Mucosal Immunity Flashcards
To where do effector B and T cells home after activation with specific antigen?
Site of infection
True or False: The Mucosal immune system can work independently of the systemic immune system.
True
What is sterile protection?
Complete blockade of pathogen entry into the host
True or False: Mucosal tissues are more vulnerable to attack than skin.
True
What is Waldeyer’s ring?
The ring of tonsils and adenoids around the entrance to the gut and airway
What are the first mucosal lymphoid aggregates contacted by inhaled or swallowed antigens?
Waldeyer’s ring
Why is it important for the mucosal immune system to modulate inflammation?
Most mucosal tissues have a critical physiological function which can be affected by inflammation
How is inflammation modulated in the mucosal immune system?
Mucosal surfaces are enriched in TGF-b, have toleragenic dendritic cells, noninflammatory macrophages, lots of Treg cells, and more IgA producing plasma cells
How does the mucosal epithelium contribute to the pre-existing defenses of the mucosal immune system?
Simple columnar epithelial cells are impermeable due to tight junctions between the cells; stratified squamous epithelium has no tight junctions allowing diffusion of IgG Ab
True or False: Mucus and antimicrobials are only produced by mucosal epithelial cells in response to a pathogen challenge
False- constitutive production
What intestinal cells are especially good at producing antimicrobials?
Paneth cells
How does mucus contribute to innate defense?
The inner mucus layer is very dense and difficult to penetrate and contains high concentrations of antimicrobials and IgA
Are TLRs expressed on the apical (lumenal) surface of mucosal epithelium cells? What is the importance of this?
They are not otherwise they would constantly be activated by commensal bacteria
How are noninflammatory macrophages produced and how do they contribute to the innate immune defense?
In the presence of of high TGF-b, macrophages down-regulate surface receptors that trigger respiratory burst/ production of proinflammatory cytokines, but they do avidly phagocytose microbes
What makes a dendritic cell toleragenic? What type of T cells do they stimulate development of?
TGF-b and downregulation of costimulatory molecules maintain mucosal dendritic cells in a quiescent state; when they present antigen to CD4+ T cells they generate Treg cells
What is the general utility of toleragenic dendritic cells?
Maintain tolerance to harmless antigens
Which TLRs are adept at recognizing viral infections?
TLR 7-9
What are NOD proteins?
Nucleotide-binding oligomerization domain proteins
What is detected by NOD-1? NOD-2? What transcription factor is stimulated?
NOD-1 detects Gram- negative bacteria; NOD-2 detects both Gram positive and Gram negative; Causes NF-kB signaling
What would result from a mutation in NOD2?
Reduced amount of defensins and other antimicrobials in secretions mean that invasive bacteria and commensals cannot be kept in check
What is microbial translocation?
Prolonged inflammatory responses reduce epithelial barrier integrity such that large amounts of commensal bacteria and microbial products enter the host
How can microbial translocation trigger a systemic immune response?
Infiltrating bacteria and shed LPS chronically stimulate BL TLRs, and LPS drains into the bloodstream
What is Crohn’s disease?
An autoinflammatory bowel disease caused by chronic inflammation due to intestinal immune dysregulation, resulting in loss of epithelial integrity and microbial translocation
How is Crohn’s disease characterized?
Loss of epithelium at inflamed sites
What are the typical symptoms of Crohn’s disease?
Belly pain, diarrhea, loss of appetite. weight loss, fever, anemia
What are the possible causes of Crohn’s?
NOD2 gene, NEMO deficiency, Treg deficiency, or defects in autophagy?
What are the treatment options for Crohn’s disease?
Anti-inflammatory drugs, immune system suppressors, antibiotics
Where are inductive sites located within the mucosa?
Just below the epithelial layer
Where can Peyer’s patches be found? Where are they located in the highest concentrations?
Small intestines- most in the ileum
What inductive sites are found within the large intestine?
Many small lymphoid follicles throughout the colon and rectum
If a mucosal surface (e.g., vagina, nose) does not have inductive sites just below the epithelium, were is the inductive site located?
Nearest draining lymph nodes
What are M cells?
Specialized epithelial cells above follicles in intestines that have processes which project into the lumen and capture antigen to present to dendritic cells
True or False: M cells are covered by thick mucus
False- no mucus
How do M cells take up, process, and transport antigen?
M cells phagocytose antigens and transports it across the cell into intracellular ‘pockets’ which contain B, T, dendritic cells, and macrophages
How can M cells be taken advantage of by pathogens?
Because M cells do not degrade or digest pathogens, some microbes can use M cell phagocytosis to gain entry into the host
True or False: M cells are only present in the intestine and palatine tonsils
True
What cells are responsible for antigen binding and uptake in mucosal tissues without M cells?
Dendritic cells
What antibody is produced by most mucosal plasma cells? What stimulates this production?
IgA; class switching mediated by TGF-b signalling
What makes IgA noninflammatory?
It doesn’t have a C1q binding site and so it cannot fix complement
How is IgA transcytosed across mucosal epithelial cells?
Dimeric or tetrameric IgA is bound by a J chain, which binds to polymeric Ig receptor stimulating transport and secretion into the lumen
What is secretory IgA?
IgA bound to part of the PIgR cleaved
What is the benefit of having a J chain and secretory component on IgA?
Makes it more resistant to proteolysis
What are four important functions of mucosal IgA?
Immune exclusion, intracellular neutralization, clearance, and neutralization of virus or toxin in lamina propria
What is immune exclusion?
IgA can bind to a pathogen or toxin and trap it in the mucus to be swept out via peristalsis
How is selective IgA deficiency compensated for?
Increased production of more defensins, S-IgM and IgG
How can serum IgG contribute to mucosal tissue defense?
Serum IgG can gain access to the mucosal tissues via leaky (fenestrated) capillaries
What adhesion molecules’ expression is stimulated in T cells activated in the small intestines? Large intestines?
Small- alpha4beta7 and CCR9; Large- alpha4beta7 and CCR10
To what does alpha4beta7 bind?
Binds to MADCAM addressin on intestinal HEVs
What molecules draws CCR9+ cells into the small intestines? CCR10+ into the large?
CCL25; CCL28
How do mucosal lymphocytes know which homing molecules they should express?
During activation, DC secrete products that up-regulate tissue-specific homing receptors on the lymphocytes
How is Vitamin A and D used by the mucosal immune system?
Retinoic acid is secreted by intestinal dendritic cells and up-regulates expression of alpha4beta7 on intestinal lymphocytes; Vitamin D metabolites are similarly used by skin DC to direct homing of lymphocytes to wounds
