Immunity to Microbes/Mucosal Defenses Flashcards
mucosae
tissues continually bathed in a thick layer of mucus that they secrete
Gut associated lymphoid tissue
- lamina propria
- mesentric lymph nodes
- peyer’s patches
Functions of mucosal tissue
- gas exchange
- food absorption
- sensory activities
- reproduction
Mucosal surfaces are thin, permeable barriers to the interior of the body. These tissues are by nature vulnerable to subversioin and breach by pathogens.
Urogenital tract
- uterus
- bladder
- vagina
gastrointestinal tract
- oral cavity
- esophagus
- stomach
- pancreas
- intestine
respiratory tract
- sinus
- trachea
- lungs
intestines (# of lymphocytes)
50x10^9
lungs (# of lymphocytes)
30x10^9
75% of the body’s lymphocytes are in
secondary lymphoid organs serving mucosal surfaces
majority of all anitbodies made by the body
are dimeric or secretory IgA which localize to mucosal surfaces
GI tract of humans
continious contact with large numbers of commensal microbes
challenge to the mucosal immune system
eliminate pathogens while limiting growth of commensals and not attack our food
surface area of small intestine
200x that of the skin
Intestinal epithelial cells are covered by
two layers of mucus
inner mucosal layer
firmly adherent and works to seperate microbes from epithelial cell
outer mucosal layer
microbes are mostly associated with the outer layer. The outer layer is loosely adherent.
Overall thickness of mucosal layer
differs in the various sections of the gastrointestinal tract
mucosal layer in stomach
corpus
- protects the gastric mucosa from the pH of the stomach
Duodenum/Jejenum (small intestine)
very very thin layer of inner layer and outer layer, covering the villi
colon
large intestine,
thickest outer layer
which layer has the most microbes?
outer layer
secondary lymphoid tissues of the small intestine
- Peyer’s patches
- lamina propria
- isolated follicles
These all drain to the mesentric lymphnodes
villus
peak/projection of tissue, into the lumen, coated with epithelial cell layer.
very important for absorption of food.
Villus also contains epithelial cells, that contain cillia that enable cells to be absorptive of food when it’s being digested and degrated.
intraepithelial lymphocytes
Paneth cells
produce anti-microbial peptides
goblet cells
produce mucus. becomes more unfolded eventually
peyer’s patch
underneath the epithelial layer
- contains both B and T cell zones
- very small
- located right below epithelial lining of the gut
M cells
specialized for transport of things from the lumen to the peyer’s patch
mesenteric lymph node
majority of anitgens and cell that migrate and be presented to B or T cells, go to the draining lymph nodes named mesentric lymph node.
major draining lymph node of the gut
mesenteric lymph node
lamina propria
it is a lymphoid tissue, but lacks the level of organization such as the peyer’s patch and mesenteric lymph nodes.
cells that live within lamina propria
- plasma cells (IgA)
- macrophages
- Mast cells
- T cells
- B cells
- Dendritic cells
classification of cells in the lamina propria
Effector cells, not many naive cells
intraepithelial lymphoid cells -> when these cells ^ go into the mucosal layer.
NLR and TLR
face the basolateral surface of the epithelial layer (NOT facing the lumen)
Intestinal epithelial cells
- polarized
- apical surface that faces the lumen
1. absorption - basolateral surface that faces the underlying tissue
1. adherent to ECM
NLR location
cytoplasm
TLR location
basolateral surface
TLR and NLR are able to
detect if a bacteria has entered the cell
M cells directly within the
Epithelial layer
Specialized in transport across the epithelial barrier
dendritic cells can also live right on the epithelial layer
DC pushes a projection through the epithelial layer, so they may sample luminal contents to present those to T cells.
Surveying of mucosal immune system
DC and M cells
Microfold (M) cells
have very little degradtive activity
Function primarily to transport of particles, pathogens, and antigens across the epithelium
M cells mechanism
- M cells take up antigen by endocytosis and phagocytosis
- Antigen is transported across the M cells in vesicles and released at the basal surface
- Antigen is bound by dendritic cells, which activates T cells
2 mechanisms of DC takeup of luminal content
- projection reached through epithelial layer and reach the antigen in the lumen and then perform endocytosis
- antigens may cross the epithalial layer through a “breach”
= Presentation of antigen to T cells in mucosa-associated lymphoid tissues or mesenteric lymph nodes
primary anitbody isotype found in the gut
dimeric IgA
IgA
neutralizing, because of its association with the J-chain, it can be moved acorss the epithelial layer by polyIG receptor.
intraepithelial lymphocytes
“specialzed cell type” that resides directly between the epithelial cells and the barrier
- effector lymphocytes
- integrated into the epithelial layer of the small intestine
- IEL’s are generally CD8+Tcells, either alphabeta or gammadelta and have limited range of antigen specificities
1 IEL
for every 7-10 epithelial cells
IELs are generally
CD8 + T cells
Naive lymphocytes activated in a Peyer’s patch, gives rise to
effector cells that travel in the lymph and blood to gain access to the lamina propria of the mucosal tissue
chemokines instruct
T cells on when to leave the certain vessel they are found in.
+ adhesion molecules = tells the T cell where to stop and perform diapedesis.
Lamina Propria
(loosely) connective tissue underlying the intestinal epithelia and where many immune components are located (plasma cells, T cells, DCs, macrophages, mast cells and eosinophils)
Peyer’s Patch
lymphoid tissue integrated in the intestinal wall and contains numerous B cell follicles with germinal centers
Mesenteric lymph node
lymph nodes located in the intestinal mesentery and are dedicated to defending the gut
Intraepithelial lymphocytes
T (typically, CD8+) cells, integrated into the epithelial layer
M (microfold) cell
cells that uptake and transport antigen and cells from the intestinal lumen to Peyer’s patches located beneath them
mechanisms of surveillance
- uptake and transport into Peyer’s Patches by M cells
- DCs extending through epithelial layer
- paracellular (in between epithelial cells)
