Candidiasis immunity
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Candidia Species Commonly (Opportunistic human Pathogens) ...

Candidia Species Commonly (Opportunistic human Pathogens)


C.albicans
C.glabata
C.guilliermandii
C.krusei
C.lusitaniae
C.parapsilosis
C.tropicalis


Candiia Species Uncommonly: 18 species

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Candidiasis immunity Presentation Transcript

  • 1. Immunity to Candidiasis Hossein Zarrinfar Medical Mycology (Ph.D.) Mashhad University of Medical Sciences
  • 2. Introduction Candidiasis  Mucocutaneous: 1. Oral: thrush, stomatitis, perlech, glossitis 2. Bronchocandidiasis 3. Respiratory Candidiasis 4. Vulvovaginitis and balanitis 5. Chronic Mucocutaneous 6. Alimentary: esophagitis, gastritis, peritonitis
  • 3.  Cutaneous: 1. 2. 3. 4.  Systemic Candidiasis: 1. 2. 3. 4.  Intertrigo Candidial Paronichia and Onychomycosis Diaper Rosh(napkin Candidiasis) Granuloma Candidial Urinary traet Endocarditis Meningitis Iatrogenic Candidemia and Septicemia Allergic Diseases: 1. Candidids 2. Eczemas, Asthma and gastritis
  • 4. Candidia Species Commonly (Opportunistic human Pathogens) 1) 2) 3) 4) 5) 6) 7) C.albicans C.glabata C.guilliermandii C.krusei C.lusitaniae C.parapsilosis C.tropicalis Candiia Species Uncommonly: 18 species
  • 5. Routs of Transmission of Candidi Speciec   Loss of the integrity and overgrowth of number of yeasts Exogenous transmission 1. 2. 3. 4. 5. 6. Postsurgical endophthalmitis (Contaminated solutions) Candidemia (parenteral nutrition) Contaminated transducers Contaminated Suppositor Intraneous injection in heroin abuser From staff to patient and from patient to patient (burn, geriatrics, intensive care, neonatal) 7. From mother to neonate in the time birth
  • 6. Virulence Factors 1) 2) 3) Adherence to surfaces (Specific: ligand-receptor interaction and nonspecific: electerostatic charge, van der wals forces) Dimor phism ( Blastoconidia are hydrophilic but germ tube is hydrophobic) Mannans (glycoproteins): a) hydrophobicity adherence b) suppress the immune response
  • 7. 4) 5) Enzyme prodyction: proteinases (aspartyl proteinases [SAP1-10]) and phospholipases Proteinases: a) Nonspecific proteolysis of proteins involved in defenses b) Entry of yeasts from tissue barriers Phenotypic switching (especially in invasive infections): adaptation to different and changing conditions in host evade from host’s defence system  Neutrophils and oxidants (H2O2 myeloperoxidase) can augment the switching process. 6) Resistance to the thrombin-induced platelet microbicidal protein
  • 8. Secreted Aspartyl Proteases (Saps)         Produced by C. albicans, C. dubliniensis, C. guilliermondii, C. parapsilosis Sap7 appears to be the most divergent of the family Sap1 and Sap3 express within 42 h post – infection of tissue Sap6 (48 h) and Sap2 and Sap8 (60 h) Sap4 and Sap5 were never detected Tissue damage was most extensive by 48 h Extensive penetration in tissue (Sap8) Extensive hyphal growth (Sap6)
  • 9.     Biochemical and proteolytic properties of the Sap7 to Sap10 Enzymes are not presently known Size of Sap1 to Sap10 proteins are 35 to 50 kDa Distinct difference in pH optima Sap1 to Sap3 having highest activity at lower pH values but Sap4 to Table 3. Relationship of the secreted aspartyl proteases (Saps) to candidiasis Assay Blood/deep seated Oral Virulence Expression Methods SAP1–4, 6 – Deletion mutants ? SAP1–3, 6, 8 RT-PCR, immune microscopy Disease Skin Vagina ? SAP2 SAP1–3, 6, 8 – RT-PCR, Mutants immune microscopy
  • 10. Adhesion molecules in cell wall of the Candida 1. Protein moiety of glycoprotein (ß2- integrin family) (fibrinogen – binding epitope in hyphae) arginine – glycine – aspartate (RGD) sequences (C3d and iC3b) 2. Lectinlike protein glucosamine) 3. Polysaccharide portion of a manno protein host receptors glycosides (Fucose or N-acetyl unknown
  • 11. Mucosal Surfaces . Als1p(agglutinin – like sequence1) vein endotelial cells, HBEC (human buccal epithelial cells) . Ala1p (Als5p)(agglutinin – adhesion1) FN (fibronectin) . Hwp1p (outer surface mannoprotein with amino – terminal in hyphal and germ tube HBEC . Int1p (Integrin – like protein) Epithelial . Mnt1p (x1,2 – mannosylteransferase) HBEC
  • 12. Antigenicity 1. 2. 3. 4. Mannan – protein complex (Particularly the polysaccharid moiety in cell wall) Enolase protein (47-48 kilodalton) (cytosol) a) Catabolic enymatic activity b) Protective role in AIDS patients Heat shock (hsp) (70-80 KDa) (cytosol): Immunogenic activity Ribosomal fractions: protective in animal models against systemic candidiasis
  • 13. Immune System Against Candida Acquired Immunity Natural Immunity Humoral Immunity Phagocytic cells Cell Mediated Immunity Complement T. Lymphocyte B. Lymphocyte Antibodies
  • 14. Complement Several line of activation by C. albicans : 1. 2. 3.    Treatment of yeast cells with serum and phagocytosis Produce chemotacticpeptides by incubation of yeast cells Conversion of C3 and factor B by incubation of candida The classical pathway is initated by an antimannan IgG (in serum of most adults)(low levels of antimannan IgM) MBL (mannan- binding lectin) in serum binds to C. albicans activation of classical pathway C. albicans yeast cells and germ tubes also the alternative pathway via antibody – dependent and antibody - independent
  • 15. References 1. 2. 3. 4. 5. . Anassie, E., Mc Ginnis, M.R., pfaller, M.A., Clinical Mycology ,2003 Richard A. Calderone and William A. Fonzi, Virulence factors of Candida albicans,TRENDS in Microbiology Vol.9 No.7 July 2001. Ken Haynes,Virulence in Candida species, TRENDS in Microbiology Vol.9 No.12 December 2001. Julian R. Naglik,1* Stephen J. Challacombe,1 and et all, Candida albicans Secreted Aspartyl Proteinases in Virulence and Pathogenesis, Mic. Mol. Bio. Revies, Sept. 2003, p. 400– 428. RICHARD A. CALDERONEl* AND PHYLLIS C. BRAUN2, Adherence and Receptor Relationships of Candida albicans, Microbiological Reviews, Mar. 1991, p. 1-20.