Block D - Pathogens of the Respiratory Tract Flashcards
Name a emerging respiratory pathogen, resistant to treatment.
Scedosporium
Briefly describe the infection process for aspergillus
Spores inhaled → reach lungs → germinate into hyphae → trigger immune response or cause disease in immunocompromised patients.
Neutrophils and macrophages attempt fungal control, but failure leads to severe disease.
Name 4 diseases you can get from an Aspergillus infection.
-Allergic bronchopulmonary aspergillosis (ABPA): Hypersensitivity reaction in asthma/CF patients.
-Pulmonary aspergilloma: Fungal balls in lung cavities, often asymptomatic.
-Chronic necrotizing pulmonary aspergillosis (CNPA): Progressive lung infection in immunocompromised patients.
-Invasive aspergillosis (IA): Systemic infection affecting multiple organs, high mortality rate.
How would you diagnose Aspergillosis?
Imaging (X-ray, CT scan), sputum cultures, antibody testing, PCR.
How would you treat ABPA?
Corticosteroids + antifungals (itraconazole, voriconazole).
How would you treat Invasive Aspergillosis?
Voriconazole, amphotericin B
How would you treat Invasive Scedosporium infections?
Highly resistant, requiring multiple antifungal agents.
What is the primary route of infection for fungal respiratory diseases?
A) Skin contact
B) Inhalation
C) Ingestion
D) Blood transfusion
B) Inhalation
Which fungal species is most commonly associated with invasive aspergillosis?
A) Candida albicans
B) Aspergillus fumigatus
C) Cryptococcus neoformans
D) Histoplasma capsulatum
B) Aspergillus fumigatus
Which of the following conditions is a hypersensitivity reaction to Aspergillus colonization?
A) Pulmonary Aspergilloma
B) Chronic Necrotizing Pulmonary Aspergillosis (CNPA)
C) Allergic Bronchopulmonary Aspergillosis (ABPA)
D) Invasive Aspergillosis
C) ABPA
What immune cells are primarily responsible for fungal clearance in healthy individuals?
A) B cells and T cells
B) Eosinophils and mast cells
C) Neutrophils and macrophages
D) Natural killer cells and dendritic cells
C) Neutrophils and macrophages
Which antifungal drug is often used as first-line treatment for invasive aspergillosis?
A) Fluconazole
B) Itraconazole
C) Voriconazole
D) Caspofungin
C) Voriconazole
Name two key host defense mechanisms of the respiratory tract. (2 marks)
-Nasal hairs (filter particles)
-Ciliated mucous membranes (trap and remove microbes)
How do Aspergillus spores lead to infection in immunocompromised patients? (6 marks)
Spores reach lungs → germinate → evade immune system → form hyphae → cause tissue damage → disseminate systemically.
What distinguishes invasive aspergillosis from other Aspergillus-related diseases?
Invasive aspergillosis spreads beyond the lungs, affecting multiple organs and causing severe illness.
Why is targeting fungal infections challenging?
Fungi share many cellular structures with human cells, making selective drug targeting difficult.
What is the primary method for diagnosing ABPA?
Antibody testing (IgE and IgG levels specific to Aspergillus antigens).
What is the estimated number of fungal spores inhaled daily by an average person?
Around 50,000 fungal spores.
Name two common species of Aspergillus that cause respiratory disease.
-Aspergillus fumigatus
-Aspergillus flavus
What is the primary function of alveolar macrophages in fungal infections?
They phagocytose fungal conidia to prevent germination and infection.
Why are immunocompromised individuals more susceptible to invasive aspergillosis?
Their immune system, particularly neutrophils and macrophages, is weakened and unable to control fungal growth.
What is the primary structural component of the Aspergillus cell wall that is recognized by the immune system?
β(1,3)-glucan.
What is a key difference between colonization and invasive infection by Aspergillus?
Colonization occurs without tissue invasion, whereas invasive infection spreads into lung tissue and beyond.
What are the symptoms of Allergic Bronchopulmonary Aspergillosis (ABPA)?
Wheezing, cough, fever, malaise, weight loss, recurrent pneumonia, and brownish mucoid plugs.
How is pulmonary aspergilloma typically diagnosed?
Through chest X-ray or computed tomography (CT) scans.
What makes Scedosporium species a concerning respiratory pathogen?
They are highly resistant to antifungal treatments.
Name two antifungal drugs commonly used to treat invasive aspergillosis.
-Voriconazole
-Amphotericin B
What role do neutrophils play in the immune response to Aspergillus infection?
They attach to fungal hyphae and damage them using oxidative and non-oxidative mechanisms.
What is the most serious form of aspergillosis, and why?
Invasive aspergillosis (IA), because it spreads systemically, affecting multiple organs and has a high mortality rate.
What type of patients are most at risk for chronic necrotizing pulmonary aspergillosis (CNPA)?
Mildly immunocompromised patients with underlying lung disease.
How do corticosteroids contribute to the treatment of ABPA?
They reduce inflammation and hypersensitivity reactions to Aspergillus antigens.
What is the function of the Dectin-1 receptor in fungal immune response?
It recognizes β(1,3)-glucan and activates macrophage proinflammatory responses.
What is the main reason antifungal drug discovery is difficult?
Fungi share many cellular structures with human cells, limiting selective drug targets.
What environmental sources are Scedosporium species commonly found in?
Soil and water.
What is a key feature of Aspergillus spores that helps their survival in the environment?
They are highly resistant to desiccation.
Why does chronic obstructive pulmonary disease (COPD) increase the risk of pulmonary aspergilloma?
It leads to lung cavity formation, which provides an environment for fungal growth.
How does Aspergillus establish an infection in the lung?
Spores are inhaled, settle in alveolar spaces, evade immune defenses, germinate into hyphae, and invade tissue.
What is the primary staining method used to identify Mycobacterium tuberculosis?
A) Gram staining
B) Ziehl-Neelsen staining
C) India ink staining
D) Crystal violet staining
B) Ziehl-Neelsen staining
How does M. tuberculosis avoid being killed by macrophages?
A) By producing toxins that kill immune cells
B) By preventing phagosome-lysosome fusion
C) By secreting an enzyme that neutralizes antibodies
D) By moving rapidly and avoiding detection
B) By preventing phagosome-lysosome fusion
What is the standard treatment duration for tuberculosis?
A) 2 weeks
B) 1 month
C) 6+ months
D) 3 years
C) 6+ months
What is the primary mode of transmission for M. tuberculosis?
A) Contaminated food
B) Inhalation of aerosols
C) Skin contact
D) Blood transfusion
B) Inhalation of aerosols
What is the role of granulomas in TB infection?
A) They help the immune system kill M. tuberculosis
B) They provide a protective barrier allowing M. tuberculosis to become dormant
C) They produce antibiotics to clear the infection
D) They remove dead cells and repair lung tissue
B) They provide a protective barrier allowing M. tuberculosis to become dormant
What are two major risk factors for tuberculosis infection?
-HIV infection
-Close contact with an infected person
How does Mycobacterium tuberculosis enter the human body?
Through inhalation of infectious droplets.
What is the main reason TB treatment requires several months?
M. tuberculosis grows slowly and has a mycolic acid-rich cell wall that makes it drug-resistant.
Name two drugs used in the initial intensive phase of TB treatment.
Isoniazid, Rifampicin.
What is DOTS, and why is it important?
Directly Observed Therapy Short-course ensures patient compliance with TB treatment.
What is the function of mycolic acids in the M. tuberculosis cell wall?
They provide resistance to desiccation, antibiotics, and immune responses.
Why is the BCG vaccine not widely effective against pulmonary TB?
It provides limited protection and mainly prevents severe forms like TB meningitis in children.
What causes latent TB to reactivate?
Weakened immune system due to HIV, aging, or malnutrition.
What is the primary way M. leprae is transmitted?
Prolonged skin contact or exposure to armadillos.
How does M. bovis primarily infect humans?
Through consumption of unpasteurized milk from infected cattle.
What genetic adaptation distinguishes M. leprae from M. tuberculosis?
M. leprae has undergone extensive gene loss (reductive evolution), losing about 50% of its genome.
What role do macrophages play in tuberculosis infection?
They phagocytose M. tuberculosis, but the bacteria survive by preventing phagosome-lysosome fusion.
What is the main difference between M. tuberculosis and M. bovis?
M. tuberculosis is human-restricted, while M. bovis infects cattle and can spread to humans.
Why is multidrug-resistant TB (MDR-TB) a major concern?
It is resistant to first-line drugs like Isoniazid and Rifampicin, making treatment difficult.
What is the primary difference between M. tuberculosis and M. leprae in terms of disease progression?
M. tuberculosis mainly causes lung infections, while M. leprae affects the skin and nerves.
What’s the pathogenesis of Mycobacterium tuberculosis? (11 marks)
-Inhalation of aerosolized droplets containing Mtb from an infected individual
-The bacteria reach the alveoli (tiny air sacs in the lungs), where they are engulfed by alveolar macrophages.
-Mtb is phagocytosed by macrophages but prevents phagosome-lysosome fusion, allowing it to survive intracellularly
-Mtb has mechanisms of immune evasion like mycolic acids in the cell wall to protect against oxidative stress and immune responses.
- it has interferes with antigen presentation, reducing T-cell activation.
-it also inhibits reactive oxygen/nitrogen species that would normally kill the bacteria.
-If the immune system does not clear the infection, granulomas form due to macrophages, T-cells, and fibroblasts surrounding Mtb, aiming to contain it.
-Over time, the granuloma may become fibrotic and calcified, leading to latent TB, where bacteria remain dormant but viable.
-In immunocompromised individuals (e.g., HIV, malnutrition, old age), granulomas break down, releasing bacteria.
-Reactivated TB spreads within the lungs, leading to cavitary lesions, lung tissue damage, and bacterial dissemination.
-In severe cases, Mtb can spread beyond the lungs via the bloodstream or lymphatic system e.g TB meningitis, Miliary TB
What’s the pathogenesis of Aspergillus? (7 marks)
-Aspergillus infections occur through inhalation of airborne spores (conidia), which are abundant in the environment.
-In healthy individuals, immune defences usually eliminate spores
-while in immunocompromised individuals, spores are more likely to evade clearance, germinate and cause infection.
-Aspergillus spores have mechanisms of immune evasion like the conidia masking pathogen-associated molecular patterns (PAMPs), avoiding recognition by host immune receptors.
-while the hyphae produce antioxidant enzymes to resist oxidative stress from immune cells and secretes gliotoxin, which suppresses macrophage and neutrophil activity.
-depending on the host immune response, Aspergillus can cause different types of infections like Allergic Bronchopulmonary Aspergillosis (ABPA), Aspergilloma (Fungal Ball), Chronic Pulmonary Aspergillosis (CPA), Invasive Aspergillosis (IA)
-In severe cases, Aspergillus spreads via the bloodstream (hematogenous dissemination) to other organs, such as the brain, kidneys, liver. It can be fatal without aggressive antifungal treatment (e.g., Voriconazole, Amphotericin B)
What type of genome does Influenza virus have?
A) Double-stranded DNA
B) Single-stranded positive RNA
C) Single-stranded negative RNA
D) Circular RNA
C) Single-stranded negative RNA
What is the function of Hemagglutinin (HA) in Influenza virus?
A) Virus attachment to host cells
B) Cleaving sialic acid for viral release
C) RNA replication
D) Immune evasion
A) Virus attachment to host cells
Which process leads to the emergence of pandemic Influenza strains?
A) Antigenic drift
B) Antigenic shift
C) RNA recombination
D) Mutation suppression
B) Antigenic shift
Which of the following antiviral drugs targets neuraminidase?
A) Amantadine
B) Rimantadine
C) Oseltamivir
D) Interferon
C) Oseltamivir
What is the primary function of Neuraminidase (NA)?
A) Allows virus attachment to host cells
B) Prevents virus clumping and aids in viral release
C) Inhibits host immune responses
D) Converts RNA into DNA
Prevents virus clumping and aids in viral release
Which two types of Influenza virus cause significant human disease?
Influenza A and B.
What is antigenic drift?
Small mutations in HA and NA genes, leading to seasonal flu outbreaks.
Why does Influenza A cause pandemics while Influenza B does not?
Only Influenza A undergoes antigenic shift, allowing reassortment between different species.
What role does the segmented genome play in Influenza evolution?
It allows reassortment of genetic material, leading to antigenic shift and new viral strains.
What is the primary target for flu vaccines?
Hemagglutinin (HA) and Neuraminidase (NA).
How is Influenza transmitted?
Respiratory droplets from coughing or sneezing.
Name one structural feature that makes Influenza highly mutable.
Segmented (-)RNA genome.
Why do flu vaccines need to be updated annually?
Due to antigenic drift, which causes frequent mutations in HA and NA.
What are two main types of flu antiviral drugs?
Neuraminidase inhibitors (e.g., Tamiflu, Relenza) and M2 inhibitors (e.g., Amantadine, Rimantadine).
What pandemic was caused by H1N1 in 2009?
Swine Flu Pandemic.
What does Oseltamivir (Tamiflu) inhibit?
Neuraminidase (NA), preventing viral release from host cells.
What are the common symptoms of Influenza?
Fever, headache, muscle aches, fatigue, cough, sore throat.
How does antigenic shift contribute to new pandemics?
It allows gene reassortment, creating novel viral strains that humans have little immunity against.
What is the main function of the M2 protein in Influenza?
It acts as an ion channel, essential for viral uncoating and replication.
Which Influenza protein binds to sialic acid receptors on host cells?
Hemagglutinin (HA).
Why does the lower respiratory tract have fewer microbial residents compared to the upper respiratory tract?
It was traditionally thought to be sterile due to mucociliary clearance and immune responses, but recent research suggests otherwise.
What are two key structural features of the Aspergillus cell wall that contribute to its pathogenicity?
-Mycolic acids (resist host immune responses).
-Conidia (asexual spores) that are resistant to desiccation.
How do neutrophils combat Aspergillus hyphae?
Neutrophils attach to hyphae and use oxidative (reactive oxygen species) and non-oxidative (enzymes, phagocytosis) mechanisms to kill the fungus.
How do Aspergillus conidia evade the immune system?
Conidia mask pathogen-associated molecular patterns (PAMPs), preventing immune recognition.
What is the function of the Aspergillus enzyme gliotoxin?
It suppresses macrophage and neutrophil function, allowing Aspergillus to evade immune destruction.
Why do Aspergillus spores form conidia?
To survive in extreme environmental conditions like desiccation.
What are the three main components of the M. tuberculosis cell wall that contribute to its resistance?
-Mycolic acids (protect against desiccation and drugs).
-Arabinogalactan (provides structural integrity).
-Peptidoglycan (resistance to host defenses).
Why does M. tuberculosis require prolonged treatment (6+ months)?
Slow growth, latency, and thick mycolic acid-rich cell wall make it difficult to target with antibiotics.
How does M. tuberculosis avoid immune destruction inside macrophages?
Prevents phagosome-lysosome fusion, allowing it to survive and replicate intracellularly.
What is the primary immune cell responsible for containing M. tuberculosis in granulomas?
Macrophages, supported by T-helper cells (Th1 response).
Why is Mycobacterium leprae considered to have undergone extensive reductive evolution?
It has lost ~50% of its genome, including many metabolic genes, making it an obligate intracellular pathogen.
What distinguishes M. bovis from M. tuberculosis in terms of host range?
M. tuberculosis is human-restricted, whereas M. bovis infects cattle and can spread to humans through unpasteurized milk.
What is miliary TB?
A disseminated form of tuberculosis where Mtb spreads via the bloodstream, forming small granulomas throughout multiple organs.
What is the major structural advantage of Influenza’s segmented genome?
Allows genetic reassortment, leading to antigenic shift and pandemic strains.
Why is Influenza A more likely to cause pandemics than Influenza B?
Influenza A can reassort with animal strains (e.g., birds, pigs), leading to major antigenic shifts, whereas Influenza B is primarily human-restricted.
What is the function of the Neuraminidase (NA) protein in Influenza?
Cleaves sialic acid to prevent virus clumping and facilitate viral release from infected cells.
Why is it difficult to develop long-lasting Influenza vaccines?
Due to antigenic drift and antigenic shift, leading to frequent changes in HA and NA proteins.
What are the main antiviral drugs used to treat Influenza, and how do they work?
-Oseltamivir (Tamiflu), Zanamivir (Relenza): Neuraminidase inhibitors, prevent virus release.
-Amantadine, Rimantadine: M2 inhibitors, block viral uncoating (but resistance is common).
How does antigenic drift differ from antigenic shift?
Antigenic drift: Small point mutations in HA/NA → seasonal flu.
Antigenic shift: Major genetic reassortment → pandemics.
Which polymerase proteins are responsible for Influenza RNA replication?
PB1, PB2, PA.
How is Influenza diagnosed?
PCR, rapid antigen tests, viral culture, serological tests, chest X-ray (in severe cases).
What genetic factor in some Influenza strains makes secondary bacterial infections more likely?
The PB1 gene predisposes individuals to secondary bacterial infections.
What was the major genetic factor that contributed to the virulence of the 1918 Spanish Flu pandemic?
Changes in HA, NA, and PA1 genes, which enhanced transmission and virulence.
