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8/2/2019 Human Immune Response
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Human Immune Response
Part 1: innate immunity
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One of these things is not like theothers..
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Our bodies are under constantattack from pathogens
A pathogen is an organism that can causedisease
Pathogens include:
Bacteria
Viruses
Protists
Fungi
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nucleic acid
capsid
envelope
Review: VIRUSES
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cell wall
plasmamembrane
cytoplasm
circular DNA
Review: BACTERIA
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There are two types ofresponses to pathogens
INNATE IMMUNITY
Non-specific: doesntdistinguish oneinfectious agent fromanother
Rapid response topathogens
Is present before anyexposure to pathogens
Is effective from the timeof birth
ACQUIRED IMMUNITY(AKA Adaptive response)
Specific response to aparticular antigen
Slower response topathogens
Requires previousexposure to the pathogen
Built over a life time ofexposure to pathogens
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Two types ofInnate Immunity
First Line of Defense
External defenses
Skin
Mucous membranes
Chemical secretions
Second Line of Defense
Internal defenses
Phagocytic cells
Natural killer cells
Antimicrobial proteins
Inflammation
Fever
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External Defense: Skin
Cannotnormally be
penetratedby bacteriaand viruses
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Secretions fromsebaceous and
sweat glandskeep the skin ina pH range of 3
to 5 (acidic)which kills mostmicrobes
External Defense: Skin
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Line digestive,respiratory, and
genitourinary tracts
Trap microbes andparticles
External Defense:Mucous Membranes
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In the trachea, ciliatedepithelial cells sweepout mucus andtrapped microbes
Prevents these fromentering the lungs
Swallowing exposesthem to the acidicenvironment of thestomach
External Defense:Mucous Membranes
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Microbialcolonization is alsoinhibited by saliva,
tears, and mucussecretions
All of thesesecretions containantimicrobialproteins
External Defense:Chemical Secretions
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An example is lysozyme, an
enzyme that digests the cell walls of
many bacteria.
External Defense:Chemical Secretions
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Two types ofInnate Immunity
First Line of Defense
External defenses
Skin
Mucous membranes Chemical secretions
Second Line of Defense
Internal defenses
Phagocytic cells
Natural killer cells Antimicrobial proteins
Inflammation
Fever
Link to video clip
http://intro%20to%20second%20line.mp4/http://intro%20to%20second%20line.mp4/8/2/2019 Human Immune Response
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Internal Defense:Phagocytic cells
White blood cells (leukocyctes) that ingestinvading organisms
3m
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Internal Defense:Phagocytic cells
Three types:
1. Macrophages
2. Esinophils
3. Neutrophils
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Internal Defense:Phagocytic cells
Macrophages Large, long-lived
phagocytes
Cells extend longpseudopodia, engulf themicrobe into a vacuolewhich fuses with alysosome.
Some microbes have outercapsules to whichmacrophages cannotattach
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Link to animation
http://highered.mcgraw-hill.com/sites/0072495855/student_view0/chapter2/animation__phagocytosis.htmlhttp://highered.mcgraw-hill.com/sites/0072495855/student_view0/chapter2/animation__phagocytosis.html8/2/2019 Human Immune Response
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Internal Defense:Phagocytic cells
Esinophils
Help fight large parasiticinvaders
Position themselvesalongside the parasite
and dischargedestructive enzymesthrough exocytosis
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Internal Defense:Phagocytic cells
Neutrophils
Most abundant whiteblood cell
Recruit and activateother cells of theimmune system
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Internal Defense:Phagocytic cellsNeutrophils
Have three strategies for directlyattacking micro-organisms
phagocytosis (ingestion)
release of anti-microbial proteins
generation of neutrophil extra cellular traps(NETs)
NET formation
http://www.youtube.com/watch?v=ZWXBViH86NE&feature=relatedhttp://www.youtube.com/watch?v=ZWXBViH86NE&feature=related8/2/2019 Human Immune Response
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Internal Defense:Natural Killer Cells
Do not attack microbes directly
They destroy infected cells (typically thoseinfected with viruses)
Also attack abnormal body cells that could
become cancerous
They attack the cells membrane and cause
the cell to lyse Natural Killer Cells
http://www.youtube.com/watch?v=HNP1EAYLhOshttp://www.youtube.com/watch?v=HNP1EAYLhOs8/2/2019 Human Immune Response
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I l D f
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Internal Defense:Antimicrobial Proteins
A variety of proteins that attack microbesdirectly or impede microbe reproduction
Example: Lysozyme
Example: Interferons
Secreted by virus-infected cells
Do not benefit the infected cell but induceneighboring cells to produce chemicals thatinhibit viral reproduction
Interferons
http://highered.mcgraw-hill.com/sites/0072556781/student_view0/chapter31/animation_quiz_2.htmlhttp://highered.mcgraw-hill.com/sites/0072556781/student_view0/chapter31/animation_quiz_2.html8/2/2019 Human Immune Response
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Knowledge Review
Give me:
5 types of cell involved in defense againstdisease
4 ways to prevent infectious agentsentering the body
3 responses of neutrophils
2 types of immunity
1 antimicrobial protein
I l D f
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Internal Defense:Inflammation Tissue damage leads to a localized
inflammatory response
Could be injury
Could be invasion by microbes Capillaries respond by:
Increased dilation
Increased permeability
Enhanced delivery of clotting elements
Enhanced migration of phagocytic cells
Leads to increased redness, heat, and swelling
Inflammatory Response
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Major events in the local inflammatory response
Pathogen Pin
Macrophage
Chemical signals
Capillary
Phagocytic cells
Red blood cell
Bloodclottingelements
Blood clot
Phagocytosis
Fluid, antimicrobial proteins,and clotting elements movefrom the blood to the site.Clotting begins.
2
Chemical signals releasedby activated macrophagesand mast cells at the injurysite cause nearby capillariesto widen and become morepermeable.
1Chemokines released by variouskinds of cells attract morephagocytic cells from the bloodto the injury site.
3Neutrophils and macrophagesphagocytose pathogens andcell debris at the site, and thetissue heals.
4
I t l D f
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Internal Defense:Fever
If damage or infection issevere, a widespread non-specific response may occur
Increased body temperature
Inhibits growth of somemicrobes
Facilitates phagocytosis
Speeds up repair of tissue
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Two types ofInnate Immunity
First Line of Defense
External defenses
Skin
Mucous membranes Chemical secretions
Second Line of Defense
Internal defenses
Phagocytic cells
Natural killer cells Antimicrobial proteins
Inflammation
Fever
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Its a race1. Pathogens are ________ that cause disease
2. _________ have a close relationship with their host, andhave a negative impact on the host
3. ________ conditions in the stomach kill pathogens
4. ___________ in tears and saliva are toxic to pathogens
5. The vaginal tract contains ______ acid
6. The _________ system is protected by goblet cells andmucus
7. ________ is an example of bacteria that can infect wounds
8. The immune system is made up of _______ blood cells
Whi h f h f ll i i NOT "fi
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Which of the following is NOT a "first
line of defense" in the immune
response?A. Fever
B. Skin
C. Mucous membranesD. Lysozyme
E. Tears
F. Saliva
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Which of the following is NOT a cellof the innate immune system?
A. Natural killer
B. Macrophage
C. NeutrophilD. T cell
E. Esinophil
F. Skin
A
B
C
D
E
F
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Which cell type is part of the innateimmune system?
A. Lymphocyte
B. LeukocyteA
B
C
D
E
F
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pH of the skin is:
A. Basic
B. AcidicA
B
C
D
E
F
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Which molecule disrupts the viral
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Which molecule disrupts the virallife cycle by preventing the
replication of DNA in infected cells?A. Lysozyme
B. Interferons
C. PhagocytolD. NETs
A
B
C
D
E
F
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Review
Second line defenses Pathogen Acquired Virus Skin
Phagocytic cells Natural killer cells Antimicrobial proteins Inflammation Fever
Macrophages Esinophils Neutrophils Interferons
Bacteria Innate First line defenses Mucous membrane Sebaceous gland
Sweat gland Cilia Trachea Lysozyme Leukocyte
Pseudopodia Lysosome Exocytosis NETs
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Human Immune Response
Part 2: acquired immunity
aka adaptive immunity
If thi i th h t i th
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If this is the answer, what is thequestion?
Lymphocyte
Bacteria
Lysozyme
Chlamydia
Chronic
Antigen
VirusLactic acid
Mucus
Parasite
Choose 3 wordsThink of a question they could be used toanswer
Eg. What causes flu? A = a virus
Phagocyte
HIV
Influenza
Goblet cells
Pathogen
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Acquired Immunity
The third line of defense
The key cells of the third line of defense arelymphocytes B cells
T Cells
Lymphocytes recognize and respond tospecific microbes and the molecules on the
foreign cells membrane (antigens)
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Antigens include:Potentially damagingmicrobes and
their toxins.
Substances such as pollenand flea and dust mite feces.
Blood cell surface proteins.The surface proteins oftransplanted tissues andorgans.
Photo:EII
Mallow pollen SEM.
Many pollens are antigens
The feces of fleas and mitesare antigenic in some people
Antigens
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The Immune System
Phagocytes footsoldiers
T-lymphocytes search
team
B-lymphocytes elite attacksquad
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Lymphocytes originatefrom pleuropotent stemcellsin the bone marrow
or liver of a developing fetus If they migrate to the
thymus to mature, theybecome T cells
If they stay in the bonemarrow to mature, theybecome B cells
Lymphocytes
H d B d T ll
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B and T cells haveantigen receptors
A single B or T cellshas about 100,000receptors, all with
exactly the samespecificity
How do B and T cellsrecognize antigens?
H d B d T ll
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There is anenormous variety ofB and T cells in the
body, each withdifferent specificity
This allows
response to millionsof potentialpathogens
How do B and T cellsrecognize antigens?
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While B cells and T cells are developing, their antigenreceptors are tested for potential self-reactivity
Will I attack cells of my own body?
If YES: rendered non-functional or destroyedby apoptosis
This leaves only lymphocytes that react toforeign substances
Autoimmune diseases result when thisself-reactivity check malfunctions
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How do T and B cells differ?
B cells: HUMORAL IMMUNE RESPONSE
T cells: CELL MEDIATED IMMUNE RESPONSE
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B ll
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B cells:HUMORAL IMMUNE RESPONSE
1.Antigen floating in the blood binds toreceptor on B cell surface
2.B cell divides into two cell types:
Plasma B cells: Memory B cells:
HUMORAL IMMUNE RESPONSE
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HUMORAL IMMUNE RESPONSE
Plasma B cells
Secrete antibodiesinto the bloodimmediately
HUMORAL IMMUNE RESPONSE
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HUMORAL IMMUNE RESPONSE
Plasma B cells
Antibodies areproteins that attach tospecific pathogen
antigens
Tip of antibodies
become specialized forspecific antigens
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Antibody Molecule
antigenbinding sites
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HUMORAL IMMUNE RESPONSE
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HUMORAL IMMUNE RESPONSE
Plasma B cells
The antibody / antigencomplex makes themicrobe easier targets
for phagocytes
Inactivation of Antigens
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Inactivation of AntigensClumping particulate
antigens
Solid antigens such as
bacteria are stuck together in
clumps.
Bacterial cell
Neutralization
Antibodies bind to viral
binding sites and coat
bacterial toxins.
VirusToxin
Antibody
Enhances Phagocytosis
Macrophage
Bacteria
Soluble antigens are stucktogether to formprecipitates.
Precipitation ofsoluble antigens
Solubleantigens
Antibodies
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HUMORAL IMMUNE RESPONSE
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HUMORAL IMMUNE RESPONSE
Memory B cells Memory B cells:
Long-lived cells bearing receptors for the samespecific antigen
Eventually, a few cells give rise to thousands ofnew cellsall clonesof the original and all specificto original invading antigen
Memory cells will continue to divide and createantibodies for the rest of the life of the organism
Division of antigen specific B
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1. A blood stem cell undergoes differentiation andgenetic rearrangement to produce:
2. immature lymphocytes with many differentantigen receptors. Those that bind to:
3. antigens from the body's own tissues aredestroyed, while the rest mature into:
4. inactive lymphocytes. Most of these will never
encounter a matching:
5. foreign antigen, but those that do are activatedand produce
6. many clones of themselves!
cells is calledCLONAL SELECTION
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B Cells
antibodies
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Activation of B Cells by
Antigenantigen
Clonal Selection
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Clonal Selection
Clonal Selection
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Clonal Selection
plasma cells memory cells
antibodies
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T cells:
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T cells:CELL MEDIATED IMMUNE RESPONSE
A viral infected cell exposes the antigen on its owncell surface, to say Ive been infectedkill me
Helper T cell binds to the antigen exposed on thesurface of an infected cell
Helper T cells release chemicals called cytokinesthat activate macrophages, natural killer cells, andkiller T cells
These cells respond by destroying the infected cell
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The rate of the immune response is different
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depending on if the body has seen the antigen
before
If its the first exposure:
About 10 to 17 days required for peakplasma B cell response
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The rate of the immune response is different
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depending on if the body has seen the antigen
before
Second (and subsequent) exposure:
Response is faster (2 to 7 days)
Magnitude is greater
Duration is longer
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Humoral Response sort it out!
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- and in response to stimulation by cytokines released by the T cell,
clonal selection of B cells occurs.
- macrophages move to engulf and digest the antigen.- and memory cells which are able to deal with the antigen if
encountered again
- Fragments of the antigen are presented on the surface of themacrophage
- clonal selection of more identical T cells.
- An antigen enters blood stream and
- to form antigen presenting cell (APC).
- Specific T cells attach to the antigen fragments presented by theAPC and release cytokines which stimulate
- Then a specific B cell binds with one of the T cells
- This produces plasma cells which make large quantities ofantibodies
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Types of
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Acquired
Immunity
Naturally Acquired Immunity
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y q y
Naturally Acquired
Active
Antigens enter the body
naturally, as when:
Microbes cause the person
to catch the disease.
There is a sub-clinical infection
(one that produces no evident
symptoms).
The body produces specialized
lymphocytes and antibodies.
Passive
Antibodies pass from the mother
to the fetus via the placenta
during pregnancy or to her infant
through her milk.
The infant's body does not produce
any antibodies of its own.
Artificially Acquired Immunity
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y q y
Active
Antigens (weakened or dead
microbes or their fragments) are
introduced in vaccines.
The body produces and
specialized lymphocytes and
antibodies.
Passive
Preformed antibodies in an
immune serum are introduced
into the body by injection
(e.g. anti-venom used totreat snake bites).
The body does not produce
any antibodies.
Artificially Acquired
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A summary of innate and acquired immunity
INNATE IMMUNITYRapid responses to a
broad range of microbes
ACQUIRED IMMUNITYSlower responses to
specific microbes
External defenses Internal defenses
Skin
Mucous membranes
Secretions
Phagocytic cells
Antimicrobial proteins
Inflammatory response
Natural killer cells
Humoral response(antibodies)
Cell-mediated response(cytotoxic lymphocytes)
Invading
microbes(pathogens)
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Immune Technologies
Monoclonal Antibodies
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A monoclonal antibody is anartificially produced antibodyfor a specific antigen.
Monoclonal antibodies areuseful for 3 reasons:
They are totallyuniform (i.e. clones).
They can be produced in largequantities.
They are highlyspecific.Monoclonal antibodies
chemically linked to a
fluorescent dye to detect the
presence of gonorrhea
Monoclonal Antibody Production
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Monoclonal Antibody Production
Stimulate the production of B-cellsin mice by injecting them with theantigen.
These B-cells produce an
antibody against the antigen. B-cells isolated and fused with
immortal tumor cells.
Immortal cells cultured indefinitelyin a suitable growing medium.
Antibodies isolated via proteinchromatography
Diagnostic Uses of
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gMonoclonal Antibodies
Monoclonal antibodies have manydiagnostic uses:
Detecting the presence of pathogens such as Chlamidiaandstreptococcal bacteria, distinguishing between HerpesvirusI and
II, and diagnosing AIDS.
Measuring protein, toxin,or drug levels in serum.
Blood and tissue typing.
Detection of antibioticresidues in milk.
Detecting pregnancy.
Direct treatment of disease (i.e. rabies)
How Pregnancy Tests Work
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Dipstick
Antibody moves
by capillary action
Antibodies
tagged
with blue
latex
HCG bound to
free antibody
HCG in the urine of a pregnant women binds to
the color-labeled antibodies. The antibodies
then travel up the dipstick by capillary action.
g yThe test area of the dipstick contains two types ofantibodies: free monoclonal antibodies and capturemonoclonal antibodies, bound to the substrate in thetest window (arrowed).
Immobilized
capture antibodies
Colored latex in
test window
The HCG-antibody complexes are bound by
capture antibodies. The labeled antibodies
create a coloured line in the test window.
Vaccination
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Vaccination
Vaccination is the purposefuladministration of antigenic material toproduce immunity to a disease.
live but weakened forms of pathogens
killed or inactivated forms of pathogens
purified material such as proteins
Vaccination
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Vaccination
The vaccine stimulates clonal selectionand development of memory cells, butwithout developing the disease symptoms.
Vaccination
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Vaccination
If an infection of the disease occursnaturally after vaccination, the body reactsas if it is the second exposure to the
disease
Vaccination
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Vaccination
Vaccination is generally considered to bethe most effective and cost-effectivemethod of preventing infectious diseases.
Vaccination
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Vaccination
BENEFITS
Eradication of diseasefrom a population (i.e. smallpox)
Reduced deathfromdisease (i.e. measles)
Reduced disabilitiesfromdisease (i.e. polio)
Decreased loss of workdays due to disease (i.e. flu)
DANGERS
Vaccine immunity lesseffectivethan naturalimmunity
Side effectsof vaccination
Antibiotics
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Antibiotics
Antibiotics are substances that killsbacteria or inhibits its growth
Antibiotic Action
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Antibiotic Action
Antibiotics block metabolic pathwaysand structures found in bacteria
the bacterial cell wall
bacterial ribosomes enzymes that are specific to bacteria
Viruses cant do metabolism, so theyarent effected by antibiotics
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