Exam 8: Chapter 10 Flashcards
How do most infectious pathogens enter the body?
Through mucosal tissues
What are mucosae?
Interfaces with our environment that are covered in mucus and contain 200x more lymphocytes than regular tissues
What are mucins?
Large glycoproteins that form networks of mucus
What are the two modes of action for mucins?
Secreted and membrane-bound
Why are the responses of the mucosal immune system different than the systemic immune system?
Mucosal immune cells are always encountering new antigens from pathogens, food, and commensal bacteria
What are the functions of commensal bacteria?
- Synthesize essential metabolites
- Break down plant fibers in food
- Inactivate toxic substances from food/pathogens
4 Prevent pathogens from benefitting from human gut resources - Interact with epithelium to trigger development of secondary lymphoid tissue
What architecture is seen in the gut?
Epithelium covered in mucus, lamina propria connective tissue beneath the epithelium
What are mesenteric lymph nodes and where are they located?
Mesenteric lymph nodes are the largest lymph nodes in the body, and they are located in the gut
What is the role of tonsils and adenoids?
To form a ring of lymphoid tissues around the entrance of the gut and airway
What is the importance of gut associated lymphoid tissues (GALTs)?
The location of numerous GALTs allows mucosal immune responses to occur locally rather than in a distant draining lymphnode
What are Peyer’s patches?
Primary GALTs found in the small intestine
What are Microfold (M) cells?
Specialized cells that are not covered in mucus and allow continual sampling of antigens and pathogens
What are probiotics designed to do?
Improve immune responses and prevent microflora changes caused by infection
What are the major differences between the system immune response and the mucosal immune response?
- Mucosal immune response is constantly activated
- Immune cells in mucosal tissues do not initiate an inflammatory response
- The TH1 response is rarely activated in mucosal tissues
What is the overall job of mucosal immunity?
To keep commensals and pathogens at bay
What do epithelial cells do once they identify a pathogen?
Locally express inflammatory cytokines and chemokines
How are pathogens and antigens brought into M cells for sampling?
Via transcytosis
What are isolated lymphoid follicles?
Small organs consisting of a single lymphoid follicle containing mostly B cells
What is the major GALT of the large intestine?
The appendix
What is the main difference between skin and mucosa?
Skin is designed to be impermeable, while mucosa actively samples antigens
How do dendritic cells respond to food?
Food is taken up by dendritic cells, brought to the mesenteric lymph node, and used to drive the differentiation of FoxP3+ T-regs
What immune response is elicited by commensals?
Commensals induce a TFH response when taken up by M cells that promotes the development of B cells that will become IgA secreting plasma cells
What role does dimeric IgA play in regards to commensals?
Dimeric IgA regulates the size of the commensal population
What immune response is elicited by pathogens?
Infection causes dendritic cells to move out of the lamina propria and GALT and capture pathogens, leading to the activation of a pathogen specific immune response
How do dendritic cells capture antigen from the gut lumen?
By extending processes across the epithelial layer
Where do dendritic cells move upon infection?
Into the epithelium
What happens to T and B cells that become activated in mucosal tissues?
They home as effector cells to the mucosal tissues
How do the effector cells of mucosal tissues know where to go?
Adhesion molecules and chemokines
What regulates the induction of adhesion molecules and chemokine receptors for mucosal tissues?
Vitamin A metabolites (like retinoic acid)
Why is the polio vaccine given orally?
The oral vaccine will establish effector memory cells that home to the mucosa, where the virus first infects cells
What are intraepithelial lymphocytes?
A specialized population of CD8+ cells that can be either ab or gd T cells, have a limited TCR repertoire, and are found in the mucosal epithelium
What property allows for a unified mucosal response?
Activated effector cells can recognize receptors in all mucosal tissues
How are toxins and pathogens removed from the lamina propria?
Via IgA dimers undergoing active transport across the epithelium
Does dimeric IgA activate complement or induce inflammation?
No
What are the two subtypes of IgA?
IgA1 and IgA2
What are the properties of IgA1?
Larger hinge region, interacts with pathogens more easily, more susceptible to protease cleavage
What are the properties of IgA2?
Observed at higher levels in tissues with concentrations of bacteria, switch to IgA2 relies on cytokine APRIL
How is IgA deficiency compensated for?
By secretion of IgM
How can the effect of IgA deficiency be lessened?
By utilizing sanitary practices in food preparation
What is the appropriate response to helminth infection?
TH2 cell response and IgE production
What response to helminths try to produce?
A TH1 response, which causes tissue damage and ineffectively controls the infection
What are goblet cells?
Cells that produce mucus
What TH2 effector functions are wanted during a helminth infection?
- Increased cell turnover and movement to help shed parasitized cells
- Eosinophil production of MBP, which kills parasites
- IgE production
- Mast cell production of histamine and other inflammatory cell recruiters
What TH1 effector functions are NOT wanted during a helminth infection?
Macrophage activation and complement fixation
What is one example that proves the co-evolution of innate and adaptive immunity?
Innate immune cells have acquired Fc receptors that recognize antibodies generated by the adaptive immune response
How are gd T cells and ab T cells different?
- gd T cells are not subject to positive and negative selection
- antigens recognized by gd T cells do not require MHC presentation
- gd T cells recognize phosphoantigens, which are pathogen specific metabolites rather than peptides
What V segment rearrangement is typically seen in gd T cells?
Vg9, Vd2
What receptors are and are not present on gd T cells
Chemokine receptors to help gd T cells be recruited into the LN are NOT present; receptors that allow gd T cells to find the site of infection ARE present
What functions can gd T cells carry out?
- Produce IFN-gamma and TFN-alpha
- Kill cells by secreting granulysin
- Become antigen presenting cells
- Activate dendritic cell maturation
- Activate ab T cells
- Activate memory T cells
What response is generated by the binding of MIC antigen with both Vg:Vd1 TCR and the NKG2D receptor?
A synergistic response that is better than either binding interaction alone
What cells other than gd T cells can also identify MIC antigen?
NK cells and CD8+ T cells that express NKG2D receptors
How does CD56 expression classify NK cells?
NK cells high in CD56 are immature, while NK cells low in CD56 are mature
Which NK cells are cytotoxic?
Mature CD56low cells
What are the two types of NK cell receptors in humans, and where are they found?
- Lectin like receptors - found in NKC region
2. Killer immunoglobulin receptors (KIRs) - found in LRC region
What are the ligands for NK cell receptors?
MHC class 1 molecules
What does it mean for NK cell receptors to be variegated?
Each cell expresses a different subset of receptors
Are Fc receptors or NK cell receptors more efficient at activating NK cells
Fc receptors (in the presence of IgG)
How do NK cells monitor class 1 expression?
By recognizing HLA-A, B, and C leader peptides presented by HLA-E
What interaction allows NK cells to indirectly measure the amount of class 1 on cell surfaces?
The interaction between HLA-E and CD94:NKG2A
What is the role of NKG2A’s ITIM motif?
To inhibit signaling
What infection response allows NK cells to target infected cells?
Pathogen-dependent down-regulation of MHC class 1 and up-regulation of MIC
Why can specific residues affect whether a KIR can recognize the allotype?
Because KIR binding only sees part of the class 1 molecule
Why are NK cells “educated?”
So they can recognize the different alleles present on MHC class 1 and thus recognize healthy vs unhealthy cells
What is the first inhibitory receptor expressed by NK cells?
CD94:NKG2A
What happens to CD94:NKG2A if the NK cell begins to express other inhibitory receptors?
It is turned off
What molecules present lipid antigens?
Non-canonical class 1 molecules of the CD1 family
What cells express CD1 molecules?
Those infected by mycobacterium
Which CD1 isoform presents lipid ligands to T cells with NK receptors (NKT cells)?
CD1d
What V-J arrangement is typically seen in NKT cells?
Va24-Ja8, combined with a variety of beta chain arrangements
