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Block 6 - week 4 > Pathogenesis - Aucoin > Flashcards

Pathogenesis - Aucoin Flashcards

1
Q

What are some cellular responses to viral infection?

A
  1. no effect - ie if virus isn’t efficient. this is also called a subclinical infection
  2. cytopathology - ie cell death or inclusion body formation
  3. hyperplasia - ie a wart
  4. cancer
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2
Q

Name some principles of viral disease.

A
  1. many viral infections are subclinical - infection with no clinical illness.
  2. the same diseases may be produced by a variety of viruses.
  3. the same virus may produce a variety of diseases.
  4. the disease produced bears no relationship to viral morphology.
  5. pathology is determined by host and viral factors and is influenced by genetics.
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3
Q

What is pathogenesis?

A

The study of the origin and development of disease.

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4
Q

What is disease pathogenies?

A

Events during infection that results in disease manifestation in the host.

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5
Q

When is a virus pathogenic?

A

When it is capable of infecting a host and causing signs of disease.

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6
Q

Why are some virus strains more virulent than others?

A

They commonly produce more severe disease.

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7
Q

What are the steps in viral pathogenesis?

A
  1. viral entry into host
  2. primary site of viral replication
  3. viral spread
  4. cellular injury
  5. host immune response
  6. viral clearance or persistent infection
  7. viral shedding
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8
Q

What are some important features of acute viral disease?

A
  1. Site of pathology - at entry or at a distant site
  2. incubation period - short or long
  3. Viremia - does it travel by blood, does it cause local disease or systemic disease
  4. duration of immunity - for local infections it may be short, for systemic infections it can be lifelong
  5. Role of IgA in the infection - more important for local infections of mucosal tissues
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9
Q

Name some methods of viral entry.

A
  1. virus may attach and enter cells through skin, respiratory tract, GI tract, GU tract or conjunctiva
  2. may enter via needle, transfusion, or insect vector.
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10
Q

What is the most common route of entry for a virus?

A

The respiratory tract.

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11
Q

Describe viral spread and tropism.

A

The virus may cause local disease at the site of initial entry or it may spread within the host - usually to lymph nodes then into blood stream. Tropism refers to the specificity of cell or tissue type that the virus infects. Replication increases a lot when virus reaches tropic tissue or organ.

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12
Q

What is viremia?

A

Presence of virus in the blood. Virus may be free or associated with a specific cell type.

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13
Q

What is the primary determinant of the type of disease or pattern of systemic illness caused?

A

Tropism. The specificity of the virus for a certain tissue or organ.

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14
Q

What determines tropism?

A

The cell must have receptors that bind to the VAP’s present on that specific virus. These receptors have separate host cell functions but also have an affinity for specific VAP’s.Sometimes a virus may enter but fails to produce an sufficient amount of viral proteins or cell may lack necessary cellular transcription factors.

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15
Q

Describe some characteristics of the host immune response to viral infection.

A
  1. Mononuclear cells and lymphocytes are activated and respond to sites of infection.
  2. Interferons are produced.
  3. Virally infected cells may be lysed by cytotoxic T cells resulting from recognition of viral polypeptides on the cell surface.
  4. Neutralizing antibody directed against capsid or glycoproteins blocks the viral infection of more cells.
  5. Secretory IgA antibody protects against infection by viruses through the respiratory or GI tract - called mucosal immunity.
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16
Q

Describe how interferons protect the host.

A
  1. Produced as part of the innate immune response so production is fast - within hours.
  2. INF’s are host encoded proteins that are part of the cytokine family - they lead to the inhibition of viral replication.
  3. Gamma interferon is especially critical for immunity against viruses.
  4. INF-y is an important activator of macrophages and it induces MHC expression.
  5. Interferons are secreted by different types of cells but especially by dendritic cells.
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17
Q

What is a strong inducer for production of INF’s?

A

Viral infection. ssRNA viruses are a stronger inducer than DNA viruses. INF is also induced by double stranded RNA and bacterial endotoxin.

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18
Q

What induces the dendritic cell to secrete INF?

A

The cell has toll like receptors that recognize PAMP’s.

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19
Q

How does INF work?

A
  1. induces the synthesis of other proteins that inhibit viral replication.
  2. bind to interferon receptor, which activates transcription factors that translocate into the nucleus to mediate interferon-inducible genes.
  3. does not protect the virus infected cell that produces it and is not itself the antiviral agent.
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20
Q

Is interferon itself an antiviral agent?

A

No, it induces the synthesis of antiviral genes.

21
Q

What protein products come from interferon-inducible genes?

A
  1. Protein kinase R (PKR) - a dsRNA dependent protein kinase which phosphorylates and inactivates cellular initiation factor eIF-2. eIF-2 prevents both cellular and viral protein synthesis.
  2. RNAse L - a ribonuclease which destroys all RNA in the cell, both viral and cellular, once activated.
22
Q

Name some mechanisms by which viruses evade host immune systems.

A
  1. may encode immunomodulatory proteins that inhibit MHC function - adenoviruses and heresviruses work this way.
  2. may inhibit cytokine activity - poxvirus and measles virus work this way.
  3. may mutate and change antigenic sites of vision proteins - HIV and influenza work this way.
23
Q

What is an acute infection?

A

Acute infection occurs when virus first infects a host, most infections are self-limiting.

24
Q

what kind of infection gives no signs of illness.

A

A subclinical infection.

25
Q

Describe chronic or persisten infections.

A

These occur when replicating virus can be continuously detected at low levels.

26
Q

What is a latent infection?

A

An infection in which the virus persists in a hidden or inactive form and no new virus is produced.

27
Q

Give an example of a latent infection.

A
  1. Herpes simplex 1 - after mild pharyngitis or stomatitis, the herpes virus travels down nerves to infect cells in the DRG. Here they remain inactive until a precipitating factor such as too much sunlight or stress causes them to become activated and they travel down the nerve and cause fever blisters.
  2. Herpes simplex 2 is exactly the same except for it begins with the varicella virus and causes shingles when activated.
28
Q

Give an example of a viral CNS infection.

A
  1. Poliovirus enters the body and multiplies at primary site of infection.
  2. the virus spreads systemically via blood stream.
  3. virus spreads to the CNS either via blood or via peripheral nerve fibers.
  4. in poliomyelitis the virus enters by way of the alimentary tract and multiplies in those tissues.
  5. spread of poliomyelitis can be prevented by antibodies from vaccination.
29
Q

How can a virus spread to the CNS?

A
  1. viral replication in endothelial cells of cerebral vessels
  2. taken up at sensory nerve endings
30
Q

What are 2 types of diseases caused by viral infection of the CNS?

A
  1. encephalitis
  2. meningitis
    Pathologic reaction to viral infection may include CNS cell necrosis, inflammation, and phagocytosis by glial cells.
31
Q

Describe acute viral respiratory infections.

A
  1. most common viral route of infection is via the respiratory tract in aerosolized droplets or saliva.
  2. infection may occur despite host defenses.
  3. many infection remain localized to the lung but some such as chicken pox, measles and rubella spread systemically.
32
Q

Name some host immune defenses against viral respiratory infections.

A
  1. mucus
  2. ciliary action
  3. lymphoid cells
  4. alveolar macrophages
  5. secretory IgA
33
Q

Describe GI viral infections.

A
  1. virus spread by fecal-oral route or through poorly cooked or contaminated food.
  2. often GI infections caused by naked capsule viruses that are able to withstand harsh elements such as acid, bile salts and proteolytic enzymes.
  3. rotaviruses and norwalk viruses are a major cause of gastroenteritis.
  4. acute gastroenteritis is a short term disease ranging from mild, watery diarrhea to severe febrile illness with vomiting and diarrhea.
34
Q

Describe congenital viral infections.

A
  1. most maternal viral infection do not result in viremia and fetal involvement.
  2. if a virus crosses the placenta and infection occurs inn utero, serious damage could result.
  3. rubella and cytomegalovirus are presently the primary agents responsible for congenital defects in newborns.
  4. congenital rubella syndrome or CRS causes deafness, eye abnormalities and congenital heart disease.
  5. congenital HCMV is the leading infectious cause of deafness, learning disabilities and mental retardation in children.
35
Q

How are viral infections treated?

A
  1. prevention via vaccine where available.
  2. antiviral chemotherapy - viruses are obligate intracellular parasites so antiviral agents must be capable of inhibiting viral and not cellular functions. Viruses such as HIV that have alot of serotypes and mutate quickly are hard to treat.
36
Q

What stages of a viral infection are most vulnerable to antiviral agents?

A
  1. attachment of virus to host cell
  2. uncoating of the viral genome
  3. viral nucleic acid synthesis
  4. translation of viral proteins
  5. release of progeny virus
37
Q

Describe some types of antiviral agents.

A
  1. nucleoside analog - these inhibit viral polymerases by incorporating a terminal nucleoside.
  2. reverse transcriptase inhibitor - binds to reverse transcriptase to disrupt enzymes catalytic site.
  3. protease inhibitor - inhibits the viral protease that is required at the late stage of the HIV replicative cycle.
  4. fusion inhibitor - blocks viral and cellular membrane fusion step involved in entry of HIV into cells.
38
Q

How do viral vaccines work?

A

Viral vaccines utilize the immune response of the host to prevent viral disease. They induce the immune system to make a response against specific antigens on the surface of the virus such as viral glycoproteins.

39
Q

Describe two types of viral vaccines.

A
  1. subunit vaccine - a piece of the virus not the whole virus is used to initiate an immune response in the host to provide immunity to later infections.
  2. attenuated virus vaccine - a live virus that is modified so that it is not as pathogenic as the wild-type is used to initiate an immune response to provide immunity in later infections. Also, they induce antibody response and resistance at the portal of entry which is important to help stop spread.
40
Q

What type of immunity is important for resistance to infection by viruses that replicate in mucosal membranes?

A

Mucosal immunity - IgA antibodies are important. Example is influenza.

41
Q

What type of immunity is important for resistance to infections by viruses that have a viremic mode of spread?

A

Serum antibodies - IgG antibodies are important. Examples are polio, hepatitis A and B and Varicella.

42
Q

What type of immunity is important against systemic infections?

A

Cell mediated immunity to control latent state. Example is herpesviruses.

43
Q

What type of virus can complicate the development of an effective vaccine?

A

Multiple viral serotypes such as with rhinoviruses and rapidly mutating viruses such as HIV.

44
Q

What are some advantages of live attenuated vaccines?

A
  1. no need for adjutants
  2. only need to give one dose
  3. get a stronger immune response
  4. mucosal immunity produced
  5. duration of immunity is longer
  6. no chance of residual virulent virus in vaccine.
45
Q

What are some disadvantages of live attenuated vaccines?

A
  1. possible interference by other viruses in host
  2. low stability at room temperature
  3. may still shed virus
  4. possible chance of reversion of virus to virulent type
46
Q

What are some advantages of a killed vaccine?

A
  1. no chance of reversion to virulent state or shedding of virus
  2. no chance of interference by other viruses in the host
  3. high stability at room temp
47
Q

What are some disadvantages of a killed vaccine?

A
  1. must give multiple doses
  2. need adjuvent
  3. duration of immunity is shorter and response is weaker
  4. does not produce mucosal immunity
  5. possible that there is residual virulent virus in the vaccine
48
Q

Describe the proper use of present vaccines.

A
  1. must be administered in the proper dosage to susceptible individual to protect populations.
  2. live virus vaccines to multiple viruses can be given in combination without reduction in immunity. ie - MMR

Block 6 - week 4 (9 decks)

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