The Mucosal Immune System Flashcards
Mucosal tissues in the human body
- The respiratory tract:
sinus, trachea, lungs - The gastrointestinal tract:
oral cavity, esophagus, stomach, intestines - The urogenital tract:
uterus, bladder, vagina - Conjunctiva
- Lacrimal gland
- Kidneys
The mucosal tissue has the particularity that are open to the environment and will be colonised with microbiota. This means that our immune system is constantly working in the mucosal tissues because we are already colonised with our own microbiota. So we have a very active mucosal immune system.
Distinctive features of the mucosal immune system
The mucosal immune system has distinct:
- anatomical features (such as close interactions of the mucosal tissues and the lymph nodes, the organised structures such as the Peyer’s patches, and the tonsils. There are also specialized antigen-uptake mechanisms, such as the M cells);
- effector mechanisms (such as activated/memory T cells that predominate in the absence of infection, multiple activated effector/regulatory T cells present, secondary IgA antibodies, presence of distinctive microbiota)
- immunoregulatory environment (such as active downregulation of immune responses, inhibitory macrophages and tolerance-inducing dendritic cells).
Mucosal tissues
In the GUT there will be some tight junctions that will separate the internal environment from the external one. In the crypts we will have the Paneth cells. In between the epithelial cells, there are going to be the intraepithelial lymphocytes. There are also going to be the Peyer’s cells which will contain the follicles with B cells.
The tonsils and the adenoid are glands in the mouth responsible for immuno-regulatory response. They make a ring called Waldeyer’s ring, around the entrance of the gut and the airway, and they will be very important in generating regulatory cells.
The M cells will collect the antigen. The antigen will be transported across the M cell in a vesicle in a process called transcytosis. And the antigen will be delivered to the dendritic cells and the effector cells.
In the mucosal tissues, we will find CD8 and 4 T cells, mast cells, macrophages, dendritic cells, plasma cells that will secrete IgA.
The T cells enter the Peyer’s patches from the blood vessels and encounter the antigen transported across the M cells and become activated by the dendritic cells.
The activated T cells will drain via the lymph nodes to the thoracic duct and return to the gut via bloodstream. Activate T cells expressing integrin and CCR9 home to the lamina propria and intestinal epithelium of small intestine.
The dendritic cells will capture the antigen from the intestinal lumen by mononuclear cells in lamina propria.
Mucosal interactions
For the mucosal tissues we will have the dimeric IgAs interacting with it. The local plasma cells will secrete the IgA, in the lamina propria can bind to the vasolateral membrane of the epithelial cells through the polymeric Ig receptor. Then the cell can transport that in a vesicle by endocytosis, so it will cross the cell, and so the antibody can be transported to the epithelial laminar surface. It will not be free of the receptor, but will be a part of it (and it becomes a secretory component), and a part of the receptor will still remain in the vesicle. The secretory component will not allow the antibody to be washed away from the laminar surface, will remain attached to the mucus layer. The antibody will do it’s normal functions of neutralization.
Epithelial cells in the mucosal tissues
The epithelial cells have a crucial role in the innate defence against pathogens, because they have TLRs. If they recognize a pathogen, or a product of the pathogen, then they will activate their antimicrobial program and release cytokines that can recruit and activate other phagocytic cells.
Pathogen manipulations in the mucosal immune system.
The M cells will be targets for some pathogens internalize through them. Because the M cells are used to take the pathogen outside, they can also be used to take the pathogens in.
Salmonella can invade the epithelial surfaces and exploit transport T cells to to get located to the lamina propria. They can also use the dendritic cells to get carried to the epithelial cells.
Shigella can also use the M cells to be transported across the barrier of epithelial cells, and even can use the epithelial cells to move across them.
Protective immunity vs mucosal tolerance
- Antigen:
toxins, bacteria, viruses - protective immunity;
food proteins, commensal bacteria - mucosal tolerance. - Antibody production:
specific antibodies present in serum for the protective immunity;
low (some local IgA) or zero antibodies in the mucosal tolerance. - Primary T cell response:
local and systemic effector and memory T cells for the protective immunity;
no local effector T cell response for the mucosal tolerance. - Response to antigen reexposure:
enhanced memory response for protective immunity;
low or no response for the mucosal tolerance.
Mucosal protection in the mouth and commensals
In the Waldeyer’s ring for the different glands in the oral cavity, we will collect samples for the antigen, and those will activate the T regulatory cells, so they can travel to the mucosal tissue to inhibit cells that have receptors for that.
What happens if we get rid of microbiota?
The pathogenic bacteria that wouldn’t cause an infection due to the presence of commensals, will now do that. The the infection will keep ongoing because the bacteria will create tissue damage, break the barriers, there will be inflammation, infiltration of the cells in the immune system, and this will cause colitis.
There will be local responses to commensals, like a local IgA to maintain the number of those commensals. But there are other responses that will have the same function. The mucus is stratified in two layers: the inner and the outer mucus layers. In the inner we will have the IgA, because they will attach to the layer due to the secretory components. But in the outer mucus layer, we will have the commensals, which don’t get access to the epithelial cells because they are also separated by the IgA.
The local responses for the commensals are the inner layer containing the IgAs and the outer layer containing the commensals.
Also:
The Goblet cells that are also interspersed throughout the epithelial layer will release the mucus. In the Peyer’s patcher we will have the M cells which can incorporate the antigen. In the M cells the mucus will be thinner, so they can take a hold of the antigen, and it can be the commensals when there is no infection, so we can generate plasma cells releasing antibodies against the commensals against them.
But because the mucus is thinner, the M cells are very active incorporating the antigen.
The commensal bacteria can also inhibit the activity of the epithelial cells because they can prevent inflammatory responses. And the epithelial cells are activated by innate immunity receptors, and activate an inflammatory response. But some commensal bacteria are able to block the transcription factors translocated to the nucleus, so they prevent the inflammatory response. So it is good because they can maintain the equilibrium within the epithelial cells.
