dr. shatha s.jumaah/lecturer - lecture notes - tiu
TRANSCRIPT
Dr. Shatha S.Jumaah/Lecturer _____________________________________________ Genetics/Practical – 4th Stage /1st Semester
[email protected] https://tiu.edu.iq/
2020 - 2021
TIU - Faculty of Science Medical Analysis Department
1- List the general steps of pathogenesis and clinical course of viral infection.
2- Differentiate between local & systemic acute viral infection.
3- Describe the mechanisms of cell tropism, types of cell injury during viral
infection .
4-State the immunopathogenesis induced by viral infection.
5- Describe the mechanisms by which virus can escape from the host.
6- Explain the mechanisms of different types of persistent viral infections.
7- Differentiate between conventional and non-conventional viral infection.
Virus that can enter to the host, produced virus- host cell interaction, causing the sign and symptoms of a disease.
1. Implantation of virus at the portal of entry. 2. Local replication. 3. Spread to target organs (disease sites). 4. Spread to sites of shedding of virus into the environment.
1. Accessibility of virus to tissue. 2. Cell susceptibility to virus multiplication. 3. Virus susceptibility to host defenses.
Requirements to ensure successful infection in an
individual host
Sufficient virus must be available to
initiate infection
Cells at the site of infection
must be accessible,
susceptible, and permissive for
the virus
Local host anti-viral defense
systems must be absent or
initially ineffective.
1-Viral entry &Mode of transmission
2-Primary viral replication
3-Viral spread
4-Cellular injury
5-Cell &tissue tropisms
6-Host immune response
7-Viral clearance & establishment of persistent infection
8-Viral shedding
Through the following systems• -Respiratory Tract
• -Gastrointestinal Tract most common routes of viral entry
• -Skin
• -Urogenital Tract
• -Conjunctiva
• -blood born: by needles, insect vectors, blood Transfusion
person- to -person (infl.v.,herpes v.,HIV).
from mother to offspring ( rubella,HIV,CMV,Hepatitis B &C,parvo B19).
from animal to man ( rabies v.) – No transmission: due to reactivation of a latent, non-replicating virus can occurs within the individual infection (HSV1, HSV2 &CMV)
virus replicate at primary site locally as: influenza v. & rota v.)
these viruses spread locally over the epithelial surfaces, and there is no necessity for further systemic spread, no invasion to under lying tissues nor spread to distant site.
viruses that produce systemic manifestation distant from the site
of entry as: polio v.& Measles v.
The place of primary replication is where the virus replicates after
gaining initial entry into the host. This frequently determines whether the infection will be localized at the site of entry or spread to become a systemic infection.
Apart from direct cell-to-cell contact, the virus may spread via the blood
stream and the CNS.
takes place at susceptible organs/tissues following systemic spread.
Changes in the cell
appearance
Multinucleated Giant cells
Inclusion bodies
uncontrolled cell growth &prolonged survival (oncogenic v.)
due to inhibition of macromolecular synthesis either by inhibition of host cell protein synthesis or inhibition of DNA and RNA Synthesis.
leads to impairment of specialized functions of cells such as a loss of hormone production.
Incubation Period(IP)
Prodromal period
Specific illness period
Recovery period
1. Incubation Period( IP): usually asymptomatic, Necessary for clinical diagnosis, outbreak tracing, infection control, Can be:-
a. Short: less than a week (RESP, ARBOVIRUSES)
b. Medium: 1-3 weeks (MMR, polio, SARS)
c. Long: weeks-months (HEPATITIS, RABIES)
d. Very long: years (SSPE,PRIONS, PML )
2. Prodromal period: associated with non- specific symptoms
3. Specific illness period: characterized by sign & symptoms of the disease.
4. Recovery period: illness declines & patient regains good health.
cell killing e.g.
Diversion of the cell's energy
Shutoff of cell macromolecular synthesis
Competition of viral promoters & transcriptional enhancers for cellular transcriptional factors such as RNA polymerases, and inhibition of the interferon defense mechanism
Competition of viral mRNA for cellular ribosomes
Direct effect may result from
Indirect effect: (immunological attack)
1) Integration of the viral genome
2) Induction of mutations in the host genome
3) Inflammation
4) Host immune response.
In general, cellular immunity plays the major role in clearing virus infection whereas humoral immunity protects against reinfection.
Enhanced viral injury could be due to one or a mixture of the following mechanisms:-
Cytokines produced by
rota
Cytotoxic T-cell
Immune- mediated
pathogenesis
Complement
Infected enterocytes that stimulate the enteric neurons resulting in excess fluid and electrolytes secretion into the bowel lumen …..causing diarrhea .
Increased secondary response to cytotoxic T-cell are involved in the pathogenesis of hepatitis A,B &C (not causing CPE ),damage is due to recognition of viral Ag by
cytotoxic T-cell. Measles v. produce rash, cytotoxic T cell attacks infected vascular endothelial cell of skin.
1. Immune complex deposition in organs like skin, brain or kidney (rubella, measles) 2. (virus-antibody complement complex) deposited in various tissues e.g. (HBV, Parvo
B19; causing arthritis), and (RSV) causing pneumonia in infant due to maternal IgG-viral Ags complex.
Complement mediated cell lysis .
viral proteins block host immune mediators (IL1 /TNF)
2-Reduce the expression of class I MHC proteins (HIV/Cytomegalovirus)
3- Inhibit complement (HSV).
4-Virokines: some viruses synthesized RNAs that block phosphorylation
of initiation factor (elf-2), so that they reduce the ability of interferon to
block viral protein replication. (HIV/ Epstein Barr/ adeno v.)
5- Multiple antigenic types; viruses with multiple serotypes (rhino v.
more than 100 serotypes
Hepatitis C Virus: more than 6 serotypes.
The majority of viral infections are cleared but certain viruses may cause persistent infections. There are 2 types of chronic persistent infections.
Some time, the virus persists for long periods either intact or in the form of a subviral component (genome).
1- Integration of a DNA provirus into host cell DNA e.g.:- retroviruses
2- Immune tolerance: causing a reduced response to an antigen (no neutralization antibodies ), may be due to genetic factors, pre-natal infection, molecular mimicry
3-Virus –antibody complexes formation: which remain infectious
4- Location in an immunologically sheltered organ(restricted gene expression) e.g. brain .
5- Rapid antigenic variations
6- Spread from cell to cell without extra cellular phase.
7- Immunosupression direct infection of the cells of the immune system
itself e.g. Herpes viruses, Retroviruses (HIV) - often resulting in immunosuppression.
are those in which replicating virus can be continuously detected, often at low levels; mild or no clinical symptoms may be evident (the viral shedding continue for long period (as in chronic HBV or HCV or neonatal rubella &CMV).
the virus persists in an occult (hidden or cryptic) form most of the time when no new virus is produced. There will be intermittent flare-ups of clinical disease; infectious virus can be recovered during flare-ups. e.g.HSV; this virus enters a latent state in the cell of sensory ganglia once it's activated by a stress factors, recurrence of infection will occur.
Subacute seclerosing pan encephalitis (SSPE) which follows several years after
measles v. infection. **progressive multifocal leukoencephalopathy (PML), which
caused by JC-virus, a papova v., disease occurs primary in patient who have
lymphomas or immune compromised patients.
Non-Conventional viruses that causing (transmissible spongioform encephalpathies )
In human: Creutzfelds-Jacob disease /Kuru .
In animal: Mad -cow disease/ Scrapie -sheep
are Infectious particles that are composed solely of protein, no detectable nucleic acid E/M: revealed filaments. It's very resistant to U/V, heat, formaldehyde, nuclease but can be only inactivated by hypochlorite, sodium hydroxide and autoclave.
Differences between Prions & conventional viral infection
conventional prions Features
Yes No particle containing nucleic acid
v. gene Cellular gene particle containing protein Encoded by
Yes No inactivated by U/v or heat
icosohedral/helical filamentous(amyliod) E/M appearance
Yes No Ab production
Yes No Induce inflammation
Thanks for your
attention
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