Download Lecture 14 - Innate Defenses

5/30/2011
Innate Immune Response
Chapter 15
How does the body protect
itself from infection?
• Protective barriers
• Sensing mechanisms to sound the alarm
• Specialized cells and mechanisms to kill
invaders
• Adaptive responses (next time)
What are the first-line of defenses?
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What are the first-line defenses?
Physical Barriers
Skin
Mucous membranes
Physical Barriers
Skin
•Sheets of tightly packed cells
•Outermost layers are dead, embedded with keratin (dry)
•Cells continually slough off
•Perspiration (salty)
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Physical Barriers
Skin
Physical Barriers
Skin
Physical Barriers
Skin
New Scientist 1/30/93
Mudlarks’ marks
….the case of seven students who attended the health clinic at the Universityy of
Washington at Seattle last spring covered in hundreds of red, pus-filled spots…
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Physical Barriers
Mucous Membranes
•Often a single layer of cells
•Layer of mucus (traps particles, including microbes)
•Often a mechanism to propel the mucus toward an “exit”
•(ex. mucociliary escalator, peristalsis)
Question
From a protection standpoint,
which is a more effective
barrier?
1. Skin
2. Mucous membrane
Antimicrobial Chemicals
•Lysozyme
•Transferrin, lactoferrin
•Gastric acid
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Normal Microbiota
(aka normal flora)
Nanamio News Bulletin, July 20, 2010
C. diff continues to bug patients at Nanaimo hospital
Two more patients at Nanaimo Regional General Hospital have acquired
Clostridium difficile in the hospital in the last week, but no new deaths were
reported.
The Cells of the Immune System
The Cells of the Immune System
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The Cells of the Immune System
Cell Communication
Surface receptors - “eyes, ears”
Cytokines - chemical messengers; proteins released by
cells that effect the behavior of other cells; “voice”
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Cell Communication
Surface receptors - “eyes, ears”
Cytokines - chemical messengers; proteins released by cells that
effect the behavior of other cells; “voice”
Adhesion molecules - “hands”
Sensor Systems
Surface receptors - “eyes, ears”
Sensor Systems
Toll-like receptors (TLRs) - surface receptors that allow cells to “see”
molecules that signify the presence of microorganisms or viruses
pattern recognition
pathogen-associated molecular
patterns (PAMPs)
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Inside cells: NLRs (NOD proteins)
Sensor Systems
Toll-like receptors (TLRs) - surface receptors that allow cells to “see”
molecules that signify the presence of microorganisms or viruses
pattern recognition
pathogen-associated molecular
patterns (PAMPs)
Sensor Systems
The complement system - series of proteins that, when activated, result in
destruction/removal of foreign material; cascade reaction
C3 → C3a + C3b
C5 → C5a + C5b
Sensor Systems
The complement system - series of proteins that, when activated, result in
destruction/removal of foreign material; cascade reaction
C3 → C3a + C3b
C5 → C5a + C5b
“prepare for eating”
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Sensor Systems
The complement system - series of proteins that, when activated, result in
destruction/removal of foreign material; cascade reaction
C3 → C3a + C3b
C5 → C5a + C5b
Sensor Systems
Sensor Systems
The complement system - series of proteins that, when activated, result in
destruction/removal of foreign material; cascade reaction
C3 → C3a + C3b
C5 → C5a
C5 + C5b
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Sensor Systems
Recognition of long double-stranded RNA
Signifies to a cell that it is infected with a virus
infected cell produces interferon
Apoptosis = programmed
cell death
Phagocytosis
Macrophages
Neutrophils (polymorphonuclear leukocytes, PMNs, polys)
Process of phagocytosis
Chemotaxis
Recognition and attachment
opsonins
•opsonins
Engulfment (ingestion)
•phagosome
Fusion of the phagosome with lysosomes
(forms a phagolysosome)
Destruction and digestion
Exocytosis
http://www.youtube.com/watch?v=VAhM9OxZDkU&feature=related
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•Specialized attributes of macrophages
Fixed in tissue or routinely wander
Clean up infection
Long-lived (months)
Can become activated
•Specialized attributes of neutrophils
First to migrate to site of infection
Short-lived (days)
Always have tremendous killing power
•Specialized attributes of macrophages
Fixed in tissue or routinely wander
Clean up infection
Long-lived (months)
Can become activated
•Specialized attributes of neutrophils
First to migrate to site of infection
Short-lived (days)
Always have tremendous killing power
Inflammation
a coordinated response to invasion
Redness, pain, swelling, heat
Purpose:
Contain a site of damage
Localize the response
Restore tissue function
Factors that initiate the inflammatory response
Microbial cell products detected by toll-like receptors
Microbial surfaces (trigger the complement cascade)
Tissue damage
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The Inflammatory Process
•Pro-inflammatory cytokines
released
•Dilation of small blood vessels
→ increased blood flow to the area
•Leakage of fluids from vessels
•Adherence of phagocytic cells to
endothelial cells
•Diapedesis
Apoptosis - programmed cell
death; does not trigger
inflammation
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