Overview of Immunology: Mucosal Immunology- the guardian of oral health

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1 Overview of Immunology: Mucosal Immunology- the guardian of oral health Jacqueline Mays, DDS, MHSc, PhD April 6, 2017 AAOM Annual Conference Statement of Disclosure: I have no actual or potential conflict of interest in relation to this presentation

2 Outline Role of the immune system in health and disease Overview of mucosal immunity Defenses of the oral cavity

3 The Oral Cavity is the Gateway to the Body Gingiva Buccal Mucosa Tonsils Sublingual Immune Response

4 Protecting the Oral Cavity 1. Physical Defenses a) Oral mucosal integrity b) Epithelial shedding c) Tissue organization d) Microbiome 2. Innate Defenses 3. Cellular Immune Defenses a) Neutrophils b) Macrophages c) Natural killer cells d) T cells (Th17) e) B cells a) Saliva b) Host defense peptides c) IgA

5 Protecting the Oral Cavity 1. Physical Defenses a) Oral mucosal integrity b) Epithelial shedding c) Tissue organization d) Microbiome 2. Innate Defenses 3. Cellular Immune Defenses a) Neutrophils b) Macrophages c) Natural killer cells d) T cells (Th17) e) B cells a) Saliva b) Host defense peptides c) IgA

6 Physical defenses of the oral cavity prevent pathogen entry Median epithelial Tissue region turnover time (days) Small intestine 4 Buccal mucosa 14 Floor of mouth 20 Hard palate 24 Skin 27 Squier and Kremer (2001) Oral mucosa (keratinized and non-keratinized) provides: Thermal protection Sensory information Physical barrier to bacteria, viruses, yeast and toxins Oral epithelial cells are constantly shed

7 Structure of the Oral Mucosa Modified from Pocket Dentistry, Ch. 12 and 2016 BioRad Laboratories Mini-review Series. The Mucosal Immune Response in Health and Disease

8 Buccal Mucosa CD4 + T cell CD8 + T cell

9 Mucosal Immune System Largest immune organ in the body Humans have a mucosal surface area of over 300m 2 Gut, nasal and oral cavities, female genital tract Mucosal inductive sites: Mucosa-associated lymphoid tissue (MALT) Gut.. GALT Nasopharyngeal NALT Bronchus BALT

10 Mucosal Immune System Overview Oral Mucosa 2016 BioRad Laboratories Mini-review Series. The Mucosal Immune Response in Health and Disease

11 Structure of the Gut Mucosal Immune System Vivier, Spita and Cupedo. Nature Reviews Immunology (2009)

12 The Lymphatic System Abbas, Lichtman and Pillai. Cellular and Molecular Immunology, 7th Edition by Saunders, and imprint of Elsevier, Inc.

13 Mastoid Maxillary Occipital Superficial Cervical Superficial Deep Cervical Submental Parotid Supramandibular Submandibular Inferior Deep Cervical

14 Antigen presenting cells interact with naïve T and B cells in the lymph node Abbas, Lichtman and Pillai. Cellular and Molecular Immunology, 7th Edition by Saunders, and imprint of Elsevier, Inc.

15 Protecting the Oral Cavity 1. Physical Defenses a) Oral mucosal integrity b) Epithelial shedding c) Tissue organization d) Microbiome 2. Innate Defenses 3. Cellular Immune Defenses a) Neutrophils b) Macrophages c) Natural killer cells d) T cells (Th17) e) B cells a) Saliva b) Host defense peptides c) IgA

16 The oral cavity is equipped with innate immune defenses Reuters

17 Protecting the Oral Cavity 1. Physical Defenses a) Oral mucosal integrity b) Epithelial shedding c) Tissue organization d) Microbiome 2. Innate Defenses 3. Cellular Immune Defenses a) Neutrophils b) Macrophages c) Natural killer cells d) T cells (Th17) e) B cells a) Saliva b) Host defense peptides c) IgA

18 Protein in Whole Saliva comes from multiple sources Serum via gingival crevicular fluid Dental Press J. Orthod. vol.16 no.6 Maringá Nov./Dec Mucosal epithelial cells Oral Microbiome

19 Key Host Defense Peptides in the Oral Cavity Heron and Elahi. Front Immunol Mar 7;8:241

20 Secreted IgA on the mucosal surface can bind and neutralize pathogens and toxins IgA is able to bind and neutralize antigens internalized in endosomes IgA can export pathogens and toxins from the lamina propria while being secreted Abbas, Lichtman and Pillai. Cellular and Molecular Immunology, 7th Edition by Saunders, and imprint of Elsevier, Inc.

21 T-Dependent IgA Class Switching in the Gut Abbas, Lichtman and Pillai. Cellular and Molecular Immunology, 7th Edition by Saunders, and imprint of Elsevier, Inc.

22 T-Independent IgA Class Switching in the Gut Abbas, Lichtman and Pillai. Cellular and Molecular Immunology, 7th Edition by Saunders, and imprint of Elsevier, Inc.

23 Protecting the Oral Cavity 1. Physical Defenses a) Oral mucosal integrity b) Epithelial shedding c) Tissue organization d) Microbiome 2. Innate Defenses 3. Cellular Immune Defenses a) Neutrophils b) Macrophages c) Natural killer cells d) T cells (Th17) e) B cells a) Saliva b) Host defense peptides c) IgA

24 Cells of the Oral Mucosal Immune System Dendritic Cells Langerhans Cells Macrophages Innate Lymphoid Cells Neutrophils NK Cells B Cells T cells CD4 + Tregs (secrete IL10) Th17 cells CD8 + Gamma Delta T cells

25 Innate and Adaptive Immunity Abbas, Lichtman and Pillai. Cellular and Molecular Immunology, 7th Edition by Saunders, and imprint of Elsevier, Inc.

26 Types of Adaptive Immunity Abbas, Lichtman and Pillai. Cellular and Molecular Immunology, 7th Edition by Saunders, and imprint of Elsevier, Inc.

27 IL-17 cells are critical for oral immunity Oral Diseases 27 DEC 2016 DOI: /odi.12598

28 Heron and Elahi. Front Immunol Mar 7;8:241 Antifungal Mucosal Defenses

29 Plenary Session 1: Oral Medicine and Immunology as Friends

30 Heron and Elahi. Front Immunol Mar 7;8:241

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