Chapter 12: The Barrier Immune System Flashcards
What does the mucosal immune system do?
- Protects internal surfaces of the body
- Comprises the internal body surfaces that are lined by mucus covered epithelium
- In gastro tract, upper and lower resp,urogenital, biliary,middle ear,exocrine eye glands, salavary gland, and lactating breast
How do the thickness of tissue in the body vary?
Mucosae:
Pseudostratified ciliated - Line nasal cavity paranasal
Simple ciliated - Single cell thickness lines bronchi
Simple ciliated cuboidal - lines terminal and resp bronchioles
Simple squamous - forms alveolar ducs and alveoli
Stratified squamous is multilayered
Skin:
Keratinized stratified squamous epithelium
What types of cells can be found in the different sections of the digestive tract? How much mucous is there in the different sections?
Corpus to pylorus has a single thick layer of mucous
Duodenum to ileum has single thin layer
Proximal to distal colon has two thick layers
What are the distinctive features of the mucosal immune system?
What happens if a mucosal surface is compromised?
- Antigens will attach to epithelium and cause invasion
-If the barrier is intact, binding is blocked and antigens can be trapped and cleared safely
Where are immune cells deployed?
Inductive site
- Where immune cells are activated
- Lymph nodes and the mucosa-associated lymphoid tissue (MALT)
Effector site
- Where immune cells act to protect the site
- (Intestinal) epithelium, lamina propria
What is a peyer’s patch? What is an isolated lymphoid follicle? Why does follicle associated epithelium lack a thick layer of mucus?
Peyer’s patches
- Mainly found in distal ileum
- Large aggregates of lymphoid tissue
- Contain multiple germinal centers
Isolated lymphoid follicle (ILF)
- Found in small and large intestine
- Single aggregates of lymphoid tissue
- Mainly B cells
- Follicle associated epithelium lacks thick layer of mucus because it does not produce mucins
How does ILFs develop? What are cryptopatches?
- ILFs develop from cryptopatches after birth in response to microbiota
- Composed of dendritic cells and lymphoid tissue inducer cells (LTi)
What does intestinal epithelium contain? What does the lamina propria contain?
- Variety of conventional and unconventional T cells, intraepithelial lymphocytes (IELs)
- Populated by innate immune cells and effector T cells as well as antibody secreting cells (Plasma cells)
How does the maturation of gut associated lymphoid tissue occur?
- Maturation of gut associated lymphoid tissue is driven by acquisition of the commensal microbiota
What happens when antibiotics kill the commensal bacteria?
- If microbiota is killed it opens a niche for bacteria such as clostridium to infect causing necrosis. This must be treated with a targeted antibiotic
What is the epithelial turn over rate like? What are intestinal stem cells?
- High turnover rate
- Days to a few weeks
- Intestinal epithelial cells (IECs shed about 3-5 days
- Intestinal stem cells give rise to transient amplifying (TA) cells which give rise to two groups of IECs
- Absorptive and secretory
What are some features of microfold cells, goblet cells, paneth cells?
- Microfold cells are from absorptive IECs and are important for antigen uptake and bacterial translocation
- Goblet cells are from secretive IECs and are important for producing mucins and antigen uptake
- Paneth cells are from secretive IECs and are important for supporting intestinal stem cells and secretion of antimicrobial peptides
What is the cellular source for alpha defensins, beta defensins, calprotectin, C type lectins, lysozymes, and phospholipase A2?
How is a continuous intercellular barrier formed?
- Membrane adjacent epithelial cells are tethered together near their apical surface by tight junctions and adhesion complexes. Claudine and occluding are responsible for permeability of tight junctions
What is the major mucin in the intestine? What does glycosylation lead to?
- The major mucin in the intestines is MUC2 a gel forming mucin
- Glycosylation leads to a bottlebrush like structure that binds water and gives mucus its lubricating gel like properties
How is invasion of intestinal microbes prevented?
- Antimicrobial peptides and mucus function prevent invasion
- Small intestine: Antimicrobial peptides from paneth cells keep the microbes away from epithelium
- Large intestine: The inner layer of mucus cannot be penetrated by bacteria due to the extensive cross linking
How is intestinal epithelium barrier maintained and defended?
- Conventional and unconventional T cells
- Intraepithelial lymphocytes
- Major function is to eliminate IEC that are infected, damaged, or stressed
- Release growth factor to promote epithelial proliferation and repair
How can intestinal cells uptake and deliver antigens to antigen presenting cells?
Intestinal cells can use secreted IgA, M cells, FcRn transport, Goblet cells, tight junctions, apoptosis dependent transfer, and trans epithelial dendritic cells
Outline important features of protective immunity and mucosal tolerance. Include antigen, primary Ig production, primary T cell response, and response to antigen reexposure.
How does adaptive immunity aid in the regulation of mucosal homeostasis?
- Intestinal dendritic cells favor the induction of antigen specific Treg cells that are critical for the maintenance of mucosal immune homeostasis
- Major factors that include protolerogenic DC functional stat include TGF-B, IL-10, retinoic acid, and thymic stromal lymphopoietin (TSLP)
- Products of bact, epithelial cells, stromal, neuronal, and dietary and microbial metabolites
What are the four stages of a bacteria penetrating the mucus layer and attaching to epithelium
- Colonization, innate response, adaptive response, clearance
What recognizes bacteria leading to the recruitment of neutrophils, macrophages, and dedritic cells?
- TLRs which start a cascade eventually recruiting leucocytes which are able to eventually manage the bacterial invasion
What cells are in the respiratory tract?
What happens when influenza attaches to the cells in the respiratory tract?
