Host Defense Against Oral Infections Flashcards
Non Specific Oral defenses
- Saliva flow
- Mucin/agglutinins-physical removal
- Lysozome-protease-anion system- lysis
- Lactoferrin
- Histatins- Antifungal, some antibacterial
- Defensins- Antimicrobe, immunomodulatory
- Chitinase-antifungal
- Cathelicidin-antimicrobe
- Neutrophils/macrophages
- Complement
- Salivary lactoperoxidase-
Neutrophil
Class, function
Granulocyte
Phagocyte
Innate
Most abundunt leukocyte
Lymphocyte
Agranulocyte\Adaptive immunity
Monocyte
Agranulocyte
Pahgocyte
Eosinophil
Granulocyte
Removal of helminths and Ab complexes
Basophil
Granulocyte
Allergy
Inflammation
Least abundunt
Soluble mediators of inflammation in oral infections
3 classes and examples
- Antibodies
- slgA, IgG, IgM
- Complement
- C3
- Cytokines
- IL-1 IL-6 TNF-alpha
Innate Immune components in Oral health and the barriers they form
- Consists of
- epithelia, phagocyes, plasma proteins
- Barriers
- Anatomic barriers
- Physiologic barriers
- Phagocytic barriers
- Inflammatory barriers
Oral mucosal epithelial cells anatomic barrier function
- Express TLR to recognize PAMPS
- TLR2 binds lipoteichoic acid on gram POSITIVE bacteria (actinomyces, strep)
- TLR4 binds lipopolysaccharide (LPS) on gram NEGATIVE (Prevotella)
- TLR binding signals epithelial cells to make
- Peptide antibiotics
- Cytokine
- Nitric oxide
- Express receptors for secretory IgA (slgA)
Swallowing
Removes bacteria from plaque and mucosa
when blocked gram negative species groq
pH
- 9 pH in healthy
- 25-8 pH in infections
A rise in periodontal pocket pH in gingivitis and periodontal disease favors periodontal pathogen growth
Temperature
- 35035 C normal
- 39 C in periodontal inflammation
- Higher temp
- alter bacterial gene expression
- immune evasion
- P gingivalis SOD is up-regulated and can neutralize super oxide anions meant to kill it
Lactoferrin
Iron binding
bacteriostatic
Lysozyme
- Found in saliva and in lysosome
- Breaks down baterial cell wall (peptidoglycan)
- effective aginst S mutans
Myeloperoxidase System
Bactericidal generating halide
hydrogen peroxide in PMN migrates to gum crevice as host inflammatory respoonse
Salivary peroxidase system
Bactericidal generating thiocyanate, hydrogen peroxide
Antimicrobial Peptides
Histatins, defensins
Small cationic
Histatins
Histidine rich broad spectrum
anti-fungal and bactereial
Defensins
Broad spectrum
anti- bacterial, fungal, viral
Beta defensins protect oral cavity
Leukocytes action in saliva
98% PMN
Secrete alpha-defensin
phagocytosis
Increase inflammation
Secretory IgA (sIgA) Activity
Major antibody in saliva
Inhibits microbial adherence
Agglutinates bacteria
Virus neutralization
Describe the phagocytic killing methods that are oxygen independent and dependent
- Oxygen Independent Methods
- Lysozyme breaks down cell wall
- Defensin- cationic peptides, antimicrobial
- Lactoferrin- binds iron
- Proteolytic and hydrolytic enzymes
- Oxygen Dependent
- Respiratory burst intermediates
- Hydrogen peroxide, superoxide anion, hydoxy radical
- Myeloperoxidase, hypochlorite, hypohalite
- Nitric oxide
- Respiratory burst intermediates
Chronic Granulomatous Disease
Etiology
- Failure of phagocytes to produce Hydrogen peroxide and superoxide
- Genetic defect in NADPH oxidase
- Cant kill pathogen
- Prone to infection
- pneumonia, lung and lymph node infection, abcesses of skin and liver
How to treat chronic granulomatous disease
- Antibiotics
- high dose, long term, prophylactic
- Amphotericin B
- Penicillin
- IFN-gamma injections to help activate macrophages
Principal events of inflammation
- Local phagocytes release of inflammatory
- Cytokines: TNF-alpha, IL-1
- Chmokines: MIP MCP
- Cytokines
- recruit and activate phagocytes
- stimulate cell response
- Vasodilation inc blood flow
- Increased cepillary permeability
- Leukocytes migrate to reach site of infection
- PMN first
- Monocytes and lymphocytes come later
- Periodontitis is inflammation based infection
Immunoglobulins and antibodies in the oral cavity
Gingival crevice and 1/3 of tooth crown is covered with GCF
Gingival Crevicular Fluid contains IgG IgM IgA
Salivary Ab is predominantly sIgA
Antibody can be locally made paticularly in inflamed gingivae
IgG
Monomer
Makes up for a lot of AB in serum
Crosses placenta
Activates complement
Major opsonizing AB
Found in GCF to protect gum and crown
IgM
Pentamer
First antibody generated against any antigen
Predominant antibody produced by fetus
Antibody for carb antigens (ABO groups)
GCF contains IgM to protect gum and crown
IgA
- 2 forms
- In serum as monomer
- Secretions as dimer (saliva) sIgA
- lines oral mucosa surfaces and protects from infection
- interferes with adhesion molecules of pathogen
- Opsonize pathogens at mucosal surface to prevent attachment
- Confers mucosal immunity
- Immune Exclusion-sIgA can differentiate which bacteria can provide a commensal or pathogenic
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sIgA
- Mediates humoral mucosal immunity
- Structure: polymeric, made locally by plasma cells in mucosal epithelium
- IgA is the most abundantlly synthesized antibody
- 2 subclasses IgA1 and IgA2
- In plasma IgA1 dominates
- in saliva they are equal
- IgA1 Ab directed against protein antigens
- IgA2 Ab is against polysaccharide antigens
- sIgA is part of enamel pellicle and good at agglutinating microbes
General Mucosal Immune system
- Mucosal epithelium- physical barrier, first line of defense against invasion
- GI & Respiratory mucosa colonized by lymphocytes and APC, respond ton Ags
- GI- lymphocytes are w/i epithelial layer, lamina propria and Peryers Patch
- each with unique phenotype and function
- Intraepithelial lymphocytes are usually CD8 T cells
- Ag stimuli at 1 site elicits an antibody response that is restricted to MALT
- Immune response to oral AGs differ fundamentally from responses encountered at other sites
Oral Mucosa Inflammation and immune protection
- Mucosal surfaces continously flushed by exocrine secretions
- DC sample Ags btw epithelial cells
- Responds to harmful organisms
- regulates influx of immune cells
- Prevents inflammatory tissue destruction
- Alterations in the normal balance of flora can cause inappropriate immune responses
- Commensal bacteria then become surrogate pathogens and stimulate chronic inflammatory response
Immune Response in Oral Mucosa
GCF
- GCF glushes gingival margin-oral cavity area, a vulnerable area
- Plaque at gingival margin results in acute inflammation
- Increases the flow of GCFto bring components to site
- Healthy: dynamic equilibrium of endogenous oral microbes and host antimicrobial factors
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What are caries and periodontal disease a result of
- Ecological imbalance btw resident microbes and host immune response
- Dental Caries
- Frequently eating fermentable barbs lead to selective advatage to higly acidogenic bacteria (lactobacilli, S. mutans)
- Colonize on sugar matrix
- Lead to biofilm or plaque
Mucosal Ag sampling and presenting
- M cells have specialized microfolds to take up Ag
- Bring Ab to Intraepithelial DC
- Initiate IgA response, that dominate mucosal surface
- sIgA first line of defense
- Oral immunization with protein Ags induce tolerance
- CD4 T cells important in generation of oral mucosal tolerance
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Mucosal epithelial secrete
- Mucins, defensins, trefoil, pellicle, lysozyme and NO
- Non-specifically shoeld mucosal from microbial damage
Specific Host factors of Mouth
- Intra-epithelial lymphocytes and Langerhans Cells
- Cellular barrier to bacteria/ag
- CD4 T cells-
- Secretion of cytokines
- sIgA-
- Prevent microbe adhesion and metabolism
- IgG, IgA, IgM
- Prevent adhesion
- Opsonization
- Complement activation
