Immunology 334Y

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Immunology 334Y

• R.D. Inman
• 2008

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• Eli Metchnikoff 1845-1916
• Russian zoologist Nobel prize 1908
• 1883 novel theory of immunity, that
• immunity involved active defense
• mechanisms, and that the phagocyte was
• the key player
• Challenged the 19C German physiologists
• claiming that biological processes were
• basically physics and chemistry
• Set up battle between
• cellularists vs humoralists
• (evolutionary (immunochemists)
• biologists)

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• Frank Burnet 1899-1985
• 1949 first use of the term self in
• the context of immunology
• Proposed that central concern of
• immunology was to discriminate
• between self and non-self
• But
• Identity of self immunologically is
• an evolving process originally
• antigenicity meant foreigness, but
• anti-DNA abs changed that. And is
• MMTV-altered repertoire us or them?
• Self/nonself discrimination has been
• challenged by the Danger theory as
• the fundamental principle underlying

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Innate and Adaptive Immunity

• Innate
• inborn existing from birth not learned
• from experience

• Adaptive
• adjusting or modifying to fit circumstances
• (vs Darwinian adaptation artistic adaptation)

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The Problem at Hand the perpetual challenge of
infection, aka the host vs pathogen struggle
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The Attackers
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Innate Immunity 0-4 hrs First Line Defense
Adaptive Immunity gt96 hr
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The Phases of an Infection
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Pathogen
Epithelium
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Bacterial Invasiveness
Pathogen
Epithelium
Host Defense
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Pathogen
Epithelium
.Vibrio cholerae . Helicobacter pylori
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Pathogen
Epithelium
Highest exposure for all pathogens exposed to
antibodies
Extracellular milieu (blood,
lymph, interstitial space)
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Epithelium
Extracellular milieu
cytoplasm
vacuole
Intracellular milieu
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Epithelium
Extracellular milieu
Viruses Chlamydia
cytoplasm
Salmonella
vacuole
Intracellular milieu
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Epithelium
Extracellular milieu
cytoplasm

• Phagolysosome
• respiratory burst
• (H202) (N0)
• NADPH oxidase

vacuole
Intracellular milieu
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Epithelium
Extracellular milieu
cytoplasm

• Phagolysosome
• respiratory burst
• (H202) (N0)
• NADPH oxidase
• chronic
• granulomatous
• disease

vacuole
Intracellular milieu
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Figure 2-7 part 1 of 2
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Figure 2-7 part 2 of 2
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Direct Mechanisms of tissue damage by pathogens.
I. Exotoxin
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Direct mechanisms of tissue damage by
pathogens II. Endotoxin
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Direct mechanisms of tissue damage by pathogens
III. Cytopathic Effect
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Indirect I.
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Bacterial endocarditis
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Indirect II.
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Indirect III.
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Figure 2-2 part 1 of 2
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Figure 2-2 part 2 of 2
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• System Breakdown
• Burns
• Trauma
• Cystic fibrosis

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Figure 2-4
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Airway Defenses
Mucociliary clearance
mucus
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Mucociliary clearance
mucus
-maintained by a chloride channel CFTR (cystic
fibrosis transmembrane regulator)
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Mucociliary clearance
mucus
-maintained by a chloride channel CFTR (cystic
fibrosis transmembrane regulator)
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Mucociliary clearance
mucus

• -maintained by a chloride channel
• CFTR (cystic fibrosis transmembrane regulator)
• single mutation (eg 508) altered chloride
  transport

sticky viscous
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Mucociliary clearance
XXXX
mucus

• -maintained by a chloride channel
• CFTR (cystic fibrosis transmembrane regulator)
• single mutation (eg 508) altered chloride
  transport

sticky viscous
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Figure 2-4
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Figure 2-5 part 1 of 2
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Figure 2-5 part 2 of 2
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Bactericidal Products from Macrophages and
Neutrophils