Mucosal Immunity Flashcards
Where are the majority of immunoglobulin producing cells located?
70-80% of Ig secreting cells are located in the mucosa
- majority of these secrete IgA
How is mucosal immunity initiated?
- initiated at inductive site
- carried out at multiple effector sites
What are some components of the MALT?
- GALT
- BALT (respiratory; bronchial)
- NALT (nasal)
- genitourinary tract
- lacrimal
- salivary
- mammary
Describe the distribution of lymphoid tissue in GALT.
- organized lymphoid structures are mostly peyer’s patches
- intraepithelial lymphocytes (IELs) are mostly CD8 T cells located in the epithelium
- lamina propria has several immune cells, including dendritic cells which can extend their arms into the lumen
Describe the mechanistic steps in the induction process.
- M cells take up antigen from the lumen
- M cells process antigen and transport it across the epithelium to the dendritic cells in the lamina propria
- dendritic cells can also reach their dendrites through the tight junctions, directly into the lumen
- antigen presentation to T cells (located in the Peyer’s patches)
- activated T cells are drained into the mesenteric lymph nodes => lymph and travel to the thoracic duct => back into bloodstream
- circulating lymphocytes have homing receptors that send them back to the mucosa
- T cells activate B cells to proliferate and differentiate into plasma cells secreting mucosal IgA
What are the T cell homing receptors?
- on the surface of the T cell = alpha4beta7 and L-selectin
allows exit from blood vessel and entrance into lamina propria and epithelium
What does mucosal immunity result in?
- mucosal encounter with an antigen will lead to systemic immunity due to activation of T and B cells
- T and B cells must home to spleen and lymph nodes
What is the function of IELs?
- kill infected epithelium cells
- infected cells will display viral peptides on Class I MHC
Describe the mucosal innate immune response.
- antigen enters the M cells and leaves on the basolateral cell
- antigen infects epithelial cells via basal entry
- TLRs recognize antigen and activate NFkB inflammasome pathway
- inflammatory cytokines recruit neutrophils to phagocytose infected cells
What are reasons for IgA deficiency? How common is it?
- no switch regions
- mutated heavy chain A region
- mutated pIgR
- prevalence = 1/500 to 1/1000
Why would you suspect an IgA deficiency?
- family history of IgA deficiency due to agammaglobulinemia
- high incidences of oral infections
- high incidences of respiratory infections
- chronic diarrhea
- some autoimmune disorders
What is another name for mucosal IgA?
secretory IgA (sIgA)
Which cells are involved in producing sIgA?
- plasma cells in lamina propria
- epithelial mucosal cells
Describe the structure of sIgA.
- dimeric
- joined by J chain
- associated with secretory component
How does sIgA associate with the secretory component?
- lamina propria plasma cells secrete dimeric IgA with J chain
- dimeric IgA binds to poly-Ig receptor on the basolateral side of epithelial cells
- dimeric IgA + J chain + pIgR are endocytosed
- on the apical membrane, the contents are secreted. The pIgR acts as the secretory component
