l11- mucosal immunity Flashcards
what does MALT, GALT and BALT stand for
Mucosal-associated lymphatic tissue
which is divided into the other 2 :
Bronchial associated lymphatic tissue
&
gut associated lymphatic tissue
3 important features of mucosal sites
- there is continuous antigen stimulation (food, endogenous flora, & pathogens)
- mucosal sites are the ports of entry for many infections and an important target site for vaccine-induced protection
- with an estimated surface area of 400 m2 it harbours 60% of all effector cells
what are mucosal sites the prime site of entry of
Infectious pathogens
What are the 3 sites of mucosal HIV transmission routes
- genitourinary
- Rectal
- Oral mucosa
what are The main defence strategies of intestinal mucosa & oropharynx
(1)
1- Endogenous flora
-10^14 bacteria, hundreds of different species
2)Epithelium and Mucus :
a-Mechanical Barriers (cells, tight junctions)
b-Specialised epithelial cells (goblet cells, absorptive epithelial cells, M cells, Paneth cells)
c- Antimicrobial substances (defensins, lysozymes, lactoferrin, phospholipases )
d-Mucins (extensively glycosylated proteins) form a viscous barrier
3) Regionalised’ Immune System & gut homing of B and T cells:
a- Waldeyer’s ring (lingual and palatine tonsils, nasopharyngeal tonsils)
b- Peyer´s patches
c- Mesenteric lymph nodes
d- Intraepithelial immune cells
e- Lamina propria immune cells, including sampling DCs
what is lactoferrin
Lactoferrin’s primary role is to sequester free iron, and in doing so remove essential substrate required for bacterial growth.[37] Antibacterial action of lactoferrin is also explained by the presence of specific receptors on the cell surface of microorganisms. Lactoferrin binds to lipopolysaccharide of bacterial walls, and the oxidized iron part of the lactoferrin oxidizes bacteria via formation of peroxides. This affects the membrane permeability and results in the cell breakdown
describe the Lymphoid complexes along the gastrointestinal tract
The volume of the rings indicates the relative amount of lymphoid tissue.
The largest amount of lymphoid tissue is found in the oropharynx (Waldeyer’s ring) and terminal ileum.
differences between primary and secondary lymphoid tissue
1) The lymphoid tissues can be divided into primary and secondary lymphoid organs. Primary lymphoid tissues are sites where lymphocytes develop from progenitor cells into functional and mature lymphocytes.
2) Secondary lymphoid tissues are sites where lymphocytes interact with each other and nonlymphoid cells to generate immune responses to antigens.
what is the structure of waldeyer’s wring
1 pharyngeal tonsil (or “adenoids”), are located on the roof of the nasopharynx, under the sphenoid bone.
2 tubal tonsils on each side, where each auditory tube opens into the nasopharynx
2 palatine tonsils (commonly called “the tonsils”), are located in the oropharynx
1 group of lingual tonsil are located on the back part of the tongue
consists of MALT
what is the function of Mcells
M cells transport antigens to subepithelial lymphoid structures
function of epithelial cells
Epithelial cells express TLRs (TLR2,4,5,6,7,9 depending on region of gut). TLR5 is expressed on the basolateral surface (activated by invading bacteria) and intracytoplasmic NLR for bacterial flagellins are activated only upon access of bacteria to the cytosol (invasion)
function of Paneth cells
produce human defensin 5 (HD5) precursor, HD6 precursor, trypsin (activates HD5 and HD6 by proteolytic cleavage)
what does TLR ligation cause
Surface TLR ligation will cause tightening of epithelial junctions, increase proliferation, epithelial motility, enhancing barrier function but not inflammation
Describe PPs
PPs contain germinal centres for B- and T cells
They are located in the distal ileum in areas of follicle associated epithelium (FAE)
The foetal human small intestine contains on average 60 PPs before week 30 of gestation and their number steadily increases reaching a maximum of about 240 at puberty
Inductive site for immune response
what are the 3 domains of PPs
The follicular area
The interfollicular area
Follicle-associated epithelium (FAE)
describe the follicular and interfollicular areas of PPs
: lymphoid follicles with a germinal center (GC) containing proliferating B-lymphocytes, follicular dendritic cells (FDCs) and macrophages. The follicle is surrounded by the corona, or subepithelial dome (SED) containing mixed-cells including B-cells, T-cells, macrophages and dendritic cells (DCs).
how does FAE differ from normal epithelium
-The FAE differs from normal epithelium in regards to microvilli regularity and length, and the presence of infiltrating immune cells
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how are PPs connected to the circulation
by endothelial venules (from blood to PP) and lymphatic vessels (from PP to mesenteric LN).
what are actions naïve lymphocytes
lymphocytes immigrate into the PP via specialized high endothelial venules. Naıve or activated lymphocytes leave the PP via efferent lymphatic vessels at the serosal side of the PPs.
PPs:describe M cells
Small microvilli (microfolds)
Large cell membrane fenestrations
these features enhance antigen uptake from epithelum (phagocytosis, fluid-phase endocytosis)
Trans-cellular transport of antigen
Exocytosis at the basolateral membrane and
Learn anatomy of slide 23
how was it
What are the mesenteric lymph nodes
These lymph nodes are located at the base of the mesentery and collect lymph, cells and antigens from the intestinal mucosa. They are the main site for oral tolerance induction.
MLN drain lymph from intestinal mucosa
Many food antigens will bypass lymphatic tissue, however, and reach the liver through the portal vein
Immune cells in liver sinuses have an important function in protecting us from microbes/microbial products in the portal vein (e.g. LPS)
Whereas the main ‘program’ is tolerance induction, in some instances, protective immune responses need to be raised.
what are the lamina propria and intraepithelial lymphocyte compartments
IEL are situated in the basolateral part of epithelium
Have an Irregular shape
Have long extensions in close contact with neighboring epithelial cells
Occur in variable numbers along the gut
There are up to 12% Eosinophils in IEL preparations
what is the consistency of IEL
In the small intestine, the great majority of IEL is comprised of TCRab+CD8aa+ cells, followed by TCRab+CD8ab+ cells, with just a small fraction of TCRab+CD4ab+. The proportion TCRab+CD4ab+ increases in the distal region of the small intestine and may reach as much as 30%of the total IEL population in that area of the colon, suggesting a compartmentalization of the different IEL subsets along the intestines in order to accomplish specific immunological functions
