Immunology Flashcards by Alexandra Chan

What are the 4 main mechanisms for protection from infection in the GI mucosa

Physical barrier - epithelium, glycocalyx, mucous, unstirred layer + peristalsis

Chemical barriers - enzymes from panted cells and acid

bacterial protection - commensal bacteria

Immunological - MALT, B and T cells and GALT + BALT

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Describe GALT and what it can be split into

Gut-Associated lymphoid tissue (adaptive and innate response)

(organised) Peyer’s patches (SI), caecal patches (LI) and lymphocytes in the mesenteric lymph nodules (organised)
or
(disorganised) sites with lymphocytes in the lamina propria - mainly IgA secreting B cells and lymphocytes in the interstitial space below the basolateral membrane

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Describe the Peyer’s patches

Found in the SI, most in the distal ileum
Aggregated lymphoid follicles covered with follicle associated epithelium (FAE)
Rich in B, T dendritic cells and macrophages
Monitors local bacteria

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Describe Peyer’s patches development

Requires exposure to bacterial flora
Have 50 in the last trimester
Hit the maximum no. of 250 in the teenage years

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Describe the M cells

The FAE contains specialised enterocytes/M cells
Transcytosis of luminal bacteria, antigens and proteins (uptake)
Express IgA receptors to transfer IgA bacteria complexes to the Peyer’s patches

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Describe antigen uptake

Combined effort of M cells and dendritic cells (trans-epithelial)
Antigens are presented to lymphocytes for assessment and response
Activated cells develop gut homing markers and migrate to the mesenteric lymph nodes to proliferate

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Explain the abundance of IgA

Most abundant antibody in the body (IgG most abundant circulating)
Highly prevalent in mucosal secretions due to MALT being associated with lots of IgA plasma cells
90% of gut B cells secrete IgA

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What is SIgA

Dimeric form of IgA produced by lamina propria B cells
Binds to pathogens to prevent their adherence to the mucosal wall
Stimulated by M cells and dendritic cells
Made up of 2 IgA, j chain and secretory component

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Describe the formation of SIgA

In a plasma cells 2 IgA molecules are bound by a j-chain
Secretion into the interstitial space
Dimer binds to a receptor on the external basolateral surface of enterocytes (PIgR)
Formation of SIgA
endocytosis of SIgA into the epithelial cell
transport via vesicle to the apical membrane
exocytosis into the gut lumen

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What are the functions of the secretory component of the SIgA

helps move IgA move through the enterocyte

Protects the antibody dimer from enzymatic and acid degradation

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Describe lymphocyte circulation

Stimulated lymphocytes in the Peyer’s patches migrate into the local mesenteric lymph nodes to enter the lymphatic system
Drain into the thoracic duct
Lymphocytes then activated by tissue specific endothelial adhesion molecules which stimulates transmigration (requires HEV) to enter the blood
Lamina propria OR skin, tonsils, BALT

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Explain the process of transmigration

L-selectin (lectin that binds to carbs) expressed on the surface of lymphocytes and mediates the interactions to allow leukocytes to roll in postcapilary venues and HEVs
L-selectin binds to mucosal addressing cell adhesion molecule-1 (MAdCAM-1)

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What is MAdCAM-1 and where is it expressed

Enables lymphocyte recruitment in chronic gut inflammation
HEVs of Peyer’s patches and mesenteric lymph nodes
flattened endothelial cells
Activation via binding to integrin

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What are the symptoms of irritable bowel syndrome

Recurrent abdominal pain
Abnormal bowel motility
Constipation and/or diarrhoea
(Does not involve inflammation, ulcers (IBD))

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What are the risk factors of IBS and what is it caused by

stress
Gastroenteritis from norovirus and rotavirus
Visceral hypersensitivity

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Describe the treatment of IBS

Diet modification - Avoiding certain foods such as apples, beans, cauliflowers.

Treatment of constipation - soluble fiber, stool softeners and osmotic laxatives

Treatment of spasms and pain - anti-diarrheals, anti-muscarinic

Management of stress, anxiety, depression

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What are the symptoms of coeliac disease

Abdominal distension (bloating)
Diarrhoea
Sometimes dermititis herpetiformis

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Explain the pathophysiology of coeliac disease

Gliadin is not broken down in the stomach and binds to IgA at the mucosal membrane
This binds to transferring receptor TFR and is transferred to the lamina propria
tissue transglutaminase (tTG) cuts the amide group
Deamidates gliadin is phagocytosed by macrophages and presented by MHC II
Activation of the immediate system to destroy the epithelial cells

How can coeliac disease be diagnosed

Antibody blood tests - anti-gliadin, anti-tTg, anti-endomysial (EMAs)
Biopsy test of duodenum

What are the suggested dietary modifications suggested for coeliac disease

Gluten-free diet (wheat, barley, rye exclusion) and medication.
Factors affecting compliance are lifestyle, eating out, cross contamination at home and holidays.

What are the symptoms of Crohn’s disease

Pain in affected area, most commonly in right lower quadrant.
Diarrhea and blood in stool.

What is inflammatory bowel disease

Ulcerative colitis, Crohn’s disease

What is the pathophysiology of Crohn’s disease

Immune-related
Mycobaterium paratuberculosis, pseudomonas and listeria
Unregulated immune response and GI tract is destroyed
associated with NOD2 gene mutation

Describe the treatment of Crohn’s disease

Anti-inflammatory drugs and antibiotics
Immunosuppressants e.g. corticosteroids
Surgical removal of the affected tissue
Liquid diet 
Low fibre
Decrease obstruction pain and gas production

What are the symptoms of ulcerative colitis

Pain in left lower quadrant due to ulcers along the inner surface of large intestine, including the colon and rectum. Severe and frequent diarrhea (sometimes bloody).

Describe the pathophysiology of ulcerative colitis

Autoimmune disorder - T cells destroy the cells lining the walls of large intestine Secondary cause - Diet and stress

Describe the treatment for ulcerative colltis

Anti-inflammatory drugs (sulasalazine and mesalamine) immunosuppressants (corticosteroids, azathioprine, cyclosporine) Colectomy Dietary manipulation Pre/probiotics to treat pouchitis

How can diarrhoea be treated

``` Drink fluid Nutritious drinks Replace salt Eat soluble fibre Avoid gas producing foods, fibre, alcohol and caffeine ```

What are the symptoms of cholera infection

Vomiting, nausea Abdominal pain Severe dehydration and diarrhoea (watery)

Describe the pathophysiology of cholera infections

vibrio cholerae transmitted through the feral-oral route and spreads through contaminated water and food Reaches the SI On contact with the epithelial cells it releases toxins Na+, K+ and Cl- (+ water) exits

Describe FAE

follicle associated epithelium No goblet cells No secretory IgA Little microvilli

Describe the dual role of the GI tract in immunology

Restrained activation Tolerance to food antigens and commensal bacteria Immunoreactivity to pathogens

What makes up the gut microbiota

10^14 gut bacteria 4 phyla of bacteria (bacteroidetes, firmicutes, actinobacteria, proteobacteria) Viruses and fungi

What is Dysbiosis

Altered microbiota composition | Infection, diet, xenobiotics, hygiene and genetics contribute to either microbiota or dysbiosis

Describe MALT

Mucosa associated lymphoid tissue Found in the submucosa below the epithelium Lymphoid mass with lymphoid follicles Follicles surrounded by HEV Oral cavity is rich in these e.g. tonsils

Describe B cell adaptive response

1. Mature naive B cells express IgM 2. upon antigen presentation class switch to IgA 3. T cells and dendritic cells influence B cell maturation via cytokine release 4. B cells mature to become IgA secreting cells 5. Population of the lamina propria

Describe the diagnosis of cholera infection

Bacterial culture from stool sample on selective agar | Rapid dipstick also available

What are some causes of infectious diarrhoea

``` Cholera E. Coli Salmonella Shigella Clostridium difficile ``` Rotavirus (children) Norovirus Giardia lamblia Entamoeba histolytica

Describe rotavirus infection

RNA virus that replicates in enterocytes Infects children Treated by oral rehydration Vaccination = rotarix

Describe norovirus infection

RNA virus acute gastroentiris Faecal-oral

Describe campylobacter infection

Undercooked meat, untreated water, unpasteurised milk Low infective dose Most common cause of food poisoning Azithromycin (macrolide)

What are the types of E. coli associated with diarrhoea

ETEC - cholera like, watery EHEC/STEC - most dangerous EIEC - shigella like, bloody 3 other types

Describe clostridium difficile infection management

``` Isolation Stop antibiotics Vancomycin, metronidazole Increasingly difficult to treat after recurrence Faecal microbiota transplantation ```