mucosal immune responses

Question 1

examples of mucosal surfaces in human body

Answer 1

• Oral Cavity
  
  • Nasopharyngeal associated lymphoid tissues (NALT)
  • Tonsils & adenoids
    
    • Responsible for sensing infections
• Lungs
  
  • Mucosal surfaces & lymph nodes
    
    • Instructions to B and T cells occur
• Gastro/intestinal tract
  
  • Gut associated lymphoid tissues (GALT)
    
    • Role in detecting pathogens here
• Genitourinary tract

Question 2

how is a mucosal immune response initiated

Answer 2

• M cells are dispersed between epithelial cells
• virus particle is taken up by M cells and transported to immune cells through transcytosis
  
  • into connective tissue where there are APCs
• APCs migrate to nearest lymph node or NALT
  
  • presents antigen to T cells
  • B cells can produce antibodies

Question 3

what is NALT

Answer 3

Nasopharyngeal associated lymphoid tissue

Question 4

how does antigen presentation effect T cells? what occurs due to it?

Answer 4

• Complex made up of MHC class I and peptide is present to T cell receptor
• Vital antigens are presented on the major histocompatibility complex on APC cells to CD8+ T-cells
  
  • Actives CD8+ T-cells and migrate to tissue which is infected with virus
  • These cells differentiate into killer T cells
• killer T cells then release enzymes to damage virus infected cells
• debris can be removed by neutrophils and macrophages

Question 5

what enzymes are released by the killer T cells after antigen presentation? what functions do they have?

Answer 5

Perforin

• Makes holes in virus infected cells
• Leading to lysis

Granzymes

• Protease

Question 6

how does antigen presentation affect antibody response? what occurs due to this interaction?

Answer 6

• viral peptide is associated with MHC class II
  
  • activates T helper cells - CD4+ T cells
• APCs interact with MHC class II carrying the viral antigen
  
  • activation of B cells after interaction with viral peptide
  • cytokine dependent proliferation of B cells takes place
    
    • interaction is specific to viral particle
    • production of soluble antibodies
• B cells then later differentiate into plasma cells

Question 7

structure, mechanism and importance of IgA

Answer 7

• Made up of two IgA molecules and J-chain
• J-chain required for epithelial crossing of IgA to mucous side
• Active process
• Requires receptor on basolateral side of epithelial cells
  
  • Receptor must recognise J-chain
  • Leads to internalisation of IgA by endocytosis
• IgA is then moved to lumen
  
  • through fusion with luminal membrane
  • IgA can then cross and reach mucosal side
• IgA has shown interaction with SARS-CoV2
  
  • Forms a neutralising complex preventing further infection of cells

Question 8

what can activated B cells differentiate into

what will their functions be?

Answer 8

• Differentiation of B cells into plasma cells
  
  • Makes soluble antibodies
  • IgM IgA or IgG
• Differentiation of B cells into memory B cells
  
  • Carry antibody on cell surface
  • Remain in body
  • Inactive - not actively dividing
  • Can be called upon to produce new plasma cells

Question 9

how does IgA cross from plasma to the lumen and fight virus at the mucous membranes?

Answer 9

• only immunoglobulin able to cross epithelial layer
• Signals from cytokines to proliferate in response to infection
• Cells differentiate into IgA producing plasma cells
• Production of J and IgA chains
  
  • Assemble into pro IgA
  • Secreted as pro IgA molecule
  • Bond to pro Ig receptor on basolateral side of epithelial cell
  • Interaction causes endocytosis of pro IgA
  • Soluble IgA is secreted into lumen and reaches saliva for example
    
    • Is able to detect virus particles in the oral cavity
    • Can also reach lung and GIT to fight viral infections

Question 10

what is the relevance of IgA to SARS-CoV2?

Answer 10

• SARS-CoV2 shedding occurs in oral cavity, lungs & gut
• Mucosal membranes contain sIgA
• Viral particles bound to IgA cannot infect new nasal, lung or gut cells
  
  • Prevents infection of other cells
• Complexes are flushed out or recognized by macrophages and neutrophils to be taken up and destroyed
  
  • Endocytose the particles
  • Enzymes in cells can destroy proteins of the virus
  • Neutralisation of it
• Other Ig-subclasses cannot cross epithelial barriers

Question 11

how can viral defence go wrong?

specifically to Covid-19?

Answer 11

• Killer T-cells can kill virus infected cells
  
  • They require interferon-gamma for a timely response in infected tissue
• Patients with severe Covid-19 have delayed immune response by T-cells
  
  • Cytokine storm leads to severe damaged tissue
  • T cell response is late Neutrophils and mast cells will degranulate into lung tissue
    
    • Destruction of lung tissue in response to cytokines
    • Inflammatory cytokines - severe tissue damage