IMMUNE MEDIATED INTESTINAL DISEASES Flashcards
(39 cards)
WHAT PERCENTAGE OF COELIAC DISEASE IS FAMILIAL?
10-20%
WHAT DOES COELIAC DISEASE CAUSE DAMAGE TO?
INTESTINAL VILLI
WHICH CELLS OF THE IMMUNE SYSTEM ARE ACTIVATED IN COELIAC DISEASE?
GLUTEN SPECIFIC T LYMPHOCYTES
WOMEN:MEN AFFECTED BY COELIAC?
2:1 (THERE COULD BE BIAS)
PEOPLE OF WHICH DESCENT ARE PARTICULARLY AFFECTED BY COELIAC?
NORTHERN EUROPEAN
WHAT PERCENTAGE OF UK POPULATION IS AFFECTED BY COELIAC?
1%
SYMPTOMS OF COELIAC, CHILDREN VS ADULTS?
CHILDREN: GASTROINTESTINAL SYMPTOMS (DIARRHEA, FATTY STOOL, CRAMPS, VOMITING..), FAILURE TO THRIVE (LOW HEIGHT AND WEIGHT)
ADULTS: INTESTINAL SYMPTOMS, BEHAVIOURAL ISSUES (DEPRESSION, ANXIETY, MEMORY LOSS, DIFFICULTY TO FOCUS..)
WHICH FUNCTION OF THE GI TRACT DOES THE COELIAC MOSTLY AFFECT?
ABSORPTION
WHICH PARTS OF THE SMALL INTESTINE DOES COELIAC AFFECT?
UPPER SMALL INTESTINE AND THE JEJUNUM
WHICH GLUTEN PROTEIN CAUSES THE IMMUNE REACTION IN COELIAC DISEASE?
GLIADIN (can also be glutenin)
PATHOPHYSIOLOGY OF COELIAC DISEASE:
- GLIADIN PROTEINS FROM GLUTEN ARE BROKEN DOWN IN PIECES CALLED EPITOPES
- EPITOPES ARE SMALL PEPTIDES RECOGNISED BY IMMUNE CELLS, 1ST BEFORE ENTRY IN THE ENTEROCYTES, AND THEN AFTER EXITING THE ENTEROCYTE (IN THE LAMINA PROPRIA)
- THIS RECOGNITION PATTERN WILL OCCUR IN EVERYONE, BUT IT IS DEREGULATED IN COELIAC
- MOLECULES PRODUCED DURING THE IMMUNE REACTION WILL ATTACK THE ENTEROCYTES AND THIS IS HOW VILLI WILL LOSE THEIR INTEGRITY
- CRYPT STRUCTURE (WHERE CCK IS PRODUCED) WILL BECOME HYPERTROPHIC SO THE SECRETIONS OF CCK WILL BE IMPAIRED
- ENTEROCYTE RENEWAL IS IMAPIRED
- GOBLET CELLS THAT NORMALLY PRODUCE PROTECTIVE MUCUS WILL ALSO BE IMPAIRED
- IMMUNE CELLS WILL BE PRESENT IN ENTEROCYTES
- DESTRUCTION OF VILLI WILL LEAD TO DESTRUCTION OF THE WHOLE MUCOSA, SO TIGHT JUNCTIONS WILL NOT FUNCTION NORMALLY WHICH LEADS TO ‘LEAKY GUT’, WHICH ALLOWS MOLECULES TO TRAVEL DIRECTLY FROM THE LUMEN TO LAMINA PROPRIA, WHICH THEN SENDS MORE SIGNALS TO THE IMMUNE CELLS THAT SOMETHING IS WRONG
WHAT IS ‘LEAKY GUT’?
LEAKY GUT REFERS TO IMPAIRED FUNCTIONING OF TIGHT JUNCTIONS WHICH CONNECT ENTEROCYTES, LEADING TO PASSAGE OF MOLECULES STRAIGHT FROM THE INTESTINAL LUMEN TO THE LAMINA PROPRIA, WHICH INDUCES IMMUNE RESPONSE.
IT IS A RESULT OF VILLUS DESTRUCTION IN COELIAC DISEASE
WHAT ARE EPITOPES?
SMALL PEPTIDES FORMED AS A RESULT OF GLIADIN BREAK DOWN WHICH ARE RECOGNIZED BY IMMUNE CELLS
WHICH IMMUNE CELLS ARE EPITOPES RECOGNISED BY?
ANTIBODIES IgA
WHAT HAPPENS IN COELIAC DISEASE AFTER EPITOPES ARE RECOGNISED BY IgA ANTIBODIES UP UNTIL THEY REACH LAMIN PROPRIA?
- THE IgA-GLIADIN COMPLEX IS NOT ELIMINATED (AS IT WOULD NORMALLY BE)
- IT IS INSTEAD RECOGNIZED BY TRANSFERRING (TfR) RECEPTOR ON VILLI SURFACE
- THE COMPLEX OF TfR, IgA AND GLIADIN MOVES THROUGH ENTEROCYTES
- GLIADIN PROTEINS ARE RELEASED ON THE BASOLATERAL SIDE OF THE ENETROCYTES FACING THE LAMINA PROPRIA
WHAT HAPPENS TO GLIADIN PEPTIDES IN THE LAMINA PROPRIA?
- THEY ARE FIRSTLY DEAMIDATED BY TRANSGLUTAMINASE 2 (TG2)
- TG2 CONVERTS GLUTAMINE TO GLUTAMATE (NEGATIVE CHARGE)
- NEGATIVE CHARGE INCREASES THE IMMUNOGENICITY OF THE GLIADINS (IMMUNE CELLS WILL BE EVEN MORE ATTRACTED BY THIS TYPE OF PEPTIDES)
- MACROPHAGES WILL ‘EAT’ THESE PEPTIDES
- ONCE INSIDE THE MACROPHAGES AKA PRESENTING MOLECULES, PEPTIDES WILL BE PROCESSED AND ASSOCIATED WITH MOLECULES OF MHC CLASS II
- MHC (MAJOR HISTOCOMPATIBILITY COMPLEX) CALLED HLA (HUMAN LEUKOCYTE ANTIGEN) IN HUMANS
- IN COELIAC DISEASE, THESE MOLECULES ARE ASSOCIATED WITH HLA DQ2 (MOSTLY) OR HLA DQ8 GENES
- T CELLS RECOGNISE HLA DQ2 ASSOCIATED WITH GLIADIN PEPTIDES AND THEN GET ACTIVATED AND SECRETE HIGH LEVELS OF PROINFLAMMATORY CYTOKINES
- AN ACTIVATION CASCADE WILL FOLLOW; CYTOKINES ACTIVATE MORE IMMUNE CELLS
- B CELLS ARE ALSO ACTIVATED AND THEY WILL PRODUCE ANTIBODIES, MEANING THE IMMUNE RESPONSE WILL BE STRONGER AFTER ANOTHER EXPOSURE TO GLUTEN
DIFFERENCE BETWEEN MAJOR HISTOCOMPATIBILITY COMPLEX (MHC) CLASS I AND II?
I: INVOLVED IN AUTOIMMUNE DISEASE
II: INVOLVED IN RECOGNITION OF PATHOGENS OF EXTERNAL ELEMENTS
EVERYBODY HAS HLA MOLECULES EXPRESSED WHERE?
SURFACE OF MACROPHAGES
CLASS II HLA MOLECULES IN PEOPLE WITH COELIAC DISEASE ARE ENCODED BY WHICH 2 GENES + PERCENTAGE FOR BOTH?
HLA-DQ2 (95% OF PATIENTS)
HLA-DQ8
EXACT T CELL TYPE THAT RECOGNISES THE HLA-DQ2 MOLECULE ASSOCIATED WITH GLIADIN PEPTIDES?
CD4+ T CELLS
WHAT IS ZONULIN AND WHAT HAPPENS TO IT IN COELIAC DISEASE?
ZONULIN IS A REGULATOR OF INTESTINAL TIGHT JUNCTIONS. IT IS OVEREXPRESSED AND THAT LEADS TO INCREASED PERMEABILITY OF THESE JUNCTIONS WHICH MASSIVELY IMPAIRS THE INTEGRITY OF THE MUCOSA (PATHOGENS CAN GO THROUGH, FURTHER INCREASING INFLAMMATION)
WHAT IS INFLAMMATORY BOWEL DISEASE?
REFERS TO IMMUNE MEDIATED DISORDERS REGROUPING CROHN’S DISEASE AND ULCERATIVE COLITIS (UC)
DIFFERENCE BETWEEN COELIAC DISEASE AND CROHN’S DISEASE?
COELIAC IS A FOOD ALLERGY; IMMUNE RESPONSE AGAINST GLUTEN PROTEINS
CROHN’S IS AN AUTOIMMUNE DISEASE
DIFFERENCE BETWEEN CROHN’S AND ULCERATIVE COLITIS?
DIFFERENT LOCATIONS OF INFLAMMATION (CROHN’S AFFECTS THE ENTIRE GI TRACT AND UC ONLY AFFECTS THE LARGE INTESTINE) + DIFFERENT LAYERS OF THE GI TRACT AFFECTED (UC AFFECTS ATHE LINING ALL ALONG, CROHN’S PENETRATES THE WHOLE INTESTINAL WALL BUT DIFFERENT AREAS ARE AFFECTED TO DIFFERENT EXTENT)
