Plenary 1. Mucosal Immunity

Question 1

What are defences of mucous membranes?

Answer 1

• Physical defences (skin; movements; flushing)
• Chemical barriers (pH, antimicrobial materials)
• Biological barriers (microbiome)
• Defence of cells (tight junctions between epithelial cells; ciliary movement in the upper respiratory tract)

Question 2

SALT

Answer 2

skin associated lymphoid tissue
- skin forms a tough physical barrier supplemented by continuous desquamation, desiccation and a low pH because of fatty acids in the sebum
- skin carries a resident microbiota that excludes pathogenic bacteria and fungi. If skin microbiota is disturbed -> its protective properties are reduced and microbial invasion may result -> skin infections tend to occur in areas such as axils or groin where both pH and humidity are high. Also animals forced to stand in water
or mud show an increased frequency of foot infections; as the skin becomes sodden, its structure breaks down and its resident microbiota changes in response to alterations in the environment.
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- professional APCs of the skin are Langerhans cells and dermal DCs They migrate to lymph nodes and present in the paracortical part of the cortex
- some of the circulating memory T-cells carry CLA (Cutaneous Lymphocyte Antigen) epitopes
- T-cell mediated immune response in the skin is mailed type 4 hypersensitivity reaction (delayed type hypersensitivity reaction (DTH))
- IgE mediated hypersensitivity reactions can also take place in the skin, which effector cells are dermal mast cells

Question 3

SALT. Keratinocytes

Answer 3

• express multiple PRRs, so they are able to recognise PAMPs associated with microbial invasion
• upon stimulation produce complex mixture of ILs, INFs, and other cytokines, growth factors and antimicrobial proteins, all of which assist in excluding microbes seeking to penetrate the skin
• keratinocytes are the main source of cathelicidins and beta-defensins (2 families of antimicrobial peptides (AMPs))
• keratinocytes also express MHC class 2 and can act as antigen-presenting cells
• can be activated by microbial stimuli, physical influences, UV radiation, cytokines and neuripeptides
• after the activation they produce inflammatory (IL-1alpha, TNF) and anti-inflammatory (IL-1Ra, IL-2R2) cytokines and antimicrobial peptides (beta-defensin)
• to the effect of IFN they produce chemotactic materials (IL-8)

Question 4

SALT. Dendritic cells

Answer 4

• once microbes invade skin, they encounter dendritic cells
• birth epidermis and dermis contain large numbers of antigen-trapping dendritic cells (Langerhans cells!)
• Langerhans cells bind exogenous antigen and present it to nearby helper T cell
• subcutaneous adipose tissue layer also contains resident dendritic cells
• (healthy skin resident T cells are mainly located in the basal layer)

Question 5

SALT. Mast cells

Answer 5

• production of cytokines based on the activating antigen
• on the surface: high-affinity FcεRI (IgE receptor) reacts upon contact with the stimuli. Can result in urticaria due to increased vascular permeability
• in rare cases mast cells activation can lead to anaphylaxia

Question 6

GALT

Answer 6

• tonsils, appendix, Payer’s patches, folliculi
• main task: local immune response
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  Dendritic cells in the mucous membrane have several antigen sources:
  1. Lumen - dendritic cells reach out through the tight junctions of mucosal epithelial cells
  2. Peyer’s patches - sponge-like M cells absorb the antigen from the lumen then release it in unchanged form
  3. Lamina propria - the antigen comes through infected or dead cells
  4. Lamina propria - IgA-bound antigen comes transcellularly

Dendritic cells having recognised the antigen, present it to T-cells

During their local antigen presentation, dendritic cells produce retinoids acid that stimulates T cell migration to the Lamina propria and a mesenteric lymph node

B cells are activated by antigen and Th cells in the lymphoid follicle. Then migrate to the Lamina propria and a mesenteric lymph node