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

2. Immunity to Candidiasis
Hossein Zarrinfar
Medical Mycology (Ph.D.)
Mashhad University of Medical Sciences

3. 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

4. 
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

6. 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

8. 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

9. 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

10. 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

11. 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)

12. 



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

13. 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

14. 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

15. 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

16. Immune System Against Candida
Acquired Immunity
Natural Immunity
Humoral Immunity
Phagocytic cells
Cell Mediated Immunity
Complement
T. Lymphocyte
B. Lymphocyte
Antibodies

17. 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

18. 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.