Host Defense Against Oral Infections Flashcards

1
Q

Non Specific Oral defenses

A
  • 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-
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2
Q

Neutrophil

Class, function

A

Granulocyte

Phagocyte

Innate

Most abundunt leukocyte

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3
Q

Lymphocyte

A

Agranulocyte\Adaptive immunity

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4
Q

Monocyte

A

Agranulocyte

Pahgocyte

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5
Q

Eosinophil

A

Granulocyte

Removal of helminths and Ab complexes

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6
Q

Basophil

A

Granulocyte

Allergy

Inflammation

Least abundunt

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7
Q

Soluble mediators of inflammation in oral infections

3 classes and examples

A
  • Antibodies
    • slgA, IgG, IgM
  • Complement
    • C3
  • Cytokines
    • IL-1 IL-6 TNF-alpha
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8
Q

Innate Immune components in Oral health and the barriers they form

A
  • Consists of
    • epithelia, phagocyes, plasma proteins
  • Barriers
    • Anatomic barriers
    • Physiologic barriers
    • Phagocytic barriers
    • Inflammatory barriers
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9
Q

Oral mucosal epithelial cells anatomic barrier function

A
  • 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)
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10
Q

Swallowing

A

Removes bacteria from plaque and mucosa

when blocked gram negative species groq

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11
Q

pH

A
  1. 9 pH in healthy
  2. 25-8 pH in infections

A rise in periodontal pocket pH in gingivitis and periodontal disease favors periodontal pathogen growth

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12
Q

Temperature

A
  • 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
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13
Q

Lactoferrin

A

Iron binding

bacteriostatic

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14
Q

Lysozyme

A
  • Found in saliva and in lysosome
  • Breaks down baterial cell wall (peptidoglycan)
  • effective aginst S mutans
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15
Q

Myeloperoxidase System

A

Bactericidal generating halide

hydrogen peroxide in PMN migrates to gum crevice as host inflammatory respoonse

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16
Q

Salivary peroxidase system

A

Bactericidal generating thiocyanate, hydrogen peroxide

17
Q

Antimicrobial Peptides

A

Histatins, defensins

Small cationic

18
Q

Histatins

A

Histidine rich broad spectrum

anti-fungal and bactereial

19
Q

Defensins

A

Broad spectrum

anti- bacterial, fungal, viral

Beta defensins protect oral cavity

20
Q

Leukocytes action in saliva

A

98% PMN

Secrete alpha-defensin

phagocytosis

Increase inflammation

21
Q

Secretory IgA (sIgA) Activity

A

Major antibody in saliva

Inhibits microbial adherence

Agglutinates bacteria

Virus neutralization

22
Q

Describe the phagocytic killing methods that are oxygen independent and dependent

A
  • 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
23
Q

Chronic Granulomatous Disease

Etiology

A
  • 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
24
Q

How to treat chronic granulomatous disease

A
  • Antibiotics
    • high dose, long term, prophylactic
    • Amphotericin B
    • Penicillin
  • IFN-gamma injections to help activate macrophages
25
Q

Principal events of inflammation

A
  • 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
26
Q

Immunoglobulins and antibodies in the oral cavity

A

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

27
Q

IgG

A

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

28
Q

IgM

A

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

29
Q

IgA

A
  • 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
    *
30
Q

sIgA

A
  • 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
31
Q

General Mucosal Immune system

A
  • 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
32
Q

Oral Mucosa Inflammation and immune protection

A
  • 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
33
Q

Immune Response in Oral Mucosa

GCF

A
  • 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
    *
34
Q

What are caries and periodontal disease a result of

A
  • 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
35
Q

Mucosal Ag sampling and presenting

A
  • 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
    *
36
Q

Mucosal epithelial secrete

A
  • Mucins, defensins, trefoil, pellicle, lysozyme and NO
  • Non-specifically shoeld mucosal from microbial damage
37
Q

Specific Host factors of Mouth

A
  • 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