Chapter 17 Parasite survival strategies and persistent infections

Question 1

What are six ways that microorganisms avoid phagocytosis?

Answer 1

1. release toxin
2. prevent opsonization (produce protein which prevents interaction between opsonizing antibody and phagocyte
3. prevents contact with phagocyte (due to capsule)
4. inhibit phagolysosome fusion
5. escape from phagolysosome into the cytoplasm and replicate within the phagocyte
6. resist killing by producing antioxidants

Question 2

How does Protein A of S. aureus promote suppression?

Answer 2

Staphylococcus aureusProtein A
Promotes Immune Suppression by binding to Fc region of IgG (remember that usually the antibody binds to the antigen at the Fab region

Question 3

How does live Mycobacterium tuberculosis interfere with phagosome maturation?

Answer 3

Live M. tuberculosis blocks maturation of phagocyte, which inhibits acidification and fusion with lysosome

Question 4

How does Listeria monocytogenes avoid phagocytosis?

Answer 4

produces hemolysin called listeriolysin O and phospholipases A and B. After a bacterium is taken up by a phagocyte, the phagosome has a pH of 5.9 to 6.5. Listeriolysin O is selectively activated within the acidic (pH 5.5) phagosomes. The hemolysin and the phospholipases B allow escape of the bacterium into the cytosol, where it can grow intracellularly.

Question 5

What helps S. aureus resist phagolysosome content?

Answer 5

superoxide dismutase and catalase together protect against ROS

Question 6

What is one way in which bacteria that infect the respiratory system evade innate defenses?

Answer 6

acutely impair mucociliary function

Question 7

Microorganisms can evade innate immunity by interfering with the activation of complement. What are six ways that they do so?

Answer 7

1. outer capsule prevents complement activation
2. outer surface proteins prevent phagocyte complement receptors from binding to C3b
3. surface structures can be expressed that divert attachment of MAC from cell membrane
4. membrane-bound enzyme can degrade fixed complement or cause it to be shed
5. complement inhibitors can be captured onto the surface
6. direct inhibition of C3 and C5 convertases

Question 8

How does Streptococcus pneumoniae prevent contact with the phagocyte?

Answer 8

capsule

Question 9

How does Listeria monocytogenes escape from the phagosome into the cytoplasm?

Answer 9

Produces hemolysin called listeriolysin O which is selectively activated at acidic pH (like that of the phagosome). It punches a hole in the phagolysosome membrane, and along with phospholipase B allows it to escape into the cytosol

Question 10

What molecule does bacteria make to scavenge iron?

Answer 10

siderophores

Question 11

Describe the host-pathogen “tug-of-war” for iron

Answer 11

Bacteria secrete siderophores to scavenge iron. In response, the host cell defensively sequesters labile and complexes siderophores, via lactoferrin and siderocalin (Lcn2). Stealth siderophores have features that render them incompatible to siderocalin binding.

Question 12

How do bacterial pathogens acquire iron?

Answer 12

Bacterial pathogens can acquire iron through receptor-mediated recognition of transferrin, lactoferrin, hemopexin, hemoglobin, or hemoglobin–haptoglobin complexes. Alternatively, secreted siderophores can remove iron from transferrin, lactoferrin, or ferritin, whereupon siderophore–iron complexes are recognized by cognate receptors at the bacterial surface. Analogously, secreted hemophores can remove heme from hemoglobin or hemopexin and deliver heme to bacterial cells through binding with hemophore receptors.
Siderophore-mediated iron acquisition is inhibited by the innate immune protein siderocalin, which binds siderophores and prevents receptor recognition. This host defense is circumvented by stealth siderophores

Question 13

What are some general strategies that pathogens use to evade innate non-adaptive immune responses?

Answer 13

1. avoid being killed by phagocytes
2. interfere with ciliary action
3. interfere with activation of complement
4. produce iron-binding molecules
5. block type I interferons
6. interfere with Toll-like receptor signaling pathway

Question 14

How does HBV use p22 protein to evade innate defenses?

Answer 14

p22 binds to Kalpha1 and blocks translocation of pSTAT1 (interferon-stimulated gene), which translocates to the nucleus upon binding Kalpha1 the nucleus, thus blocking gene transcription

Question 15

What are two generals strategies that pathogens use to evade or interfere with adaptive immune defense?

Answer 15

1. The polysaccharide capsule of bacteria prevents non-immune contact between phagocytes and the bacterial cell wall (quickly recognized as foreign by B-cell surface receptors->Ab formed->opsonization and phagocytosis)
2. many microorganisms including bacteria and fungi can resist intracellular destruction by macrophages (as long as peptides are not present on the cell surface by MHC, otherwise Th produce macrophage-activating cytokines like IFM-gamma, and CTL kill infected cell.

Question 16

Why are viruses able to impede immune defenses?

Answer 16

• Their invasion of tissues and cells is often ‘silent’. Unlike most bacteria, they do not form toxins, and as long as they do not cause extensive cell destruction there is no sign of illness until the onset of immune and inflammatory responses, sometimes several weeks after infection, as occurs in hepatitis B virus and EBV infections.
• Viruses such as rubella virus, human papillomaviruses, hepatitis B virus and EBV can infect cells for long periods without adverse effects on cell viability.

Question 17

What is the key to a pathogen being able to persist inside a host that makes the persistence worthwhile for the pathogen?

Answer 17

Shedding (e.g. Typhoid Mary)

Question 18

How does SARS coronavirus conceal its antigens?

Answer 18

Coronaviruses (SARS-CoV) display their proteins on intracellular vacuoles and bud into these vacuoles.
Thus, viral molecules are never displayed on the cell surface.

Question 19

How can colonizing privileged sites keep the pathogen out of reach of circulating lymphocytes?

Answer 19

The vast numbers of pathogens that colonize the skin and the intestinal lumen, together with those that are shed directly into external secretions, are effectively out of reach of circulating lymphocytes. They are exposed to secretory antibodies, which although able to bind to the microbe (e.g. influenza virus) and render it less infectious, are generally unable to kill the pathogen or control its replication in or on the epithelial surface (Figs 17.3 and 17.4). A local inflammatory response, however, can enhance host defenses

Question 20

What are some possible methods of immune modluation for pathogens to evade adaptive host defenses?

Answer 20

• infection during early embryonic life—Immune Tolerance
• the production of large quantities of the microbial antigen or of antigen–antibody complexes—Depressed T-cells
• upsetting the balance between cell and antibody-mediated immune responses – or between T-helper cell (Th) 1 and 2 responses—promotes survival of pathogen
• inducing regulatory T cells or molecules that down-regulate protective immunity

Question 21

What is the cause of pandemics as it pertains to influenza?

Answer 21

Pandemics can arise when there is antigenic shift with reassortment of genes

Question 22

What is the effect on infection by a microbe with ‘superantigen’?

Answer 22

some microbial toxins will induce the proliferation of families of T cells resulting in activation of much larger number of cells than is seen with antigens. This leads to excessive release of cytokines (cytokine storm) and severe illness

Question 23

What are three possible mechanisms by which staphylococcal toxins may interfere with immune defenses?

Answer 23

• excessive local liberation of cytokines by activated cells in a ‘cytokine storm’
• killing of T cells or other immune cells
• diversion of T cells of all specificities into immunologically unproductive activity by polyclonal activation.

Question 24

What are some general mechanisms of immune evasion?

Answer 24

• concealing parasite antigens from the host (staying inside host cells, infecting ‘privileged sites’)
• changing parasite antigens, either in the infected individual (e.g. trypanosomiasis) or during spread through the host population (e.g. influenza)
• direct action on immune cells (e.g. HIV on CD4+ T cells) or on immune signalling systems (e.g. production of fake cytokine molecules)

Question 25

What does adenovirus use to avoid antigen display to evade adaptive host defenses?

Answer 25

One of the adenoviral proteins (E19) combines with class I MHC molecules and prevents their passage to the cell surface so that infected cells are not recognized by cytotoxic T cells.

Question 26

Which pathogens evade the adaptive host defense through production of Fc receptors?

Answer 26

staphylococci, HSV, varicella-zoster virus, and CMV