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Microbiology > 2. Mucosal Immunity > Flashcards

2. Mucosal Immunity Flashcards

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Biology 101 flashcards
1
Q

what is the most frequent portal of entry of infections (viral, bacterial, parasitic)

A

mucosal surfaces

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2
Q

systemic immunizations are often not effective against which type of infections

A

viral, bacterial, parasitic infections at mucosal surfaces

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3
Q

1927 Besredka

A

proposed a regional immune system independent of the systemic immune system

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4
Q

1959 Heremans

A

proposed that IgA was an antiseptic paint on mucosa

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5
Q

1963-65 Tomasi

A

showed that IgA was the predominant Ig in secretions and that serum IgA and secretory IgA were chemically and biologically different

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6
Q

where is MALT (mucosa associated lymphoid tissue) located

A

in anatomically defined microcompartments throughout the gut

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7
Q

mucosal immune system contains a distinct repertoire of ___

A

lymphocytes
- T cells bearing gamma-delta TCR are very abundant
- other T cells have unusual surface phenotypes

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8
Q

what is the predominant isotype in mucosal immunity

A

secretory IgA

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9
Q

true or false: most Ag presented to mucosal immune system induce tolerance

A

true

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10
Q

true or false: mucosal immune system can mount an immune response to the normal bacterial flora of the gut

A

true

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11
Q

enteric pathogens cause a local ___ response and the development of __ immunity

A

inflammatory, protective

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12
Q

IgA

A
  • exists as monomer, dimer, trimer, or secretory IgA (sIgA)
  • predominant class in extravascular secretions, in form of sIgA
  • contains a J chain (makes it possible to be in polymeric form)
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13
Q

biological activity of IgA

A
  • neutralizes toxins
  • neutralizes viruses at point of entry
  • blocks viral attachment to receptors
  • blocks uptake of viruses by cells
  • participates in antigen disposal by coupling antigen for its elimination
  • decreases colonization of bacteria to epithelial cells and teeth by interfering with initial adherence
  • blocks IgG and IgM complement-dependent reactions and regulate immune responses (not physical blocking, but induces cytokines to downregulate mucosal antigens)
  • participates in IgA antigen-dependent cellular cytotoxicity which involves T cells, macrophages and neutrophils with Fc receptors for IgA molecules
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14
Q

secretory IgA

A
  • two subclasses: IgA1 (90%) and IgA2 (10%)
  • double “Y” shaped structure consisting of two monomers linked through C terminal end, a J chain, and a secretory component
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15
Q

J chain

A
  • necessary for initiating and maintaining the polymerization of IgA and IgM
  • synthesized by plasma cells producing IgA
  • gene for J chain is not linked to any loci encoding for Ig
  • no sequence homology with Ig domains
  • beta barrel structure similar to Ig fold
  • regulation of expression of J chains is in synchrony with expression of Ig
  • only one J chain per Ig polymer
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16
Q

secretory component (SC)

A
  • synthesized by epithelial cells, not plasma cells
  • dimeric IgA secreted by the submucosal plasma cells actively binds SC as it transverses through the epithelial cell layers
  • aka poly-Ig receptor (poly IgR)
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17
Q

what does SC help with

A
  • help in transport of IgA from lumen to secretion
  • help shield IgA from being digested out in harsh environments
18
Q

poly-IgR-IG complex

A

internalized, transported to the apical surface of cells, then exocytosed

19
Q

what does SC act as a receptor for

A

SC acts as a receptor for Ig polymers at the basolateral surface of epithelial cells

20
Q

during transport, SC-Ig polymer is cleaved from __

A

poly-IgR

21
Q

what does SC facilitate transport of

A

facilitates transport of secretory IgA into secretions (tears, breast milk, saliva)

22
Q

what does SC protect Ig from

A

protects Ig from proteolysis by intestinal enzymes (stomach)

23
Q

Antigenic environment of mucosal system differs from systemic immune system because mucosa is in constant contact with lots of immunostimulatory substances. Lymphoid tissues would undergo excessive stimulation resulting in unwanted immune responses (food allergies). How is the problem avoided?

A

by different immunoregulatory events
- induction of oral tolerance
- class-specific regulation of mucosal antibody production
*these lead to specific induction of secretory antibodies

24
Q

induction of specific antibodies

A
  1. local antigens stimulate glandular precursor cells
    - these cells differentiate to form specific B-lymphocytes from resident IgA precursors that eventually produce secretory IgA
  2. parenteral antigens enhance secretory immune responses in individuals by priming for mucosal immunity
    - specific mechanism unclear
  3. fed oral antigens result in antibodies in milk, saliva, tears and other extravascular secretions
    - antibodies are also found in genitourinary tract and tracheobronchial tracts as well as intestine
    - little or no systemic immunity occurs
25
Q

antigen processing and induction of IgA

A
  • antigen transport and processing achieved by specialized mucosa-associated lymphoid tissue
  • M cells transport antigens to macrophage-like or dendritic cells from peyer’s patches
  • macrophage-like or dendritic cells from peyer’s patches present antigens to lymphocytes
  • process antigen is presented to Th cells
  • Th cells stimulate pre-B cells committed to making IgA –> turn into plasma cells that produce IgA
26
Q

antigen transporting/presenting cells

A
  • microfold cells (M-cells) overlaying the dome of peyer’s patches
    • M-cells lack MHC class II molecules, so they are unlikely APC
    • transport antigens to the macrophage-like or dendritic cells from peyer’s patches
  • macrophage-like or dendritic cells from peyer’s patches
    • gut associated lymphoid tissue (GALT)
27
Q

upregulation of IgA production

A
  • subset of Th cells have Fc receptors for IgA (Th cells –> cytokines –> more IgA synthesis)
  • also secrete IL-5, which in concert with IL-4,6,10,13 promotes IgA synthesis
28
Q

upregulation of IgA production: TGFbeta1 alone or in combination with IL-4,6,10,13 __ IgA secretion by __ cells

A

increases, B

29
Q

upregulation of IgA production: TGFbeta1 acts as an IgA switch factor and causes an __ switch from __ to __

A

isotype, IgM, IgA

30
Q

upregulation of IgA production with TGFbeta1 also results in __ of IgM and IgG secretion

A

decrease

31
Q

upregulation of IgA production: IL-5,6,10 ___ the production of IgA and the proliferation of IgA secreting cells

A

increase

32
Q

B cell homing

A
  • IgA-committed B cells migrate to the mesenteric nodes, thoracic duct, and into circulation back to the lamina propria or gut (or other sites)
  • homing is independent of antigen and appears to be random
  • once cells have homed to a site, they will be stimulated and expanded if antigen is present
33
Q

functions of secretory immune system: secretory antibodies

A
  • limit absorption of protein antigens through mucosal membranes
  • inhibit attachment of bacteria to epithelial cells (significance: pathogen cannot interfere without colonizing, need to colonize by adherence; adherence is first step)
  • neutralize viruses that infect epithelial cells
34
Q

functions of secretory immune system: protective immunity

A
  • secretory IgA in breast milk may protect against infection by coating the upper respiratory and GI tracts of the infant
  • protection is achieved by similar mechanisms in adult
35
Q

oral tolerance

A
  • fed antigens often induce tolerance with no serum antibodies and no delayed hypersensitivity
  • TGFbeta1 alone or in combination with IL-2, and IL-5 increases IgA secretion by B cells
  • they also downregulate IgM and IgG secretion leading to oral tolerance
  • different doses of orally administered antigens may induce anergy in antigen-specific T cells (tell immune system NOT to respond to foreign substance)
36
Q

physiological significance of oral tolerance

A

mechanism to prevent immune responses to food antigens or to bacteria that normally reside in the intestinal lumen and are needed for digestion and absorption

37
Q

exploitation of M-cells

A

some pathogens directly exploit M-cell as a mean of invasion (ex: salmonella is pathogenic enteric bacteria that does this, also some viruses are polio and retroviruses)

38
Q

paradox of mucosal immunity

A
  • exposure to food antigens results in oral tolerance but exposure to pathogens results in a strong response… how? INFLAMMATION
  • pathogens –> inflammation
  • food –> no inflammation
  • inflammation –> costimulatory signals
39
Q

T cell mechanisms of oral tolerance

A
  • anergy: T cells presented with antigen peptides in the absence of costimulatory signals become refractory to further stimulation with antigen
  • regulatory T cells: these cells actively suppress antigen-specific responses following re-challenge with antigen
40
Q

protection by sIgA at mucosal surfaces

A
  • inhibition of microbial adherence
  • virus neutralization
  • neutralization of enzymes and toxins
  • inhibition of antigen penetration
  • interaction with innate antimicrobial factors
41
Q

2 purposes of mucosal vaccines

A
  • stimulate the immune system at the site where infection enters the host (geared to a pathogen where we know it will enter the system)
  • prevent the infection agent from entering the body systemically
42
Q

advantages of mucosal vaccines

A
  • vaccines can be used strategically depending on which area the disease is more likely to enter:
    • nasally: upper respiratory infections
    • orally: gastrointestinal disorders
    • vaginally: sexually transmitted diseases

Microbiology (7 decks)

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