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Immunology > Mucosal Immunity > Flashcards

Mucosal Immunity Flashcards

1
Q

Combined area of mucosal surfaces

A

Greater than that of the skin

- small intestine has a surface area 200x the skin

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2
Q

Body’s lymphocytes

A

3/4 are in secondary lymphoid tissues serving mucosal surfaces
- similar proportion of all antibodies made by the body is secreted dimeric IgA

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3
Q

GIT

A

Continuous contact with large populations of commensal microorganisms and substantial quantities of proteins derived from animals and plants (food)

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4
Q

Challenge of mucosal immunity

A

Making immune responses to eliminate pathogens, limit the growth and location of commensal microorganisms, and to NOT attack food

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5
Q

Gut-associated lymphoid tissues

A
  • lamina propria
  • mesenteric lymph nodes
  • palatine tonsils
  • adenoids
  • lingual tonsils
  • Peyer’s patches
  • M cells
  • isolated lymphoid follicles
  • intestinal epithelium
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6
Q

Peyer’s patch

A

T cell and B cell rich areas

- function like secondary lymphoid tissues

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7
Q

M cells

A

Microfold (multifenenestrated)

  • specialized to transport microorganisms to GALT
  • surface is designed for microbes to fall into sunken area
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8
Q

Antigen uptake and transport by M cells

A

M cells are interspersed between enterocytes and in close contact with DC –> take up antigens from gut lumen via endocytosis –> antigens are released beneath M cells and taken up by APCs (DC) –> DC dendrites span the gut wall and engulf antigens

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9
Q

Dendritic cell periscopes

A

Extend processes across the epithelial layer to capture antigen from the lumen of the gut

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10
Q

Most immune system cells in the mucosal tissues are activated ________

A

Effector cells

  • have already been primed by antigens against certain pathogens
  • ex: CD8 T cell, plasma cell, IgA, DC, mast cell, macrophage, CD4
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11
Q

Naive lymphocytes

A

Naive lymphocytes activated in Peyer’s patch give rise to effector cells that travel in the lymph and blood to gain access to the lamina propria of the mucosal tissue (return to tissue as effector cells)

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12
Q

Secretory IgA

A

Export toxins and pathogens from the lamina propria while being secreted –> IgA is able to bind and neutralize antigens internalized in endosomes –> secreted IgA on the gut surface can bind/neutralize pathogens and toxins –> secreted IgA binds pathogens on M cell surface and takes it to lymphoid tissue –> IgA picks up antigen in endosomes of M cell and takes it to lymphoid tissue

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13
Q

Cytoplasmic NOD-like receptors

A

Are a type of signaling PRRs
- binding of PAMPs to their signaling PRRs promotes synthesis and secretion of intracellular regulatory molecules (cyto/chemokines, defensins) to initiate innate and adaptive immunity

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14
Q

NOD2 proteins are found ____

A

In the cytosol of enterocytes

- respond to bacterial products by activating NFkB

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15
Q

Naive CD4 T cells activated during helminth infection can differentiate to ____ or _____ effector cells

A

Th1; Th2

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16
Q

Th2 cells produce IL-13, which induces _____

A

Epithelial cell repair and mucus

  • increased cell turnover and movement helps shedding of parasitized epithelial cells
  • mucus prevents adherence and accelerates loss of parasite
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17
Q

Th2 cells produce IL-5, which recruits/activates ____

A

Eosinophils

- produce MBP, which kills parasites and mediate ADCC using parasite-specific Ig

18
Q

Th2 cells drive B cells to produce ___

A

IgE

- arms mast cells and eosinophils to recognize parasite antigens

19
Q

Th2 cells drive _____ via IL-3, IL-9

A

Mast cell recruitment

- produce mediators (histamine, TNF-alpha, and MMCP) to recruit inflammatory cells and remodel the mucosa

20
Q

Th2 is _____

A

Protective for the host!

21
Q

Th1 cells activate _____

A

Macrophages

- products of activated macrophages cause tissue damage and tissue remodeling

22
Q

Th1 cells activate B cells to produce ______

A

IgG2a

- complement fixing antibodies

23
Q

Th1 is _____

A

Host damaging!

- can not kill helminths, macrophages will damage tissues while trying to get rid of helminth

24
Q

Features of helminth-induced immune resonpse

A
  • helminth infected populations exhibit lower levels of immunological diseases
  • helminth infection is a feature in developing countries, while allergy is an issue of developed/industrialized countries
25
Q

Helminth hypothesis

A

Immune system has coevolved to operate in the presence of helminths, while in the absence or exposure to helminths, the immunoregulatory components that would normally prevent allergy and autoimmunity become weakened

26
Q

Helminths have unique evolutionary dialogue with hosts immune system due to

A
  • longevity within the host
  • complex life cycle
  • multicellular nature
27
Q

Th2 type immune responses

A
  • inflammation
  • wound repair
  • resistance to helminths
28
Q

Key players of helminth induced immune response

A
  • dendritic cells
  • CD4+ Th2
  • IL-4,5,9, 10, 13
  • IgE
  • chemokines
    = recruitment of eosinophils, basophils, mast cells, and expansion of alternatively activated macrophages (AAM)
29
Q

Modified Th2 type response

A

Induced by helminths to limit a possibly detrimental Th2 immunity
- helps restrain extreme symptoms (allergy, fibrosis, etc)

30
Q

Mechanisms of helminth immune responses lead to

A
  • attenuation of pathology
  • tolerance and persistance of the worm = long term survival of parasite within the host
  • sustained parasite feeding
  • completion of life cycle, successful reproduction
31
Q

Helminth/host immune interaction summary

A
  • helminth infection induces a protective Th2 immune response
  • helminths induce immunoregulation via modulation of immune cells (AAM, Treg, and B cells = inhibitory antibodies)
  • allergic inflammation may be suppressed by spill over effect of immunomodulatroy mechanisms of helminth infection
32
Q

What kind of cells are helminths targeting to protect themselves?

A
  • induced alternatively activated macrophages, Tregs (stop Th17), and B cells
33
Q

Antibody dependent cell mediated cytotoxicity

A

IgE coats large parasites –> Fc receptor of eosinophil recognizes IgE –> interaction between Fc receptor and Fc portion of helminth-bound IgE signals eosinophil to degranulate

34
Q

Mucosal barrier and mucus

A
  • 1st arm of innate immunity
  • goblet cells + antibodies, defensins, etc release protective agents that produce a hostile environment, reducing chances of microorganisms from reaching host epithelium
35
Q

Mucins

A

Essential anti-parasitic effector molecules due to importance in mucus structural integrity

36
Q

How are type 2 inducing stimuli sensed?

A
  • pathogens/allergens are sensed by PRRs
  • proteolytic cleavage of host proteins by the protease activity of allergens, tissue damage, and metabolic changes are sensed by DCs
37
Q

Anatomical features of mucosal immune system

A
  • intimate interactions between mucosal epithelia and lymphoid tissues
  • discrete compartments of diffuse lymphoid tissue and more organized structures (peyer’s patches, isolated lymphoid follicles, tonsils)
  • specialized antigen-uptake mechanisms provided by M cells in Peyer’s patches, adenoids, and tonsils
38
Q

Effector mechanisms

A
  • activated effector T cells predominate even in absence of infection
  • plasma cells are in the tissues where antibodies are needed
39
Q

Immunoregulatory environment

A
  • dominant and active downregulation of inflammatory immune responses to food and other innocuous environmental antigens
  • inhibitory macrophages and tolerance-inducing DC
40
Q

____ of the immune system’s cells are dedicated to the mucosal surfaces defense

A

75%

41
Q

________ continuously sample the gut’s luminal contents and stimulate adaptive immune responses to pathogens, commensals, and food

A

Secondary lymphoid tissues

42
Q

Healthy gut

A

Chronic adaptive immune response, which is not inflammatory

- ensures that microorganisms are confined to the lumen of the gut and prevented from breaching the mucosal barrier

Immunology (28 decks)

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