8 - viral infection Flashcards
most common recurrent infection in humans
viral
transient
feature of viral infections
last only for a short time
zoonotic
jumped species barrier
viral infection caused in humans, originally from another animal
why do zoonotic infections have high mortality rates in humans
new to humans so have not co-evolved
examples of zoonotic infection s
HIV –> originally from chimpanzees in africa
hantavirus –> originally from rodents in N/S america
severe acute respiratory sydrome (SARS) –> coronavirus from bats in china
viral replication
depend on host proteins and machinery
features of viral genomes
3 –> 300 genes
single or souble stranded RNA/DNA
enclosed within capsid
capsid
coat protein
recognised by immune cells
cytopathic effect
virus infects cell and causes lysis
induces autophagy or apoptosis on exit of cell
example of cytopathic virus
polio virus
influenza
latent virus
infect cells but only activated when immunity wanes
activation prodces infectious virions
example of latent virus
herpes
non-cytopathic virus
replicate without destruction of cells
e.g. Hep B
how do viruses cross epithelial barriers in intestinal infections
example
using antigen-sampling M cells
HIV
poliovirus
how do viruses cross epithelial barriers in respiratory viruses
example
establish infection in airway lining
INfluenza
rhinovirus
other methods to cross epithelial barriers
insect vectors physical trauma (causes bloodborne viruses)
what mediates viral innate immunity
type 1 interferons
complement
NK cells
type 1 interferons
host proteins that interfere with viral gene transcription
viral invasion
viruses exploit specific molecules on cells as receptors for invasion
(tissue tropsim)
HIV tropism
tissues support growth of virus
CD4 important
chemokine receptor CXCR4 and CCR5
indirect antibody binding
couples antibody binding to classical pathway of complement
C1 q/r/s complex
direct antibody binding
Fc receptors bind directly to neutralising antibody which is an opsonising virus particle
role of NK cells on antibody binding
Fc receptors on surface of NK cell bind to antibody as virus leaves infected cell
stimulated to kill infected cell using using perforins and granzymes
epidemic
new case of disease in a population at a higher rate than expected
outbreak
disease in one location
can be contained
global epidemic
pandemic
main mech of AIDS
infects and destroys CD4+ T cells
Gay-Related ImmunoDeficiency (GRID)
1980s
original name for HIV
prevalence of AIDS
39+ million deaths globally since 1st clinically recognised
AIDS patients show symptoms of …
PCP pneumonia
PCP pneumonia
pneumocystic pneumonia
common lung infection
bad in immunocompromised patients
trreatable if found early
HIV-1 retrovirus spread
zoontoic
requires high risk transmission for human to human spread
spread due to prostitution in african colonies
when was HIV-1 first seen in humans
congo 1959
HIV protein structures
GP 120 - Docking glycoprotein
GP 41 - transmembrane glycoprotein
HLA-DR
human leukocyte antigen - antigen D related
MHC class II receptor
ligand for the T cell receptor
HIV epithelial entry mechanisms
M cells
epithelial damage
langerhan cells
chemokine receptor CCR5
M cells used by HIV for epithelial entry
transfer through and present to dendritic cells
importance of langerhan cells
projections stick out to sample antigens
where is the chemokine receptor CCR5 found
small intestine
HIV-1 binds to chemokine receptor CCR5
mechanism
HIV-1 binds via gp120
virus is transcytosed across membrane and exposed to dendritic cells
consequences of HIV infection
dendritic cells translocate HIV from mucosa i
viral proliferation and viremia
loss of helper T activities
therefore no maintenance of CD8 cels and no antibody response of `b cells
timescale of HIV infection
dendritic cells translocate HIV from mucosa in 30 mins - quick
by 3 weeks all lymphoid tissues are infected
why flu symptoms shown in HIV
loss of CD4 T cells in the blood
opportunistic infection when CD4 T cells <200ul
3 classes of influenxa
A
B
C
influenza A
most common
responsible for pancdemic outbreaks
flu is zoonotic
bird (avian) virus that adapts to humans
spread via aerosol droplets
influenza cytolytic effects
infections created in respiratory tract epithelium
structure of influenza virus
spherical or rod
enveloped
2 x spike glycoproteins on surface (HA and NA)
HA
trimeric haemaglutinin
mediates binding to cell surface (sialic acid)
mediates internalisation of viral particles (endocytosis)
NA
tetrameric haemaglutinin
cleaves sialic and promotes viral release from cells using ennzymes
bird genotypes
diverse
HA subtypes
H1 to H5
NA subtypes
N1 to N9
importance of pigs in influenza virus transfer to humans
pigs carry both types of linkage (e.g. alpha-2,6)
pigs infected by both linkages and exhange viral genomes
crucial for transfer
antigenic drift in influenza virus
point mutations in HA and NA
means virus is no longer recognised by neutralising antibodies
common cause of antibiotic
antigenic shift in influenza virus
reassortment of human/bird genomes inside pig
whole cell change
therefore highly transmissable
pandemic caused
3 major pandemics
1918 - spanish flu
1957 - asian flu
1968 - hong kong flu
spanish flu
1918-1920
H1N1 subtypes
brought over by US after WWI
targets active immune systems (20-40 yr olds)
high infection rates - 5% population died
hypercytokinemia
response of immune system to spanish flu
cytokine storm
release of over 150 inflammatory mediators
