T1 L11 Mucosal immunity Flashcards
What is mucosa-associated lymphatic tissue divided into?
Bronchial associated lymphatic tissue (BALT)
Gut associated lymphatic tissue (GALT)
Why is the mucosal immune system important?
Largest immune compartment of organism
In direct contact with outside environment
Mucosal sites are port of entry for many infections and target site for vaccine-induced protection
What is the estimated surface area of the mucosal immune system?
400m2
What are the HIV transmission routes?
Genitourinary
Rectal
Oral
What are the main mucosal defence strategies of the mucosa and oropharynx?
Endogenous flora
Epithelium and mucus
Regionalised immune system and gut homing of B and T cells
Lymphoid complexes along GI tract
Describe the adaptions of the epithelium and mucus
Mechanical barriers - cells and tight junctions
Specialised epithelial cells - goblet cells, absorptive epithelial cells, M cells, paneth cells
Antimicrobial substances
Mucins form viscous barrier
What are mucins?
Extensively glycosylated proteins
What are some antimicrobial substances?
Defensins
Lysozymes
Lactoferrin
Phospholipases
Where is the greater and least amount of lymphoid tissue found along the GI tract?
Greatest in oropharynx and terminal ileum
Least in small and large bowel
What are some intestinal epithelial cells?
Goblet cells
Epithelial cells
M cells
Paneth cells
What do goblet cells do?
Produce mucus to form physical-chemical barrier
What do epithelial cells do?
Express TLRs
What does surface TLR ligation lead to?
Tightening of epithelial junctions
Increased proliferation
Increased epithelial motility
Enhance barter function
What do M cells do?
Transport antigens to subepithelial lymphoid structures
What do Paneth cells produce?
Human defensin 5 (HD5) precursor
HD6 precursor
Trypsin which activates HD5 and HD6
What do Peyer’s patches contain?
Germinal centre for B and T cells
Where are Peyer’s patches located?
In distal ileum in areas of follicle-associated epithelium (FAE)
How many Peyer’s patches are there?
Before 30 weeks gestation, the foetus has 60
Reaches maximum of 240 by puberty
What are the 3 main domains of Peyer’s patches?
Follicular areas
Interfollicular areas
Follicle-associated epithelium
How does follicle-associated epithelium differ from normal epithelium?
Due to microvilli regularity and length
Presence of infiltrating immune cells
What do the follicular areas of Peyer’s patches contain?
Proliferating B-lymphocytes
Follicular dendritic cells
Macrophages
What do the interfollicular areas of Peyer’s patches contain?
Proliferating B-lymphocytes
Follicular dendritic cells
Macrophages
How are Peyer’s patches connected to circulation?
By endothelial venues (from blood to PP) and lymphatic vessels (from PP to mesenteric lymph nodes)
What are the features of M cells?
Small microvilli
Large cell membrane fenestrations
Trans-cellular transport of antigen
Exocytosis at basolateral membrane
How many M cells per Peyer’s patch?
100 to 150
Where are mesenteric lymph nodes located?
At base of mesentery
What do mesenteric lymph nodes do?
Collect lymph, cells and antigens from intestinal mucosa
What is the main site for oral tolerance induction?
Mesenteric lymph nodes
Describe the IEL in the basolateral part of epithelium
Irregular shape
- long extensions in close contact with neighbouring epithelial cells
Occur in variable numbers along gut
What are the 3 groups that intraepithelial T cells can be divided into?
TCRaB+CD8aB+
TCRaB+CD4aB+
TCRaB+CD8aa+
What are MIC-A and MIC-B?
Ligands for NK cell activating receptor NKG2D
What is T-cell differentiation influenced by?
Epithelial cells and dendritic cells
What are Treg cells important in?
Establishing and maintaining food tolerance and class switch including TGF-B and others
What do Th1 cells do?
Produce IFN-gamma
Important in killing virally infected epithelial cells
What do Th2 cells do?
Induced by worm infection
Produce IL-4 and IL-113 which increase fluid secretion, mucus secretion, bowel motility and smooth muscle contraction
What do Th17 cells do?
Produce IL-17 and IL-22
Cytokines interact with receptors on epithelial cells to regulate production of mucins or defensins
What do dendritic cells do?
In lamina propria
Long extensions that reach through epithelium to sample contents of intestinal tube
Antigens get presented to T cells
Describe the protection of secretory IgA against epithelial invasion
Cross-reactive innate-like (low affinity) and infection or vaccine induced specific (high affinity) protection
What do pIgA and pIgM do?
Exert non-inflammatory effects inside and below epithelium
Neutralisation of virus or endotoxin
Antigen excretion
Describe IgA antibody
IgA against food antigens provides immune exclusion
IgA weakly activates complement system
Secretion of IgA coupled to J chain depends on trans-cellular transport mechanisms
How do activated T cells and circulating memory cells exit the lymph nodes?
Via efferent lymphatics
Return to circulation through thoracic duct
Reach target tissues via blood stream
What guides effector cells to different tissues?
Different combinations of homing receptors
At the tissue, up regulation of respective ligand molecule is related to the situation in the tissue
What are the inductions sites?
Peyer’s patches
Mesenteric lymph nodes
What does priming in the induction sites lead to?
Expression of a4B7 and CCR9 (homing receptors)
What do homing receptors do?
Facilitate migration from blood to effector sites
What are the effector sites?
Lamina propria
Gut epithelium
What type of cells does IEL include?
Treg
Th1
Th2
Th17
Why are regulatory T-cell responses important in regard to food antigens?
Absorption of nutrients and inflammation are incompatible
