CONTROL OF VIRAL INFECTIONS - kau



CONTROL OF VIRAL INFECTIONS

• Nonspecific Defenses of the Host

• Specific (Immune) Natural Defenses

Humoral (Antibody mediated) immunity

Cell - mediated immunity

• Active Prophylaxis

Schedule of routine vaccinations

Vaccines used in special situations

• Passive Immunoprophylaxis

• Sanitation and Vector Control

Screening of donated blood

• Antiviral Drugs, Interferons

Nonspecific Defenses Against Viral Infections

❖ Anatomic Barriers:

skin, mucus layer, endothelium

❖ Nonspecific Inhibitors:

acid (stomach); bile salts; enzymes (lysozyme in tears)

lipids, polysaccharides, glycoproteins; inhibitors

related to viral receptors.

❖ Phagocytosis:

Possible outcome: virus destruction

virus survival in phagocytes

virus multiplication in phagocytes (e.g. in AIDS)

❖ Fever:

decreased virus multiplication

❖ Inflammation:

decreased virus multiplication

❖ Interferons:

types (alpha, beta, gamma)

production

mechanism of action

early response to infection

host specific

not specific for virus type

manufacture of recombinant interferon

antiviral, anticancer indications

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FIGURE 14-8 Antigen-specific antiviral immunity. The immune response is initiated by phagocytosis, proteolysis, and antigen presentation on macrophage lineage cells. Antigen-specific CD4 T cells are activated and release Iymphokines, which activate DTH, cytolytic T cells, and B cells. Antibody binds to virus and neutralizes or opsonizes free virus. Macrophages phagocytise virus particles and restart the cycle. Ifn, Interferon.

[pic]

FIGURE 14-6 Induction of the antiviral state by interferon-alpha or interferon-beta. Interferon is produced in response to viral infection but does not affect the initially infected cell. The interferon binds to a cell surface receptor on other cells and induces production of antiviral enzymes (antiviral state). The infection and production of double.

Summary of Antiviral Responses

INTERFERON

Interferon is induced by double-stranded RNA or inhibition of cellular protein synthesis.

Interferon initiates the antiviral state in surrounding cells.

Interferon blocks local viral replication.

Interferon initiates systemic antiviral responses.

NK CELLS

NK cells are activated by interferon-alpha and interferon- beta.

NK cells are activated by interferon-alpha and 11-12 and activate macrophages (interferon-gamma).

NK cells target and kill virus-infected cells (especially enveloped viruses).

MACROPHAGES (FAMILY OF CELLS)

Macrophages filter viral particles from blood.

Macrophages inactivate opsonized virus particles.

Macrophages present viral antigen to CD4 T cells.

T CELLS

T cells are essential for controlling enveloped and nancytolytic viral infections.

T cells recognize viral peptides presented by MHC molecules on cell surfaces.

T CELLS.—cont’d

Antigenic viral peptides (linear epitopes) can come from any viral protein (e.g., glycoproteins, nucleoprateins).

TH 1 CD4 responses are more important than TI-12 responses.

CD8 cytotoxic I cells respond to viral peptide—class 1 MHC protein complexes on the cell surface.

TH2 CD4 responses are important for the maturation of antibody response.

TH2 CD4 responses may be detrimental if they prematurely limit the THl inflammatory and cytolytic responses.

ANTIBODY

Antibody neutralizes extracellular virus:

It blocks viral attachment proteins (glycoproteins, capsid proteins).

It destabilizes viral structure.

Antibody opsonizes virus for phogocytosis.

Antibody promotes killing of target cell by the complement cascade and antibody-dependent cellular cytotoxicity.

Antibody resolves lytic viral infections.

Antibody blocks viremic spread to target tissue.

1gM is an indicator of recent or current infection.

lgG is more effective than 1gM.

Secretary lgA is important for protecting mucosal surfaces.

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FIGURE 49-4 Induction of beta interferon, alpha interferon, and gamma interferon, respectively, by foreign nucleic acids, foreign cells, and foreign antigens.

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FIGURE 49-3 Production of virus, interferon, and antibody during experimental infection of humans with influenza wild-type virus. Nonspecific defenses include anatomic barriers, inhibitors, phagocytosis, fever, inflammation, and IFN. Specific defenses include antibody and cell-mediated immunity. Data from a study by B. Murphy et al, National Institutes of Health (personal communication).

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EdwudJamer (1749-182S)

The English physician Edward Jenner is regarded as the founder of modern vaccination, but he was by no means the tint to try the technique. The ancient practice of 'variolation' goes back to tenth century China. and arrive Europe in the early 18th century by way of Turkey. The technique involved the inoculation of children with dried material from healed scabs of mild smallpox cases, and was a striking foretaste of the principles of modem attenuated viral vaccines. This practice was, however, both inconsistent and dangerous, and Jenner's innovation was to show that a much safer and more reliable protection could be obtained by deliberate inoculation with cowpox. (vaccinia) virus. Milkmaids exposed to this infection were traditionally known to be resistant to smallpox and so retain their smooth complexions. In 1796, Jenner tested his theory by inoculating eight-year-old James Phipps with liquid from a cowpox pustule on the hand of Sarah Nelmes. Subsequent inoculation of the boy with smallpox produced no disease. (Note that such an experiment would today be considered extremely unethical!). Jenner's book “An inquiry into the causes and effects of variolae Vaccinae, a disease discovered in some of the Western countries of England particularly Cloucestershire, and known by the name Cow Pox.” published in 1798, is a classic of its kind lively, stylish and well-argued. Although greeted with skepticism at first, Jenner's ideas soon became accepted and he went on to inocuate thousands of patient, in a shed in the garden of his house at Berkeley,

Gloucestershire. He ultimately achieved world fame, though his fellowship of the Royal Society was conferred for a quite different piece of work on the nesting habits of the cuckoo! His house at Berkeley is now preserved as a museum, and is used for small symposia by the British Society of Immunology.

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Fig. 13.6. The global eradication of smallpox by the World Health Organization. (Taken with permission from Fenner. F. et al. (1988). Smallpox and its eradication. World Health Organization, Geneva.)

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Control of Viral Infections

A. Nonspecific Defense Mechanisms

1. List several nonspecific defenses of the body against viral infections (e.g. barriers, acid, fever, phagocytosis, etc.)

2. Can cytokines, interferons, NK cells be considered nonspecific

defenses against viruses? (p. 131)

3. Review the properties of interferons (table 14-3) and their mode of action (Fig. 14-7, Fig. 14-8, Box 14-7)

B. Specific Antiviral Immune Response

1. Which cells are involved in the antigen-specific immune response? What function does each cell play? (Fig. 14-6)

2. What roles are played by the humoral and cell-medicated responses? (p. 133, Box 14-8)

C. Viral Vaccines

1. List the main viral vaccines available for public use. (table 15-4)

2. Which vaccines are used in routine immunization (handout)

3. What is the difference between attenuated, inactivated, and subunit vaccines?

4. How successful have viral vaccines been?

5. Is passive immunization (i.e. administration of inimunoglobulins) useful in certain situations?

6. In which situations has vaccination been impractical?

D. Antiviral Drugs

1. Why are antiviral drugs needed

2. List the names of several antiviral drugs and the viruses against which they are used. (table 47-2)

3. Under which categories are these drugs classified? (p.444)

4. Explainthemechanismofactionof: (table 47-1)

- amantadine - Acyclovir - Saquinavir - Oselatinivir – Amtisense oligonucleotides

5. How is interferon made for use as an antiviral drug?

Against which viruses is it used?

6. Discuss the principle of highly active antiretroviral therapy

(HAART) (Box 61-4)

BOX 61-4. Potential Antiviral Therapies for HIV Infection

Nucleoside Analogue R verse Transcriptase Inhibitors

Azidothymidine (AZT) (Zidovudine)

Dideoxycytidine (ddC) (Zalcitabine)

Dideoxyinosine (ddI) (Didanosine)

d4T (Stavudine)

3TC (Lamiyudine)

ABC (Abacavir)

Non-nucIeoside Reverse Transcriptase Inhibitors

Nevirapine (Viramune)

Delavirdine (Rescriptor)

Efavirenz (Sustiva)

Pt(jtea e Inhibitors'

. , .

, . .

Saquinavir (Invir'aselF ortovase)

ill tonavii (N oryir) Indinavir (Cfixivan)' Nelfinavir {Viracipt) Amprenavir (Agenerase)

Highly ActiveAntip: troviral Therapy (HAART)

(Combination».' ,. . ,

Indinavirl AZT /3TC

Ritqnavirl AZT/3TC N elfinavir / AZT/3TC' Nevirapine/AZT I ddI

Common Immunization Schedule

for GCC Countries

_____ we.f. January 2008

|Age at vaccination |Adopted schedule by GCC states |

|At birth |BCG |

| |HBV-1 |

|2 months |PENTA-1 (HBV-2, DIP-], Hib-]) IPv—1 |

|4 months |PENTA—2 (HBV-3, DTP-2, Hib-2) OPV-2 |

|6 months |PENTA—3 (HBV-4, DTP-3, Hib- 3J OPV-3 |

|12 months |MMR-1 |

| |OPV—4 |

|18 months |MMR—2 (]8m -6y) |

| |DTP--4 |

| |OPV-5 |

|4-6 years |OPV—6 DTP—5 |

|12 years |dT—1 |

|15 to >65 years |dl (single dose) every 10 years |

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