WK 2- Viral Pathogenesis Flashcards
What are the most common modes of transmission of a virus- give examples of what virus is transmitted this way
- Inhalation of droplets e.g. rhino, flu
- Ingestion of contaminated food or water e.g. HAV, Norovirus
- Direct transfer from other infected hosts e.g. HIV, HBV (ie. Through body fluids)
- Congenital spread e.g. CMV, Rubella
- Via bite of a vector e.g. dengue, RRV
What is viral tropism
A particular virus will usually only infect one or a restricted range of host species
-This is due to the ability of the virus particle to attach to the host cell via a specific receptor
→e.g. influenza attaches by its haemagglutinin to a glycoprotein (sialic acid) on cells of the respiratory tract epithelium→ the receptors need to be exactly the same to enter the cell
What are the 7 steps in infection of a host cell
- Entry→ skin, mucous membranes, respiratory tract, GIT, genitourinary tract
- Attachment→ tropism
- Penetration → fusion of cell membrane and virus membrane or uptake by phagosome
- Uncoating→ shedding of genetic material
- Replication→ of nucleic acid
- Assembly→ of viral particles
- Release→ can be through rupture and lysis of cell
What is immunopathogenesis
In some cases the immune response to the viral infection may be the cause of the disease–> eg: Increased secondary response to Tc cells e.g. HBV
- Immune-mediated cell lysis
- Immune enhancement e.g. DHF, HIV
- Deposition of immune complexes e.g. rash of measles and rubella
What are the 4 potential outcomes of an acute infection
- Complete recovery with no lasting effects
- Recovery with long-term effects
- Progression to chronic infection
- Death
What are the 5 potential outcomes of a chronic infeciton
- Lifelong subclinical infection e.g. CMV, EBV
- Long silent period before disease e.g. HIV, SSPE
- Reactivation to cause acute disease e.g. HSV, VZV
- Chronic disease with relapses and exacerbations e.g. HBV, HCV
- Malignancies e.g. EBV, HTLV-1, HPV, HBV, HCV, HHV-8
What is a persistant infection
-Virus continues to replicate at very low levels e.g. HIV, HBV, CMV, EBV→ pt may not be aware they are infected-> facilitates spread
What is a latent infection
-Virus remains quiescent following primary infection & replication doesn’t occur until triggered e.g. HSV, VZV (ie. Triggered when patient becomes immunocompromised)
What are the 6 ways in which viral replication/survival can persist in a host
- Antigenic variation
- Immune tolerance
- Restricted gene expression
- Immune response modulation by virus
- Infection of immunoprivileged sites
- Direct infection of immune cells
Does HIV cause significant cell damage
No- because it buds from the cell and does not cause cell lysis- Rhinovirus causes cell lysis leading to cell death/fever
What is a prion
Prions are NOT viruses, they are proteinaceous infectious particles→ they are a form of a normal protein found in humans in the CNS but something triggers the protein to change conformation and causes production of infective aggregates and altered function
How do prions cause disease
They form infective aggregates and plaques which accumulate in the CNS and cause degeneration-> they do not elicit and immune or inflamm reaction and have a slow replication rate
How are prions destroyed
Prions are highly resistant to heat, chemical agents and irradiation→ unable to be killed so difficult to treat patients-> must use disposable equipment
What diseases are caused by prions
Spongiform encephalopathies
- Kuru→ Fatal neurologic disease in PNG, no longer seen
- CJD (Creutzfeldt-Jakob disease)→ Rare chronic encephalopathy, occurs world wide, small amount of cases familial with mutated prion protein gene
- GSS (Gerstmann-Straussler-Scheinker)
- FFI (Fatal familial insomnia)
What is are the 3 major types of parasites
protozoa, arthropods and helminths
How are protozoa most commonly acquired
Most acquired through ingestion of contaminated food or water, or via insect vectors (ie. Malaria) & occasionally via vertical transmission (toxic plasmosis)
What is the pathogenesis of protozoa
- Can infect all major tissues & organs of humans and live both outside cells (extracelluar parasites) and within cells (intracellular parasites)
- most important protozoa disease is malaria
What are some mechanisms that protozoa use to evade the immune system
→Extracellular parasites evade immune recognition→ Eg. Malaria and Trypanasomes use antigenic variation (change protein on their surface so that the body cannot make Ab), amoebae consume complement
→Intracellular parasites are protected from the host immune response (due to being inside cell)
What are helminths
Parasitic worms including: Tapeworms (cestodes- large but relatively harmless), Flukes (trematodes), Roundworms (nematodes)
What type of helminth has suckers and hooks and which do not
Tapeworms & flukes have flattened bodies with suckers &/or hooks that allows them to attach to the host
- Roundworms have long, worm-like bodies & usually don’t have suckers or hooks
How are helminths transmitted
Ingestions of eggs of larvae (faecal oral route ie. Pinworm, or ingestion in meat eg. Trichinella via pork), Penetration of skin by larvae (eg. Hookworm, shistosomes), Via a bite of vector (eg. Loa loa- deer fly)
How do helminths evade the immune system
- Helminths are typically large & too big for phagocytosis, or cytotoxic T cells & unaffected by specific Ab
- they are able to disguise themselves→e.g. schistosomes acquire host molecules on their surface
- Others actively suppress the host immune response by releasing factors that interfere with, or divert, protective responses
How do helminths cause disease
Helminths are able to cause chronic disease, either as a consequence of their activity, or because of misdirected & pathological host immune responses->Most serious helminth infection = schistosomiasis(blood flukes) –due to hypersensitivity reaction to eggs in tissues of body
What is an arthropod
include Insects, ticks, mites
How do arthropods cause disease
- Directly by their feeding → irritation → scratching→ e.g. scabies, head lice
- Indirectly by transmitting infections→ e.g.
Mosquitoes -viruses (e.g. dengue), Protozoa (e.g. malaria), Worms e.g. filariasis, Ticks -bacteria (e.g. plague), Flies –trypanosomes (e.g. Trypanosomiasis)
How is measles spread
highly contagious and spread via resp droplets (through coughing and sneezing) or direct contact with secretions from the nose or mouth
What is the pathogenesis of measles
measles virus infects via the respiratory tract→ will move into local lymphatics and lymph nodes→ the virus will then replicate and spread to other lymph nodes and the spleen→ the virus will cause temporary and severe immunosuppression making T lymphocytes susceptible to infection and causes apoptosis of encountered macrophages (allowing it to escape destruction and causes lymphopaenia)→ the presence of the virus in the blood allows it to manifest in the epithelia and cause necrosis→ causing a decreased resistance to secondary bacterial infection→ destruction of the epithelia appears as a rash/red eyes
- Antigen/antibody complexes in capillary endothelium → vasodilation, plasma leakage
What are the symptoms of measles
host immune response is responsible for fever, tiredness, cough, runny nose and/or red inflamed eyes – severity ↑s over 3 days
→Kopliks spots: small white spots on a red base
on the inside of the cheek→ then turns to blotchy, dark red rash appears starting
on face, then spreads over entire body (24 to 48 hours) & lasts ~6 days
What is severe measles
if the infection is severe enough it will allow for opportunistic bacterial super infections (such as bronchopneumonia and otitis media due to damage of epithelium), primary viral pneumonia (due to decreased T cell immune response), acute encephalitis (result of attack of Ag in CNS) and SSPE (subacute sclerosing panencephalitis→ rare and develops 1-10 years after recovery from an acute infection→ virus remains latent and when activated is universally fatal – death within 1-3 years- not caused by vaccine strain of measles)
What does the severity of measles depend on
effects of malnutrition, poor local mucosal defences, poor medical services, exposure to higher viral load, high exposure to bacteria in the environment, impaired immune defences, longer infective period → major cause of death in resource poor countries
What is an advantage of the HIV virus invading host cells
the viruses genome can be spliced and integrated into host genome→ allows it to replicate when host cell replicates, allows it to evade host immune system
-allows it to kill host cells and evade immune system
What does variability mean in reference to the HIV virus
high variable virus that mutates easily (due to not having checking mechanisms)→ causes multiple different strains of HIV (even within a single infected individual)→ mutation rate of 3 x 10-3 per day→ so if going to treat with antiviral drugs must require numerous drugs that attack numerous strains of the virus
What are the 3 main stages of a HIV infection
- Acute infection→ pt is typically highly infections due to a enormous viral burden in blood and genital secretions (may be unaware they are infected)
- Clinical latency→ with or without persistent generalised lymphadenopathy
- Aids
What is the pathogenesis of HIV
-HIV penetrates the mucosa epithelium then infects submucosal CD4T cells, DC and MO→ will then spread to the lymph nodes via these cells and then into the plasma→ once it enters the blood there is widespread dissemination to organs such as the brain, spleen and lymph nodes
What is the cellular immune response to HIV
Primary infection→ large number of susceptible CD4T cells and no HIV specific immune response
- Once T cell is infected there is rapid replication and high HIV RNA levels (Peak usually coincides with seroconversion (4-10 weeks after exposure))
- Following this, a specific CD8+ cytotoxic T lymphocyte response develops → causing a decrease in plasma HIV levels→ levels of the virus stabilise within 6 months of infection
What is the clinical latent period of HIV
asymptomatic except for possible lymphadenopathy (due to lymphoid tissue being a major reservoir for HIV)→ high rates of HIV replication and CD4 T cell destruction occur in this period→ virus is mainly intracellular in this period
→ there are high concentrations of extracellular HIV on the follicular dendritic cell processes within germinal centres of lymph nodes→These dendritic cells trap free virus and infected
CD4T cells→ causes disruption of the lymph node architecture and the release of HIV into the blood stream
What is schistosomiasis
caused by infection of schistosomes–>large cause of death (main in rural areas of developing world)→ 4th most prevalent helminthic disease in the world
What is the pathogenesis of schistosomiasis
the early immune response is stimulated by parasites entering through the skin and then migrating through the lungs→ involves macrophages and T cell mediated inflamm immune response (cause fatigue, coughing, fever)→ when the adult worm is in the portal circulation produce eggs there is a shift to TH2 mediated immune response→ the Ag produced by the eggs cause an anti-inflamm response → causes production of cytokines that reduce inflammation and promote the formation of granulomas around the parasite eggs in the lungs, pancreas, liver and lymph nodes
What is the chronic phase of schistosomiasis
down regulation of TH2 response limits the tissue damage→ most are asymptomatic but can be severe through production of persistent granulomatous inflammation (causing fibrosis) and if the eggs are trapped in the liver sinusoids it will cause periportal fibrosis and occlude portal veins→ leading to portal HTN, ascites and GI bleeding, hepatosplenomegaly
How do schistosomes evade the immune system
by releasing Ags that trigger the release of cytokines that reduce inflammation and promote the formation of granulomas around the eggs
