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Immunology > Immunity at mucosal surfaces > Flashcards

Immunity at mucosal surfaces Flashcards

1
Q

why are mucosal surfaces more prone to infection

A

they are thinner (because they have to be semipermeable to exchange molecules)

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2
Q

which regions of the body does the mucosal immune system involve

A

the urogenital tract
the gastrointestinal tract
the respiratory tract

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3
Q

what are the different types of protective epithelial lining in the mucosal immune system depending on the organ

A

single columnar epithelium
pseudo stratified columnar epithelium
nonkeritinized stratified squamous epithelium

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4
Q

what are the 4 distinct features of the mucosal immune system

A
  • intimate interactions between mucosal polarized epithelia and lymphoid tissues
  • compartments of diffuse lymphoid tissue and more organized structures such as Peyer’s patches, isolated lymphoid follicles and tonsils
  • specialized antigen uptake mechanisms (e.g. M cells)
  • broad surface area in contact with environmental microbes
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5
Q

true or false mucosal infections are one of the biggest health problems worldwide

A

true

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6
Q

what is MALT

A

mucosa-associated lymphoid tissue
GALT = GI tract
NALT = respiratory (nasal)
BALT = respiratory (bronchiole)

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7
Q

what are the induction sites in mucosal immunity

A
  • GALT
  • BALT
  • NALT
  • urogenital tract
  • Lacrimal glands
  • salivary glands
  • mammary glands
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8
Q

what kind of cells make up the GALT

A

peyer’s patches
ILFs
appendix

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9
Q

induction vs effector sites

A

induction = where the process of mucosal immune response is initiated
effector = where the mucosal immune response occurs

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10
Q

peyer’s patches vs ILF’s

A

peyer’s patches they are bigger than ILF’s and have more germinal centres (therefore more B cells)

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11
Q

what are the induction sites (lymphoid tissues) in the intestine

A

peyer’s patches and isolated lymphoid follicles (ILF)

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12
Q

characteristics of peyers patches and ILF’s in the GALT

A
  • contain M cells
  • follicle-associated epithelium that covers peyer’s patch lacks mucus (so antigens can cross)
  • the sub epithelial dome is rich in DC’s and lymphocytes
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13
Q

what are M cells

A

cells between the FAE that are specialized for transcytosis of microbes and antigens into peyer’s patches

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14
Q

what is a cryptopatch

A

form of GALT - a collection of DCs and LTi cells that is present at birth

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15
Q

in germ-free mice peyer’s patches do not develop normally. what components of immunity will develop and what would be decreased?

A
  • NO ILFs
  • decreased IELs
  • decreased IgA secreting plasma cells
  • decreased AMPs
  • decreased immune mediators (cytokines)
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16
Q

what drives maturation of GALT

A

acquisition of commensal microbiota

17
Q

what components of Galt are present at birth and whoich ones will develop after

A

cryptopatch = present at birth
ILF’s = develop after birth
peyers patch = present at birth, grows after birth

18
Q

what are the effector sites of GALT

A

single layer of the intestinal epithelium
lamina propria

19
Q

what does the single layer of the intestinal epithelium consist of

A

IELs - CD8+
No B cells
ILCs

20
Q

what does the lamina propria consist of

A

innate cells
CD4
CD4+ and CD8+ T cells
B cells
Tregs
ILCs

21
Q

what are the innate immune defenses of the intestinal immune system

A

absorptive subsets - enterocytes and M cells
secretory subsets - goblet, paneth, enteroendocrine and tuft cells

22
Q

what is the function of each absorptive cell in the intestinal immune system

A

enterocytes: cells of the intestine
M cells: take up the antigen

23
Q

what is the function of each secretory cell in the intestinal immune system

A

goblet cells: secrete mucus
paneth cells: secrete AMPs
enteroendocrine cells: secrete hormones and NTs
tuft cells: secrete cytokines and lipid mediators

24
Q

what are intraepithelial lymphocytes (ILE’s)

A
  • lymphocytes that are positioned within the intestinal lumen
  • help in barrier maintenance and defense
  • the bigger effector site
  • when referring to ILE, ALWAYS talking about mucosal immune system
25
Q

type A vs type B ILE’s

A

Type A = function like cytotoxic T cell (TCR activation leads to perforin, granzyme and FasL release)
Type B = function like NK cells (act independently of TCR activation through NKG2D)

26
Q

how do ILCs act in the GALT

A
  • respond to microbes that breach the epithelium
  • abundant in mucosal tissue - predominated by ILC3
27
Q

2 ways that Gut DCs promote oral tolerance

A
  • induce Tregs
  • Ag presentation to CD4 T cells which causes B cells to produce IgA
28
Q

what are the 6 routes of antigen uptake

A
  1. M cells facilitate bulk and receptor-mediated transcytosis
  2. FcRn-dependent transport via endocytic vesicles
  3. uptake of soluble antigens via goblet cells
  4. paracellular transport across tight junctions
  5. apoptosis-dependent transfer
  6. antigen capture by TEDs
29
Q

How do Tregs achieve balance between active immunity and immunological tolerance

A

active immunity: promote clearance of infections
immunological tolerance: limit immune-mediated damage and responses to self

30
Q

what do IL-10 and CTLA-4 achieve when released from Tregs

A

they limit inappropriate immune activation in mucosal immunity

31
Q

how is transcytosis of IgA across epithelia mediated by pIgR receptor

A
  • IgA dimer binds to receptor on basolateral side of epithelial cell
  • endocytosis
  • transcytosis to apical side of epithelial cell
  • release of IgA dimer + secretory component at apical face
32
Q

what is secretory IgA (sIgA)

A

IgA dimer + pIgR secretory component

33
Q

what are the functions of mucosal IgA

A
  • bind and neutralize pathogens and toxins on gut surface
  • bind and neutralize pathogens internalized in endosomes
  • export toxins and pathogens from the laminate propria while being secreted
  • binding of IgA to Dectin-1 on M cell allows transport of antigen to DC-SIGN+ (receptor) dendritic cells
34
Q

How do macrophages promote intestinal tolerance

A
  • promote phagocytosis
  • induce Tregs and Th17 T cells
  • PGE2 for intestinal repair
  • decrease naive T cell activation and pro-inflammatory cytokines
35
Q

characteristics of mucosal tolerance

A

antigens = from food or commensal bacteria
primary Ig produced = local IgA, low Ab in serum
Primary T-cell response = Treg cell activation, no local effector T-cell response
response to antigen re-exposure = no memory response and no systemic response

Immunology (22 decks)

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