Pathogenese Flashcards
When is a germ classified as pathogen?
as soon as a germ can lead to disease
Define endemic and give an example
disease which occus within a defined area for an indefinite time periode and without having the tendence to spread –> rabies
low morbidity, spatial but no temporal limitation
define epidemic
massed occurance of a dangerous infectios disease with a temporal and spatial limitation while having a high index of minifestation –> FMDV in UK 2001
definde pandemic and give an example
spreading of an epidemic across whole countries or continents
–> widespread diesease without spatial limitation in a certain time period
–> SARS CoV-2
what is morbidity?
number of sick hosts * 100 / number of hosts at risk in %
what is mortality?
number of hosts which died from the viurs * 100 / total number of hosts at risk
what is lethality?
nmber of deaths * 100 / number of hosts with symptoms (infected)
what is incidence?
number of new cases of illness within a certain time period
what is prevalence?
number of all existing infection cases * 100 / size of population
what is seroprevalece
number of antibody positive individuals * 100 / size of population
Which body surfaces are involved in virus entry and excretion?
infection through body surfaces:
- conjunctiva
- respiratory tract
- alimentary tract
- urogenital tract
- anus
parenteral inoculation
- arthropod
- capillary
- scratch, injury
- skin
Which virus enters via small surface wounds?
human papillomavirus (HPV)
How is HPV transmitted? What does an infection lookmlike?
- transmission by skin contact or sexually
- chronic persistent infection of basal cells
- development of warts through cell proliferation
- benign lesions in genita area –> can become malignent
- integration of the virus genome leads to transformation –> cervical carcinoma
Name different types of virus entry via deep wounds and example viruses
- iatrogenic (by non sterile inhection needles): HIV, HBV
- arthopods as vector: Alpha, flavi, Reo, Bunya
- bite by virus carrier: rabies
Where does rabies replicate?
shortly in muscle cels and then in neurons in the CNS –> transport into neurons may take several months
How can rabies be treated?
via vaccination:
- passive: anti rabies IgG
- active: inactivated vaccine
How can rabies be diagnosed
- direct detection via IFA or RT-PCR in alive patients
- direct detection via IFA, RT-PCR, Negri-bodies, virus isolation from brain tissue in dead patients
What are negri bodies and what do negri bodies contain (rabies infection)
= cytoplasmic spherical structures formed by liquid-liquid phase separation and they contain:
- TLR3 (central)
- nucleocapsid protein N (periphery)
name countermeasures of the respiratory tarct against viral infection
- translocation of mucous layer by ciliated epithelium
- only small particles can migrate to the alveoli
- control by alveolar macrophages
What is the difference between aerosols and droplets?
aerosols vs droplets:
- travel more than 1 meter vs less than 1 meter
- can float in air for hours vs cannot
- can be inhaled vs cannot be inhaled
Why is influenza transmission between birds and humans inefficient?
- HA binds to different sialic acid residues in birds and humans
- mucosal epithelial cells of the upper and lower respiratory tract carry different sugar residue structures on their surface
- sugar topology
When can viruses infect gastric and intestinal areas?
only when virions are stable against acidic pH
which viruses that infect the gastric and intestinal area are coatedand which are not coated?
uncoated: Enetroviruses, Calcivirus, Reovirus
coated: enteral coronavirus
Why is the intestinal mucosa an effective barrier?
- different pH value
- mucus
- phagocytes and antiboides
- GALT (gut associated lymphoid tissue) –> e.g. Peyers Patches
What cells do the lymph follicles in the mucosa of the GIT contain and what is their function?
M- cells –> do Transcytosis = transfer through M-cells with out degradation –>present antigens to lymphocytes which are located beneathh
they sit on the luminal side
Which viruses replicate in M-cells and which only pass through?
no replication: Reo, Polio
replication: Rotavirus
Which viruses have a minor host specificity and which have a high specificity?
minor:
- alphaviruses
- flavivirus
- rabies
high:
- herpes
- papilloma
- retro
- HCV, HBV
What is viral tropism?
preferred locations of replication in the body
Name example viruses which are hepatotropic, neurotropic, pneumotropic, epithelotropic, dermatotropic, lymphotropic
- hepatotropic: HAV, HBV, HCV
- neurotropic: Rabies, FSME
- pneumotropic: Influenza
- epithelotropic: Papilloma
- dermatotropic: Parapoxvirus
- lymphotropic: Eppstein Barr Virus
What determines host specificity and tissue tropism? Give examples
- receptor: CD155 in Polio
- cellular factors of viral replication (cellular transcription factor): liver specific enhancers in HBV
- cellular factors of virus maturation: proteases in Influenza
which tryptase cleaves HA in Infleunza extracellularly?
Clara
What is often crucial for susceptibility and virus spread?
Polarity of cells
How are viruses spread within the body?
- replication at the site of entry
- primary viremia
- sites of repöication (e.g muscle, spleem, liver…)
- secondary viremia
- sites of replication (brain, skin, kidney, lung, GIT etc)
- Transmission to other hosts via 5.
How can the infection and exit site in epithelial cells (polarity) be tested in the lab?
- cell culture in a membrane coated chamber
- selective release of viruses into the media above or under the cells
Which viruses infect the apical site of epithelial cells?
- SARS
- Influenza
- West Nil Virus
Which viruses infect the basolateral site of epithelial cells?
- marburg virus
- crimean congo
- VSV
Which virus infects the basolateral surface and is released from the apical site?
reovirus
What happens after viruses are released from the basolateral site?
- viruses reach the lymphatic system
- reach lymp nodes
- antigen presentation in lymphnodes or virus replication takes place
What is primary viremia?
- direct virus infection of the host
- without clinical symptoms
What is secondary viremia?
- after virus replication in infected organs a huge number of viruses is released
- mostly accompanied by clinical symptoms
How can viruses exist in the blood?
- non associated
- adsorbed to cell, erythrocytes, platelets
- intracellular
How can viruses escape from the capilary lumen?
- fenestrae
- trafficking lymphocyte or monocyte
- transcytosis
- replication in endothelial cells
How can the CNS be invaded?
- Transfer from the blood to the CNS
- infection of peripheral neurons –> migration to the CNS via axonal transport
what is the consequence of the separation of blood circulation of mother and fetus in ruminants and swine?
if the mother is infected and produces antibodies against it, they doi not reach the fetus and because the fetus has no own innate immunsystem it stays infected –> diaplacental infections
How can viruses be excreted?
local infection: virus excretion often via the same way as invasion, only reverse direction
systemic infection: virus excreted from one or multiple sites
what is pathogenicity?
feature of a microorganism to cling to the host, replicate inside a host sepcies and thereby cause an infectious disease
what is virulence?
quantitative statement about the grade of disease causing features
How is virulence quantified?
LD50 value:
slightly virulent: 10^6 virions
moderate virulent: 5*10^3 virions
highly virulent: 5 virions
What causes differences in virulence?
virulence based on genetics of pathogen and host
–> changes in virulence based on mutations
- point mutation
- insertion, deletion
- recombination
- reassortment
what is host resistance?
- unspecifc defence against pathogens
- can be divided into susceptibility (host can be infected) and sensitivity (extent of disease after infection)
what determines susceptibility and sensitivity?
susceptibility: genetically determinded (receptors, factors of target cells)
sensitivity: physiologically determinded (age, immunosuppresion, hormonal status, nutritional condition)
What leads to host resistance? Give examples
absence of essential factors:
- Polio: mouse have no receptor for human poliovirus
- HIV: CCR delta 32 variant in chemokine receptor gene
- Norovirus: FUT2 gene homozygous negative individuals resistent
What is the reason for a disease?
- direct damaging of tissues and organs: cytopathic effect
- immuno pathological
Do cytopathic effect correlate in vitro and in vivo?
no
what benefits secondary infections?
viral immune suppresion
Which viruses damage the immune system?
- HIV
- Pestivirus
- Parvovirus
- measles
Name types of persisting infections and examples
- chronic infectiosn: HCV
- latent infections: herpes
- slow infections: measles
- transforming infections : DNA viruses
what is the difference between acute and persitent infections?
persistent infections are temporally unlimited
is infection always detectavle during latency and chronic infections? Why?
latency: during latency no infectious virus can be detected –_> viral nucleic acid is present as a episome
chronic: infectious virus always detectable –> permanent virus secretion
What is the relationship between the immune system and acute, latent and persisting chronic infections?
acute: IFN block, cell lysis
latent: not providing a targetm infection of immune privileged cells
chronic: always IFN block, inducing immune tolerance or immune evasion
How can viral diseases be communicated?
- horizontal: direct physical contact, indirect contact (nnedles, clothes), transmission by an agent (food, water), transmission via air, live vectors
- vertical (in temporal and factual context of birth): virus integrated DNA copies in germ cells, diaplacental, perinatal
