Humans and Microbes
• Since Leeuwenhoek’s discovery of microorganisms in 17th
century led people to suspect they might cause diseases,
most research and funding has gone towards
understanding pathogens.
• Robert Koch (1876) offered proof of what is now
considered germ theory of disease; showed Bacillus
anthracis causes anthrax
• Today, we now know that most of the bacteria we
associate with are not pathogens, and many are critical for
our health.
Bacteria Are Ubiquitous
 We contact numerous microorganisms daily
• Breathe in, ingest, pick up on skin
• Vast majority do not make us sick, or cause infections
• Some colonize body surfaces; or slough off with dead
epithelial cells
• Most that are swallowed die in stomach or are
eliminated in feces
• Relatively few are pathogens that
cause damage
Microbes, Health, and Disease
 Most microbes are harmless
• Many are beneficial
• Normal microbiota (normal flora) are organisms that
routinely reside on body’s surfaces
• Relationship is a balance, and some can cause disease
under certain conditions-- opportunistic infections
• Weaknesses in innate or adaptive defenses can leave
individuals vulnerable to invasion
– malnutrition, cancer, AIDS or other disease,
surgery, wounds, genetic defects, alcohol or drug
abuse, and immunosuppressive therapy
The Anatomical Barriers as Ecosystems
 Skin, mucous membranes are barriers
• Also host complex ecosystem of microorganisms
• Example of symbiosis, or “living together”
• Mutualism: both partners benefit
– In large intestine, bacteria synthesize vitamin K and
B’s, which host can absorb; bacteria are supplied with
warmth, energy sources
• Commensalism: one partner benefits, other is unharmed
– Many microbes living on skin neither harmful nor
helpful, but obtain food and necessities from host
• Parasitism/pathogenicity: one organism benefits at
expense of other
– pathogens and parasites
Human commensals and mutalistic microbes
Resident microbiota inhabit
sites for extended periods
Transient microbiota inhabit
temporarily
• Important to human health
• Relatively little is known
• Human Microbiome
Project aimed at studying
http://en.wikipedia.org/wiki/Huma
n_Microbiome_Project
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Nose
Staphylococcus
Corynebacterium
Mouth
Streptococcus
Fusobacterium
Actinomyces
Leptotrichia
Veillonella
Throat
Streptococcus
Moraxella
Corynebacterium
Haemophilus
Neisseria
Mycoplasma
Skin
Staphylococcus
Propionibacterium
Urethra
Streptococcus
Mycobacterium
Escherichia
Bacteroides
Large intestine
Bacteroides
Escherichia
Proteus
Klebsiella
Lactobacillus
Streptococcus
Candida
Clostridium
Pseudomonas
Enterococcus
Vagina
Lactobacillus
The Normal Microbiota
The Protective Role of the Normal Microbiota
• Significant contribution is protection against pathogens
• Covering of binding sites prevents attachment
• Consumption of available nutrients
• Production of compounds toxic to other bacteria
• When killed or suppressed (e.g., during antibiotic
treatment), pathogens may colonize, cause disease
• Some antibiotics inhibit Lactobacillus (predominate
vagina of mature females, suppress growth of Candida
albicans); results in vulvovaginal candidiasis
• Oral antibiotics can inhibit intestinal microbiota, allow
overgrowth of toxin-producing Clostridium difficile
The Normal Microbiota
 The Protective Role of the Normal Microbiota
(continued…)
• Stimulation of adaptive immune system-CRITICAL
• Mice reared in microbe-free environment have greatly
underdeveloped mucosal-associated lymphoid tissue
(MALT); antibodies against normal microbiota bind to
pathogens as well
• Important in development of oral tolerance
• Immune system learns to lessen response to many
microbes that routinely inhabit gut as well as food
– Basis of hygiene hypothesis, which proposes
insufficient exposure to microbes can lead to allergies
The Normal Microbiota
 The Dynamic Nature of the Normal Microbiota
• Healthy human fetus sterile until just before birth
• Exposure during birth and through contact with people, food,
and environment lead to microbes becoming established on
• find that families often share similar microbial populations, and
important gut microbes are acquired from the mother
• Critical for proper gut development—first colonizers from mom
• Composition of normal microbiota is dynamic
• Changes occur over the life of a person. Younger people tend
to have different compositions than older people.
• Responses to physiological changes (e.g., hormonal changes),
activities and diet (e.g., consuming food)
Microbiota alter the chemistry of your gut
Ruth Ley, Peter Turnbaugh, Jeffrey Gordon and
colleagues at Washington University
link between the microbiota and obesity by studying
a special strain
-Obese mice had 50% fewer Bacteroidetes and
50% more Firmicutes in their bowels than their lean
counterparts.
The link between the microbiota and obesity
became even clearer when Gordon looked at a
special strain of mice with no microbiota of their
own.
When the team transplanted the microbiota from fat
and lean mice into the germ-free strains, those
colonized by microbiota from fat donors packed on
far more weight than those paired with lean donors.
Comparisons of microbiota of fat and lean mice at a
genetic level:
--fat mice showed much stronger activation of
genes for carbohydrate-destroying enzymes, which
break down otherwise indigestible starches and
sugars. As a result, these mice were extracting
more energy from their food than their lean
cousins.
The bacteria were also manipulating the animals’
own genes,
--triggered biochemical pathways that store fats in
the liver and muscles, rather than metabolize them.
Fat Bacteria
More Firmicutes
--break down
carbohydrates better
--trigger biochemical
pathways to store fat
Thin bacteria
More Bacteroidetes
Principles of Infectious Disease
Key Terms.
Colonization--microbe establishes on body surface
internal or external
• Infection usually refers to pathogen
• subclinical: no or mild symptoms
• Infectious disease shows noticeable impairment
– Symptoms are subjective effects experienced by
patient (e.g., pain and nausea)
– Signs are objective evidence (e.g., rash, pus
formation, swelling)
• Initial infection is primary infection
– Damage can predispose individual to developing a
secondary infection (e.g., respiratory illness
impairing mucociliary escalator)
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Fig. 24.1
Clostridium difficile
Parotid salivary gland
•Oral cavity
Gr+,containing
rod, spore forming, obligate
anaerobe.
Mumps
tongue
and teeth
Produces
cytotoxins
Dental caries
disease of gut microbiome, in Salivary
•Periodontal
Member
low glands
numbers,
Esophagus
Esophagitis
--It most commonly occurs in patients
in hospitals on antibiotic therapy.
•Liver
Can also be acquired
Hepatitis
Stomach
Gastritis
Gastric ulcer
Pancreas
Difficult to kill with disinfectants
(spores)
Organ
Function
Oral cavity
Obtains and
processes food
Salivary
glands
Secrete saliva
Esophagus
Transports food to
stomach
Stomach
Stores food; mechanical
digestion; breaks down
some proteins
Pancreas
Secretes digestive
enzymes
Liver
Produces bile to assist
in fat digestion
Gallbladder
Pancreatitis
Small intestine
Enteritis
Duodenal ulcer
•
Mild to severe symptoms including
Large colitis
intestine
Dysentery
(inflammation of the colon).
Appendix
Colitis
Appendicitis
Rectum
• Treatment: Often stopping the antibiotics,
Anus
if possible, alleviates the problem. Food
molecules
This is a secondary infection
Capillaries
Lymphatic vessel
Small
intestine
Site of most digestion
and absorption
of nutrients
Large
intestine
Absorbs some water
and minerals;
prepares waste
Villus
Epithelial cells
Microvilli
Gallbladder Stores bile until
needed
Smooth
muscle
Nerve fibers
Upper digestive tract
Lower digestive tract
Principles of Infectious Disease
 Pathogenicity
• Primary pathogen is microbe or virus that causes
disease in otherwise healthy individual
• Diseases such as plague, malaria, measles, influenza,
diphtheria, tetanus, tuberculosis, etc.
• Opportunistic pathogen (opportunist) causes disease
only when body’s innate or adaptive defenses are
compromised or when introduced into unusual
location
• Can be members of normal microbiota or common in
environment (e.g., Pseudomonas; E. coli; C. difficile)
• Virulence refers to degree of pathogenicity
• Virulence factors are traits that allow microorganism
to cause disease
16.3. Principles of Infectious Disease
 Characteristics of Infectious Disease
• Communicable or contagious diseases easily spread
• Infectious dose is number of microbes necessary to
establish infection
• ID50 is number of cells that infects 50% of population
• Shigellosis results from ~10–100 ingested Shigella
• Salmonellosis results from as many as 106 ingested
Salmonella enterica serotype Enteritidis
– Difference partially reflects ability to survive
stomach acid
Course of Infectious Disease
• Incubation period: time between infection and onset
• Illness: signs and symptoms of disease
• May be preceded by prodromal phase (vague symptoms)
• Convalescence: recuperation, recovery from disease
• Carriers may harbor and spread infectious agent for
long periods of time
Incubation period
Illness
Convalescence
Acute. Illness is short term because the pathogen is eliminated by the host
defenses; person is usually immune to reinfection.
Incubation period
Illness (long lasting)
Chronic. Illness persists over a long time period.
Incubation period
Illness
Latent. Illness may recur if immunity weakens.
Convalescence
Latency
Recurrence
 Acute and Persistent Infections
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• Acute:
• Persistent/chronic:
• May develop slowly,
Continue for
years or lifetime
• May or may not
have symptoms
Infectious virions
Disease
Influenza
State of Virus
Virus disappears
after disease ends.
Time (days)
(a)
Chronic infection (hepatitis B)
Appearance of
symptoms and
infectious virions
• Rapid onset
• Short duration
Appearance of
symptoms and
infectious virions
Acute infection (influenza)
Hepatitis B
Days
State of Virus
After initial infection with
or without disease
symptoms, infectious virus
is released from host with
no symptoms.
Release of virus
Time
Years
(b)
• Latent infections:
never completely
eliminated; may
reactivate
Appearance of
symptoms and
infectious virions
Latent infection (cold sores)
Cold
sores
Virus
activation
Non-infectious
Days
Time
Cold
sores
State of Virus
After initial infection, virus
is maintained in neurons
in non-infectious state.
Virus
activated to produce new
disease symptoms.
Years
(c)
These apply to both viruses and bacteria (Mycobacterium
tuberculosis, M. leprae, S. typhae (Typhoid Mary))
Distribution of Pathogen
• Localized infection: microbe limited to small area (e.g.,
boil caused by Staphylococcus aureus)
• Systemic infection: agent disseminated throughout body
(e.g., measles)
• Suffix -emia means “in the blood”
• Bacteremia: bacteria circulating in blood
– Not necessarily a disease state (e.g., can occur
transiently following vigorous tooth brushing
• Toxemia: toxins circulating in bloodstream
• Viremia: viruses circulating in bloodstream
• Septicemia or sepsis: acute, life-threatening illness
caused by infectious agents or products in bloodstream
Koch’s Postulates
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1
2
The microorganism must be present in every case of the disease,
but not in healthy hosts.
The microorganism must be grown in pure culture from diseased
hosts.
Koch’s Postulates continued
3
4
The same disease must be produced when a pure
culture of the microorganism is introduced
The same microorganism must be recovered from the
experimentally infected hosts.
Establishing the Cause of Infectious Disease
 Koch’s Postulates (continued…)
• There are limitations
• Some organisms don’t grow in lab medium (e.g., causative
agent of syphilis)
• Infected individuals do not always have symptoms (e.g.,
cholera, polio)
• Some diseases are polymicrobial (e.g., periodontal)
• Suitable animal hosts not always available for testing
 Molecular Koch’s Postulates (kinda the same but using
genes)
• Virulence factor gene or product found in pathogenic
strains of organism
• Mutating gene to disrupt function should reduce virulence
• Reversion or replacement of gene should restore
Mechanisms of Pathogenesis—how do pathogens
make us sick?
 General patterns
• Produce toxins that are ingested
• E.g., Clostridium botulinum, Staphylococcus aureus
• Colonize mucous membranes, produce toxins
• E.g., Vibrio cholerae, E. coli O157:H7, Corynebacterium
diphtheriae
• Invade host tissues, avoid defenses
– E.g., Mycobacterium tuberculosis, Yersinia pestis,
Salmonella enterica
• Invade host tissues, produce toxins
• E.g., Shigella dysenteriae, Clostridium tetani
• Pathogens and hosts usually evolve toward balanced
pathogenicity (e.g., myxoma virus and rabbits)
Establishing Infection
 Adherence
• Adhesins attach to host cell receptor
• Often on tips of pili (or fimbriae)
• Can be component of capsules or various cell wall proteins
• Binding highly specific; exploits host cell receptor
 Colonization
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Bacterial cell
• Growth in biofilms
• Siderophores-bind iron
• Avoidance of secretory IgA
• Rapid pili turnover-shed the IgA,
antigenic variations—avoid detection,
IgA proteases—cut IgA
• Compete with normal
microbiota, tolerate toxins
Pili with
adhesins
Receptor
Host cell
Invasion—Breaching the Anatomical Barriers
 Penetrating the Skin
Borrelia burgdorferi
(Lyme’s disease)
• Difficult barrier to penetrate; bacteria rely on injuries
• Staphylococcus aureus enters via cut or wound; Yersinia
pestis is injected by fleas, Lyme’s disease by tick bite
 Penetrating Mucous Membranes-respiratory and gut tracts
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• CommoneEntry point pathogens
• Directed Uptake by Cells
• Pathogen induces cells to
engulf via endocytosis
– Salmonella uses type III
secretion system to inject
effector proteins; actin
molecules rearrange, yield
membrane ruffling
Ruffle
M-cell surface
10 µm
Bacterial cell
Courtesy of Mark A. Jepson, from Trends in Microbiology v6, issue 1:359-365, 1 Sept 1998,
"Studying M cells and their role in infection"; M.A. Jepson and M.A. Clark, Elsevier Press
Invasion—Penetrating mucus membranes
 Delivering Effector Proteins to Host Cells
• Secretion systems in Gram-negatives
• Several types discovered; some can inject molecules other
than proteins
• Type III secretion system Effector
Bacterial
(injectisome)
cytoplasm
– Effector proteins
induce changes
(e.g., altering of cell’s
Bacterial
periplasm
cytoskeleton structure)
– Can induce uptake
of bacterial cells
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Recall from CH 24 pathogens
Shigella, Salmonella, E. coli
Host cell
Courtesy of Chihiro Sasakawa, University of Tokyo
Salmonella attach to cells at the end
of the small intestine
T3SS injects effectors and the cells
are taken into cell in phagosomes.
These are transported across the
cell and exported (exocytosis)
where they are picked up by
macrophage which are often
destroyed. The infection remains
localized. Inflammatory response
results in fluid secretion.
Invasion—Penetrating mucus membranes
3 Within an epithelial cell, Shigella cells cause
 Exploiting Antigen-Sampling
Processes of the Pyer’s patches
(Mucosal-associated lymphoid tissue
(MALT) and their M cells)
the host actin to polymerize. This propels
the bacterial cell, sometimes with enough
force to push it into the next cell.
Lumen of the intestine
Mucous
membrane
Shigella
M cell
• Shigella survives
phagocytosis by
macrophages; induces
apoptosis;
binds to base of mucosal
epithelial
cells and induces uptake.
Salmonella typhae also.
• Some invade by
alveolar(lung) macro-phages
(e.g., Mycobacterium
tuberculosis produces surface
proteins, directs uptake,
Tissue
Macrophages
2
Shigella cells attach to the
base of the epithelial cells
and induce these cells to
engulf them.
1 Macrophages in the Peyer’s patches engulf material that
passes through M cells. Shigella cells survive and
replicate, causing the phagocytes to undergo apoptosis.
Avoiding the Host Defenses
 Hiding Within a Host Cell
• Allows avoidance of complement proteins, phagocytes,
and antibodies
• Shigella directs transfer from intestinal epithelial cell to
adjacent cells by causing host cell actin polymerization
• Listeria monocytogenes (meningitis) does the same
 Avoiding Killing by Complement System Proteins
• Serum resistant bacteria resist
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Alternative pathway
Lectin pathway
Classical pathway
Triggered by
Triggered by
Triggered by
C3b binding to microbial invaders
Mannose-binding lectin (MBL) binding to
microbial invaders
Antibodies binding to microbial invaders
C3b
MBL
Antibody
Formation of C3 convertase
Splits C3
C3
Inflammatory response
C3a and C5a induce changes that
contribute to local vascular permeability
and attract phagocytes.
C3a
Opsonization
C3b binds to microbial cells,
functioning as an opsonin.
C3b
C3b
C5
The complement system revisitedpathogens have ways to avoid
binding to the C3b, deactivating
C5a and C5b to avoid attracting
phagocytes or being attacked by
the membrane attack complex
(MACs). The MAC attack.
C5a
Combines with C3
convertase to form an
enzyme that splits C5
C5b
C5b
Lysis of foreign cells
C5b combines with complement
C6
C9
proteins C6, C7, C8, and C9
C7
C9 C9 C9
to form membrane attack
C8
complexes that insert
into cell membranes.
MAC
Avoiding Destruction by Phagocytes
Preventing Encounters with Phagocytes
•C5a peptidase: degrades chemoattractant
C5a
(Streptococcus pyogenes)
Microbes •Membrane-damaging toxins: kill phagocytes,
S. pyogenes makes streptolysin O
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1 Prevent encounters
with phagocytes
• C5a peptidase
• Cytolytic toxins
C5a
2 Avoid recognition
and attachment
• Capsules
• M protein
• Fc receptors
Pseudopod
C3b receptors
on phagocyte
C3b
Phagocyte
Lysosomes
C3b
Phagosome
Phagolysosome
Digestive
enzymes
3 Survive within phagocytes
• Escape from the phagosome
• Prevent phagosomelysosome fusion
• Survive within the phagosome
Avoiding Destruction by Phagocytes
• Avoid Recognition and Attachment
• Capsules: interfere with opsonization; some bind host’s
regulatory proteins that inactivate C3b
– E.g., Streptococcus pneumoniae
• M protein: cell wall of
Streptococcus pyogenes binds
regulatory protein that inactivates C3b
--So does Neisseria gonorrhoerae.
Regulation of the complement system
Neisseria gonorrhoeae hijacks host system, binds
complement regulatory proteins to avoid activation of
membrane attack complex
Avoid recognition by antibodies
Fc receptors: bind Fc region of antibodies
Staphylococcus aureus, Streptococcus pyogenes
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Antigenbinding site
Variable
region
Fab region
Light
chain
Fc region
Constant
region
Heavy
chain
(a)
(b)
(c)
What can happen when antibody binds antigen.
Opsonization
Bacterium
Complement System Activation
Neutralization
Phagocyte
Complement
system protein
Virus
Toxin
Bacterium
Opsonization by C3b
Inflammatory response
Lysis of foreign cells
Antibody-Dependent Cellular
Cytotoxicity (ADCC)
Infected
“self” cell
Immobilization and Prevention
of Adherence
Natural
killer cell
Cross-Linking
Bacterium
Bacterium
Kills cell
Flagellum
Fc receptors: bind Fc region of antibodies
Staphylococcus aureus, Streptococcus pyogenes
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Bacterium
Fab region of the antibody
(binds to antigen)
Antibody
(a)
Fc receptor on
bacterium (binds
the Fc region of
an antibody)
Fc region of the antibody
(phagocytes recognize
and bind this region as
an initial step in phagocytosis)
(b)
Avoiding Destruction by Phagocytes
• Surviving Within Phagocytes
• Escape from phagosome: prior to fusion with
lysosomes
Listeria monocytogenes -- pores in membrane;
Shigella species lyse phagosome
• Prevent phagosome-lysosome fusion: Salmonella
produce protein that blocks fusion process
• Survive within phagolysosome: few can survive
Phagocyte
destructive environment.
• Coxiella burnetii (Q fever)
Phagosome
Phagolysosome
Digestive
enzymes
Lysosomes
Capsules and biofilms also
help bacteria hide from the
immune syetem
Avoiding Destruction by Phagocytes, continued…
Avoiding Antibodies
• IgA protease: cleaves IgA, found in mucus, secretions
– Neisseria gonorrhoeae and others produce
• Antigenic variation: alter structure of surface antigens, stay
ahead of antibody production
– Neisseria gonorrhoeae varies antigenic structure of pili
(recall the gene swapping that N. gon. does through transformation
by DNA uptake)
• Mimicking host molecules: cover surface with molecules
similar to those found in host cell, appear to be “self”
– Streptococcus pyogenes form capsule from hyaluronic
acid, a polysaccharide found in tissues
Damage to the Host
 Exotoxins: proteins with damaging effects
• Secreted or leak into tissue following bacterial lysis
• Foodborne intoxication results from consumption (Botulism)
• Destroyed by heating; most exotoxins heat-sensitive
• Can act locally or systemically
• Proteins, so immune system can generate antibodies
• Many fatal before immune response mounted
• Vaccines therefore critical: toxoids are inactivated toxin
• Antitoxin is suspension of neutralizing antibodies to treat
• Neurotoxins damage nervous system
• Enterotoxins cause intestinal disturbance
• Cytotoxins damage variety of cell types
Damage to the Host
 Direct or indirect effects
• Direct (e.g., toxins produced)
• Indirect (e.g., immune response)
Three main categories of Exotoxins based on structure
and mechanisms (Table 16.1 lists many examples)
1) A-B toxins
2) Membrane damaging toxins
3) Superantigens
Exo- vs Endotoxin : Exotoxin is a protein made by the cell in the
cytoplasm, may be exported.
Endotoxin refers to the part of the cell membrane of Gram Negative
bacrteria—usually the lipid A
16.8. Damage to the Host
16.8. Damage to the Host
 Exotoxins (continued…)
• A-B toxins have two parts
• A subunit is toxic, usually an enzyme
• B subunit binds to cell, dictates cell type to be infected
– Structure allows novel
approaches for vaccines
and therapies; can use Active subunit A
B
Binding subunit
B subunit to deliver
medically useful
compounds to specific Binding site
cell type
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RECALL these from intestinal
diseases-CH 24
1 B subunit binds to a
specific molecule
on the host cell.
2
Toxin is taken up
by endocytosis.
3 Toxin subunits separate
allowing the A subunit
to enter the cytoplasm.
A-B toxin
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B binds to cell
A enters
V. cholerae
bacterium
1
The A-B toxin’s B subunit attaches
to receptors on cell membrane;
the A subunit enters the cell.
B
2
The A subunit locks a G protein
in the “active” mode, turning on
adenylate cyclase.
4
A
OFF
10 µm
Plasma membrane
of intestinal cell
A
G protein
ON
cAMP activates ion transport
channels in the membrane
causing Cl– and other electrolytes
to pour out of the cell.
ATP
Cl–
3
Adenylate cyclase causes the
conversion of ATP to cAMP.
Adenylate
cyclase
K+
Na+
●
HCO3–
H2O
cAMP
5
Water follows electrolytes
out of the cell by osmosis.
© VeronikaBurmeister/Visuals Unlimited
16.8. Damage to the Host
 Exotoxins (continued…)
• Membrane-Damaging Toxins
• Cytotoxins that disrupt plasma membranes, lyse cells
• Hemolysins lyse red blood cells
• Some insert into membranes, form pores
– E.g., streptolysin O from Streptococcus pyogenes
• Phospholipases hydrolyze
phospholipids of membranes
– α-toxin of Clostridium perfringens
(gas gangrene)
Exotoxins (continued…)
• Superantigens: simultaneously bind MHC class II and
T-cell receptor
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• T-cell interprets as
antigen recognition
• Toxic effect is from
massive cytokine
release from TH
• Include toxic shock
syndrome toxin
(TSST) and several
by Staphylococcus
aureus, Streptococcus
pyogenes
Antigen-presenting cell
Antigen-presenting cell
MHC class II
molecule
Peptide
recognized by
T-cell receptor
Peptide not
recognized by
T-cell receptor
Superantigen
T-cell
receptor
Helper T cell
a
Helper T cell that recognizes peptide is
activated; it proliferates and releases
cytokines.
Helper T cell
b
Helper T cell that does not recognize
peptide is activated because of superantigen;
it proliferates and releases cytokines.
Adapted from Arousing the Fury of the Immune System, 1998 Howard Hughes Medical Institute.
Effector functions of Cytotoxic T cells
Exotoxins (continued…)
• Other Toxic Proteins
• Some damaging proteins are not A-B toxins, membranedamaging toxins, or superantigens
• E.g., exfoliatin from Staphylococcus aureus causes
scalded skin syndrome
– Destroys material that binds together skin layers
– Bacteria may be growing in small lesion, but toxin
spreads systemically
• Various hydrolytic enzymes including proteases, lipases,
and collagenases break down connective tissue
– Destroy tissues, some help bacteria spread
Damage to the Host
 Endotoxin, Other Bacterial Cell Wall Components
• Endotoxin is lipopolysaccharide (LPS)
• Lipid A triggers inflammatory response
– When localized, response helps clear
– When systemic, causes widespread response: septic
shock or endotoxic shock
• Lipid A typically released following cell lysis
– Phagocytosis, MAC formation, certain antibiotics
• Activates innate and adaptive defenses
– Toll-like receptors (monocytes, macrophages, others)
induce cytokine production; also T-independent
antigen response of B-cells at high concentrations
• Heat-stable; autoclaving does not destroy
• Peptidoglycans, other components also trigger
Damaging Effects of the Immune Response
• Damage Associated with Inflammation
• Phagocytic cells can release enzymes and toxic products
• Damage Associated with Adaptive Immunity
• Immune complexes: antigen-antibody complexes can
form, settle in kidneys and joints, and activate
complement system leading to inflammation
– E.g., acute glomerulonephritis following skin, throat
infections of S. pyogenes
• Cross-reactive antibodies: may bind to body’s own
tissues, promote autoimmune response
– E.g., acute rheumatic fever following S. pyogenes
infection