Fungi

Question 1

Fungi

Answer 1

• Eukaryotic mircoorganisms
• Can occur as yeasts, molds, or a combination of both (dimorphism)
• Morphology
  
  • Contains bilayered cell membrane containing sterols. Ergosterol is the essential sterol in fungi (vs. cholesterol in humans). Most antifungals works by disrupting ergosterol.
  • Cell wall surrounds cell membrans (cell walls are antigens to human immune system)
  • Capsule - polysaccaride coating surrounding cell wall

Question 2

Yeast

Answer 2

• Microscopic fungi consisting of solitary cells that reproduce by budding.
• Can appear spherical to ellipsoidal.
• Different types of yeast can be distingusihed base on the presence or absence of capsules, the size and shape of the yeast cell, the mechanism of daughter cell formation, the formation of pseudohyphae (buds that don’t separate), presence of sexual spores, and physiologic data (differences in the ability to ultilize different carbon sources)

Question 3

Molds

Answer 3

• Characterized by development of hyphae (threadlike, branching, cylindrical, tubules composed of fungal cells attached end to end).
• Molds are differentiated on the basis of conidiogenesis (asexual production of a spore).

Question 4

Dimorphic fungi

Answer 4

• Fungi that can exist as a yeast or mold depending on the environmental condition

Question 5

Mycoses

Answer 5

• Fungal infections in animals
• Classified based on
  
  • Site of infection
    
    • Superifical - epidermis, no inflammation
    • Cutaneous - Skin, hair, nails
    • Subcutaneous - Wounds, usually inflammatory
    • Deep or systemic - Lungs, abdominal viscera, bones, CNS (occurs through ingestion, inhalation, or introduction into blood stream)
  • Route of acquisition
    
    • Exogenous - environment, airbone, cutaneous, percutaneous
    • Endogenous - latent reactivation, commensl organism
  • Virulence
    
    • Primary - inherently virulent, infects healthy host
    • Opportunistic - low virulence, infects immunocompromised host

Question 6

Vulvovaginal Candidiasis

Answer 6

• Vaginal inflammation caused by candida species (yeast)
• Presences of vulvovaginal candida alone is not indicative of the disease as candida species are part of the normal flora in 25% of women

Question 7

Pathogenesis Vulvovaginal Candidiasis

Answer 7

• Candida albicans is responsible for most yeast infections
• Canadida glabrata accounts for almost all of the remainder
• All Candida species produce similar symptoms
• Candida organisms likely access the vagina via migration from the recum across the perianal area and less commonly from sexual transmission, or relapse from a vaginal reservoir
• Symptomatic disease - associated with overgrowth of the organism and penetration of superifical epithelial cells
• Generally, C. albicans is a commensal organism. However, it is capable of causing opportunistic infection following disruption of the normal flora, breach of mucocutaneous barriers, or defect in host cellular immunity.

Question 8

Risk factors for yeast infection

Answer 8

• Diabetes mellitus - women with poor glycemic control are more prone to vulvovaginal candidiasis. Women with DM2 are more prone to nonalbicans candida species
• Antibiotic use - use of broad-spectrum antibiotics greatly increases risk. Inhibition of normal bacterial flora favours growth of potential fungal pathogens
• Increased estrogen levels - tends to occur more often durng OCP use, pregnancy, and estrogen therapy
• Immunosuppression
• Potentially use of certain contraceptive devices (vaginal sponges, diaphragms, IUDs) and sexual activity may increase risk.

Question 9

Clinical Presentation of Yeast Infection

Answer 9

• Symptoms - vulvar burning, soreness, and irritation, dysuria, and/or dyspareunia
  
  • Symptoms are often worse during the weel prior to menses
  • Severity varies from mild to severe
• Physical exam
  
  • Examination of the external genitalia, vagina, and cervix often shows erythemia of vulva and vaginal mucosa and vulvar edema
  • Vulvar excoriation (abrasion of the skin) and fissures may be seen
  • Dischrage - white, thick, adherent to vaginal sidewalls, and clumpy (cottage cheese-like) with no or minimal odour (may also present with little or no discharge, or thin and watery discharge).

Question 10

Investigations Yeast Infection

Answer 10

• Vaginal pH - should be normal (4-4.5). Distinguishes candidasis from other causes of vaginitis
• Microscopy - shows up negative in 50% of people with vulvovaginal candidiasis
• Cultures - Do not culture of microscopy is positive. Obtain culture if:
  
  • Women has clinical features, normal pH, and no pathogens on microscopy
  • Women has persistent or recurrent infections - these women may have nonalbicans infection (need to use different treatment)
• Diagnosis if made based on presence of Candida on wet mount, gram stain, or culture in women with characterist clinical findings and no other pathogen to account for symptoms

Question 11

Classification of Candidal Vaginitis

Answer 11

• Uncomplicated Disease (Patient must have ALL features)
  
  • Symptom severity: Mild or moderate
  • Frequency: Sporadic
  • Organism: Candida albicans
  • Host: Normal
• Complicated Disease (Patient may have ANY feature)
  
  • Symptom severity: Severe
  • Frequency: Recurrent
  • Organism: Nonalbicans species
  • Host: Abnormal - uncontrolled DM, immunosuppression, pregnancy, etc.

Question 12

Treatment Yeast Infection

Answer 12

• Uncomplicated Infection:
  
  • One dose oral fluconazole (anti-fungal medication), or
  • 1-3 day course of topical azole
• Complicated Infection
  
  • 2-3 sequential doses of oral fluconazole 72hrs apart
  • 7-14 day course of topical azole
• Pregnant women
  
  • Use topical azole for 7 days
  • Best to avoid oral therapy due to potential risks with pregnancy (miscarriage and birth defects)

Question 13

Candida albicans infection in normal vs. immunocompromised patients

Answer 13

• Normal
  
  • Oral thrush - patches of white creamy exudate with reddish base covering the mucous membrane of the mouth
  • Vaginitis
  • Diaper rash - warm moist area under diapers and in adults between skin folds - becomes red and macerated
• Immunocompromised
  
  • Esophagitis - extension of thrush into esophagus causing burning substernal pain worse with swalowing
  • Disseminated - candida can invade bloodstream and virtually every organ. May see candidal patches with opthalmoscope

Question 14

Innate vs. Adaptive Immunity

Answer 14

Question 15

Adaptive Immune System

Answer 15

• Subset of overall immune system composed of highly specialized, systemic cells, and processes that eliminate pathogens or prevent their growth
• Creates immunolgical memory after first encounter witha specific pathogen
• Includes humoral immunity and cell-mediated immunity
• Memory and specificity are the hallmark features of adaptive responses

Question 16

Transition from innate to adpative responses

Answer 16

• Preformed wehn antigen-presenting cells (APC; dendrits, macrophages, or B cells) interact with a T cell that is specific for a given antigen (APC brings antigen from tissue to the lymph)

Question 17

Antigen

Answer 17

• Any moleculre to which an antibody can specifically bind
• Results in the generation of antibodies

Question 18

Antibody (Immunoglobulin)

Answer 18

• A golbular protein produced by B cells that can bind to a specific antigen
• When an antibody binds to an antigen, it tags the pathogen for destruction by phagocytes like macrophages and neutrophils

Question 19

Antigen Presentation

Answer 19

• Important that we have cells that can present an antigen because T cells are unable to recognize “native” antigen (non-broken down antigen)
• APCs pick up the antigen, process it, and present it on major histocompatibility complex (MHC) proteins
• MHC I - expressed on almost all nucleated celleds (not just APCs). If there is something abnormal being produced inside the cell, it will be presented on MHC I. Present to CD8 cells
• MHC II - only expressed on professional APCs due to their ability take in extraceullar material. Present to CD4 cells

Question 20

Antigen Processing Pathway

Answer 20

• MHC I - intracellular pathogens and endogenous proteins (Ex. tumor or viruses (take over cellular machinary). MHC I is presented to CD8 cytoxic T cells (killer T cells). Killer T cells then go out into the tissues and finds other cells presenting the antigen and destroys them.
• MHC II - extracellular pathogen gets phagocytosed and digested by phagolysosome. Peptide fragments from pathogen gets presented on MHC II and is presented to CD4 T cells (helper T cells). The helper T cells activate the B cells to proliferate and make antibodies. (Only APCs)

Question 21

Immune Response to Fungus

Answer 21

1. Barriers
2. Neutrophils, macrophages, and monoctyes - phagocytes already in the tissue attempt to kill or damage the fungi (via. PRR). Next, additional effector cells (neutrophols and monocytes) are recruited via inflammatory singals (cytokines, chemokines, and complement). Fungi are killed or damaged by production and/or release of ROS and antimicrobial peptides.
   
   • Fungi that cannot be killed via phagocytosis (ex. hyphea are too big) are killed by neutrophils releasing toxic substances onto the fungi extracellularly.
3. Dendritic and other APCs process fungal antigens and display them on MHC II. APCs then present the antigen to CD4 -T-helper (Th) cells.
   
   • Th1 - cellular immunity - recruits macrophages via release of IFN-y and IL2 to phagocytose the fungus
   • Th2 - humoral immunity (B cells). Secretes IL4 and IL10. Downregulates phagocytosis and actually gives fungi the oppurtunity to proliferate
   • Th17 - Plays important role in maintaining mucosal barries and contributing to pathogen clearance at mucosal surfaces - have anti-fungal effect via neutrophil recruitment (IL17) and secretion of defensins that lyse the fungal cell wall (IL-22)