3: Immunology - role of mucosal immunity in disease Flashcards
Which cells initiate presentation of antigen to T cells in lymph nodes to start the adaptive immune response?
Dendritic cells
Macrophages
Which signal molecules trigger activation of immune cells following a cellular insult?
Cytokines
Chemokines
Defensins
The appropriate immune response to a pathogen tends to have a ___ effect for the host.
The inappropriate immune response to a pathogen ___ the host’s cells.
protective
damages
Which pathogen is notable for causing mucosal immune dysregulation?
HIV
Upon HIV infection of the mucosa, which immune cell takes it up for presentation and inadvertently spreads it throughout the gut and lymphoid tissue?
Dendritic cells
Which T cells are infected and killed by HIV?
CD4+ T cells (helper / memory)
someone says this in Trainspotting
In which types of tissue is HIV infection common?
Mucosal tissue
What is primary immunodeficiency?
Part of the immune system is missing from birth
HIV infection is a (primary / acquired) immunodeficiency.
acquired
What immunoglobulin is the most common in the mucosal immune response?
IgA
Which primary immunodeficiency is responsible for Coeliac disease?
IgA deficiency
What is CVID?
Collection of immunodeficiencies which causes sinopulmonary and GI infections
If someone presents with recurrent infections, what should you check?
Immunoglobulin levels
What is XLA?
X-linked agammaglobulinaemia
What immunodeficiency is seen in people with XLA?
No B cells
No IgG
What will you see in someone with XLA?
Recurrent infection
XLA is only present in (males / females).
males
What is used to treat XLA patients?
Immunoglobulin infections
What is the phagocyte respiratory burst?
Phagocytes produce reactive oxygen species (superoxide) to kill pathogens
What is CGD?
What is the primary immunodeficiency?
Chronic granulomatous disease
Failure of phagocytes to produce superoxides for respiratory burst
What does SCID stand for?
What is the immunodeficiency?
What will the patient present with?
Severe combined immunodeficiency
No B cells; No T cells
Constant infection (pulmonary and GI), opportunistic
What immunoglobulin is associated with allergy?
Which immune cell is activated and degranulates due to the action of this antibody?
What symptoms present after?
IgE
Mast cells
Allergy symptoms - bronchoconstriction, increased permeability of blood vessels, runny nose, anaphylaxis
Mast cell activation by IgE is self-perpetuating because:
Activated ___ ___ produce ___ which stimulates B cells to produce more IgE.
(mast cells, IL-4)
mast cells , IL-4 , TH2
What immune cells are activated by allergens?
What happens systemically if this isn’t treated?
Mast cells, Basophils, Eosinophils
Anaphylaxis
Which diseases causes small intestine damage leading to malabsorption ⇒ malnutrition?
Coeliac disease
IBD (Crohn’s, UC)
Which foods does gluten come from?
Wheat
Barley
Rye
Is coeliac disease an allergy?
No
Genetically linked autoimmune disorder which can develop at any time
Which foodstuff triggers the symptoms of coeliac disease?
Gluten
Which genes trigger the development of Coeliac disease?
HLA-DQ2
HLA-DQ8
Is Coeliac disease antibody-mediated or T cell mediated?
T cell mediated
Gluten specific T cells produce IFgamma which triggers other T cells.
Which T cells are triggered?
What happens?
Intraepithelial lymphocytes (CD8+ T cells)
Killing of epithelial cells
What will patients with undiagnosed Coeliac disease present with?
Abdominal pain
Bloating
Diarrhoea - steatorrhoea
Weight loss
What components of epithelial cells atrophy in Coeliac disease?
Villi
The immune response associated with Coeliac disease ___ the intestinal epithelium.
damages
Patients with Coeliac disease will have a ___ epithelium on endoscopy.
flattened
Why do damaged villi and a flattened epithelium, associated with Coeliac disease, cause malnutrition?
Loss of villi - less absorption
Smaller surface area - less absorption
What structures, usually found between villi on intestinal epithelium, are the only things visible on someone with damaged epithelium due to Coeliac disease?
Crypts
Coeliac disease is caused by an adaptive T-cell mediated reaction to gluten.
Which genes are responsible for the protein which activates the T cells?
HLA-DQ2 / HLA-DQ8
How do you treat Coeliac disease?
Stop eating gluten
the gut then returns to normal
How is Coeliac disease diagnosed?
Positive tTG-IgA antibody test with the patient still eating gluten
Then positive biopsy (flattened epithelium)
What is the usual method of diagnosing Coeliac disease?
Who’s excluded from this?
Biopsy to confirm damage to small intestine
Children
What are the symptoms of Coeliac disease?
Weight loss
Anaemia
Diarrhoea - steatorrhoea
Abdominal pain
Bloating
i.e all of them, impossible to do serology on ALL of these people
Which test is done to confirm Coeliac disease instead of biopsying or doing serology on every patient who has GI symptoms?
tTG-IgA test
tissue transglutaminase test
Under what circumstances will the IgA autoantibody test give a false negative?
If the patient is complying with “no gluten” before they’re officially diagnosed
catch 22 because you can only be formally diagnosed if you eat gluten, which causes your symptoms
What is the gold standard method of diagnosing Coeliac disease?
Duodenal biopsy
AFTER positive tTG-IgA test
Why may a person with diagnosed Coeliac disease experience symptoms again?
Non-compliance with gluten-free diet
Which enzyme modulates gluten when it enters the gut to form a complex with it?
Tissue transglutaminase
Are B cells specific for the gluten itself or tTG enzyme which has formed a complex with it?
tTG
The more gluten you eat, the more ___ that will be presented to B cells and the more epithelial damage which will be done.
tTG
Which inflammatory bowel disease can appear anywhere from the rectum to the mouth?
Crohn’s disease
What inflammatory bowel disease tends to move progressively from the rectum up the GI tract?
Ulcerative colitis
