Lecture 14: Mucosal Immunity Flashcards

1
Q

what is the primary antibody at mucosal surfaces

A

IgA

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2
Q

common intranasal vaccines

A

influenza
bordetella

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3
Q

common oral vaccines

A

sabin polio (humans)
rabies

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4
Q

2 primary functions of mucosal immunity

A
  • defensive: against pathogens that gain entry via mucosal surfaces
    —> exclusion , elimination
  • Permissive: actions to accommodate commensal organisms
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5
Q

what immunoglobulin responds to parasites that avoid IgA

A

IgE

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6
Q

what immunoglobulin responds to organisms other than parasites that avoid IgA

A

IgG

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7
Q

what is the structure of IgA

A

Y shaped
monomer or dimer
binds 2 - 4 antigen molecules
secretory component

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8
Q

what cells make IgA

A

submucosal B cells

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9
Q

What does pIgR (polymetric immunoglobulin receptor) bind

A

binds IgA on the basolateral surface

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10
Q

what controls the production of IgA

A

TLR ligands and IL4, IL5, IL10

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11
Q

what controls IgM to IgA class switching

A

TGF-B

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12
Q

what interleukin controls terminal differentiation of IgA-producing plasma cells

A

IL6

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13
Q

what are the co-stimulatory molecules needed for class switching of IgM to IgA

A

BAFF / APRIL

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14
Q

what body fluids have high IgA levels

A
  • colostrum
  • tears
  • nasal mucus
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15
Q

what are addressins

A

molecules that regulate lymphocyte trafficking

  • MadCAM-1 and ligand a4/B7
  • intestine and mamary gland
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16
Q

what subclass of T cells acts at the lamina propria

A

alpha-beta T cells

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17
Q

what subclass of T cells are specialized for epithelial defense

A

gamma delta T cells

  • prevent oral tolerance, regulate B-cells, attack parasites
  • ruminants have them in circulation, other mammals don’t really
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18
Q

what interleukin is responsible for neutrophil chemotaxis

A

IL-17
(Th17 cells)

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19
Q

what interleukin is involved in mucosal healing (triggers regeneration of mucosal surfaces)

A

IL-22
(Th17 cells)

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20
Q

80% of activated B - cells are located where

A

the GI tract (GALT, MALT, Peyer’s patches)

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21
Q

what are the sites of IgA production (effector sites)

A
  • diffuse lymphoid nodules
  • isolated plasma cells
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22
Q

where are commensals (bacteria species) found

A

in GI lumen behind the glycocalyx barrier

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23
Q

what are the important cytokines in the immune response to commensals?

A

IL-10, IL-2

24
Q

what is the function of IL-10

A

inhibits inflammatory response to commensals by blocking TLR-MyD88 pathways

25
Q

what is the function of IL-2

A

inhibits inflammatory response to commensals by blocking TLR independent pathway

26
Q

if pathogens breach the glycocalyx, what damage can they cause

A
  • attach to enterocytes and produce toxins
27
Q

commensals inhibit pathogens by _______

A

competition

28
Q

what are some common antimicrobials in airway mucus

A
  • lysozyme
  • lactoferrin
  • surfactants (A,D and B,C)
  • cationic peptides (defensins, cathelicidins)
29
Q

what do surfactants A and D do

A
  • bind microbes and act as opsonins
  • enhance clearance apoptotic cells
  • modulate actions of T-cells and dendritic cells
30
Q

what do surfactants B and C do

A

reduce surface tension

31
Q

what is the goal of oral / intranasal vaccines

A

to stimulate IgA production

*must use live organisms

32
Q

contagious mastitis

A
  • staphylococcus
  • streptococcus
33
Q

environmental mastitis

A

coliforms
ex: E.coli

34
Q

gangrenous mastitis

A

cows become systemically ill
- septic condition

35
Q

how does the urinary tract naturally protect itself from infection?

A
  • flushing from urine flow
  • low pH of urine
  • small amounts of IgA are in urine
  • urinary stasis leads to ascending infection
36
Q

immunity of the lower female reproductive tract

A

antimicrobial mucus over the epithelium
- keratinocytes express PRRs, produce cytokines, abx peptides
- IgA is the most prominent antibody in mucus layer

37
Q

immunity of the upper female RT

A

macrophages, dendritic cells, innate lymphoid cells
- IgG most prominent in mucus layer

38
Q

immunity of the male reproductive tract

A
  • macrophages and dendritic cells in urethral epithelium
  • T cells in urethra, testes and prepuce
  • IgG predominates in seminal fluid (IgA also present)
  • antimicrobial peptides
39
Q

how to test for mastitis

A

California mastitis test
- looks for somatic cells, if present, DNA from the somatic cells forms gel

40
Q

what are lactenins?

A

antimicrobial substances w/in milk
- complement
- lysozyme
- lactoferrin
- lactoperoxidase

41
Q

what cells are involved in antigen presentation in the intestinal wall

A
  • M cells, Dendritic cels, intraepithelial lymphocytes (IELs)
42
Q

what usually happens to antigens that enter enterocytes

A

get degraded in lysosomes

43
Q

what happens to antigens that enter M cells

A

They don’t get degraded and are either
- presented to IELs within the M cell
or
- pass into tissue fluid and then into draining lymph nodes

44
Q

why do live organisms have to be used in mucosally administrated vaccines

A

since the organisms have to invade the mucosa and persist long enough to stimulate a response

45
Q

what is one main disadvantage to administering live organism vaccines

A

potential to cause disease

46
Q

what are the physical barriers of the innate mucosal immune system

A

mucus, cilia, defensin molecules, extreme pH
actions like blinking, coughing, sneezing

47
Q

what are the innate immune cells that act at mucosal surfaces

A

neutrophils
eosinophils
APCs
macrophages, dendritic cels

48
Q

Exclusion mechanisms are Ig_____ mediated, while elimination mechanisms are mediated by Ig_ or Ig____.

A

exclusion - IgA mediated
elimination - IgE or IgG

49
Q

IgA is present in mammals and birds but not in _____?

A

reptiles or amphibians

50
Q

explain how mucosal stimulation at one mucosal site can protect other, distant mucosal sites, and contributes to what we call the common mucosal immune system

A

A small amount of IgA is released into the peripheral circulation. As this passes through the liver, some of the IgA is secreted in bile and enters the lumen of the small intestine.

51
Q

T-cells specialized for epithelial defense

A

γδ T-cells
- reside beneath and between enterocytes and therefore are also sometimes called intraepithelial lymphocytes (IELs).

52
Q

γδ T-cells effector functions

A

antigen presentation, prevention of oral tolerance, regulation of B-cells, and defense against parasites.

53
Q

cell types involved in antigen processing in the intestinal wall

A

M-cells, dendritic cells, and IELs

54
Q

what 2 cytokines are involved in the response to commensals?
* These inhibit inappropriate innate immune responses to innocuous commensals

A

IL-10 - which inhibits an inflammatory response to commensals by blocking the TLR-MyD88 pathway
IL-2 - which inhibits an inflammatory response to commensals by blocking TLR independent pathways

55
Q

term for the lymphoid tissue present in the bronchi and nasal passages

A

BALT (bronchus associated lymphoid tissue).

56
Q

The mammary epithelium is protected by the physical barrier of a _______ in non-lactating animals.

A

keratin plug