Lecture 18; Mucosal and Cutaneous Immunity Flashcards
What are the most common routes of pathogen entry?
Most human pathogens gain access to the body by penetrating its skin or mucosae.
What are two mucosal tissues that function as independent arms of the immune system?
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
What are the ALTs?
Collections of lymphocytes at sites of primary pathogen entry
What makes SALT and MALT so special?
There is no need for antigen transport as everything is there already
What are mucosae?
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
What is found in the mucous covering the mucosae?
Mucus contains;
SIgA (type I mucosae)
SIgG (type II mucosae)
& antimicrobial peptides i.e Lactoferrin and Lysozyme
List the ALTs;
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
What are two important mucosal immunity terminologies?
Inductive Site
Effector site
What is the inductive site in terms of MALT?
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.
What is the effector site in terms of MALT?
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).
What do the mucosal exocrine glands secrete in terms of defence molecules?
IgA and antimicrobial peptides
Whats special about payers patches?
Specialised patches that can sample from the gut/food antigens
Write some notes on GALT epithelium;
Known as Follicle Associated Epithelium (FAE) - it has;
- sub-epithelial follicles
- M cells
- Laminar propria
What specific cell type in the epithelium samples from the gut lumen?
M cells
Describe the basic structure of get epithelium and how these cells relate to GALT;
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
What else can the enterocytes release?
Enterocytes have pathways for cytokine i.e TLR, PRR, NLRs
What cell types exist below the epithelium in GALT?
Macrophages Neutrophils Mast Cells NK cells Plasma IgA cells B cells DC cells AB T cells GD T cells
NOT BASOPHILS OR ESINOPHILS
Whats different about GD T cells?
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
How do the genes of DG T cells relate to its function?
GD T cells have specific genes for specific parts of the body. Responding to broadly to specific microbes
What are the effector cells formed by GD T cells?
CTL
Th1
Th2
Th17
Function of GD CTL
Target cell cytolysis
Function of GD Th1
NK and macrophage activation
Function of GD Th2
AB T cell differentiation
B cell isotype switching
Leukocyte trafficking
Wound healing
Function of GD Th17
NK cell, macrophage and neutrophil activation
What does M cell stand for?
Microfold cell
What is also found in the laminar propria of GALT?
Germinal centers of cell proliferation
Describe the structure of the M cell;
- No glycocalyx, brush border, mucous
- Intraepithelial pocket (dome)
What is found within the M cell intraeptihelial pocket?
- IDC
- AB T cell
- B cell maturation follicles
- Macrophages
How many enterocytes are M cells?
10%
What are the functions of M cells?
- Important in the transcytosis of antigens
- Receptor mediated transcytosis
- Bulk Sampling (passive)
- DC can sample directly via long processes
Describe the basic structure of GALT; (overview)
• Gut epithelium – crypts and villus
• Lamina propria – macrophages, neutrophils,
immature DCs, NKTs, memory ab T cells, memory B cells
Describe antigen sampling in GALT;
• 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
What is the function of NALT and BALT?
Function: Immune protection from dubious substances & pathogens in inhaled air
What is the basic structure of NALT?
• NALT: nasal submucosal glands, tonsils, upper airway epithelial layers; nose hairs, cilia
(same sort of cellular set up as MALT)
What is the basic structure of BALT?
• BALT: bronchial submucosal glands, tracheal epithelium, bronchi and lung epithelial layers, cilia
(same sort of cellular set up as MALT)
How do mucosal B cells (MALT) migrate for an effector response?
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
Describe the migration process of B cells from the MALT;
Mucosal homing receptors bind to addressins at mucosal effector sites
Describe what traditional vs mucosal b cells binding sites are;
- 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
What are the mucosal t cells and DC binding sites?
Mucosal T cells a4b7 and CCR9 induced by DCs at inductive sites (CCR9 binds to TECK secreted by epithelial cells at effector sites)
Describe mucosal IgA
- Constitutively localised in mucus
- Bind adhesion molecules in many pathogens
- Cross-reactive
- Not efficient activator of complement
- Polymeric Immunoglobulin Receptor
Describe the production of mucosal IgA;
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
What is the purpose of SALT?
Defend skin against damage caused by infection or injury
What is the basic structure of skin;
- Epidermis: keratin layer, lower epidermis
- Basement membrane
- Dermis
Describe the immune cells of SALT;
• 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)
Describe the innate immune response to pathogen entry of SALT;
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
Describe the adaptive immune response of pathogen entry of SALT;
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.
What is IBD?
Chrons or Ulcerative Collitis
- Balance between pro and anti inflam cytokines
Cytokines produced to heal injuries of IFD but can also cause tumerogeneis
Describe the pathogenesis of IBD;
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
