L12 GI Immunology Flashcards
What are the major components of the innate immune system?
- Pattern Recognition receptor - Toll-like receptors
- Antimicrobial peptides - defensins, probiotics, granulsyin. Naturally occurring antimicrobial peptides are found In all bodily secretions including saliva and tears. This creates a barrier to infection.
- Cells
- Complement components (Do not have a large role in the gut)
- Cytokines which mediate host defence and inflammation as well as recruit and regulate adaptive immune response.
What are PRRs?
Pattern recognition receptors: play a crucial role in the proper function of the innate immune system. Pattern Recognition Receptors (PRRs) are proteins capable of recognizing molecules frequently found in pathogens (the so-called Pathogen-Associated Molecular Patterns—PAMPs), or molecules released by damaged cells (the Damage-Associated Molecular Patterns—DAMPs). They are found on the surface of endoscopes of innate immune cells and found circulating freely.
These are found on the surface of macrophages and dendritic cells. These can recognise broader patterns such as lipopolysaccharides bacterial cell walls, single-stranded RNA and double stranded RNA. These structure alert the immune system that there is a potential invasion by a pathogen. It will not detect which particular organism it is but that there is a microbe.
Give cells of the innate immune system.
The innate leukocytes include: natural killer cells, mast cells, eosinophils, basophils; and the phagocytic cells include macrophages, neutrophils, and dendritic cells, and function within the immune system by identifying and eliminating pathogens that might cause infection.
What is the difference between the adaptive and innate immune system?
The adaptive immune system has evolved in response to changing pathogen structures. It is now able to provide far more specific recognition and is able to expand in response to specific threats and has a high degree of specificity unlike the innate immune system.
What are the immune and specific defences of the gut immune system?
Innate Immune System:
• Commensal bacterial flora
• Epithelial barrier
Biochemical factors produced by epithelial cells
Specific defences:
○ Lymphoid tissue associated with mucosal surfaces
[Gut associated lymphoid tissue; GALT]:
What are prebiotics and probiotics?
Prebiotics is food for bacteria that encourages a specific type of bacteria over another. E.g. in breast milk there is inulin which is indigestible to humans but is digestible by the flora later on in the column. This encourages certain bacteria to grow as part of the flora.
Probiotics are living microorganisms that, when ingested, provide numerous health benefits.
What are the benefits of gut microflora?
- Leads to resistance to colonisation of pathogens as gut flora out compete pathogens
- Stimulate local immunity
- Oral tolerance
- Nutrition
- Epithelial cell turnover - microflora stimulate cell turnover, regulated by short chain fatty acids
- Intestinal motility
What are the problems associated with gut microflora?
- Diseases of the Gi tract such as Irritable bowel syndrome and Ulcers via H. Pylori
- Extraintestinal disease - Septicaemia is when bacteria enter the bloodstream, and cause blood poisoning which triggers sepsis. Sepsis is an overwhelming and life-threatening response to infection that can lead to tissue damage, organ failure and death.
- Allergy
- Autoimmunity
What do stem cells differentiate into in the epithelial barrier?
Stem cells lie at the level of the base of the Crypts of Lieberkhun.
What is the different cells of the epithelial barrier?
- Enteroendocrine cells
- Goblet Cells - Produce mucins to provide for mucus layers that resist microbial access. Acts to trap the macrobacterium to control the numbers. This prevents excess proliferation.
- Enterocytes - are simple columnar epithelial cells which line the inner surface of the small and large intestines. A glycocalyx surface coat contains digestive enzymes. Microvilli on the apical surface increase its surface area. Produce antimicrobial peptides
- Paneth Cells - Their main function is to produce, package and export a variety of antimicrobial proteins and peptides including α-defensins, angiogenin-4, lysozyme and secretory phospholipase A2.
- Secretory IgA cells
What are Peyer’s patches?
Lymphoid tissue is arranged into Peyer’s patches. There is also a lot of immune cells in the gut; just underneath the mucosa or lymphocytes interspersed within the epithelial cells.
Peyer’s patches have a combination of antigen presenting cells such as dendritic cells, specialised M cells and follicles which contain B cells and T cells. Found throughout the ileum region of the small intestine. Also known as aggregated lymphoid nodules, they form an important part of the immune system by monitoring intestinal bacteria populations and preventing the growth of pathogenic bacteria in the intestines.
What is the organisation of lymphoid elements in the gut?
The gut-associated lymphoid tissue consists of organized lymphoid tissues, such as mesenteric lymph node (MLN) and Peyer’s patches (PPs), and more diffusely scattered lymphocytes in the intestinal LP and epithelium.
What are intraepithelial lymphocytes? What is their role?
• Found between intestinal epithelial cells
• Large granular lymphocytes
Mostly CD8+ (Cytotoxic T Cells). They produce IL-2, IFN-g and CCL5. Produce perforin and granzyme to perform the cytotoxic function.
Perforin is a cytolytic protein found in the granules of CD8+ T cells (& NK cells). Upon degranulation, perforin inserts into the target cell’s plasma membrane, forming a pore. This enables entry of granzymes, which trigger cell death via membrane lysis.
What are Lamina Propria lymphocytes? What is their role?
Found in loose connective tissue, the lamina propria, that lies under the epithelium – together make up the mucosa
Mostly CD4+ (Helper T Cells). These cells orchestrate the majority of immune responses.
What are M cells?
Microfold cells - found in the follicle-associated epithelium of the Peyer’s patch; have the unique ability to sample Ag from the lumen of the small intestine and deliver it via transcytosis to APC and lymphocytes. Their basolateral surface is invaginated to form a pocket-like structure to which macrophages and lymphocytes migrate.
