Intracellular Infections and Immunity Flashcards
Define obligate pathogen.
Which type of pathogens are exclusively obligate pathogens?
- Pathogens that require a host to fulfil their life cycle.
- Viruses.
List 3 types of parasites that have a choice between intracellular and extracellular environments.
1 - Bacteria.
2 - Fungi.
3 - Parasites.
List 2 locations within the cell in which a pathogen may reside.
1 - Free in the cytoplasm.
2 - Restricted to vacuoles.
List 2 advantages and 1 disadvantage of pathogen survival within phagocytes.
Advantages:
1 - The intracellular environment provides a continuous supply of nutrients to the pathogen.
2 - The pathogen is shielded from the extracellular immune system.
Disadvantage:
1 - There is a need to overcome innate antimicrobial killing mechanisms of the phagocyte.
Describe the role of each immune cell involved in the killing of intracellular pathogens.
1 - CD4+ Th1 cells target vacuole restricted bacteria.
2 - CD8+ T cells target cytoplasmic bacteria.
3 - NK cells target both vacuole restricted and cytoplasmic bacteria.
List 3 immune defences that target extracellular pathogens.
1 - Complement.
2 - Phagocytosis.
3 - Antibodies.
List 2 immune defences that target pathogens found on epithelial surfaces.
1 - Antimicrobial peptides.
2 - Antibodies, especially IgA.
List the stages of the phagosome processing pathway in a macrophage.
1 - The pathogen is taken up by phagocytosis to form an early phagosome at pH 6.3.
2 - The early phagosome becomes a late phagosome at pH 5.5.
3 - At pH 4.0, the phagosome merges with a lysosome to form a phagolysosome, which digests the pathogen into its components.
4 - MHC class 2 loading occurs.
5 - The loaded MHC is presented on the plasma membrane and non-peptide material is released.
How does Mycobacterium tuberculosis survive intracellularly?
Is it vacuole restricted or free in the cytoplasm?
- The pathogens block the phagosome processing pathway at an early stage of phagosome development, preventing contact with the lysosome contents.
- This process involves the pathogen surface glycolipid lipoarabinomannan (LAM).
- The bacterium replicates and survives in the early phagosome, where it remains vacuole restricted.
- More detail on survival mechanisms on later card.
How does Listeria monocytogenes survive intracellularly?
Is it vacuole restricted or free in the cytoplasm?
- The bacterium uses cytolysins to escape the early phagosome.
- The bacterium replicates and survives freely in the cytosol.
List 5 mechanisms of intracellular microbial killing.
1 - Acidification.
2 - Toxic oxygen-derived products.
3 - Toxic nitrogen oxides.
4 - Antimicrobial enzymes.
5 - Competitors.
What pH is achieved with acidification?
What is the effect of acidification on bacteria?
- 3.5-4.0.
- Has a bacteriostatic or bactericidal effect and improves phagolysosome maturation.
List 2 toxic oxygen-derived products.
1 - Superoxide (O2 -).
2 - Hydrogen peroxide (H2O2).
Give an example of a toxic nitrogen oxide.
Nitric oxide.
List 3 antimicrobial enzymes.
What are their functions?
1 - Lysozymes dissolve the cell walls of gram-positive bacteria.
2 - Acid hydrolases further digest bacteria.
3 - Defensins (broad antimicrobial function).
Give an example of an antimicrobial competitor.
What does it compete for?
- Lactoferrin.
- Lactoferrin binds Fe and vitamin B12-binding protein.
What is the role of IFN-gamma and CD40 in CD4+ Th1 immunity?
They are both involved in macrophage activation, which leads to destruction of macrophage-engulfed bacteria.
What is the role of Fas ligand and LT-alpha in CD4+ Th1 immunity?
The molecules directly kill chronically infected cells, releasing bacteria to be destroyed by macrophages.
What is the role of IL-2 in CD4+ Th1 immunity?
IL-2 induces T cell proliferation.
What is the role of IL-3 and GM-CSF in CD4+ Th1 immunity?
They are both involved in inducing macrophage differentiation in the bone marrow.
What is the role of TNF-alpha and LT-beta in CD4+ Th1 immunity?
They are both involved endothelium activation to induce macrophage binding and extravasation to the site of infection.
What is the role of CCL2 in CD4+ Th1 immunity?
It causes macrophages to accumulate at the site of infection.
Which cell primes CD4+ Th1 cells?
How are they primed?
Where does this occur?
- Dendritic cells prime CD4+ Th1 cells by presenting peptides through MHC class 2.
- This occurs in the lymph node and spleen.
What is the effect of priming a CD4+ Th1 cell?
1 - It causes the T cell to proliferate.
2 - It causes the T cell to acquire an effector function through differentiation.
What is the main function of a primed CD4+ Th1 cell?
To seek out infected macrophages that present antigens through MHC class 2, and subsequently activate the infected macrophages.
How does CD4+ Th1-induced macrophage activation facilitate killing of pathogens?
Activation increases expression / production of:
1 - MHC Class 1 and 2.
2 - CD40.
3 - CD80.
4 - CD86.
5 - Fas.
6 - TNF and TNFRs.
7 - Lysosymes.
8 - Toxic oxygen products.
9 - Factors that promote phagolysosome maturation, such as acidification and fusion.
Give an example of how activated macrophages differ in appearance from unactivated macrophages.
They are double the size of unactivated macrophages.
How is the antigen of cytosolic bacteria presented differently from that of vacuole restricted bacteria?
- Antigen from cytosolic bacteria is presented through MHC class 1 (CD8+ T cells).
- Antigen from vacuole restricted bacteria is presented through MHC class 2 (CD4+ Th1 cells).
Give an example of a common mycobacterium species in cows.
Mycobacterium bovis.
What proportion of the global population is latently infected with tuberculosis?
30%.
List 4 characteristics of Mycobacterium tuberculosis.
1 - Gram positive.
2 - Bacilli morphology.
3 - Slow growing; 12-24 hours to replicate.
4 - Complex lipid envelope.
List 3 mechanisms of tuberculosis host avoidance.
1 - Inhibition of phagosome fusion with lysosomes.
2 - Inhibition of ROS generation.
3 - Inhibition of nitrogen radical generation.
List 2 enzymes involved in the inhibition of ROS generation.
1 - Superoxide dismutase (SOD).
2 - Catalase.
Describe the mechanism of superoxide dismutase (SOD).
It catalyses the breakdown of superoxide (O2 -) into hydrogen peroxide.
Describe the mechanism of catalase.
It catalyses the breakdown of hydrogen peroxide into water.
List 4 symptoms of tuberculosis.
1 - Breathlessness.
2 - Chest pains.
3 - Coughing up blood.
4 - Weight loss.
Why do some TB infections manifest as latent infections whereas others don’t?
If the initial host immune response is inadequate, the disease will manifest early.
*Some TB infections reactivate even after an early manifestation.
What is the function of a granuloma?
Which cells form the granuloma?
Where are granulomas often found?
- By surrounding the infected area, they prevent spread of the infection.
- The granuloma is formed of T cells and macrophages.
- Granulomas are most commonly found in the lungs.
What is caseous necrosis?
When does it form?
- A mass of dead macrophages released from collapsed granulomas (looks like cheese).
- It often forms with tuberculosis infection.
List 5 characteristics of caseous tissue.
1 - Anaerobic.
2 - Low pH.
3 - Presence of cytokines.
4 - Presence of macrophages.
5 - Presence of Mycobacteria.
List 3 cytokines found in caseous tissue.
1 - IFN-gamma.
2 - LT-alpha.
3 - TNF-alpha.
How is tuberculosis transmitted?
Via infected sputum.
What is the name of the vaccine for tuberculosis?
Bacillus Calmette-Guérin vaccine (BCG).
How effective is the vaccine for tuberculosis?
75% for the most severe forms such as TB meningitis, but less effective for respiratory disease.
From which strain of tuberculosis is the tuberculosis vaccine developed?
Mycobacterium bovis.
Why should the tuberculosis vaccine not be given to patients with an immunodeficiency or are on immunosuppression?
Because it is a live vaccine.
List 5 risk factors for tuberculosis infection.
1 - HIV infection.
2 - Malnutrition.
3 - Stress.
4 - Diabetes.
5 - Immunosuppression.
List 2 immunodeficiency diseases.
1 - Severe combined immunodeficiency (SCID).
2 - Common variable immunodeficiency (CVID).
List 3 other Mycobacterium species that infect humans.
1 - Mycobacterium avium.
2 - Mycobacterium kansasii.
3 - Mycobacterium marinum.
