Infection and immunology Flashcards
What is the consequence of the GI tract having such a large surface area
- It has a massive antigen load
- Resident microbiota bacteria
- Dietary antigens
- Exposure to pathogens
what does the immune system of the gut have to be in a state of?
State of “restrained activation” - Tolerance to food and commensual bacteria vs. active immune response – Dual immunological role.
How was it shown that we require microbiota for a healthy immune system
- we used germ free mice, with no microbiota
- and the development of T cells is fewer, and B cells
what does the microbiota consist of and what happens when our body is in equilibruim and when it isn’t?
- Symbionts: symbiotic relationship, important for regulation of our body
- commensals: prevent the adhesion of pathogens and bactera in the endothelial lining
- pathiobionts: can cause inflammation
All these are balanced when our body is in equilibruim.
Dysbiosis – Altered microbiota composition
This is what happens when the components are imbalanced, regulation is disrupted which causes inflammation.
what factors play a role in causing dysbiosis?
- Infection or inflammation
- diet
- xenobiotics
- hygeine
- genetics
- healthy microbiota
These can go and affect all over the body
what is the first defence mechanims in the mucosa?
Mucus layer - Goblet cells Epithelial monolayer - Tight junctions Paneth Cells (small intestine) -Bases of crypts of Lieberkühn. -Secrete Antimicrobial peptides (defensins) and lysozyme.
what happens if the bacteria go through the first line defence mechanism?
We have immunological defence mechanisms.
- MALT (mucosa associated lymphoid tissue)
- GALT (gut associated lymphoid tissue)
where are MALT found?
- Found in the submucosa below the epithelium, as lymphoid mass containing lymphoid follicles (collection of T and B lymphocytes)
- Follicles are surrounded by HEV postcapillary venules, allowing easy passage of lymphocytes
Found mainly in the mouth e.g. tonsils (M cells) which can initiate an immune response
MALT is a umbrella term for many immunological tissues
where about is GALT found?
- As you go down, you have the GALT
- Responsible for both adaptive & innate immune responses through generation of lymphoid cells & Abs
GALT is presented in 2 forms.
- Not Organised
Intra-epithelial lymphocytes – Make up one-fifth of intestinal epithelium, e.g., T cells, NK cells. lymphocytes below basolateral membrane of the epithelium of the gut
Lamina propria lymphocytes—-IgA secreting B cells
Organised: Peyer’s patches (small intestine) Caecal patches (large intestine) Isolated lymphoid follicles Mesenteric lymph nodes (encapsulated)
Describe how the different lymphoid tissue are organised?
- intra-epithelial lymphocytes
- below epithelium: peyers Patch
All these drain into the mesenteric lymph nodes
where is peyers patches found?
- Found in small intestine, mainly distal ileum
- Aggregatedlymphoid follicles covered with follicle associated epithelium (FAE).
- Mucus contains naiive B cells and T cells
what are the features of the FAE?
FAE - no goblet cells, no secretory IgA, lack microvilli
where are the tran-epithelial dendritic cells?
- between epithelial cells, through the peyers patch
- this however does not compromise the tight junctions and still functions to not let any pathogens through the tight junctions.
How is the epithelium above Peyer’s patches different to normal gut epithelia?
It is Follicle Associated Epithelium (FAE) - there are no goblet cells, no microvilli and no secretory IgA
In which layer of the gut wall are Peyer’s patches found?
Lamina Propria
Where do activated T and B cells go to proliferate?
Superior Mesenteric Lymph Nodes
What is the role of secretory IgA?
Prevent attachment and entry of pathogens
What immune cell makes up 1/5 of intestinal epithelium?
Intraepithelial lymphocytes
What is the difference between conventional and unconventional T cells?
Conventional - migrate from other tissues
Unconventional - resident
what other innate cells are involved?
NK cells
What three signals determine the T cell response?
Presentation of antigen on MHC
Costimulation
Cytokines
what are the mechanisms of immune tolerance?
Anergy
Deletion
Regulation (Tregs)
What is Crohn’s disease?
Inflammatory thickening of the bowel wall - leads to ulceration, diarrhoea and pain
Name 4 structures where GALT is ORGANISED
Cryptopatches
Peyer’s Patches
Isolated lymphoid follicles
Mesenteric lymphoid follicles
Name 2 places where GALT isn’t organised
Intra-epithelial lymphocytes
Lamina propria lymphocytes
State three infections of the GIT.
Oral candidiasis
Helicobacter pylori
Traveller’s Diarrhoea
What does H. pylori cause?
Increased acid secretion
State three causes of Traveller’s Diarrhoea.
Escherichia coli
Salmonella
Shigella
Name a superbug.
Clostridium difficile
What is the treatment for C. difficile?
Metronidazole and Vancomycin
What components make up mucosal defence?
Anatomical and chemical barriers
Commensal bacteria
GALT and MALT
What makes up the epithelial barrier?
Goblet cells, Paneth cells, antimicrobial peptides, secretory IgA
What is GALT and what does it do?
Collections of T and B cells which generate lymphoid cells and antibodies
Produces secretory and interstitial IgA, IgM, IgG and cell mediated immunity
What do Peyer’s Patches consist of?
naïve T and B cells
what is cholera?
Cholera is an acute bacterial disease caused by Vibrio cholerae.
The bacteria reaches the small intestine where on making close contactwith the epithelium releasescholera toxin.
Cholera toxin on entering the epithelial cell, starts a series of biochemical reactions resulting in exit of ions such as Na+, K+, Cl- and water from the epithelial cell.
How is cholera diagnosed, treated and transmitted?
Transmitted through faecal-oral route,
: bacterial culture from stool sample on selective agar is the gold standard, rapid dipstick tests also available.
Treatment: oral-rehydration is the main management
what are the causes of diarrrhoea?
Viral
Bacterial
Protozoal parasitic
how does rotavirus cause dirrahoea?
RNA virus, replicates in erythrocytes. 5 types A – E, type A most common in human infections
