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Components of Viruses of Bacteria
- Nucleic Acids- DNA or RNA
- Capsid
- Nucleocapsid
- Attachment proteins or spikes
- Naked or enveloped
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Nucleocapsid
Nucleic acid + capsid
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Enveloped
Extra layer, lipid, or protein
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Isometric
- Adenovirus
- A sphere made of triangles
- No envelope
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Helical
- Tobacco mosaic virus
- Rod shaped
- No envelope
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Complex
- T4 bacteriophage
- Has a tail and collar
- No envelope
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Productive Phage/Host Infection
- Lytic phage replication
- Continuous production
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Latent State of Phage/Host Interaction
- Virus DNA integrates
- Host modified
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Attachment of Lytic Phase Multiplication
- Phage binds receptor on host cell
- Major basis for host specificity
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Penetration of Lytic Phase Multiplication
- Nucleic acid enters host cell
- Intracellular state begins
- Vulnerable to restriction endonucleases
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Transcription and Translation of Lytic Phase Multiplication
- Copy and express phage genes by host machinery
- Early proteins- nuclease, phage DNA synthesis
- Late proteins- assembly and lysis of host
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Assembly of Lytic Phase Multiplication
Assembly into intact virions
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Release of Lytic Phase Multiplication
- Lysozyme
- For T4, burst size of 200, total time 30 min
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Steps of Lytic Phase Multiplication
- Attachment
- Penetration
- Transcription and translation
- Replication of DNA and synthesis of proteins
- Assembly
- Release
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Filament Phage
- M13 and fd
- Adsorb on the tip of F+ pilus
- Assembles as they exit
- Bacterial host multiplies slowly
- -Carrier cells
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Cholera
- Severe watery diarrhea, vomiting
- Ingestion of bacteria by drinking fecally contaminated water or foods
- Bacteria produces toxin
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Toxin of Cholera
- Causes intestinal cells to continuously secrete chloride ions into lumen
- Other electrolytes follow resulting in large volume of fluid released
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Replication Pathway of Latent Phage Replication
- Lytic
- Quickly takes over host; ultimately kills
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Integration Pathway of Latent Phage Replication
- Lysogenic
- Phage genome integrates into host DNA – prophage
- -Done by site specific recombination
- Will remain in cell and passed onto daughter cells
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Site Specific Recombination of Integration of Phage DNA
- Specific phage genomes will synapse and insert at the same point in bacterial chromosome
- Between the galgene and biogene
- Phage is specific to certain receptors
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Lysogenic Cells
- No other phage can infect
- Lambda phage and E. coli protect the phage from others
- Conversion
- -Confer new properties to lysogen
- -Toxins of
- •Clostridium botulinum
- •Corynebacterium diphtheriae
- •Vibrio cholerae
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Lysogenic to Lytic
- During lysogenic state
- A repressor controls genes for excision (removal) of phage DNA
- Upon damage of cell, repressor removed and excisase made
- Phage induction ensues
- Excision of phage genome
- Productive infection begins with creation of new phage and eventual lysis of host
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Specialized Transduction
- Performed only by temperate phages
- Removes part of chromosome during excision
- Phage becomes defective
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Generalized Transducion
- T4 Bacteriophage
- Occurs during assembly
- Only 1 transduces
- Bacterial DNA and randomized pieces are transduced
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Specialized Transduction
- Lambda
- Occurs during excision
- All transduce
- Specific (gal/bio) is transduced
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Animal Virus
- DNA/RNA; ss or ds; segmented or single
- Isometric, helical, pleomorphic
- Presence (or absence) of envelope
- Matrix protein inside envelope
- Attachment spikes/proteins
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Types of Animal Viruses
- Enteric Viruses
- Respiratory Viruses
- Zoonotic Viruses
- Sexually Transmitted Viruses
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Enteric Viruses
- Gastroenteritis by rotavirus
- Ingest these
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Respiratory Viruses
Influenza by influenza virus
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Zoonotic Viruses
- Rabies by rabies virus
- Transmitted from animal to human
- Bats, inhaling feces
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Sexually Transmitted Viruses
Genital warts by papillomaviruses
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Acute Infections
- Short duration
- Productive infection
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Persistant Infections
- Latent infection
- Chronic infection
- Slow infection
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Acute Infection Reproduction
- Attachment
- Entry
- Uncoating
- Transcription and replication
- Maturation
- Release
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Attachment of Acute Infection Reproduction
- Several attachment proteins required- usually glycoprotein receptors
- May bind to more than one kind of receptor
- Usually species specific, unless mutated
- Use our receptors as the viruses inceptor
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Entry of Acute Infection Reproduction
Envelope fusion or endocytosis
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Envelope Fusion
Viral envelope fuses with host membrane
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Endocytosis
- Host membrane surrounds virus
- Can be done with naked or enveloped virus
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The whole variant enters with animal
Can enter the host by endocytosis or by envelope fusing
What are two ways animal viruses differ from phage in entry of their host cell?
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Uncoating of Acute Infection Reproduction
Nucleic acid separates from protein coat
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Transcription and Replication of Acute Infection Reproduction
- Based on RNA or DNA; ds or ss
- Virus may bring own enzymes for replication
- -RNA dependent RNA polymerase
- -Enzyme does not exist in host
- Otherwise, all enzymes/proteins are encoded on viral genome or used from host
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Needs to become double stranded
•Could wait for another DNA polymerase to become dsDNA or brings his own
Transcription from dsDNA to mRNA
Translation of virus proteins
•Could make more nucleocapsids
Has a DNA strand that only synthesizes single strands of DNA
You have to come or bring something as a dsDNA virus
If a virus entered a host cell as a single stranded DNA genome what would it require to begin synthesis of viral proteins as well as genome replication?
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Maturation of Acute Infection Reproduction
- Assembly of nucleic acid with capsid protein
- Usually takes place in an organelle
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Release of Acute Infection Reproduction
Lysis or budding
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Lysis
Host cell dies due to lack of metabolic functions
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Budding
- Often associated with persistent infections
- Picks up envelope from host
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Genetic Reassortment
- Infection of one cell by two different segmented viruses
- Usually causes zoonoses
- -West Nile virus
- -Avian influenza
- -Swine influenza
- -Can cause pandemics – worldwide epidemics
- Influenza strains for infecting different species of animals and birds
- •Can be coinfected by 2 different strains of flu
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Influenza Genome
- Eight segments of RNA
- •Hemagglutinin encoded for attachment to host
- A human can have antibodies that recognize human influenza hemagglutinin
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Coinfection of Genetic Alterations
Avian influenza and human influenza can infect the same host cell of a pig or duck
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Antigenic Shift
- Human influenza with avian segment encoding hemagglutinin
- Human antibodies do not recognize the avian hemagglutinin
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Spanish flu
Asian flu
Hong Kong flu
Russian flu
4 Influenza Pandemics
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DNA polymerase from host
As a dsDNA virus, what enzyme would you use to make more genome?
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Latent Infections
- Infection to symptomless to reactivation
- -Herpesvirus: HSV-1, genital herpes HSV-2
- -Varicella-zoster virus causing chicken pox then shingles upon reactivation
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Chronic Infections
- Infectious virus is detected at all times
- Continues to produce more virus
- Hepatitis B and C
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Hepatitis B and C
- Infects the liver and causes inflammation and scarring
- Can be acute, but generally turns chronic
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Slow Infections
- Infectious agent gradually increases
- HIV
- Prions (made of protein not a virus)
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Prions
- Exclusively protein
- Transmissible spongiform encephalopathies (mad cow, Creutzfeldt-Jakob)
- Infects brain
- -Brain material degrades, holes of no brain matter
- Interacts with normal proteins and causes change in
- quaternary structure
- Miss folded proteins
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Viroids
- Circular RNA
- Infects only plants
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Stanley Pursiner
Identified prions
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Creutzfeldt and Jakob
Discover similar disease found in sheep in a man
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Gajdusek
- Studies kuru spread by cannibalistic rituals in new Guinea
- Won Nobel Prize in 1976
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Innate Defense
- Proactive in keeping out microbes
- Limited in identifying “foreigners”
- •Pattern recognition
- •Limited capability of identifying outside bacterias
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Adaptive Defense
- Specialized
- Must learn foreigner first then will “memorize"
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Types of Innate Defenses
- First-line defenses
- Cell communication
- Phagocytes
- Complement system
- Inflammation
- Fever
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First Line Defense
- Physical barriers
- Antimicrobials
- Normal flora
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Physical Barriers
- Skin – epithelial cells
- -Carotene level constantly flaking off any skin that has microbes
- Mucous membranes (surfaces inside the body)
- Cilia
- Mucus- traps mucus
- Peristalsis; mucociliary escalator- moves mucus up to throat to be swallowed into stomach
- Urine- washes the urethra, cleanses the surface
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Antimicrobial Substances
- Sweat- high salt
- Lysozome
- Peroxidase enzymes
- Lactoferrin
- Defensins
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Lysozome
- Targets peptidoglycan
- Tears, saliva, mucus
- Antimicrobial substance
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Peroxidase Enzymes
- Produces oxidizing compounds
- Toxic to bacteria
- Saliva, milk, phagocytes
- Antimicrobial substance
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Lactoferrin
- Iron-binding
- Bacteria need iron to grow, but body uses all of it
- Saliva, mucus, mother’s milk
- Antimicrobial substance
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Defensins
- Disrupt bacterial membranes
- Causes holes to form in cell walls
- Antimicrobial substance
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Normal Flora
- The mixture of microorganisms regularly found on body surface: bacteria (majority), fungus, protozoa
- Provide competition- good bacteria uses nutrients so pathogens must fight for the nutrients to affect body
- Can produce toxic substances to other bacteria
- Termed opportunistic only when introduced to a new area and cause disease
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Probiotics
- Oral administration of specific bacterial cultures
- Found in yogurt products
- -Lactobacillus bulgaricus, L. casei, S. thermophilus
- Used to combat infectious diarrhea
- Prevention of postoperative infections
- Enhancement of immune functions
- Give the intestinal tract an extra layer of protection
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Young child suffering from Cholera
- Which of the following individuals would most
- benefit the MOST from probiotics?
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Cells of Innate Immune System
Leukocytes (white blood cells)
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Leukocytes
- Immune defense cells
- Granulocytes
- Mononuclear phagocytes
- Dendritic cells
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Granulocytes
- Neutrophils: rapid response phagocytes; found in blood
- Ready to respond to inflammatory signals
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Mononuclear Phagocytes
Macrophages: engulfment and destruction; found in tissue
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Dendritic Cells
Brings info to adaptive immunity
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Formation and Development of Blood Cells
- Hematopoiesis
- Originate from bone marrow’s hematopoietic stem cells
- Develop from stem cells into special cells via signals called colony stimulating factors
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Cell Communication
- Done by surface receptors and protein signals
- Cytokines are specific signals
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Types of Cytokines
- Chemokines
- Colony-stimulating factors
- Interleukins
- Interferons
- Tumor necrosis factors
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Chemokines
- Cell chemotaxis
- Cell movement
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Colony-Stimulating Factors
- Multiplication and differentiation
- Proteins that attach to surface receptors
- Help differentiate between cells
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Interleukins
- Diverse function usually stimulates cell, ex. inflammatory response
- Play part in viruses, start to metabolize to respond to what’s going on in the body
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Interferons
Cell responds to viral infections
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Tumor Necrosis Factors
Inflammatory response, cell death
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Surface Receptor
- On cell membrane
- Receives signals and relays the signal to the interior of the cell
- Signals are molecules that bind to the receptors
- -ligands
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Sensor Systems of Cells
- Toll-like receptors
- NOD proteins
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Toll-Like Receptors
- Found on cell surfaces
- Identifies bacterial compound
- Signals to cell nucleus
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NOD Proteins
- Receptors in cell cytoplasm
- Identifies bacterial compounds
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Complement System
- System of inactive proteins circulating in blood and body
- Proteins bind to “foreign” cells and immune system responds with other complement proteins to destroy invader
- Find invader and take care of it
- 3 ways to activate: classical, lectin, or alternative pathway
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Classical Pathway
- Antibody recognizes foreign invader’s surface
- Can attach to DNA or RNA
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Lectin Pathway
- Mannose binding lectins (proteins) (MBL) recognizes mannose on bacterial surfaces
- Combines to mannose
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Alternative Pathway
- C3b binds to all surfaces; foreign surfaces allow C3b to remain
- Body removes C3b cells
- Bacteria and viruses don’t
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Classical, Lectin, and Alternative
If a virus, then only classical and alternative would bind
A bacterial cell enters through a cut. Which of the three complement proteins could bind?
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Activities of Complement
- Inflammation
- Bacterial cell lysis via membrane attack complex (MAC)
- Opsonization
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Inflammation
- Recruitment of phagocytes
- C3b binding to cell
- Dilation of blood vessels
- Leakage of fluid from vessels
- Migration of leukocytes to infected tissue
- Signs include: redness, warmth, pain, swelling, altered function
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To recruit phagocytes to area of infection
What is the main purpose of inflammation?
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Foreign Cell Lysis
Assembly of complement proteins into a membrane attack complex to form pores in bacterial membrane
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Phagocytosis
- 1.Chemotaxis
- 2.Recognition/attachment
- 3.Engulfment
- 4.Fusion with lysosome
- 5.Destruction
- 6.Exocytosis
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Phagocytosis and Opsonization
- C3b (opsonin) binds to cell surface – causes enhanced phagocytosis
- Easily identified by phagocyte
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Fever
- Triggered by macrophages emitting cytokines during inflammation
- •Pyrogens
- Reduces microbial growth
- Activates and speeds up body defenses
- Increases enzymatic rates
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Immunity
- Acquiring an antibody response that protects against future infection of the same agent
- Passive
- Active
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Passive Immunity
- Ig’s are given to body
- Natural vs. artificial
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Active Immunity
- Ig’s are generated by body
- Natural vs. artificial
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Natural Passive Immunity
Mother's milk
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Artificial Passive Immunity
- Serum given
- Immune serum globulin
- Hyperimmune serum globulin
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Natural Active Immunity
Natural exposure
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Artificial Active Immunity
- Given infection on purpose
- Vaccine
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Immune Serum
- Pooled IgG by donor plasma
- Several types of IgG offers some protection
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Hyperimmune Serum
- Selected pooled Ig’s in high amount for a
- specific disease
- To treat or prevent disease
- Examples; Hep A and B, tetanus, rabies
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Why Vaccines Work
- Body is exposed to new antigen via vaccine imposing a primary immune response from the innate and adaptive
- Memory is generated by the adaptive response
- When exposure to antigen is experienced again, secondary immune response jumps in
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Clonol selection and expansion
Which of the following terms best describes what occurs during an initial infection that eventually generates memory T and B cells specific for that particular infection?
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Vaccine
- A pathogen or its products
- Benefit of widespread vaccinations
- -Herd immunity
- Attenuated
- Inactivated
- –Whole agent vaccines
- –Subunit vaccines
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Herd Immunity
Although one person may not be immunized, if the people surrounding him are immunized, then they are protected
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Attenuated Vaccines
- Living virus or bacterial cell
- Can infect and replicate but does not cause symptoms or only mild symptoms
- Different growth conditions or animal host; genetic engineering
- Advantages- long lasting immunity- more antigens to react against (whole virus cell) and longer period of time the antigen will be in the body; exposure to non-immunized individuals
- Disadvantages- exposure to non-immunize individuals; require refrigeration; not applicable to pregnant women; could mutate
- Babies can’t handle flu mist because of low immune systems
- Examples; yellow fever, rubella, typhoid fever
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Inactivated Vaccines
- Microorganisms that cannot replicate
- -Whole agents (whole cell or virus) and toxoids killed virus or bacteria by chemical
- -Subunit agents: protein subunit: key
- protein of surface, recombinant and polysaccharide: T independent B cell activation
- Conjugate: polysacchaide linked to protein – initiate T dependent and T independent
- Advantages- self contained; cannot mutate; subunit causes less side effects
- Disadvantages-only one or a few antigens recognized; requires boosters due to low exposure time
- Hepatitis A- inactivated virus
- Hepatitis B- subunit agent
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Poliomyelitis Vaccine
- Salk vaccine- inactivated
- Sabin vaccine- attenuated
- 1980 US is polio free; goal of eradication by 2000
- -Money and culture
- -Don’t want any part of western medicine
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Primary Response in Antibodies
- Creates memory
- New antigen
- Slow – 10 days to 2 weeks
- Clonal selection occurs
- Low affinity
- Memory cells formed
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Secondary Response in Antibodies
- Anamnestic
- Enhanced response to same agent
- Stronger
- Higher affinity
- Faster
- Longer lasting
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Specific Immunity Components
- Humoral immunity (B cell and antibodies)
- Cellular immunity (T cells)
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Humoral Immunity
Eliminates pathogens and agents that don’t appear to be “self”
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Cellular Immunity
Targets infected human cells
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Adaptive Immunity
- B cells activated by antigens and T cells to make antibodies
- T cells activated by dendritic and other T cells to identify cells in trouble
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Lymphoid System
- Central area for B and T cells to come in contact with antigens
- Lymph enters lymphatic vessel from tissue
- Empties into vein
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Secondary Lymphoid Organs
- Lymph nodes
- Spleen
- Tonsils
- MALT
- SALT
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Antigens
- Interacts with cells of immune system
- Antibody
- Lymphocyte
- Can be proteins, nucleic acids, polysaccharides or glycolipids
- Consist of antigenic determinants or epitopes
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Epitopes
Specific regions on antigen that are recognized
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Antibodies
- Immunoglobulins (Ig)
- Glycoprotein
- Structure- Arms of Ig are termed Fab region, stem is termed the Fc region
- Function: bind to antigens
- Produced by B cells
- Five classes: IgM, IgG, IgA, IgD, IgE
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Variable Region of Antibody Structure-Function
- Functions in binding to antigen
- Accounts for specificity of antibody
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Constant Region of Antibody Structure-Function
Heavy chain constant region determines antibody class
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IgG
- Major Ig in serum – 80%
- Opsonizes pathogens
- Neutralizes toxins
- Activates classical pathway
- Crosses placenta
- Produced in colostrum
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IgM
- First Ig made
- Cannot cross the placenta
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Secretory IgA
- Produced at mucosal surfaces
- Synthesized by B cells in MALT (Mucosa associated lymphoid tissue)
- Abundant in breastmilk
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Dendritic Cells
- Found under skin and mucosal linings
- Samples all material for “foreign” proteins
- Displays information on MHC
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Major Histocompatibility Complex (MHC)
- On human cells present antigen fragments (protein, etc.) from inside cell
- Two Classes: I and II
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MHC I
All human cells present endogenous (self) proteins
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MHC II
Macrophages, dendritic cells, B cells present exogenous (other than self) proteins
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T Cells
- Have receptors on surface
- Before activation T cytotoxic or T helper cells are termed naive
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Activated cytotoxic T cells (Tc)
- Attack virus–infected cells
- Have CD8 protein associated with T-cell receptor
- Binds MHC I on other cells
- Triggers apoptosis or cytolysis by release of perforin
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Activated helper T cells (Th)
- Binds MHC II on other cells
- Have CD4 protein on surface associated with T-cell receptor
- Th1: macrophage activation; stimulate T cells
- Th2: B-cell antibody response
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T Cell Activation
- Dendritic cells pick up foreign antigens from periphery
- Present antigen to T cells along with co-stimulatory molecule
- T cell matures to produce surface receptors and release cytokines
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Tc Cell Activation
- Binds to MHC I on human cell surface
- If recognition occurs, cytotoxins are released
- Cytokines released to “alert” neighbor cells
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Th1 Cell Activation
- Recognizes antigens on MHC II by macrophage
- Stimulates more active killing in macrophage
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B Cell Activation-T Dependent Antigen (Th2)
- Antigen bound by B cell and internalized
- Presented at B cell surface by MHC class II
- Recognized by Th2 cell
- B cell stimulated by T cell to proliferate into plasma cells and memory cells
- Plasma cells make antibodies
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B Cell Activation-T Independent Antigens
- No need for T-helper cell
- B cell proliferation stimulated by polysaccharides or lipopolysaccharides on a bacterial surface
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Clonal Selection Theory
- Ability of lymphocytes to recognize a specific antigen
- For example: ability to respond to 100 million different epitopes due to production of almost 1 billion B cells
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Clonal Selection
- Proliferation & differentiation of only subset of T or B cells stimulated by antigen and secondary signal
- Yields active cells and memory cells
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