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95 Cards in this Set
- Front
- Back
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6 type of virus-cell infections
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Acutely Cytopathogenic Infections (ACI), Persistent, Latent, Transforming, Abortive, Null
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Acutely Cytopathogenic Infections (ACI)
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kill cell
Cytopatogenic effects (CPE) - infection, viral release, then see effects |
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Mechanisms of Viral Cytopathology
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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) |
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apoptosis
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programmed cell death, cell suicide, host kill own cell to stop viral factory
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Persistent Infections
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cell loss balanced out by new cell gensis
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persistent infection mechanisms
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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 |
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Latent infections
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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)
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Transforming infections
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provirus integrates and alters properties of cell (--> change function)
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Abortive infections
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cell has correct receptor but not right cell type (right key, wrong room)
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Null infections
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cell lacks correct receptor (wrong key, right room) -- can be injected directly = receptor CRUCIAL
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antigen
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any substance which ellicits an immune response - perceived as dangerous and foreign
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epitope
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particular region of antigen recognized by immune system that creates reaction
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2 branches of immune system
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Innate (non-specific) - automatic
Adaptive (specific) - specific threat, takes time |
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Innate immunity
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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 |
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Adaptive immunity
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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 |
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Antibody 3 functions
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Neutralize - swarm, dysfunctional
Opsonize - coat cell Complement activation |
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Antibody structure
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2 chains (light/heavy), 2 regions (variable/constant)
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Light chain of antibody
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top, short pieces, Kappa/lambda
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heavy chain of antibody
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determine antibody class, long part
Aplha/Delta/Epsilon/Gamma/Mu |
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Variable region of antibody
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combo of heavy and light, at top, C-terminus, Fc region, bound to leukocyptes by Fc receptor
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antigen
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any substance which ellicits an immune response - perceived as dangerous and foreign
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epitope
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particular region of antigen recognized by immune system that creates reaction
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2 branches of immune system
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Innate (non-specific) - automatic
Adaptive (specific) - specific threat, takes time |
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Innate immunity
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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 |
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Adaptive immunity
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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 |
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Antibody 3 functions
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Neutralization - swarm, dysfunctional
Opsonization - coat cell Complement activation |
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Antibody light chain
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at top, short peices
Kappa/Lambda |
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Antibody heavy chain
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bottom, big peice, *determine antibody class*
Alpha/Delta/Epsilon/Gamma/Mu |
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antibody variable region
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combo of heavy and light chain
N-terminus binding region - bind to epitope |
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antibody constant region
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C-terminus/Fc region
bound by Fc receptors on leukocytes |
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Antibody classes
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5, non enter cell, distiguish by heavy chain, each has different localization/function/in-permization
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IgD
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on surface of naive B cells
B cells not activate dby mature most primitive antibody not secreted after activation, no longer expressed - class switching |
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IgM
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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 |
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IgE
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worm infections, associated with hypersensitivites (allergies), not involved with viruses
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IgA
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in mucosal membranes
can be secreted across epithelia and into tract important in virus neutralization |
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IgG
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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 |
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neutralization
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loss of infectivity of virus when antibody binds to virus
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Epitope
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component of antigen recognized by antibody
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Paratope
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portion of variable region that actually connects with epitope
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Ways antibodies neutralize
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Interfere with docking or interfere with penetration/uncoating
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Interfere with docking (neutralization)
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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 |
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interfere with penetration/uncoating (neutralization)
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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 |
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Interferons defined
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Cytokines (chemical), interfer with replication by inducing cells to resist viral replication; Type I and II
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Type I interferons
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more innate, IFNa and IFNb; produced only in respinse to viral replication/infection,
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How Type I interferons works - Direct Effects
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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 |
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How Type I interferons work - Indirect Effects
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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. |
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Type II interferons
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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 |
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diseases treated with IFN
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Hep B (virus depressed MHC class I, IFNa offsets this by increasing MHC expression); Hep C, HPV
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Pegylated interferon
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'slow-release' capsule, binds molecularly to IFN
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Virus-Host Interactions
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Acute, Subclinical, Chronic, Persistent, Latent, Slowly Progressing, Tumorigenic
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How Type I interferons work - Indirect Effects
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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. |
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Type II interferons
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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 |
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diseases treated with IFN
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Hep B (virus depressed MHC class I, IFNa offsets this by increasing MHC expression); Hep C, HPV
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Pegylated interferon
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'slow-release' capsule, binds molecularly to IFN
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Virus-Host Interactions
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Acute, Subclinical, Chronic, Persistent, Latent, Slowly Progressing, Tumorigenic
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Acute interaction
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Infectious Progeny Produced: +
Cell Death: + Clinical Signs of Disease: + Duration of infection: short Example: Measles, flu |
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Stages of Acute Infection
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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 |
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Immune response to acute infection
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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) |
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Subclinical interaction
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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) |
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Chronic interactions
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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 |
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Persistent interactions
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Infectious Progeny Produced: +
Cell Death: + Clinical Signs of Disease: - Duration of Infection: long Example: Rubella analogous to subclinical but body can't clear - lingers |
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Latent interaction
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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 |
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What determines HSV-1 latency?
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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 |
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Immune response to HSV-1
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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 |
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Slowly progressive interaction
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Infectious Progeny Produced: +/-
Cell Death: + Clinical Signs of Disease: + (eventually) Duration of Infection: long Example: HIV, prions |
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Tumorigenic
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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 |
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Routes of Transmission
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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) |
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2 forms of vaccination
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Passive (borrow immune response from another - doesn't learn anything)
Active (create immunity yourself - generate memory cells) |
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Two types of new passive antibodies
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Immune serum globulin (ISG) - general
Specific immune globulin (SIG) - specific |
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Types of Active vaccines
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Inactivated ('killed'), Live-attenuated, antigenic molecule/subunit, DNA vaccines, recombinant
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Inactivated vaccines
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'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 |
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Live attenuated
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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 |
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Antigenic molecules/subunit (acellular)
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not whole viruses, just viral components that elicit immunity
Example: HIV, HPV, (dengue fever, HSV) |
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DNA vaccines
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naked viral DNA injected into muscle
Elusive success: bird flu, West nile in horses Working on: dengue fever, Ebola, Hep, influenza |
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Recombinant
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generated multiple ways
Example: HBsAG (Hep B), Ebola in VSV not successful |
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Ways to generate viral vaccine
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chemical, mechanical, genetic engineering, subculturing
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Why don't we have more vaccines?
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scientific barriers, financial barriers, legal/political barriers, scaremongering, pain, boosters needed, logistics
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Smallpox History
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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 |
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Polio history
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Pandemic 1st 1/2 of 20th century
1940 - USNFIP 1952 - Salk (IPV - inactivated, killed) 1960 - Sabin (OPV - oral attenuated) |
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Influenza history
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1931 - influenza in eggs
1950 - civilian vaccine WHO - H1N1,H3N2,B Ford re-election - mass vaccination |
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HIV history
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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 |
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Antivirals
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40 on market, over 30 = HIV, specific for few viruses (not broad like antibiotics)
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Problems with antiviral development
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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
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Major Classes of Antivirals
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1. Antibodies
2. Interferons 3. Attachment/Entry inibition (docking) 4. Ion channel blockers 5. Replication inhibitors 6. Protease Inhibitors 7. Release Inhibitors |
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Antivirals: Antibodies
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Example: RespiGam, Synagis (IgG)
neutralize virus - coat exterior |
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Antivirals: Interferons
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Type I - Direct: induction-->antiviral state
- Indirect: MHC class I expression, increase NK activity Type II: similar function, different structure may be pegylated |
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Antivirals: Attachment/Entry inibitors (docking)
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Example: Picornaviruses - Pleconaril (bind to hydrophobic pocket and blocks)
Example: HIV (interfere with docking of CD4) --> BMS8085, SCH-C, T20 |
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BMS8085 - Bristol-Myers Squibb
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blocks gp120 from binding to CD4, stop at 1st step
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SCH-C - Schering-Plough
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blocks gp120 from binding coreceptor, stop at 2nd step
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T20 (ZFuzeon, Pentafuside, Enfuviritide)
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blocks gp120 from binding cell membrane, stop at 3rd step/seperation of trimers
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Antivirals: Ion Channel Blockers
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Example: Amantadine (Symmetrel), Rimantadine (Flumadine), influenza
interfer with uncoating disrupt M2 protein of ion channel, influenza relies on drop in pH, block channel |
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Antivirals: Replication inhibitors
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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 |
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Antivirals: Protease Inhibitors
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Examples: all anti-HIV, Sanguinavir, Viracept
prevent post-translational cleavage of polyproteins (pac-man blocked) |
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Antivirals: Release inhibitors
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Examples: Oseltamavir (Tamiflu)
interfere with neuraminidase - prevent viral budding (can't escape cell) - specific for influenza |
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HAART
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does not spur CD4, but rather keeps pre-existing CD4 T cels from being infected and increases CD4 cell longevity
Mitochondriosis = side effect |
