mucosal immunity

Question 1

what are two problems the mucosal surfces have?

Answer 1

have physiological functions that reuqire interaction with the outside(gas exchange and nutrient uptake)

outside is full of microbes, some pathogenic

Question 2

define the following

1. microbiome
2. commensal microbes
3. induction site
4. effector site
5. IgA, IgG, IgM
6. plasma cell

Answer 2

1. microbiome-the microbes normally found in a given location.
2. commensal microbes-microbes in the microbiome that live relativly harmoniously, and are tolerated by the immune system
3. inductio site-physical location where immune cells are activated
4. effector site-physical location where immune cells attack pathogens
5. IgA,G andM-types of antibodies
6. plasma cell - an effector B cell that makes secreted antibodies

Question 3

define the following

1. Tregs
2. integrins and selectins
3. HEV
4. tolerance

Answer 3

1. Tregs-T cells that turn off responses to self or non-dangerous antigens
2. integrins and selectins- molecules that tether immune cell together to help with homing to a particular physical location
3. HEV-location in the blood vessels wher lymphocytes can move in and out of the blood stream
4. tolerance-when the immune system does not attack an antigen ( typically self antigens).

Question 4

what are 5 important keys to a healthy tissue b/c of microbiome?

add photo

Answer 4

microbiomes are the key to healthy mucosal tissue

1. synthesize essential metabolites
2. break down plant fibers, host cells cannot
3. inactivate toxic substances in food made by pathogens
4. prevent pathogens from benefiting forom the resources of a human gut
   
   1. do this throughcompeting for space. “take up all the seats in the house”
5. interact with epithelium to trigger development of secondary lymphoid tissue (MALT)

when measured accross demographics, the answers vary. So, its more or less down to function, not specific species

Question 5

What is the mucosal defensive protection measures from the outside in?

Answer 5

1. microbiome
2. mucus
3. secreted molecules
4. epithelial cells
5. MALT
6. immune cells in the mucosa

Question 6

a content in mucus is very important. what are 3 important function of this structure?

1. sticky
2. something for viruses
3. two version

purpose/ function of Mucous.6

1. between
2. gradient Ag
3. S-S
4. H2O
5. what forms on teeth? why is that bad for gut?
6. speed

how is it managed?

Answer 6

1. mucus is made of mucinogen + H20 +Mucin.
   
   1. ​mucin-secreted plymeric glycoprotein.
      
      1. can form branches, that is sticky and hard to get through
      2. glycosylated with sialic acid
         
         1. important for viruses to bind to
      3. secreted and membrane bound
         
         1. membrane bound-think about the epithelial cell that has it attached to the surface
2. purpose
   
   1. provide barrier between the epithelium and microbes
   2. maintain the local antibody concentration and prevent antibodies from being physically carries away
   3. creates disulfide bonds with antibodies and defensins
   4. maintain hydration on the mucosal surface
   5. prevents bacteria from forming biofilms
   6. slows microbes and allos them to be exposed to antimicrobial moleculse
3. managed
   
   1. muccus is motile and constantly being replaced

Question 7

list secreted molecules from the following categories

1. antimicrobial peptides
2. antimicrobial enzymes
3. antibodies

Answer 7

these are secreted to act in their secreted enviornments.

1. antimicrobial peptides
   
   1. defensins
      
      1. embed in the cell wall of bacteria disrupting osmosis
   2. cathlicidins
      
      1. act as detergent for the cell membrane of bacteria
2. antimicrobial enzymes
   
   1. lysozyme
      
      1. degrade peptidoglycan of of bacterial cell wall (gram +)
   2. phospholipase A
      
      1. degrade bacterial membrane
      2. two function
         
         1. host defense
         2. stimulate inflammation
   3. peroxidases
      
      1. removes e- from bacterial membrane causing disruption
   4. lactoferrin
      
      1. directly interacts with microbe, sequestering iron (which bacteria need to survive)
3. anitbodies
   
   1. IgA
      
      1. 98% mucosal IgA produced in mucosal tissue, antiinflammatory, inhibit phagocytosis. tend to be low-affinity, limit bystander damage, can’t fix complement
   2. IgG
   3. IgM

Question 8

define and describe function of antibacterial enzymes. 3

Answer 8

1. phospholipase A2- same molecule with different function (host defense or chemokine)
   
   1. secreted by paneth cellsand PMN
   2. degrade bacterial membranes
   3. effective against Gram+
   4. amplifies inflammation signals
2. peroxidases
   
   1. released by PMN
   2. catalyze reaction of H2O2
   3. acts on electron acceptor in oxidation reactions
      
      1. removes e- from bacterial membranse causing disruption of cell integrity
   4. disrupts the formation of biofilms by degrading extracellular proteins
3. lactoferrin
   
   1. Fe-binding glycoprotein
   2. sequesters iron
      
      1. many bacteria need to grow
   3. directly interacts with microbe surfaces causing cell lysis and preventing attachment to host cells

Question 9

IgA

1. composition
2. affect on bacteria
3. how they interact with other immune functions/cells
4. how they are secreted

Answer 9

• composition
  
  • dimeric antbody connected by a J chain molecule
  • gives FOUR binding sites instead of two.
• affect on bacteria
  
  • four binding sites- crosslink antigens leading antigen agglutination(makes the antigen too big to cross the epithelium)
  • 98% of mucosal IgA is produced in the mucosal tissue
    
    • compare to the systemic Ig, where IgG is the dominant Ab.
  • tend to be low-affinity. Do to low affinity, this category can bind to many types
• how they work with other immune cells
  
  • anti-inflammatory - alows the layer of mucous do its job
  • INHIBIT phagocytosis, help limit bystander damage
  • CAN’T fix complement
• secretion
  
  • Transported through epithelial cells visa polymeric Ig receptor
  • dimeric IgA binds receptor and is cleaved at the apical surface, leaving a secretory component on the IgA molecule
  • secretory component allows the IgA to bind mucin

Question 10

what are the layers of the mucus and purposes

Answer 10

Two layers- both aid in protection of the mucosa

1. thick, mucin rich
   
   1. slow down bacteria/antigens allowing for interaction with secretions
2. thin, watery
   
   1. allow secretions to
   2. location of peptides, antimicrobial proteins…

notabale cells and structures

1. krypts of lieberkhans
2. panteth cells-generate anti-microbial peptides
3. goblet cells-generate mucus layer
4. plasma cells
5. PMN
6. myloids cells

Question 11

How are epithelial cells are active players in mucosal defense.

Answer 11

1. molecules derive from here
   
   1. secretions
2. moving fluid and contents along
   
   1. ciliated
3. physical barrier
   
   1. tight junctions,
4. communiate with rest of body
   
   1. chemokine interaction

Question 12

Describe the FAE structure and function.

define structure and function of cells involved

Answer 12

1. Bacterial cells drive the production of FAE
   
   1. nobodies is in the same location
2. no goblet cells
   
   1. less mucus covering than other epithelial sections
3. infiltrated with lymphocytes and APCs
4. highly populated with Microfold cells (Mcells)​
   
   1. enterance to the inductive site. located near effector site.
   2. have microvill, and apear less dense than neighboring cells
   3. offers entry of antigens to the mucosal lymphoid tissue
   4. invagination is full of lymphocytes and APCs
   5. microvesicle system and endosomes transfer microbes and antigens.
      
      1. pinocytosis and phagocytoses

Question 13

Define and diagram the microfold cell.

Answer 13

1. House series of immune cells
2. constantly phagocytozing and pinocytosis(ing)
3. have microvilli
4. allow immune cells to survey the enviornment

Question 14

Describe the inductive and effector location involved in immune response

Answer 14

1. not as structured and secure as MALT
2. T and B get activated in inductive site
   
   1. either in the FAE, Lymphnode or else.
3. they enter circulation and go to all mucosal tissues effective site
   
   1. exposure at one site leads to a wide response on ALL mucosal sites.
   2. how that site responds to effetctor cell vairies.
   3. Each location will have its own niche for cellular diversity, but common mucosal immune system they can SHARE lymphocytes(BandT).

image below

1. antigen get in through FAE
2. mingles with B andT (inductive site)
3. activated TandB cells travel to effector site, near by.