pathogenesis of viruses and host defense sk (1).pptx

pathogenesis of viruses and host defense

1. Pathogenesis of viruses and host defense Dr shahida kashif

2. Learning objective Describe transmission and portal of entry of virus Differentiate pathogenesis and immunopathogenesis Differentiate nonspecific defences and specific defences

3. INTRODUCTION The ability of viruses to cause disease can be viewed on two distinct levels: the changes that occur within individual cells. the process that takes place in the infected Patient.

4. THE INFECTED CELL There are four main effects of virus infection on the cell: No apparent morphologic or functional change Cytopathic effect. Malignant transformation. Death

5. Effect of virus on host cell 5 [email protected] Viral Infection Dea t h No M o r phologi c a l or F un ct iona l Change Cytopathic effect Malignant ( C PE ) T r an sf o rm a t io n Herpes viruses P a r a my x o - v i r u s e s Hepatitis B virus EBV

6. Cytopathic effect (CPE) : 6 Cellular changes are- Rounding of cells D isinte gration of cell s Multinucleated giant cell formation Inclusion body formation

7. Inclusion Bodies Infected cells frequently contain inclusion bodies, which are discrete areas containing viral proteins or viral particles. They have a characteristic intranuclear or intracytoplasmic location and appearance depending on the virus. examples of inclusion bodies : Negri bodies( rabies virus) Owl’s eye inclusion seen in the nucleus of cytomegalovirus.

8. Inclusion body 8 Owl’s eye inclusion seen in the nucleus of cytomegalovirus Negri bodies( rabies virus)

9. Multinucleated gaint cell Fusion of virus-infected cells produces multinucleated giant cells, which characteristically form after infection. Fusion occurs as a result of cell membrane changes, which are probably caused by the insertion of viral proteins into the membrane Example: herpesviruses and paramyxoviruses .

10. Multinucleated gaint cell 10

11. Laboratory importance of CPE: Viral detection by observing the CPE in cell culture Viral quantification by plaque assay 11

12. Laboratory importance of CPE: 12

13. Malignant change: Characterized by- Unopposed cell growth Prolonged survival Rounded, piled-up cells 13

14. Death Death of the cell is probably due to inhibition of macromolecular synthesis. Inhibition of host cell protein synthesis (first effect) Inhibition of DNA and RNA synthesis may be a secondary effect.

15. THE INFECTED PATIENT Pathogenesis in the infected patient involves transmission of the virus and its entry into the host. Replication of the virus and damage to cells spread of the virus to other cells and organs. the immune response, both as a host defense and as a contributing cause of certain diseases. persistence of the virus in some instances.

16. Stages of a typical viral infection Incubation period: Patient is asymptomatic Prodromal period: Non specific symptom Specific-illness period: Specific sign and symptoms Recovery period: Illness wanes and regaining of good health 17

17. Persistent viral infection Presence of either intact virus or a sub viral component after clinical recovery of disease Types: Chronic carrier Latent Infection 18

18. 1. Chronic-Carrier Infection: Continuous viral detection low level virus production Mild or no clinical symptoms Example: Chronic hepatitis by hepatitis B virus or hepatitis C virus infection 19

19. 20 2. Latent infection Virus persist in occult, cryptic form Viral production stops for some period Viral reactivation and disease recurrence Example: Herpes simplex virus Sensory ganglion (Latency) ( Reactivation) Blisters

20. TRANSMISSION & PORTAL OF ENTRTY Viruses are transmitted to the individual by many different routes, and their portals of entry are varied. For example, person-to-person spread occurs by transfer of respiratory secretions, saliva, blood, or semen and by fecal contamination of water or food. The transfer of blood, either by transfusion or by sharing needles during intravenous drug use, can transmit various viruses.

21. Transmission between mother and offspring is called vertical transmission . Person-to-person transmission that is not from mother to offspring is called horizontal transmission . Animal-to-human transmission can take place either directly from the bite of a reservoir host as in rabies or indirectly through the bite of an insect vector, such as a mosquito, which transfers the virus from an animal reservoir to the person. In addition, activation of a latent, nonreplicating virus to form an active, replicating virus can occur within the individual, with no transmission from an external source.

22. LOCALIZED OR DISSEMINATED INFECTIONS Most viral infections are either localized to the portal of entry or spread systemically through the body. Example: localized infection is the common cold caused by rhinoviruses, which involves only the upper respiratory tract. Influenza is localized primarily to the upper and lower respiratory tracts. Respiratory viruses have a short incubation period because they replicate directly in the mucosa.

23. Some viral infections spread systemically, not via the bloodstream, but rather by retrograde axonal flow within neurons. Four important human pathogens do this: rabies virus, herpes simplex type: herpes simplex type varicella-zoster virus

24. PATHOGENESIS & IMMUNOPATHOGENESIS The signs and symptoms of most viral diseases undoubtedly are the result of cell killing by virus-induced inhibition of macromolecular synthesis. Death of the virus-infected cells results in a loss of function and in the symptoms of disease. For example, when poliovirus kills motor neurons, paralysis of the muscles innervated by those neurons results.

25. Also, the hemorrhages caused by Ebola virus are due to the damage to the vascular endothelial cells caused by the envelope glycoprotein of the virus. T here are some diseases that are not caused by the virus damaging or killing the infected cell. For example, rotavirus-induced diarrhea is caused primarily by stimulation of the enteric nervous system.

26. Host immune response [email protected] 27 Non Specific Specific Cell mediated Antibody mediated PMN cells M ucoc illi a ry clearance Macrophage Cytotoxic T-cell NK cell Interferon IgA, IgM, IgG N eu tr a li za ti o n Opsonization Cytolysis Perforins G r anzy m e s C o m p l e m en t ac ti va ti o n

27. PERSISTENT VIRAL INFECTIONS In most viral infections, the virus does not remain in the body for a significant period after clinical recovery. However, in certain instances, the virus persists for long periods either intact or in the form of a subviral component (e.g., the genome). The mechanisms that may play a role in the persistence of viruses include:

28. Integration of a DNA provirus into host cell DNA, as occurs with retroviruses. Immune tolerance, because neutralizing antibodies are not formed. Formation of virus–antibody complexes , which remain infectious. Location within an immunologically sheltered “BE SAFE ” (e.g., the brain). Rapid antigenic variation. Spread from cell to cell without an extracellular phase, so that virus is not exposed to antibody. Immunosuppression, as in acquired immunodeficiency syndrome (AIDS).

29. CHRONIC-CARRIER INFECTIONS Some patients who have been infected with certain viruses continue to produce significant amounts of the virus for long periods. This carrier state can follow an asymptomatic infection as well as the actual disease and can itself either be asymptomatic or result in chronic illness. Important clinical examples: are chronic hepatitis,e.g hepatitis B , hepatitis C virus carriers, and neonatal rubella virus and CMV infections .

30. LATENT INFECTIONS In these infections, best illustrated by the herpesvirus group, the patient recovers from the initial infection and virus production stops. Subsequently, the symptoms may recur, accompanied by the production of virus. In herpes simplex virus infections, the virus enters the latent state in the cells of the sensory ganglia .

31. Herpes simplex virus type 1, which causes infections primarily of the eyes and face, is latent in the trigeminal ganglion, whereas herpes simplex virus type 2, which causes infections primarily of the genitals, is latent in the lumbar and sacral ganglia. Varicella-zoster virus, another member of the herpesvirus family, causes varicella (chickenpox) as its initial manifestation and then remains latent, primarily in the trigeminal or thoracic ganglion cells. It can recur in the form of the painful vesicles of zoster (shingles), usually on the face or trunk.

32. Interferon Interferons are heterogeneous group of Glycoproteins produced after viral infection Types: Alpha-Interferon Beta-Interferon Gama-Interferon 34

33. Mechanism of action Interferon acts by inducing the synthesis of three cell encoded proteins that inhibit the translation of viral mRNA with out affecting the translation of cellular mRNA 35

34. Viral vaccines Prevention of viral disease can be achieved by active immunization or passive immunization ⦿ Common types of vaccines: Live attenuated vaccine: OPV, Measles Killed viral vaccine: Influenza A & B Recombinant DNA vaccine: Hepatitis B 36

35. Advantage of live vaccine ⦿ Can induce both IgA and IgG antibodies ⦿ Long duration protection ⦿ Effective in producing herd immunity ⦿ Easy to administered 37

36. Disadvantage of live vaccine ⦿ Revert to virulence ⦿ Can not be used in pregnant and immuno-compromise person 38

37. Herd immunity Immunization of 80% of an homogenous population results in development of immunity to remaining 20% of the “Herd”. Example: OPV produce herd immunity Killed viral vaccine is less efficient in producing herd immunity 39