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95 Cards in this Set

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6 type of virus-cell infections
Acutely Cytopathogenic Infections (ACI), Persistent, Latent, Transforming, Abortive, Null
Acutely Cytopathogenic Infections (ACI)
kill cell
Cytopatogenic effects (CPE) - infection, viral release, then see effects
Mechanisms of Viral Cytopathology
through some TP (toxic product)
1 - inhibits reading mRNA (ex. Poliovirus [change to read uncapped], adenovirus, influenza, reovirus)
2 - alters cell ion balance - alters membrane(ex. rotavirus [alters membrane permeability, adds extra channel], semliki forest virus [messes with Na+/K+ pump])
3 - virus outcompetes cellular mRNA wih viral mRNA (ex. semliki forest, VSV)
4 - virus degrades mRNA (ex. influenza)
5 - viruse inhibit translocation of cell mRNA from nucleus to cytoplasm (ex. adenovirus)
6 - virus triggers apoptosis (ex. adenovirus, semliki, HIV, influenza, measles, sindbis virus)
apoptosis
programmed cell death, cell suicide, host kill own cell to stop viral factory
Persistent Infections
cell loss balanced out by new cell gensis
persistent infection mechanisms
Just V-C interactions --> Simian virus 5 - little demand on host cell in monkey kidney cells; Sindbis - steps trigger for apoptosis (bcl-s inhibits)
V-C interactions and Host immune interactions --> balance, virus can't do anything, limit spread of infection
V-C interactions and DI nucleic acid - defective replication, less DI = less genome
Latent infections
genome present but not actively replicating itself; 2 forms (provirus and episome); Ex. EBV (episome, B cells infected) and Adeno-associated (adeno/herpes = wake up)
Transforming infections
provirus integrates and alters properties of cell (--> change function)
Abortive infections
cell has correct receptor but not right cell type (right key, wrong room)
Null infections
cell lacks correct receptor (wrong key, right room) -- can be injected directly = receptor CRUCIAL
antigen
any substance which ellicits an immune response - perceived as dangerous and foreign
epitope
particular region of antigen recognized by immune system that creates reaction
2 branches of immune system
Innate (non-specific) - automatic
Adaptive (specific) - specific threat, takes time
Innate immunity
physical barriers/inflammation/complement
Cells of Innate immunity -
Antigen-presenting cells (APC) = machrophage (eat invaders and secrete effector molecules) and dendritic cells (stimulat other cells to action, lots branches)
Granulocytes - Neutrophils (land mines)
NK cells - guided missle, more discriminatory
Adaptive immunity
T-cells - cell mediated immune response --> helper T (CD4) (activate other cells); and Killer T (CD8) (gobble up damaged - specific)
B-cells - humoral/anti-body mediated immune response --> stimulated by APC, mature into plasma cells, produce antibody
Lymphocytes
Cytokines - cause cell to move and stimulate another
Antibody 3 functions
Neutralize - swarm, dysfunctional
Opsonize - coat cell
Complement activation
Antibody structure
2 chains (light/heavy), 2 regions (variable/constant)
Light chain of antibody
top, short pieces, Kappa/lambda
heavy chain of antibody
determine antibody class, long part
Aplha/Delta/Epsilon/Gamma/Mu
Variable region of antibody
combo of heavy and light, at top, C-terminus, Fc region, bound to leukocyptes by Fc receptor
antigen
any substance which ellicits an immune response - perceived as dangerous and foreign
epitope
particular region of antigen recognized by immune system that creates reaction
2 branches of immune system
Innate (non-specific) - automatic
Adaptive (specific) - specific threat, takes time
Innate immunity
physical barriers/inflammation/complement
Cells of Innate immunity -
Antigen-presenting cells (APC) = machrophage (eat invaders and secrete effector molecules) and dendritic cells (stimulat other cells to action, lots branches)
Granulocytes - Neutrophils (land mines)
NK cells - guided missle, more discriminatory
Adaptive immunity
T-cells - cell mediated immune response --> helper T (CD4) (activate other cells); and Killer T (CD8) (gobble up damaged - specific)
B-cells - humoral/anti-body mediated immune response --> stimulated by APC, mature into plasma cells, produce antibody
Lymphocytes
Cytokines - cause cell to move and stimulate another
Antibody 3 functions
Neutralization - swarm, dysfunctional
Opsonization - coat cell
Complement activation
Antibody light chain
at top, short peices
Kappa/Lambda
Antibody heavy chain
bottom, big peice, *determine antibody class*
Alpha/Delta/Epsilon/Gamma/Mu
antibody variable region
combo of heavy and light chain
N-terminus
binding region - bind to epitope
antibody constant region
C-terminus/Fc region
bound by Fc receptors on leukocytes
Antibody classes
5, non enter cell, distiguish by heavy chain, each has different localization/function/in-permization
IgD
on surface of naive B cells
B cells not activate dby mature
most primitive antibody
not secreted
after activation, no longer expressed - class switching
IgM
on surface of naive B cells with Iga/b forms B-cell receptor (BCR)
bound to antigen, presents to CD4 T cells that 'double-check' match (Negative = discard antigen, Positive = stimulate B cell to become plasma cell)
B-cell activated --> class switching (can't swtich to D) and new class displayed on surface of cell
Secreted = circulated in blood, important in virus metabolism
IgE
worm infections, associated with hypersensitivites (allergies), not involved with viruses
IgA
in mucosal membranes
can be secreted across epithelia and into tract
important in virus neutralization
IgG
most abundant antibody in body
circulated through blood - can exit into tissues and pass through placenta
transmits immunity to fetus, activates complement, and neturalizes virus
neutralization
loss of infectivity of virus when antibody binds to virus
Epitope
component of antigen recognized by antibody
Paratope
portion of variable region that actually connects with epitope
Ways antibodies neutralize
Interfere with docking or interfere with penetration/uncoating
Interfere with docking (neutralization)
Model: rhinovirus - indirectly inhibits, binds to epitope near site - blocky
Model: HIV - directly by to receptor
Model: theoretical - gums up complements so physically prevented from docking
interfere with penetration/uncoating (neutralization)
Model: Poliovirus - triggers endocytosis, virus internalized but can't uncoat inside
Model: Influenzavirus - after endocytosis, envelop fuses with vesicle membrane but virus can't escape
Interferons defined
Cytokines (chemical), interfer with replication by inducing cells to resist viral replication; Type I and II
Type I interferons
more innate, IFNa and IFNb; produced only in respinse to viral replication/infection,
How Type I interferons works - Direct Effects
Induction (infected, sense virus, chromosom 9 transcribed to make IFNa/b, IFNa/b secreted;
Antiviral State (neighboring cells receive IFN, cells 'primed', virus infects primed neighboring cell = full activation [EIF2a (host transcriptional factor) phosphorylated to slow protein synthesis and RNasL activates (degrades mRNA to stop protein translation)]:
stops translation, slows transcription
How Type I interferons work - Indirect Effects
1. MHC Expression - Class I (presents sytosolic peptides, specific for CD8 t cells), Class II (only in antigen-presented cells, present peptides from intracellular vesicles, specific for CD4 T cells)
IFNa/b stimulates MHC class I expression - viral peptides chance to displayed on surface, CD8 function increase b/c target more easily ID
2. NK cell activity - IFNa/b heighten NK cell activity (warning flag)
Need both NK and cytokines for response
2.
Type II interferons
IFN-y; more adaptive
produced by activated NK cells and T cell ONLY so later in disease process
Compared to IFNa/b: different structure, same function, if virus change for IFNa/b may still be ok for y
diseases treated with IFN
Hep B (virus depressed MHC class I, IFNa offsets this by increasing MHC expression); Hep C, HPV
Pegylated interferon
'slow-release' capsule, binds molecularly to IFN
Virus-Host Interactions
Acute, Subclinical, Chronic, Persistent, Latent, Slowly Progressing, Tumorigenic
How Type I interferons work - Indirect Effects
1. MHC Expression - Class I (presents sytosolic peptides, specific for CD8 t cells), Class II (only in antigen-presented cells, present peptides from intracellular vesicles, specific for CD4 T cells)
IFNa/b stimulates MHC class I expression - viral peptides chance to displayed on surface, CD8 function increase b/c target more easily ID
2. NK cell activity - IFNa/b heighten NK cell activity (warning flag)
Need both NK and cytokines for response
2.
Type II interferons
IFN-y; more adaptive
produced by activated NK cells and T cell ONLY so later in disease process
Compared to IFNa/b: different structure, same function, if virus change for IFNa/b may still be ok for y
diseases treated with IFN
Hep B (virus depressed MHC class I, IFNa offsets this by increasing MHC expression); Hep C, HPV
Pegylated interferon
'slow-release' capsule, binds molecularly to IFN
Virus-Host Interactions
Acute, Subclinical, Chronic, Persistent, Latent, Slowly Progressing, Tumorigenic
Acute interaction
Infectious Progeny Produced: +
Cell Death: +
Clinical Signs of Disease: +
Duration of infection: short
Example: Measles, flu
Stages of Acute Infection
1. Incubation - agent enters healthy body, latent, end = communicable, apparent
2. Prodome - first symptoms, high communicable
3. Clinical - characteristic symptoms (Peak), communicable
4. Decline - first signs of recovery, disease ends, becomes latent, end communicable, carrier
5. Convalescent - return to full health/recovery
Immune response to acute infection
Innate immnity sometimes clears virus (NK, macrophages, etc.)
If not - cellular immunity (CD8); humoral immunity (Abs, plasma cells)
Antibodies for RNA (Picornaviruses, Orthomyxoviridae)
Killer T cells for DNA (herpesviridae, poxviridae)
Subclinical interaction
Infectious progeny produced: +
Cell Death: +
Clinical signs of diease: -
Duration of Infection: short
Example: polio
most infections are of this type - viruses that have adapted to host (HIV)
Chronic interactions
Infectious progeny produced: +
Cell Death: +
Clinical Signs of Disease: +
Duration of Infection: long
Example: Hep B
analogous to acute infection that immune system can't clear - lingers
Persistent interactions
Infectious Progeny Produced: +
Cell Death: +
Clinical Signs of Disease: -
Duration of Infection: long
Example: Rubella
analogous to subclinical but body can't clear - lingers
Latent interaction
Infectious progeny produced: -
Cell Death: -
Clinical Signs of Disease: -
Duration of Infection: long
Example: Herpesvirus, HSV-1
all latent begin and end as acute infections, latency in middle as seperate phase
What determines HSV-1 latency?
cell activator proteins present = VP15 stimulates a gene expression --> b --> y
cell activator proteins absent = no a gene expression, LAT produced from complement to ICP0, inhibiting ICP0 transcription, break latency and start acute cycle
Immune response to HSV-1
HSV-a temporarily reigns --> Intm-early ICP47 protein prevents poptide loading into MHC class I - slows down warning signals --> another protein shuts down host protein synthesis --> infected cells not recognized by immune system
Immune Sytem Triumphs --> MHC Class II presented by APC --> CD4 T --> NK stimulated --> IFN-y --> MHC Class I expression increases --> CD8 stimulated --> virus knocked down
Slowly progressive interaction
Infectious Progeny Produced: +/-
Cell Death: +
Clinical Signs of Disease: + (eventually)
Duration of Infection: long
Example: HIV, prions
Tumorigenic
Infectious Progeny Produced: +/-
Cell Death: -
Clinical signs of disease: +
Duration of Infection: long
Example: EBV, HPV
these viruses normally cause other types of infection and only rarely proceed to tumorigenic phase
Routes of Transmission
Horizontal - one birthed organism to another (respiratory, oral-fecal route, conjuctival, sexual, urine, skin-to-skin)
Mechanical (breach in epitheial)
Vertical (mother to child)
Zoonoses (non-human to human)
2 forms of vaccination
Passive (borrow immune response from another - doesn't learn anything)
Active (create immunity yourself - generate memory cells)
Two types of new passive antibodies
Immune serum globulin (ISG) - general
Specific immune globulin (SIG) - specific
Types of Active vaccines
Inactivated ('killed'), Live-attenuated, antigenic molecule/subunit, DNA vaccines, recombinant
Inactivated vaccines
'killed'
Advantage - lesser risk of reversion, may destroy any contaminant viruses
Disadvatage - need to kill EVERY virion, mimics natural infection
Example: Hep A/B, influenza, Polio (Salk), rabies
Live attenuated
virus still viable but not coplete normal disease state, weakened 'live' virus
original strain = 'virulent'
resultant less-damaging = 'avirulent'
Example: MMR, Polio (Sabin), smallpox, yellow fever
Antigenic molecules/subunit (acellular)
not whole viruses, just viral components that elicit immunity
Example: HIV, HPV, (dengue fever, HSV)
DNA vaccines
naked viral DNA injected into muscle
Elusive success: bird flu, West nile in horses
Working on: dengue fever, Ebola, Hep, influenza
Recombinant
generated multiple ways
Example: HBsAG (Hep B), Ebola in VSV not successful
Ways to generate viral vaccine
chemical, mechanical, genetic engineering, subculturing
Why don't we have more vaccines?
scientific barriers, financial barriers, legal/political barriers, scaremongering, pain, boosters needed, logistics
Smallpox History
variolation - India, Turkey, China
Montagu to Turkey, back to Europe in 1717 --> US (Boston) with Mather and Boylston --> Jenner (Nelmes and Philips)/Jetsy [cowpox] -->government mandate switch (1842 in England, 1843-1855 in US)
1895 - Sweden smallpox free
1960 - CDC/WHO serious - herd immunity, Foege (ring immunity)
Eradicated 10/26/1979
routine American vaccinations stopped in 1972
Polio history
Pandemic 1st 1/2 of 20th century
1940 - USNFIP
1952 - Salk (IPV - inactivated, killed)
1960 - Sabin (OPV - oral attenuated)
Influenza history
1931 - influenza in eggs
1950 - civilian vaccine
WHO - H1N1,H3N2,B
Ford re-election - mass vaccination
HIV history
AIDS public in 1981
1985 - Margaret Heckler/Gallo
1990's - Clinton
No vaccine yet b/c lack retrovirus knowledge, HIV mutates, funding, immune response short lived
DNA/RNA and subunit only options left
Antivirals
40 on market, over 30 = HIV, specific for few viruses (not broad like antibiotics)
Problems with antiviral development
viruses non-living (use metabolic pathwyas of host, thus interfer with them), work better as preventative measure, viruses mutate quickly, can't target latent virus
Major Classes of Antivirals
1. Antibodies
2. Interferons
3. Attachment/Entry inibition (docking)
4. Ion channel blockers
5. Replication inhibitors
6. Protease Inhibitors
7. Release Inhibitors
Antivirals: Antibodies
Example: RespiGam, Synagis (IgG)
neutralize virus - coat exterior
Antivirals: Interferons
Type I - Direct: induction-->antiviral state
- Indirect: MHC class I expression, increase NK activity
Type II: similar function, different structure
may be pegylated
Antivirals: Attachment/Entry inibitors (docking)
Example: Picornaviruses - Pleconaril (bind to hydrophobic pocket and blocks)
Example: HIV (interfere with docking of CD4) --> BMS8085, SCH-C, T20
BMS8085 - Bristol-Myers Squibb
blocks gp120 from binding to CD4, stop at 1st step
SCH-C - Schering-Plough
blocks gp120 from binding coreceptor, stop at 2nd step
T20 (ZFuzeon, Pentafuside, Enfuviritide)
blocks gp120 from binding cell membrane, stop at 3rd step/seperation of trimers
Antivirals: Ion Channel Blockers
Example: Amantadine (Symmetrel), Rimantadine (Flumadine), influenza
interfer with uncoating
disrupt M2 protein of ion channel, influenza relies on drop in pH, block channel
Antivirals: Replication inhibitors
Impair reverse transcriptase activity
Nukes - mimic nucleotides (ACGT), anti-HIV (AZT), anti-HSV, funny block doesn't work
Non-nukes - directly interfere with RT enzyme, binds to enzyme oval
Antivirals: Protease Inhibitors
Examples: all anti-HIV, Sanguinavir, Viracept
prevent post-translational cleavage of polyproteins (pac-man blocked)
Antivirals: Release inhibitors
Examples: Oseltamavir (Tamiflu)
interfere with neuraminidase - prevent viral budding (can't escape cell) - specific for influenza
HAART
does not spur CD4, but rather keeps pre-existing CD4 T cels from being infected and increases CD4 cell longevity
Mitochondriosis = side effect