Chap 14 - 18
Selected Topics in Immunology
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The Nature of Infectious Disease
• Infection is the invasion of the host by a pathogen
• Disease results if the invading pathogen alters normal body functions
• Disease is also referred to as morbidity
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The Nature of Infectious Disease
• Manifestations of Disease: Symptoms, Signs, and Syndromes
– Symptoms– Subjective characteristics of disease felt only by the
patient– Signs
– Objective manifestations of disease observed or measured by others
– Syndrome– Symptoms and signs that characterize a disease or
abnormal condition– Asymptomatic, or subclinical, infections lack
symptoms but may still have signs of infection
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The Nature of Infectious Disease
• Causation of Disease: Etiology– Study of the cause of disease
– Germ theory of disease– Disease caused by infections of pathogenic
microorganisms
– Robert Koch developed a set of postulates to prove a particular pathogen causes a particular disease
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Figure 14.7 Koch’s postulatesThe suspected agent must be presentin every case of the disease.
Diseased subjects
Agent not typically foundin healthy subjects
Healthy subjects
Petri plate
BacterialcoloniesThe agent must be
isolated and grownin pure culture.
Streaked plates
Injection
The cultured agent must causethe disease when it is inoculatedinto a healthy, susceptibleexperimental host (animal or plant).
The same agent mustbe reisolated from thediseased experimentalhost.
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The Nature of Infectious Disease
• Causation of Disease: Etiology– Exceptions to Koch’s postulates
– Some pathogens can’t be cultured in the laboratory
– Diseases caused by a combination of pathogens and other cofactors
– Pathogens that require a human host– Difficulties in satisfying Koch’s postulates
– Diseases can be caused by more than one pathogen
– Pathogens that are ignored as potential causes of disease
.
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The Nature of Infectious Disease
• Virulence Factors of Infectious Agents– Pathogenicity
– Ability of a microorganism to cause disease– Virulence
– Degree of pathogenicity– Virulence factors contribute to virulence
– Adhesion factors– Biofilms– Extracellular enzymes– Toxins– Antiphagocytic factors
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Figure 14.9a Some virulence factors: Extracellular enzymes
Bacterium
Epithelialcells
Collagen layer
Invasive bacteriareach epithelialsurface.
Hyaluronidase and collagenase Coagulase and kinase
Extracellular enzymes
Hyaluronidase
Collagenase
Bacteria producehyaluronidase andcollagenase.
Bacteria invade deeper tissues.
BacteriumCoagulase
Clottingprotein
Clot
Kinase
Bacteria producecoagulase.
Clot forms. Bacteria later producekinase, dissolving clotand releasing bacteria.
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The Nature of Infectious Disease
• Virulence Factors of Infectious Agents– Toxins
– Chemicals that harm tissues or trigger host immune responses that cause damage
– Toxemia refers to toxins in the bloodstream that are carried beyond the site of infection
– Two types– Exotoxins
– Endotoxins
.
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Figure 14.9b Some virulence factors: Toxins
Bacterium
Exotoxin
Toxins
Endotoxin
Exotoxin
Bacteria secrete exotoxins, in thiscase a cytotoxin.
Cytotoxin kills host’s cells.
Phagocyte
PhagocytizedGram bacteria
Exocytosis
Endotoxin
Dead Gram bacteria
Blood vessel
Dead Gram-negative bacteria release endotoxin (lipid A), which induceseffects such as fever, inflammation, diaarrhea, shock, and blood coagulation.
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The Nature of Infectious Disease
• Virulence Factors of Infectious Agents– Antiphagocytic factors
– Factors prevent phagocytosis by the host’s phagocytic cells
– Bacterial capsule – Composed of chemicals not recognized as foreign– Slippery
– Antiphagocytic chemicals– Prevent fusion of lysosome and phagocytic vesicles– Leukocidins directly destroy phagocytic white
blood cells
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Figure 14.9c Some virulence factors: Antiphagocytic factors
Capsule aroundbacterium
Phagocytosis blocked by capsule
Antiphagocytic factors
Incomplete phagocytosis
Phagocyte
Capsule aroundbacterium
Bacteria reproduce
Phagocyticvesicle
Lysosome
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The Nature of Infectious Disease
• The Stages of Infectious Disease– The disease process occurs following infection
– Many infectious diseases have five stages following infection
– Incubation period– Prodromal period– Illness– Decline– Convalescence
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Modes of Infectious Disease Transmission
• Transmission is from a reservoir or a portal of exit to another host’s portal of entry
• Three groups of transmission– Contact transmission
– Direct, indirect, or droplet
– Vehicle transmission– Airborne, waterborne, or foodborne
– Vector transmission– Biological or mechanical
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Figure 14.12 Droplet transmission
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Figure 14.13 Poorly refrigerated foods can harbor pathogens and transmit diseases
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The Body’s Second Line of Defense
• Nonspecific Chemical Defenses Against Pathogens– Interferons
– Released by host cells to nonspecifically inhibit the spread of viral infections
– Cause many symptoms associated with viral infections
– Two types– Types I (alpha and beta)
– Type II (gamma)
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Figure 15.7 The actions of alpha and beta interferonsVirus infects cell.
Virus
Double-strandedRNA
IFNgene
mRNA
IFN
Infected cell
Viral replicationin cell triggerstranscription andtranslation of IFN- or IFN-,depending ontype of host cell.
Nucleus
Interferon is released,diffuses to neighboringuninfected cells, andbinds to receptors.
Timepasses Meanwhile, the
infected cell dies,releasing viruses.
Infected cellat a later time
Inactive AVP
Double-strandedviral RNA
Active AVPsTimepasses
Ribosome
mRNA
When the secondcell becomes infectedwith viruses, double-stranded RNA of thevirus activates AVP.
Active AVPs degrade mRNAand bind to ribosomes,which stops proteinsynthesis and viralreplication.
Sameneighboringcell now protectedat the later time
Binding triggerstranscriptionand translation ofinactive antiviralproteins (AVPs).
Interferon receptor
AVPgene
mRNA
Uninfectedneighboring cell
Inactive AVPs
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The Body’s Second Line of Defense
• Nonspecific Chemical Defenses Against Pathogens
– Complement– Set of serum proteins designated numerically
according to their order of discovery– Complement activation results in lysis of the
foreign cell– Complement can be activated in three ways
– Classical pathway– Alternative pathway– Lectin pathway
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Figure 15.8 Pathways by which complement is activated
Classical pathway Alternative pathway Lectin pathway
Antigen
Antibody
Complementproteins1, 2, 4
C3b
C3b
Endotoxin andglycoproteins
Factors B,D, and P
Mannose
Lectins
Complement cascade
OpsonizationInflammation
Inflammation
Membrane attackcomplex and cell lysis
Activation(C3 C3a C3b)
C5 convertasesC5 C5a C5b
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Figure 15.9 The classical pathway and complement cascade
C3b opsonin
Membraneattackcomplexes
Pathogen
Antigen
Antibody
Enzymatic C1
C1 becomesan active enzymewhen it binds toantibody-antigencomplexes.
Acts as opsonin
Causes chemotaxisof phagocytesand inflammation
Cytoplasmic membrane
C5b combines with C6, C7, C8,and several molecules of C9to form a membrane attackcomplex (MAC). A MAC drills acircular hole in the pathogen’s cytoplasmic membrane,leading to lysis ofthe cell.
This enzyme cleavesC5 into C5a and C5b.
Enzyme
C3b combineswith the remainingfragments of C2and C4 to form athird enzyme.
Acts as opsonin
Causes chemotaxisof phagocytesand inflammation
Enzyme
Fragments of C2and C4 combineto form a thirdenzyme thatsplits C3 intoC3a and C3b.
Enzyme C1splits moleculesof C2 and of C4.
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Figure 15.10 Membrane attack complexesMembrane attack complex
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The Body’s Second Line of Defense
• Nonspecific Chemical Defenses Against Pathogens– Complement
– Inactivation of complement– Body’s own cells withstand complement cascade
– Proteins on many cells bind and break down activated complement proteins
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Immunization
• Two Artificial Methods of Immunity– Active immunization
– Administration of antigens so patient actively mounts a protective immune response
– Passive immunization – Individual acquires immunity through the transfer
of antibodies formed by immune individual or animal
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Immunization
• Brief History of Immunization– Chinese noticed children who recovered from
smallpox did not contract the disease again
– They infected children with material from a smallpox scab to induce immunity
– This process known as variolation
– Variolation spread to England and America but was stopped because of risk of death
.
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Immunization
• Brief History of Immunization– 1796 – Edward Jenner discovered process of
vaccination
– 1879 – Louis Pasteur developed a vaccine against Pasteurella multocida
– Antibody transfer developed when it was discovered vaccines protected through the action of antibodies
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Figure 17.1 Effect of immunization-overview
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Immunization
• Brief History of Immunization– Many developing nations do not receive
vaccines
– Effective vaccines not developed for some pathogens
– Vaccine-associated risks discourage investment in developing new vaccines
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Immunization
• Active Immunization– Vaccine types
– Attenuated (live) vaccines– Use pathogens with reduced virulence
– Can result in mild infections
– Active microbes stimulate a strong immune response
– Can provide contact immunity
– Modified microbes may retain enough residual virulence to cause disease
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Immunization
• Active Immunization– Vaccine types
– Inactivated (killed) vaccines– Whole-agent vaccines
– Subunit vaccines– Both safer than live vaccines
– Microbes don’t provide many antigenic molecules to stimulate the immune response
– Often contain adjuvants – Chemicals added to increase effective antigenicity
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Immunization
• Active Immunization– Vaccine types
– Toxoid vaccines– Chemically or thermally modified toxins used to
stimulate immunity
– Useful for some bacterial diseases
– Stimulate antibody-mediated immunity
– Require multiple doses because they possess few antigenic determinants
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Immunization
• Active Immunization– Vaccine types
– Combination vaccines– Administration of antigens from several pathogens
– Vaccines using recombinant gene technology– Attempts to make vaccines more effective,
cheaper, safer
– Variety of techniques used to improve vaccines
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Figure 17.2 Some uses of recombinant DNA technology for making improved vaccines-overview
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Immunization
• Active Immunization– Vaccine safety
– Problems associated with immunization– Mild toxicity most common
– Risk of anaphylactic shock
– Residual virulence from attenuated viruses
– Allegations that certain vaccines cause autism, diabetes, and asthma
– Research has not substantiated these allegations
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Figure 17.3 The CDC's recommended immunization schedule for the general population
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Immunization
• Passive Immunotherapy– Administration of antiserum containing preformed
antibodies– Immediate protection against recent infection or
ongoing disease– Antisera have several limitations
– Contain antibodies against many antigens– Can trigger allergic reactions called serum sickness– Viral pathogens may contaminate antisera– Antibodies of antisera are degraded relatively quickly
– Limitations are overcome through development of hybridomas11/11/11 MDufilho 36
Figure 17.4 The production of hybridomas
Mouse is injectedwith antigen.
Plasma cells,which secreteantibodies,are removed.
Antibodies
Long-lived myeloma celllines are grown in culture.
Hybridomas are formedby mixing and fusingplasma cells and myelomacells; they are long livedand produce antibodies.
Hybridoma
Hybridomas areplaced individuallyin small wells, andtheir antibodies aretested for reactivityagainst the antigen.
A hybridoma that makesantibodies that reactwith the antigen is cloned.
Monoclonalantibodies
Hybridoma clone
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Figure 17.5 The characteristics of immunity produced by active immunization and passive immunotherapy
Passiveimmunotherapy
Injection
BoostersActiveimmunization
Time
InitialinoculationA
nti
bo
dy
(Ig
G,
IgM
) co
nce
ntr
atio
n (
tite
r)
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