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Immunology #2 > Immunity at Mucosal Surfaces > Flashcards

Immunity at Mucosal Surfaces Flashcards

1
Q

Size of mucosal surfaces in humans

A

When stretched out and combined, would cover an entire basketball court

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2
Q

Mucosal surfaces as an immune compartment

A
  • More than 90% of all infections start at mucosal site
  • Largest immune compartment in the body
  • Includes gastrointestinal, genital tract, eyes, ears, glands, etc.
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3
Q

Function of mucosal surface

A

Distinguish between harmful antigens and food, and environmental antigens and commensals

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4
Q

Mucosal vaccines

A
  • Highly effective as this is the site for so many infections
  • Vaccine delivery is an issue
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5
Q

Licensed mucosal vaccines

A
  • Canine: Bordetella
  • Feline: calicivirus
  • Equine: influenza virus
  • Porcine: rotavirus
  • Bovine: rotavirus or coronavirus
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6
Q

Respiratory tree

A
  • Gets smaller and smaller
  • Trachea to bronchus (main, lobar, segmented) to bronchioles and eventually alveoli
  • Alveoli- one layer of cells where all gas exchange takes place
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7
Q

Alveoli and mucous

A

Mucous is preventing pathogens from reaching alveoli and moving it up and out of lungs

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8
Q

Respiratory epithelium

A

One layer of epithelial cells only between the environment and the host tissue
- Cilia on surface for mucus transport
- Goblet cells for mucus production
- Lamina propria- tissue under the connective tissue that is full of immune cells

Slight differences throughout the respiratory tree
- Alveoli only have alveolar cells making a very thin layer and there is less organized

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9
Q

Intestinal mucosa

A

One layer of epithelial cell only between environment and the inside of host
- Vili stick into the lumen of the gut
- Lamina propria full of immune cells (where we find most of the immune cells of the body)
»Immune cells high prevalence due to the fact that this area is where high levels of absorption is occurring and pathogens are trying to enter.

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10
Q

Inductive sites

A
  • Where the immune response is being induced (lymphoid tissues)
  • Site of antigen uptake
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11
Q

Effector sites

A
  • Site of immune response
  • Where we can find effector lymphocytes. These lymphocytes have seen their specific antigen and after clonal expansion are migrating from lymph nodes to tissue

Ex. Lamina propria and intraepithelial layer of the tissues

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12
Q

Inductive site in the upper respiratory tract

A

Tonsils

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13
Q

Inductive sites in the gastrointestinal tract

A

Peyer’s patch

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14
Q

Cells of the inductive sites

A
  • M cells
  • Dendritic cells
  • Epithelial cells
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15
Q

Cells of the effector sites

A
  • B cells
  • T helper cells
  • Cytotoxic T cells
  • Regulatory T cells
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16
Q

Mechanisms of Antigen uptake at inductive sites

A
  1. M cells
  2. Dendritic cells
  3. Sneaking in during IgA release at mucosal surfaces when the pinch off occurs. Comes inside with the recycling of the pIgR?
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17
Q

Antigen uptake by M cells (microvilli cells)

A

M cells are highly specialized epithelial cells that form a “trap” while sitting on top of the Peyer’s patch in the epithelial layer
- They have shorter glycocalyx on their surface and thus particles fall into trap and allow cells to take them up
- They also have pockets on their basal side which immune cells can get access to the antigen

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18
Q

Antigen uptake by dendritic cells

A
  • Dendritic cells can hang out their dendrites into the lumen and fish for antigens
  • They will then present the antigen to the T cells for activation of immune response, and then the T helper cells activate the B cells
  • Occurs at all mucosal surfaces
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19
Q

Mucosal surfaces of Oral cavity and vagina

A
  • Also has dendritic cells uptaking antigens
  • They need mechanical protection so have more layers of epithelial (dying or dead cells). Dendrites are able to migrate up and sit in the dead cells
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20
Q

Steps of antigen uptake at inductive sites

A
  1. Antigen taken up at inductive sites
  2. Lymphocytes are induced when presented antigens
  3. Activated lymphocytes leave the inductive sites and migrate to the effector sites where they do their job. (Remember there are different effector cell populations in these tissues. Ex. B cells/plasma cells producing IgA or T helper cells releasing cytokines)
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21
Q

Two different effector populations in the tissues

A
  • Lamina propria lymphocytes
  • Intraepithelial lymphocytes
22
Q

Lamina propria lymphocytes (LPL)

A
  • Mainly B cells (humoral immune response)= IgA
  • T helper cells
23
Q

Job of the B cells in the Lamina propria lymphocytes

A

Secretion of antibodies/immunoglobulins
- IgA: most important immunoglobulin on mucosal surfaces
- IgG: transudated across mucosal surfaces
- IgE: allergies, parasitic infections (strong Th2 response)

24
Q

Job of the T helper cells in the lamina propria lymphocytes

A

Provide microenvironment for B cells (release cytokines and interleukins)

25
Q

Intraepithelial lymphocytes (IEL)

A
  • Mainly T cells (cytotoxic immune response)
  • Cells that are found within the epithelial layer (they squeeze between the epithelial cells)
  • Trying to find infected cells to kill them before virus can spread
26
Q

Transport of IgA to the mucosal surfaces

A
  • IgA is secreted by plasma cells in tissues underneath the epithelial layer
  • Epithelial cells use pIgR (polyimmunoglobulin receptor) receptor to grab the IgA molecules and transport it up to the surface where they release it into the lumen
  • Secreted IgA is found in large quantities in the lumen of the gut and on other mucosal surfaces where it binds to pathogens and prevents infection by these pathogens
27
Q

Role of antibodies at the mucosal surfaces

A
  • Pathogens need to adhere to receptors on cells so that they can cause damage and become internalized
  • Antibodies can prevent adherence by binding to pathogen
28
Q

The common mucosal immune system

A

Old idea that everything is interconnected. When an immune response is induced at one site, cells migrate to all other mucosal sites
- Now we know that cell trafficking is much more specific

29
Q

Specificity of immune cell trafficking

A
  • Highly specific
  • Different locations have different adressins which immune cells use to find and home in on their final destination
30
Q

Trafficking and the CCR9 knockout

A

CCR9 is needed for immune cells to find the intestine. When CCR9 is knocked out in mice, IgA stops appearing in the intestine because they are not receiving the signal and homing addressin

31
Q

Vaccine sites and their destination/response

A

Administration of vaccines (the specific site) will impact the response at a specific site

32
Q

Oral vaccine trafficking route effective response

A
  • Small intestine (proximal)
  • Ascending colon
  • Mammary and salivary glands
33
Q

Rectal vaccine trafficking route effective response

A

Rectum

34
Q

Nasal or tonsillar vaccine trafficking route effective response

A
  • Upper airway
  • Regional secretions
  • Genital mucosa
35
Q

Vaginal vaccine trafficking route effective response

A

Genital mucosa

36
Q

Skin vaccine trafficking route effective response

A

gut

37
Q

Oral vaccine trafficking route non-effective response

A
  • Distal large intestine
  • Genital mucosa
  • Tonsils
38
Q

Rectal vaccine trafficking route non- effective response

A
  • Small intestine
  • Proximal colon
39
Q

Nasal or tonsillar vaccine trafficking route non- effective response

A

gut

40
Q

Vaginal vaccine trafficking route non- effective response

A

intestine

41
Q

Skin vaccine trafficking route non- effective response

A

Most mucosal sites

42
Q

Regulation of the immune response at mucosal surfaces

A

Need to have the ability to determine what is actually a danger and what is not. Use oral tolerance

43
Q

Oral tolerance

A
  • Ability to tolerate certain antigens that are environmental or food antigens that are not harmful, including commensal bacteria
  • ORAL TOLERANCE: If it is food and there is no breach in the barrier and no danger signal by epithelial cells, oral tolerance will occur and Treg cells will suppress the response
  • IMMUNE EXCLUSION: If material gets trapped in M cells or taken up by dendritic cells and danger signals are present, immune responses are being induced and secretory antibodies are produced to keep antigens away
44
Q

Oral tolerance and Treg

A

When there is a food or environmental antigen present, oral tolerance will occur and Treg will be used to suppress the response.
- T reg secrete CD25, CTLA-4+, Foxp3+/- , IL-10, TGF-beta

45
Q

Shift from homeostasis to inflammatory response

A
  1. Normal permeability
  2. Minor defect of barrier
  3. Increases permeability
  4. Breach of epithelial layer
  5. Increase in Antigens and Mucosal associated molecular pattern (MAMPs)
  6. Trigger inflammatory response- switch from T regular to other T cells
46
Q

Can our immune system distinguish bad and good bacteria? Commensals vs. pathogens?

A
  • We cannot distinguish. Immune cell sees them as the same. The difference is their location. If they don’t belong then they will be considered bad
  • Bacteria sitting on top of the mucus then we don’t recognize it as a danger signal and all is good. If mucus layer is broken then would be considered dangerous
47
Q

Pathobionts

A

Half symbionts and half pathogens able to make contact with our cells. Mucus still intact, but the immune system is on high alert

48
Q

Pathogens

A

Mucus barrier is no longer intact, our epithelial cells recognize the danger signals and start inflammation.
- See the switch from homeostasis to inflammation

Therefore intact mucus layer is key!

49
Q

Intact mucus layer as key

A

Anything that disturbs the intact mucus layer can have extreme effects and result in full blown inflammation response.
- Stress, drugs, antibiotics, infections

50
Q

Inflammatory response to commensal bacteria or food antigens

A

Occurs when there is a damage to the mucus layer. If we damage it somehow such as by antibiotics, we create that response
- Often reason why we become sensitive to certain foods

Immunology #2 (17 decks)

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