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Medsci 314 > Lecture 18; Mucosal and Cutaneous Immunity > Flashcards

Lecture 18; Mucosal and Cutaneous Immunity Flashcards

1
Q

What are the most common routes of pathogen entry?

A

Most human pathogens gain access to the body by penetrating its skin or mucosae.

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2
Q

What are two mucosal tissues that function as independent arms of the immune system?

A

MALT – mucosa-associated lymphoid tissue
SALT – skin-associated lymphoid tissue

Function as independent arms of the immune system responsible for mucosal immune responses & cutaneous immune responses

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3
Q

What are the ALTs?

A

Collections of lymphocytes at sites of primary pathogen entry

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4
Q

What makes SALT and MALT so special?

A

There is no need for antigen transport as everything is there already

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5
Q

What are mucosae?

A

Mucosae are layers of epithelial cells that line the body passage such as gut, respiratory tract or urogenital tract

Name from the capacity to make mucus – viscous solution of polysaccharides in water that covers the apical surface membrane of an epithelial cell

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6
Q

What is found in the mucous covering the mucosae?

A

Mucus contains;
SIgA (type I mucosae)
SIgG (type II mucosae)

& antimicrobial peptides i.e Lactoferrin and Lysozyme

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7
Q

List the ALTs;

A

MALT – mucosae of the body tracts

Subsystems:
GALT – gut-associated lymphoid tissue
NALT – nasopharynx-associated lymphoid tissue BALT – bronchi-associated lymphoid tissue

SALT – skin-associated lymphoid tissue

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8
Q

What are two important mucosal immunity terminologies?

A

Inductive Site

Effector site

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9
Q

What is the inductive site in terms of MALT?

A

Inductive site: an area in the mucosae where an antigen is encountered and a primary adaptive response in initiated. Inductive sites in the GALT include the Peyer’s patches, appendix.

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10
Q

What is the effector site in terms of MALT?

A

Effector site: an area in the mucosae where effector lymphocytes are dispatched after mucosal T and B cells are activated in a given inductive site. Important mucosal effector sites are the exocrine glands (salivary, lacrimal glands).

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11
Q

What do the mucosal exocrine glands secrete in terms of defence molecules?

A

IgA and antimicrobial peptides

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12
Q

Whats special about payers patches?

A

Specialised patches that can sample from the gut/food antigens

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13
Q

Write some notes on GALT epithelium;

A

Known as Follicle Associated Epithelium (FAE) - it has;

  • sub-epithelial follicles
  • M cells
  • Laminar propria
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14
Q

What specific cell type in the epithelium samples from the gut lumen?

A

M cells

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15
Q

Describe the basic structure of get epithelium and how these cells relate to GALT;

A

Enteroendocrine cells; Can release hormones to influence enterocytes and mucous

Paneth Cells; Antimicrobial peptides

Goblet Cells; Antimicrobial peptides and mucous

NK and NKT cells can exist within this epithelial layer

  • Type 1 mucosae
  • Brush Border
  • Glycocalyx (-ive charge to repel microbes)
  • Mucous layer (IgA) as type 1
  • Villi
  • Commensual organisms
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16
Q

What else can the enterocytes release?

A

Enterocytes have pathways for cytokine i.e TLR, PRR, NLRs

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17
Q

What cell types exist below the epithelium in GALT?

A 
Macrophages
Neutrophils
Mast Cells
NK cells
Plasma IgA cells
B cells
DC cells
AB T cells
GD T cells

NOT BASOPHILS OR ESINOPHILS

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18
Q

Whats different about GD T cells?

A

More innate like, PRR, Mostly in ALTs

  • non-specific
  • Very rapid proliferation in 1-2 days
  • Can differentiate into the same effector T cells as AB T cells But dont really do memory cells
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19
Q

How do the genes of DG T cells relate to its function?

A

GD T cells have specific genes for specific parts of the body. Responding to broadly to specific microbes

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20
Q

What are the effector cells formed by GD T cells?

A

CTL

Th1
Th2
Th17

21
Q

Function of GD CTL

A

Target cell cytolysis

22
Q

Function of GD Th1

A

NK and macrophage activation

23
Q

Function of GD Th2

A

AB T cell differentiation
B cell isotype switching
Leukocyte trafficking
Wound healing

24
Q

Function of GD Th17

A

NK cell, macrophage and neutrophil activation

25
Q

What does M cell stand for?

A

Microfold cell

26
Q

What is also found in the laminar propria of GALT?

A

Germinal centers of cell proliferation

27
Q

Describe the structure of the M cell;

A
  • No glycocalyx, brush border, mucous

- Intraepithelial pocket (dome)

28
Q

What is found within the M cell intraeptihelial pocket?

A
  • IDC
  • AB T cell
  • B cell maturation follicles
  • Macrophages
29
Q

How many enterocytes are M cells?

A

10%

30
Q

What are the functions of M cells?

A
  • Important in the transcytosis of antigens
  • Receptor mediated transcytosis
  • Bulk Sampling (passive)
  • DC can sample directly via long processes
31
Q

Describe the basic structure of GALT; (overview)

A

• Gut epithelium – crypts and villus
• Lamina propria – macrophages, neutrophils,
immature DCs, NKTs, memory ab T cells, memory B cells

32
Q

Describe antigen sampling in GALT;

A

• Intestinal follicles and follicle-associated epithelium –
at inductive sites in the gut lymphocytes usually organised into intestinal follicles. M cells.

• GALT DCs – GALT immature DCs function to tolerize
naïve T cells.

No transport of Antigens

33
Q

What is the function of NALT and BALT?

A

Function: Immune protection from dubious substances & pathogens in inhaled air

34
Q

What is the basic structure of NALT?

A

• NALT: nasal submucosal glands, tonsils, upper airway epithelial layers; nose hairs, cilia

(same sort of cellular set up as MALT)

35
Q

What is the basic structure of BALT?

A

• BALT: bronchial submucosal glands, tracheal epithelium, bronchi and lung epithelial layers, cilia

(same sort of cellular set up as MALT)

36
Q

How do mucosal B cells (MALT) migrate for an effector response?

A

Migration of mucosal B cells from an inductive site through the blood & lymphatics to several effector sites is governed by shared expression of mucosal homing receptors

37
Q

Describe the migration process of B cells from the MALT;

A

Mucosal homing receptors bind to addressins at mucosal effector sites

38
Q

Describe what traditional vs mucosal b cells binding sites are;

A
  • Conventional B cells , specific for VCAM-1 (sites on inflammation)
  • Mucosal B cells , specific for MAdCAM-1 (endothelial cells in mucosae)

These are binding molecules in the lymphatics that can cause migration into the tissue

39
Q

What are the mucosal t cells and DC binding sites?

A

Mucosal T cells a4b7 and CCR9 induced by DCs at inductive sites (CCR9 binds to TECK secreted by epithelial cells at effector sites)

40
Q

Describe mucosal IgA

A
  • Constitutively localised in mucus
  • Bind adhesion molecules in many pathogens
  • Cross-reactive
  • Not efficient activator of complement
  • Polymeric Immunoglobulin Receptor
41
Q

Describe the production of mucosal IgA;

A

Induction site; M cell, antigen sampled, B cells proliferate in follicles of M cell.

B cells migrate through lymphatics and vasculature via HEV and to the effector site Releases IgA

42
Q

What is the purpose of SALT?

A

Defend skin against damage caused by infection or injury

43
Q

What is the basic structure of skin;

A
  • Epidermis: keratin layer, lower epidermis
  • Basement membrane
  • Dermis
44
Q

Describe the immune cells of SALT;

A 
• Commensal microbes (space/nutrients/antimicrobials- lipases)
• gd versus ab T cells, LCs
• B cells rare
• Keratinocytes produce growth
factors/cytokines
• Dermis has blood vessels,
lymphatics, hair follicles, low
numbers of cells
• Macrophages, mast cells, DCs
and ab T cells (memory)

No granulocytes and few B cells. (additionally keritoncytes)

45
Q

Describe the innate immune response to pathogen entry of SALT;

A 
Pathogen enters (innate)
• gd T cells recognise PAMPs and
DAMPs
• Damaged keratinocytes
stimulate others to produce
chemokines
• Dermal macrophages respond
to gradients (cytokines and chemokines)
- Neutrophils Extravasate (produce hydrolases)
• Leukocytes penetrate epidermis
46
Q

Describe the adaptive immune response of pathogen entry of SALT;

A

Pathogen enters (adaptive)
• Ags from microbes engulfed by LCs
• LCs mature and activate ab T cells
• Primarily memory cells so response is rapid
• Differentiate into CTLs and Th effector cells

Langerhan cells APC and classic.

47
Q

What is IBD?

A

Chrons or Ulcerative Collitis

  • Balance between pro and anti inflam cytokines

Cytokines produced to heal injuries of IFD but can also cause tumerogeneis

48
Q

Describe the pathogenesis of IBD;

A

Chronic relapsing disorders of the gastrointestinal tract that are characterized pathologically by intestinal inflammation and epithelial injury

• Impaired barrier function in gut
• Immune cell activation from
commensals bacteria/microbes
• If not resolves chronic inflammation ensues

Medsci 314 (31 decks)

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