Mucosal immunity + NK cells/B cell subsets Flashcards
What is the role of M cells in mucosal immunity
Primarily transcytosis of antigen.
(note that they don’t chew up the bug and present antigen. they just transport it to where the T and B cells are)
How is antigen recognized in the mucosa and what are the steps following antigen recognition (basically what are the different steps that can lead to activation of B and T cells in the Peyers patches or other lymphoid sites)?
Macrophages can send their projections through the tight junctions and grab antigen, pull it in and do a few things. They can either present it to nearby T cells or they can migrate to Peyers patches or mesenteric lymph nodes.
There are also the M cells that’ll allow for movement of antigen inside and DCs can activate lymphocytes in the Peyers patches, or they can migrate to the mesenteric lymph nodes
A third thing is that the epithelial cells which express both MHCI and MHCII can capture the antigen and present it on either class to lamina propria or intraepithelial lymphocytes, or the antigen can be taken up by DCs or m-phages and then those guys can go to the mesenteric lymph nodes
What are the types of IgA and what are their differences/where do you find them?
There’s two types of IgA: IgA 1 and IgA 2
IgA 1 is mostly present in serum and is the monomeric form
IgAa 2 is present in the intestine and female reproductive tract and is dimeric
T/F: IgA fixes complement just like IgM and IgG
Falsehood. It surely does no such thing.
Difference between IgA and some other Ig’s:
Doesn’t fix complement or induce an inflammatory response
Describe the T-independent pathway of IgA induction
T-independent pathway = production of low affinity IgA. Happens in the Peyers Patches and isolated lymphoid follicles
Basically you have DC’s that bind the bug and releases molecules such as APRIL, TGFbeta, BAFF (there’s also retinoic acid that’s made by the epithelial cell), all of which stimulate an IgM producing B cell to undergo class switching and start making IgA. The IgA then goes to the lumen via the usual transcytosis process.
This process does not require interaction with T cells and B cells (T/B cell cognate recognition)
So you can probably guess that the IgA made here is nonspecific
Describe the T dependent pathway of IgA induction
The T dependent pathway involves T and B cell interaction
The DC’s that gobble up antigen activate naïve CD4+ T cells. The activated T cells express CD40L, and interact with naive B cells that express CD40. There are also DC’s expressing NO an TGF beta, all of which cause the B cells to differentiate into plasma cells that secrete IgA (in the presence of retinoic acid)
The IgA produced here is specific to the antigen that was gobbled up by the DCs earlier in this story
Describe the immune exclusion mechanis of IgA action
Immune exclusion:
The IgA dimer binds the antigen and forms complexes that I guess end up somewhere
Describe the intracellular neutralization process of IgA
Intracellular neutralization
IgA can also bind intracellular pathogens, mainly enteric viruses. During that transcytosis process, IgA can bind the virus and the two will be expelled together in the lumen
**note that this how we have defense from polio**
Explain the antigen excretion action of IgA
IgA binds antigen that has crossed the mucosal barrier and is in the submucosal space. IgA binds the antigen then they both get kicked out to the lumen side via transcytosis
What are the functions of mucosal IgM and IgG?
sIgM is the 2nd most abundant Ig in secretions.
Potentially inflammatory, activates complement. Transported via pIg receptor
Neutralization (i.e. toxins, virus)
Potentially inflammatory, activates complement and phagocytes
Mucosal T cells can be located in the M cell pocket. These cells have which type of TCR and which type are they? (CD4 or 8?)
TCRαβ CD4+ T cells
T/F: The T cells in the lamina propria are only CD4+
Name 3 functions of these T cells
Falsehood. Both CD4+ and CD8+ T cells are present in the lamina propria (and they both have TCRab)
- Express homing markers:
alpha4beta7, CCR9 – small bowel, and CCR10 – large bowel
- Cytokine secretion:
IL10, TGFb, IL5 and IL17
- Effector memory
Describe the function of T cells in the epithelial layer
T cells can also be found in between the intestinal epithelial cells. These are mostly CD8+ T cells that don’t really require priming and instead release perforin and granzyme.
They express CD103 (which you will recall is the tolerogenic phenotype one), and homing molecules such as CCR9
They also kill infected and malignant cells
Describe the function of Tuft cells
Tuft cells are chemosensory cells, specifically the sense succinate that is released by bugs
They express IL25 which activates ILC2 cells (what tha heck) that induce Type 2 inflammation (which is what exactly?)
Describe the process of lymphocyte migration into the effector sites in the gut
This is again, a similar migration process that you’ve learned that neutrophils do and all that
T cells express alpha4beta7 which binds MAdCAM1 expressed on the lamina propria venules
T cells also express CCR9, which binds to CCL25 expressed by epithelial cells
In the presence of retinoic acid and TGFbeta, ___ can release IL10 and home to the lamina propria via alpha4beta7 and are maintained by other Il10 producing cells
In the presence of retinoic acid and TGFbeta, inducible Tregs (iTregs) can release IL10 and home to the lamina propria via alpha4beta7 and are maintained by other Il10 producing cells
Describe the role of commensal bacteria in the promotion of mucosal tolerance
Commensal bacteria upregulate Tregs and IL10 which promote the tolerogenic pathway. They also promote IgA secreting plasma cells
What is the function of Vitamin D in mucosal immunity?
Its basically also anti-inflammatory like Vitamin A
(see image below)
Which T cell receptor is expressed by NK T cells, MAIT cells and g/d T cells?
NK T and MAIT cells express TCRalpha/beta, whereas the gamma/delta T cells express TCRgamma/delta
The ILCs express a somatically rearranged receptor, one of the receptor chains like the alpha or gamma chain is usually invariant (or semi invariant, which means what exactly?)
Innate lymphoid cells come from a common lymphoid progenitor then gets split into 3 groups
Group 1 consists of which 2 cell types?
ILC2 cells are in which group?
ILC3 and Lti are in which group?
Group 1: NK and ILC1
Group 2: ILC2
Group 3: ILC3 and LTi (lymphoid tissue inducer)
What pathogens do ILC1 cells recognize? Which cytokine is the main one that they secrete?
Which cytokines activate ILC1 cells?
See image below
**IL12 and IL18**
Which pathogens are seen by ILC2 cells? The cytokines that induce ILC2 cells include IL4, __ and ___
This class of cells can also be induced by some pro-inflammatory molecules, such as ___ and ___
See image below
Which pathogens are recognized by ILC3 cells?
These cells are stimulated by which cytokines? They secrete which cytokines?
