Inflammatory Bowel Disease Flashcards
What is the innate immune system?
First response to infection
What are the 3 main components of the innate immune system?
- Toxic/inhibitory substances
- Complement system
- The cells that make up the innate part
What are examples of toxic/inhibitory substances?
- Enzymes e.g. lysozymes in tears
- C-reactive protein (CRP)
What does CRP do?
Enhances phagocytosis and complement binding
What is the complement cascade?
A series of proteins in blood which, when activated, promote inflammation, opsonisation and lysis of pathogens
What are the cellular components of the innate immune system?
- Phagocytes (neutrophils, monocytes/macrophages, dendritic cells, eosinophils)
- Mast cells & basophils (release mediators (e.g. histamine when activated)
- Natural killer cells
Why is the innate immune system insufficient protection?
Rapid response
BUT
- No memory formation
- Recognises limited numbers of sites on foreign organisms
Where are B cells produced/matured?
Produced and matures in bone marrow
What is life cycle of B cells?
Produced throughout life, survive only a few days
How do B cells work?
- Have antibodies on their surface which act as antigen receptors
- When activated proliferate and differentiate into plasma cells producing specific antibody
- Memory cells formed
Where are T cells produced/matured?
Produced in bone marrow and matures in thymus
What is life cycle of T cells?
Most produced before puberty, so long-lived
How do T cells work?
Have T cell receptors with variable regions which recognise presented antigens
Memory cells are formed
What are the different types of T cells?
Distinguished by proteins expressed on surface:
- CD4+ (Helper T cells)
- CD8+ (cytotoxic T cells)
Also regulatory T cells (Treg)
How do B and T cells interact?
- Activated B cell engulfs and digests antigen
- B cell displays antigen fragments bound to its unique MHC molecules
- Combination of antigen and MHC attracts matching T cell
- Cytokines secreted by T cell help B cell to multiply and mature into antibody producing plasma cells
What is MHC?
Major Histocompatibility Complex is a region on chromosome 6 coding for proteins involved in immune function
Includes genes for proteins on cell surfaces which have a cleft that holds a small peptide derived from proteins within the cell (HLA)
Where is MHC class I found?
On all nucleated cells
What does MHC I display in healthy cells?
display fragments of normal intracellular proteins
What does MHC I display in infected cells?
display fragments of bacterial or viral protein
Where is MHC class II found?
Found on antigen presenting cells (APCs) – macrophages, dendritic cells, B-lymphocytes
What does MHC II display?
fragments of internalised antigens
What does CD4 facilitate the binding of?
T helper cells to MHC II
What does CD8 facilitate the binding of?
Cytotoxic T cells to MHC I
What are the 3 different types of T helper cells (CD4+ lymphocytes)?
- Th1
- Th2
- Th17
What is role of Th1?
Promote inflammation, stimulate phagocytosis by activating macrophages. Predominantly involved in responses to microbial pathogens
What is role of Th2?
Promote strong antibody production, particularly IgE. Predominantly involved in responses to parasites, and atopic (allergic) responses
What is role of Th17?
Not fully understood. Have important roles in intestinal lamina propria, may be implicated in inflammatory bowel disease
What are the 3 parts associated with the mucosal immune system?
- Gut Associated Lymphoid Tissue (GALT)
- Intraepithelial lymphocytes
- Lamina propria lymphocytes
What does GALT include?
- Tonsils
- Adenoids
- Peyer’s patches
- Appendix
What does GALT contain?
Contain B and T lymphocytes, macrophages and dendritic cells
What are intraepithelial lymphocytes?
Interspersed amongst epithelial cells – mainly CD8+ T cells
What are lamina propria lymphocytes?
CD4+ (helper) T cells, B lymphocytes, mast cells
What does ulcerative colitis affect?
Only affects the mucosa in the colon/rectum (bottom of GI tract) –> inflammation starts at rectum
Continuous areas of inflammation
What does Crohn’s disease affect?
Anywhere in the GI tract
Inflammation extends through the full thickness of the bowel wall
Patchy “cobblestone” appearance
What does ulcerative colitis lead to?
- Mucosal/submucosal inflammation
- Crypt abscesses, loss of goblet cells
- Colonic dilatation
What does Crohn’s disease lead to?
- Transmural inflammation
- Granulomas – spherical areas formed during chronic inflammation if non-degradable foreign matter or persistent presence of pathogens
- Fistulas
What are the 2 main types of inflammatory bowel disease?
- Crohn’s disease
2. Ulcerative colitis
What is IBD thought to be triggered by?
Inappropriate response to stimuli in genetically susceptible individuals (genes, environment, gut microbiota)
How does smoking affect Crohn’s disease/ulcerative colitis?
Smoking worsens / smoking may improve condition
Is there a surgical cure for Crohn’s disease/ulcerative colitis?
No (as affect whole GI tract) / yes
Difference between symptoms and signs?
Symptoms - volunteered by patients
Signs - observed by doctor
Common symptoms of IBD?
- Diarrhoea
- Rectal bleeding and mucus
- Faecal urgency/incontinence
- Abdominal and perianal pain
- Weight loss
- Fatigue/lethargy
- Mouth ulcers
Common signs of IBD?
- Abdominal tenderness
- Mass on palpation
- Anaemia
- Fistulae (not in ulcerative colitis)
- Perianal abscess (not in ulcerative colitis)
What is IBD?
Chronic relapsing and remitting inflammatory disorders of unknown aetiology
Caused by Failure to maintain oral tolerance (suppression of immune response to antigens consumed orally)
Describe intestinal homeostasis dynamic in normal people?
Normal interaction between invasive organisms and harmless antigens (e.g. food, proteins and commensal bacteria)
Describe intestinal dynamic in IBD?
- Ag activation of innate immune cells
- Adaptive immune response maintains inflammatory response with abnormally activated CD4+ Th cells releasing pro-inflammatory mediators leading to chronic tissue damage (sensitive to own gut bacterial antigens)
What response is CD/UC more associated with?
CD - Th1 response
UC - Th2 response
Mutations in what genes are associated with increased susceptibility to Crohn’s?
Genes NOD2 –> involved in intracellular processing of bacterial antigens
What can polymorphisms in IL–23R lead to?
Increased susceptibility (CD and UC)
What is IL-23R produced by and involved in?
IL-23 produced by dendritic cells and involved in regulation of Th-1 and Th-17 cell differentiation and regulation of chronic inflammation
What is a panproctocolectomy?
The removal of the entire colon, rectum and anal canal.
What is transmural?
Occurs across entire wall of a vessel/ organ
What is ulcerative colitis?
UC is a form of colitis (i.e. inflammation of the colon) that includes characteristic ulcers (visible in scans)
Why are steroids only used as short term medication for IBD?
not long term as cause other complication e.g. hypertension, diabetes
