Test 2: lecture 1 barriers Flashcards
___ are organized lymphoid structures in the small intestine that contain specialized mechanisms to sample the intestinal lumen. These mechanisms include M cells and specialized dendritic cells.
Peyer’s Patches
Communication between ___ bacteria and the mucosal immune system is essential for normal mucosal immune functioning. The microbiota therefore plays an essential role in establishing and maintaining tissue homeostasis
commensal
The ___immune system is directly exposed to the environment. Most pathogens invade through mucosal surfaces that in many cases forms a monolayer that is on epithelial cell thick and provides a verey large surface area for contact with foreign microbes.
mucosal
___ is the major antibody isotype found in the intestinal lumen. It is secreted into the lumen by a specialized secretion mechanism involving the poly-Ig receptor
IgA
____: specialized lymphocytes for surveillance of mucosal epithelial tissue
Intra-epithelial lymphocytes
3 anatomical features of the mucosal immune system
mucosal epithelia close to lymphoid tissues
can be organized into compartments such as peyer’s patches or more diffuse
they have special ways to take up antigens - M cells in the peyer’s patch
2 effector mechanisms of the mucosal immune system
even in the absence of infection there are activated/memory T cells
there are also “natural” effector/regulatory T cells present
2 immunoregulatory things the mucosal immune system will do
decrease immune response to food and non-pathogen antigens
inhibitory macrophages and tolerance-inducing dendritic cells
the mucosal immune system includes the :
epithelial layer
lamina propria
what is in the lamina propria
Lamina Propria: the “space” under the epithelial cell layer: rich in connective tissue and contains abundant innate and adaptive immune cells
→ Lymphatic vessels collect fluids, antigens, pathogens
secondary lymphoid organs in the mucosal tissues can be ___ or organized.
scattered
both filter lymph and connect to the mesenteric lymph nodes
an example of organized lymphoid tissue is the __-
peyer’s patch in the GI tract
M cells
found in the GI tract
part of the epithelial layer that separates the peyer’s patch from the gut lumen.
ruffled membrane→ no mucous secretion or surface glycocalyx
allows for uptake of pathogen
how do M cells work
they will take up antigen (endocytic)
transcytosis in membrane bound vesicles
give pathogen to lymphoid cells- DC cells that carry the pathogen to peyer’s patch
Dendritic cells sample the material, become activated by PAMPs, activate T cells
___ can extend processes across the epithelial layer of the GI tract to capture antigen from the lumen.
dendritic cells
T cell priming and redistribution in the MALT
immature T cells with CCR7, LFA-1 and L-selectin enter lamina propria by HEV
they get activated by dendritic cells → drain via mesenteric lymph nodes → back into blood stream
activated T cells will express alpha4beta7 integrin and CCR9/CCR10 → this will pull activated T cells out of blood and back to the lamina propria
___ on immature T cells direct them to peyer’s patch
CCR7 and L-selectin
T cells activated in the MALT are ___ with adhesion molecules that mediate distribution throughout the MALT
imprinted
alpha4:Beta7 integrin and CCR9
gut homing effector T cells that express a4:B7 and L-selectin bind to ___
MAdCAM-1 on the endothelium of blood vessels in mucosal sites
___ expressed on endothelium of blood vessels in all mucosal sites
MAdCAM-1
gut epithelial cells express chemokines,____, specific for gut homing T cells
E-cadherin (on epithelial cells of mucosal surface) will attach to the alphaE:beta7
CCL25 and CCL28 will bind to the CCR10 and CCR9 receptors on the activated T cells
Movement of IgA
made in the lamina propria by plasma cell
will release IgA (dimer connected by a J chain)
this attaches to poly-Ig receptor on the basal layer of the epithelial cell
eats IgA and transports it to the lumen
IgA and part of the PIGR (secretory component) is released into the lumen
where does IgA work
can work in the lumen- binding and neutralizing pathogens and toxins
can work inside the epithelial cell
can work in the lamina propria and carry pathogens out to the lumen
___have direct contact with epithelial cells allows for close communication and rapid effector responses
IEL
intraepithelial lymphocytes
Type A IEL
conventional CD8+ T cells Effector CD8 T cells require signal 1 only
only needs to see antigen presented in MHC class 1 to trigger kill response
will release perforin/granzyme and Fas-dependent pathway and kill target cell
Type B IEL
T cells with limited TCR diversity detect stress signals: “induced self” Largely MHC-peptide-independent
NKG2D binds to MIC-A, B: costimulation
CD8α:a homodimers bind to a nonclassical MHC molecule called TL
epithelial cells will send out stress signal→ type B IEL will bind to MIC-A,B and TL and will kill cell
___ receptors on the type B IEL will bind to TL on stressed epithelial cell and trigger kill response
CD8 alpha:alpha
___ receptors on the type B IEL will bind to MIC-A,B on stressed epithelial cell and trigger kill response
NKG2D
when epithelia cells are stressed or damaged that produce ___ that can be seen by Type B IEL
MIC A and MIC B
TL
restitution of GI cells
when epithelial cells are killed
neighboring cells will spread out and migrate to cover space -→ prevent pathogens from leaking through
then they will divide
oral tolerance
body will not react the same way to food as it does to an antigen
mouse study- if you feed an antigen to a mouse, the mouse will become tolerant to that antigen( will not react), if you later inject that same antigen the mouse will not have an immune response
commensal bacteria fill a ___ that function to prevent overgrowth of pathogenic bacteria
niche
if good bacteria is there it prevents bad bacteria from entering that area
-when things go wrong is when good bacteria is wiped out and bad bacteria can grow and attack
pathogens that invade the cell will trigger ___
TLR, NOD2 and activation of NFkB that triggers the release of cytokines that trigger the activation of the immune system
