Oral Mucosa Immune System PDF

# Oral Mucosa - Epithelial barrier function and antimicrobial peptides ## Types of AMPs - **Defensins**: Alpha-defensins (e.g. HNP-1 to HNP-4) and beta-defensins (e.g. hBD-1, hBD-2, hBD-3) are produced by epithelial cells. They are affective against both Gram-positive and Gram-negative bacteria...

# Oral Mucosa - Epithelial barrier function and antimicrobial peptides ## Types of AMPs - **Defensins**: Alpha-defensins (e.g. HNP-1 to HNP-4) and beta-defensins (e.g. hBD-1, hBD-2, hBD-3) are produced by epithelial cells. They are affective against both Gram-positive and Gram-negative bacteria and can disrupt microbial membranes. - **Cathelicidin (LL-37)**: Produced in response to microbial invasion, LL-37 exhibits antimicrobial, immunomodulatory, and wound-healing properties. - **Histatins**: Salivary AMPs such as histatin-5 are known for their antifungal properties, particularly effective against Candida albicans. | AMP | Function | |--------------------|-----------------------------------------------------------------------------------| | α-Amylase | Inhibits *P. gingivalis* | | Defensins (α&β) | Cationic peptides with antibacterial, antiviral and immunomodulatory properties. | | Cystatins, secretory leukocyte protease inhibitor | Inhibits microbial protease and thus its ability to metabolise proteins into amino acids | | Histatins 1, 3 & 5 | Inhibits Candida albicans | | Chitinase | Antifungal with cell wall lysis | | Statherin | Inhibits anaerobic bacterial growth. | | Secretory IgA (also s-IgG. s-IGM) | Inhibits adherence. Agglutinates bacteria. Virus neutralisation. IgA is the major antibody in saliva. | | Lactoferrin | Fe³⁺ chelator that inhibits metabolic activity of microorganisms. | | Lysozyme | Hydrolyzes glycosidic bond to damage bacterial cell wall - effective against *S. mutans*. | | Agglutinins | Glycoproteins, mucins, fibronectin, 2-macroglobulin, proline rich proteins. | | Myeloperoxidase system | Bactericidal in presence of thiocyanate/halide-H2O2 | | Salivary peroxidase system | (enzyme thiocyanate/halide-H2O2) | | Complement (trace amounts) | C3 - probably largely derived from GCF | | Leukocytes | > 98% are neutrophils, but up to 50% may not be capable of phagocytosis. | ## MALT in Gastro-intestinal Tract - Specialised cells within the columnar, ciliated epithelial lining - Goblet Cells —> mucus - Paneth cells —> antimicrobial peptides (AMPs) - Increased blood supply - Bound by tight junctions ## Peyer's patches & MLNs - No mucus production - Sample antigen via M cells & DCs - Regulation by MΦs & Tregs ## Lamina Propria - T cell differentiation - IgA production ## Microbiome and tolerance ## Mucosa-associated lymphoid tissue (MALT) - No goblet, paneth or M cells - Specialised lymphoid tissues —> Waldeyers ring - Oral lymphoid loci —> collection of lymphocytes and APCs in lamina propria (Th1, Th2, Th3) - Langerhans cells: specialised dendritic cells express fewer activation molecules. ## Oral Langerhans Cells - Immature dendritic cells (no CD*#) - Constitutively endocytose - High levels of co-stim molecules, Fc receptor, MHC I + II - Express co-inhibitory molecules B7-H2 + B7-H3 —> up-regulated in response to TLR4 activation —> IL-10 up-regulation - Prevents excess inflammation and auto-immune attacks ## Th1 - Activated by IL-12 + IL-18 signals - Produces IFN-γ —> stim macrophages to destroy intracellular bacteria + increases activity from cytotoxic T cells - Effective against bacteria, virus + parasites - Also makes IL-2 ## Th2 - Activated by IL-4 - Targets extracellular pathogens + parasites + allergy - Makes IL-4 + IL-13 - Mast cell activation - B cell proliferation - Ig class switching - Increased MHC II expression ## Th17 - Activated by IL-6, TGF-β - Mucosal immunity - Extra- and intracellular bacteria and fungi - Makes IL-17A + IL-22 - Stimulates epithelial cells to produce IL-8 —> neutrophil recruitment - Increases AMP production by macrophages and neutrophils - Causes inflammation ## Treg - Activated by TGF-β - Makes IL-10 - Immune suppression - Stops macrophage activation - Pushes towards M2 phenotype - Stops t-helper cells differentiation - Stops t and b proliferation - Stops dendritic cell activation ## Lymphocyte homing - **Activation**: When an infection or inflammation occurs, signals (such as cytokines) are released that guide lymphocytes to the affected area. - **Sensing Signals**: Lymphocytes have special "address labels" on their surface called receptors. These receptors help them recognize and respond to specific chemical signals (called chemokines) released by the tissues or organs where they are needed. - **Movement**: Lymphocytes travel through the bloodstream and "hone in" on the tissue where their help is needed, such as infected or inflamed areas. - **Importance**: This process helps ensure that immune cells are directed to the right places, where they can fight infections, repair tissue damage, or regulate inflammation. T cells return to point of origin after circulating to look for antigen. ## Th17 - Stimulates AMP expression from karatinocytes - Chemo-attractant for neutrophils from apithelial cells - Maintains barrier junction proteins ## Site Specific Responses (Periodontal Tissues vs Buccal Mucosa) ## Examples of Oral Mucosal Immune-Pathologies - Periodontal disease - Lichen planus - Pemphigus vulgaris - Pemphigid - Sjogren's syndrome - Mucosa-associated lymphoid tissue lymphoma