Flashcards in Lecture 18 Specialized Immunity at the GI Epithelial Barriers Deck (147)
What organ/tissue has the largest number of lymphocytes?
The Intestines: 50 x 10^9
The GI immune system is the largest and most complex
*reflects large surface area which must also resist invasion by bacteria in the lumen
The oral cavity and vagina has what type of epithelial barrier?
At the epithelial layer, how are Ags captured?
DCs congregate immediately under epithelia, migrate into the epithelial layer, and even extend dendrites into the lumen to capture Ags
The DCs that capture Ags at the epithelia travel to where?
The nearest draining LN to present Ag to naive T cells
At sites of organized mucosal lymphoid tissues, how are Ags captured?
Specialized microfold (M) cells deliver Ags across the epithelial barrier directly to subepithelial DCs that then present Ag locally in adjacent mucosal T-cell areas
What are sites where some adaptive immune responses specialized for the particular mucosa are initiated?
These collections of immune cells are called Gut-associated lymphoid tissue (GALT)
The effector lymphocytes that are generated in the draining lymph nodes or GALT of a particular regional immune system (small bowel) will enter the blood and the travel where?
Preferentially home back to the same organ (e.g. dermis, lamina propria)
There are specialized cells which are restricted to one or more regional immune systems but are not present throughout the immune system including:
M cells in the gut
γδ T cells in epithelia
Subsets of IgA producing B cells
Regional immune systems have what important regulatory functions?
Functions that serve to prevent unwanted responses to nonpathogenic microbes and foreign substances that are likely to be present at different barriers
What layer is underlying the epithelium?
A layer of loose connective tissue in the gut called the lamina propria that contains blood vessels, lymphatic vessels, and mucosa-associated lymphoid tissues
The GI tract has what two remarkable properties?
First, total surface area is more than 200m^2
Second, the lumen of the gut is teeming with more than 500 different species of bacteria, amounting to approximately 10^14 bacteria
What functions do commensal organisms have?
1. degradation of components of our diet that our own cells cant digest
2. compete with potentially pathogenic microbes in the gut and prevent harmful infections
When do commensal organisms become potentially lethal?
If they cross the mucosal barrier
How can non-commensal pathogenic organisms possibly become part of GI organisms?
If they are ingested in contaminated food or water
*these pathogenic organisms include bacteria, viruses, protazoa, and helminthic parasites
Non-commensal pathogenic organisms often cause disease without doing what?
Invading the epithelial cells
What trick must the mucosal immune system pull off?
Must be able to recognize and eliminate pathogens while maintaining the symbiotic relationship with normal microflora
The innate immune protection in the gut is mediated in part by what barrier?
Physical and chemical barrier provided by the mucosal epithelial cells and their mucus secretions
How are adjacent intestinal epithelial cells held together?
By proteins that form tight junctions preventing the movement of microbes between the cells into the lamina propria
Epithelial cells produce what type of defensins?
anti-microbial peptides defensins
What immune cells are in the lamina propria that can induce inflammation?
DCs, Mo, and neutrophils
Most of the responses are induced by ______ but, instead, these responses can be ___-______ actions in the gut
The physical/chemical barrier is formed by several viscous proteins called what?
What do mucins prevent?
Prevent microbes from contacting epithelial cells
What type of glycoproteins do mucins include?
Both secreted and cell surface glycoproteins
Secreted mucins form a two layer gel:
Outer less-dense layer that is normally colonized by bacteria
Inner more-dense layer that is bacteria-free
There are anti-microbial substances in the mucus layers produced by what cells?
The apical surface of GI epithelial cells is coated with what?
Membrane-bound mucin proteins called the glycocalyx
What does the glycocalyx serve as?
Like the secreted mucus, it serves as a physical barrier to prevent microbial contact
Mucins are constitutively produced by what?
Epithelial cells and submucosal glands