Chap 14 - 18

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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• 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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• 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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• 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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• 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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• 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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• 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


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



• 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


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


Figure 14.12 Droplet transmission


Figure 14.13 Poorly refrigerated foods can harbor pathogens and transmit diseases


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)


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



• 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


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


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.


Figure 15.10 Membrane attack complexesMembrane attack complex



• 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


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


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

.


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


Figure 17.1 Effect of immunization-overview


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


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


Immunization


– 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


Immunization


– 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


Immunization


– 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


Figure 17.2 Some uses of recombinant DNA technology for making improved vaccines-overview


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


Figure 17.3 The CDC's recommended immunization schedule for the general population


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


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)


Chap 14 - 18

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