and Th17 (IL-17 producing) cells
    • Play important roles in the induced response against infection
  • Th17 cells precede Th1
    • Important for inducing the Th1 response (Shi et al., 2010)
  • IL-17 also plays a role in recruiting neutrophils to the site of infection (DeLyria et al., 2009).
  • In mice infected with Helicobacter species
    • Neutrophil depletion
      • Slowed clearance
      • Limited inflammation-mediated pathology (Ismail et al., 2003; DeLyria et al., 2009)
  • Neutrophil-induced pathology
    • Hp phagosome escape strategies
      • Causing reactive oxygen species to leak into the extracellular environment
        • Elicit tissue damage (Allen et al., 2005)
  • Eosinophils and mast cells
    • Identified within the gastric mucosa of Hp-infected individuals
      • Exact contributions to disease progression and/or infection clearance remains unclear (Nakajima et al., 1997; Moorchung et al., 2006)
  • Antigen-presenting cells
    • Hp-mediated inflammation through the activation of autoreactive CD4+ T cells
  • Dendritic cells presenting Hp antigen
    • Stimulate CD4+ T cells in vitro to produce IFN-gamma, TNFalpha, and IL-17
  • Classical dendritic cells expressing Programmed Death Ligand 1 (PDL1)
    • Were recently found in the gastric submucosa of Hp-infected individuals
      • Interacting with effector T cells to promote tolerance and limit gastric pathology (Go et al., 2021)
  • Epithelial cells within the inflamed gastric tissue
    • May also be responsible for lymphocyte activation
    • HLA-DR (MHC II), ICAM-1 (lymphocytic adhesion), B7-1 and B7-2 (T cell co-stimulation), and Fas/FasL (receptor mediated apoptosis) have increased expression
      • Contribute to immune cell-mediated epithelial cell apoptosis
      • Epithelial cell-mediated T cell proliferation and activation
  • Infection with Hp causes an infiltration of immune cells
    • Leads to chronic inflammation
      • Inflammation-mediated pathology
  • Autoreactive CD4+ T cells
    • Mainly target the H+/K+ ATPase proton pump found on parietal cells
    • Predominantly differentiate into the Th1 phenotype
      • Producing IFN-gamma upon stimulation with this antigen (D'Elios et al., 2001)
  • Th1 cells are also capable of
    • Inducing IgM, IgG and IgA production from autologous B cells in vitro
    • Can induce pathology via perforin/granzyme or Fas/FasL-mediated cell death
  • Dendritic cells (DC) have also been identified
    • In gastric biopsies from AIG patients and in mice
    • Increase in gastric DCs correlated to enhanced pathology (Ninomiya et al., 2000)
  • Women who developed AIG were found to have T cell and macrophage infiltration
    • In their stomach biopsies
    • Increased HLA-DR (MHC II) expression on epithelial cells (Burman et al., 1992)
  • Mast cells and eosinophils
    • Identified in the setting of AIG
    • Contribution to disease and the significance of infiltration have not yet been determined (Park et al., 2013; Bockerstett et al., 2020).

Mice models

  • IL-17 and IFN-gamma in this model
    • Induce parietal cell atrophy initiating pathology in the corpus of the stomach (Bockerstett et al., 2018; Osaki et al., 2019)
  • IL-13 was also found to have a profound impact on progressing gastric pathology in TxA23 animals
    • Driving metaplastic transformation in the tissue (Noto et al., 2021).
  • Increases in pSTAT3 and IL-6
    • Associated with human carcinomas (Nguyen et al., 2013)
  • IL-27, produced by macrophages in the gastric mucosa
    • Is protective against inflammation and metaplastic development
    • By acting on CD4+ T cells to dampen the inflammatory response (Bockerstett et al., 2020)
O úroveň výše

Poslední aktualizace: 27. 10. 2023 19:24:00