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IIH > Intracellular Infections and Immunity > Flashcards

Intracellular Infections and Immunity Flashcards

1
Q

Define obligate pathogen.

Which type of pathogens are exclusively obligate pathogens?

A
  • Pathogens that require a host to fulfil their life cycle.

- Viruses.

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2
Q

List 3 types of parasites that have a choice between intracellular and extracellular environments.

A

1 - Bacteria.

2 - Fungi.

3 - Parasites.

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3
Q

List 2 locations within the cell in which a pathogen may reside.

A

1 - Free in the cytoplasm.

2 - Restricted to vacuoles.

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4
Q

List 2 advantages and 1 disadvantage of pathogen survival within phagocytes.

A

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.

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5
Q

Describe the role of each immune cell involved in the killing of intracellular pathogens.

A

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.

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6
Q

List 3 immune defences that target extracellular pathogens.

A

1 - Complement.

2 - Phagocytosis.

3 - Antibodies.

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7
Q

List 2 immune defences that target pathogens found on epithelial surfaces.

A

1 - Antimicrobial peptides.

2 - Antibodies, especially IgA.

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8
Q

List the stages of the phagosome processing pathway in a macrophage.

A

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.

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9
Q

How does Mycobacterium tuberculosis survive intracellularly?

Is it vacuole restricted or free in the cytoplasm?

A
  • 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.
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10
Q

How does Listeria monocytogenes survive intracellularly?

Is it vacuole restricted or free in the cytoplasm?

A
  • The bacterium uses cytolysins to escape the early phagosome.
  • The bacterium replicates and survives freely in the cytosol.
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11
Q

List 5 mechanisms of intracellular microbial killing.

A

1 - Acidification.

2 - Toxic oxygen-derived products.

3 - Toxic nitrogen oxides.

4 - Antimicrobial enzymes.

5 - Competitors.

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12
Q

What pH is achieved with acidification?

What is the effect of acidification on bacteria?

A
  • 3.5-4.0.

- Has a bacteriostatic or bactericidal effect and improves phagolysosome maturation.

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13
Q

List 2 toxic oxygen-derived products.

A

1 - Superoxide (O2 -).

2 - Hydrogen peroxide (H2O2).

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14
Q

Give an example of a toxic nitrogen oxide.

A

Nitric oxide.

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15
Q

List 3 antimicrobial enzymes.

What are their functions?

A

1 - Lysozymes dissolve the cell walls of gram-positive bacteria.

2 - Acid hydrolases further digest bacteria.

3 - Defensins (broad antimicrobial function).

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16
Q

Give an example of an antimicrobial competitor.

What does it compete for?

A
  • Lactoferrin.

- Lactoferrin binds Fe and vitamin B12-binding protein.

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17
Q

What is the role of IFN-gamma and CD40 in CD4+ Th1 immunity?

A

They are both involved in macrophage activation, which leads to destruction of macrophage-engulfed bacteria.

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18
Q

What is the role of Fas ligand and LT-alpha in CD4+ Th1 immunity?

A

The molecules directly kill chronically infected cells, releasing bacteria to be destroyed by macrophages.

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19
Q

What is the role of IL-2 in CD4+ Th1 immunity?

A

IL-2 induces T cell proliferation.

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20
Q

What is the role of IL-3 and GM-CSF in CD4+ Th1 immunity?

A

They are both involved in inducing macrophage differentiation in the bone marrow.

21
Q

What is the role of TNF-alpha and LT-beta in CD4+ Th1 immunity?

A

They are both involved endothelium activation to induce macrophage binding and extravasation to the site of infection.

22
Q

What is the role of CCL2 in CD4+ Th1 immunity?

A

It causes macrophages to accumulate at the site of infection.

23
Q

Which cell primes CD4+ Th1 cells?

How are they primed?

Where does this occur?

A
  • Dendritic cells prime CD4+ Th1 cells by presenting peptides through MHC class 2.
  • This occurs in the lymph node and spleen.
24
Q

What is the effect of priming a CD4+ Th1 cell?

A

1 - It causes the T cell to proliferate.

2 - It causes the T cell to acquire an effector function through differentiation.

25
Q

What is the main function of a primed CD4+ Th1 cell?

A

To seek out infected macrophages that present antigens through MHC class 2, and subsequently activate the infected macrophages.

26
Q

How does CD4+ Th1-induced macrophage activation facilitate killing of pathogens?

A

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.

27
Q

Give an example of how activated macrophages differ in appearance from unactivated macrophages.

A

They are double the size of unactivated macrophages.

28
Q

How is the antigen of cytosolic bacteria presented differently from that of vacuole restricted bacteria?

A
  • 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).
29
Q

Give an example of a common mycobacterium species in cows.

A

Mycobacterium bovis.

30
Q

What proportion of the global population is latently infected with tuberculosis?

A

30%.

31
Q

List 4 characteristics of Mycobacterium tuberculosis.

A

1 - Gram positive.

2 - Bacilli morphology.

3 - Slow growing; 12-24 hours to replicate.

4 - Complex lipid envelope.

32
Q

List 3 mechanisms of tuberculosis host avoidance.

A

1 - Inhibition of phagosome fusion with lysosomes.

2 - Inhibition of ROS generation.

3 - Inhibition of nitrogen radical generation.

33
Q

List 2 enzymes involved in the inhibition of ROS generation.

A

1 - Superoxide dismutase (SOD).

2 - Catalase.

34
Q

Describe the mechanism of superoxide dismutase (SOD).

A

It catalyses the breakdown of superoxide (O2 -) into hydrogen peroxide.

35
Q

Describe the mechanism of catalase.

A

It catalyses the breakdown of hydrogen peroxide into water.

36
Q

List 4 symptoms of tuberculosis.

A

1 - Breathlessness.

2 - Chest pains.

3 - Coughing up blood.

4 - Weight loss.

37
Q

Why do some TB infections manifest as latent infections whereas others don’t?

A

If the initial host immune response is inadequate, the disease will manifest early.

*Some TB infections reactivate even after an early manifestation.

38
Q

What is the function of a granuloma?

Which cells form the granuloma?

Where are granulomas often found?

A
  • 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.
39
Q

What is caseous necrosis?

When does it form?

A
  • A mass of dead macrophages released from collapsed granulomas (looks like cheese).
  • It often forms with tuberculosis infection.
40
Q

List 5 characteristics of caseous tissue.

A

1 - Anaerobic.

2 - Low pH.

3 - Presence of cytokines.

4 - Presence of macrophages.

5 - Presence of Mycobacteria.

41
Q

List 3 cytokines found in caseous tissue.

A

1 - IFN-gamma.

2 - LT-alpha.

3 - TNF-alpha.

42
Q

How is tuberculosis transmitted?

A

Via infected sputum.

43
Q

What is the name of the vaccine for tuberculosis?

A

Bacillus Calmette-Guérin vaccine (BCG).

44
Q

How effective is the vaccine for tuberculosis?

A

75% for the most severe forms such as TB meningitis, but less effective for respiratory disease.

45
Q

From which strain of tuberculosis is the tuberculosis vaccine developed?

A

Mycobacterium bovis.

46
Q

Why should the tuberculosis vaccine not be given to patients with an immunodeficiency or are on immunosuppression?

A

Because it is a live vaccine.

47
Q

List 5 risk factors for tuberculosis infection.

A

1 - HIV infection.

2 - Malnutrition.

3 - Stress.

4 - Diabetes.

5 - Immunosuppression.

48
Q

List 2 immunodeficiency diseases.

A

1 - Severe combined immunodeficiency (SCID).

2 - Common variable immunodeficiency (CVID).

49
Q

List 3 other Mycobacterium species that infect humans.

A

1 - Mycobacterium avium.

2 - Mycobacterium kansasii.

3 - Mycobacterium marinum.

IIH (26 decks)

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