6. Mavetarm

• Slimhindernes immunitet


  Omfattende adgang til kroppen, beskyttelse mod infektioner og tolerance overfor føde/mikrobiota antigener
• 2/3 af alle kroppens leukocytter befinder sig i tarmen
• Sekundært immunologisk væv i slimhinderne


  • Findes i mundhulen og tyndtarmen
  • Leukocytter er i umiddelbar kontakt med mucus
• Uddifferentiering af T-celler via dendritiske celler

  Til hjælper/regulatoriske Th-celler
• Dendritiske celler og M-celler


  • Aktiverer det adaptive immunrespons mod relevant antigen

  
• Antigener fra "ufarlige" kilder


  Inducerer anergi i T-celler via IL-10 producerende dendritiske celler

  
• Antigener fra "farlige" kilder

  Aktiverer T-celler via IL-12

  
• IgA


  • Det antistof, der er mest af i kroppen, dominerende på tarmepitelet
  • Dimert struktur giver høj aviditet og god evne til at neutralisere mikrobielle toksiner og adhæsionsmolekyler
  • Sekretorisk komponent og polyIgR transporterer dimert IgA over tarmepitel
• IgAs effektorfunktion


  Primært neutraliserende
• Mikrobiota regulerer immunsystemet systemisk via transport af signalstoffer

  
• Mikrobiota påvirker "innate-like lymphoid cells" (ILC)

  
• Fæcestransplantation kan afhjælpe visse inflammatoriske respons i tarmen (Crohns sygdom, IBS)
• Sygdomme, hvor ændring i mikrobiota kan have potentiel effekt


  • Clostridioides difficile
  • Inflammatorisk tarmsygdom
  • Irritabel tarm
  • Fedme
• Slimhinde immunitet


  Immunsystemets funktion i slimhinderne
• Slimhinderne


  • Udgør en omfattende adgang til kroppen
  • Indeholder meget lymfoidt væv, f.eks. Peyer'ske pletter og mandler

  
• Tarmens immunsystem


  • 2/3 af alle kroppens leukocytter befinder sig i tarmen
  • Leukocytter er i umiddelbar kontakt med mucus

  
• Uddifferentiering af T celler via dendritiske celler


  1. Dendritiske celler aktiverer det adaptive immunrespons mod relevant antigen

  2. Dendritiske celler kan også inducere anergi i T celler via IL-10 produktion

  
• Antigener fra "ufarlige" kilder

  Inducerer anergi i T celler via IL-10 producerende dendritiske celler
• Antigener fra "farlige" kilder


  Aktiverer T celler via IL-12
• IgA


  • Det antistof, der er mest af i kroppen
  • Dimert IgA er det dominerende Ig på tarmepithelet
  • Sekretorisk komponent tillader transport over epithel via poly IgG receptor
  • IgAs effektorfunktion er primært neutraliserende
• Microbiotaen regulerer immunsystemet systemisk via transport af signalstoffer

  
• Microbiotaen influerer "Innate-like lymphoid cells"

  
• Fæcestransplantation kan afhjælpe visse inflammatoriske respons i tarmen (Crohns sygdom, IBS)
• Leukocytes in mucous membranes


  Leukocytes in mucous membranes protect the body against pathogens by recognizing and responding to their presence, engulfing and destroying them, and coordinating the immune response.
• Pattern recognition receptors (PRRs)


  PRRs are proteins on the surface of leukocytes that can bind to specific molecular patterns found on pathogens, known as PAMPs. This allows leukocytes to recognize and respond to the presence of pathogens.
• IgA structure


  IgA is made up of four polypeptide chains: two heavy chains and two light chains. These chains are held together by disulfide bonds. The heavy chains of IgA have a region called the Fc region, which is responsible for interacting with other cells and proteins in the body.
• IgA and toxins


  IgA can neutralize toxins by binding to them and blocking their active sites, which prevents them from interacting with their target cells. IgA can also help to remove toxins from the body by facilitating their uptake and clearance by immune cells.
• Dendritic cells activate T cells


  Dendritic cells activate T cells through a process called antigen presentation, in which they present pieces of an antigen (a foreign substance) to T cells in the context of a major histocompatibility complex (MHC) molecule. This interaction activates the T cell, which then proliferates and differentiates into effector T cells that can attack and eliminate the antigen-containing cells.
• MHC molecules


  MHC molecules are proteins found on the surface of most cells in the body. They present pieces of proteins (peptides) from inside the cell to T cells, which are a type of white blood cell that plays a central role in the adaptive immune response. MHC class I molecules present peptides derived from proteins produced within the cell to CD8+ T cells, while MHC class II molecules present peptides derived from proteins taken up by the immune cell from the outside environment to CD4+ T cells.
• ÅRSAGER til GASTROENTERITIS / AKUT DIARRE


  • Virus
  • Bakterier (fx Campylobacter, Salmonella, E. coli)
  • Protozoer (fx Giardia lamblia)
  • Forgiftninger (fx svampetoxiner, kontaminerede fødemidler, tungmetaller)
  • Antibiotika
  • Medicin (fx laksantia, antacida, cytostatika)
• ALDER OG GASTROENTERITTER


  • Akutte virale gastroenteritter forekommer gennem hele livet
  • Alvorlige tilfælde ses hyppigst hos små børn og ældre mennesker
  • Hos børn: oftest rotavirus
  • Hos voksne: oftest norovirus
  • Endvidere: adenovirus, astrovirus og picornavirus
• Rotavirus


  Nøgent, resistent RNA-virus fra Reoviridae
• Norovirus


  Nøgent, resistent RNA-virus fra Caliciviridae
• Rotavirus er en væsentlig dødsårsag blandt mindre børn 0 - 4 år, specielt i Asien, Afrika og Latinamerika
• I I-lande har ca. 4 ud af 5 børn haft rotavirusinfektion inden de fylder 5 år. I DK 1.200 indlagte per år. Mortalitet lav (<1 per år)
• I U-lande har alle været inficeret med rotavirus inden de fylder 5 år. Mortalitet ca. 1/2 mio år.
• Rotavirus 


  • RNA-genom omkranset af et tre-lags icosahedral protein capsid og ingen envelope
  • VP8* interagerer med receptorer på værts-celler og er nødvendig for viruspartikel-binding og infektion
  • Antistof mod VP7 definerer G serotype/genotype, antistof mod VP4 definerer P serotype
• Campylobacter spp.


  Gram-negative, comma-shaped (curved), polar flagellum, motile, microaerophilic (5% oxygen), thermophilic (optimal growth 37 - 42 °C)

  
• Campylobacter jejuni


  Most common cause of bacterial gastroenteritis in Denmark, around 3500-5500 cases annually, 93% of the strains belong to C. jejuni (around 6% to C. coli)
• Campylobacter is the most common cause of bacterial gastroenteritis in Denmark