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16
Innate
Immunity:
Nonspecific
Defenses
of the Host
SLOs
Differentiate between innate and adaptive immunity.
Define toll-like receptors.
Differentiate physical from chemical factors, and list examples of
each.
Describe the role of normal microbiota in innate resistance.
Classify phagocytic cells, and describe the roles of granulocytes and
monocytes.
Define and explain phagocyte and phagocytosis.
Explain the different stages of inflammation.
Describe the cause and effects of fever.
Describe two of the three pathways of activating complement and
describe the 3 outcomes.
Compare and contrast the actions of -IFN and -IFN with -IFN.
Describe
the role of transferrins and antimicrobial peptides in innate
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TLRs on Ms,
dendritic cells,
epithelial cells
Cytokines!
PAMPs recognition
Horseshoe structure of TLR3, showing attached sugars
(spheres) and internal structures
Fig. 16.7
The Concept of Immunity
 Susceptibility: Lack of resistance to a disease.
 Immunity: Ability to ward off disease.
 Innate immunity: Defenses against any pathogen.
 Adaptive immunity: Immunity, resistance to a specific
pathogen.
Fig 16.1
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First Line of Defense:
Skin and Mucous Membranes
Physical Factors
 Epidermis: consists of tightly packed cells with
keratin, a protective protein
 Two other protective physical factors of skin?
 Mucus of mucous membranes
 Lacrimal apparatus
 Saliva
 Nose hairs
 (Muco)-ciliary escalator
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Fig 16.3
Chemical Factors
 Fungistatic fatty acids in sebum
 Low pH (3-5) of skin
 Lysozyme in _______________________
 Low pH (?) of gastric juice
 Transferrins in blood
Also important: Antagonism and
competitive exclusion of normal microbiota
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1st Line
Defense in
Human
ANIMATION Host
Defenses: The Big Picture
Second Line of Defense: Formed Elements
in Blood
Compare to Table 16.1
60-70%
2-4%
0.5-1%%
3-8%
20-25%
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Process of Phagocytosis
Phagocytes engulf and kill microorganisms
Steps of phagocytosis:
•
Chemotaxis
•
Recognition and attachment
•
Engulfment and creation of phagosome
•
Fusion of phagosome with lysosome
•
Destruction and digestion
•
Residual body  Exocytosis
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Fig 16.7
Phagocytosis
Foundation Fig
16.7
Microbial Evasion of Phagocytosis
Inhibit adherence: M
protein, capsules
Kill phagocytes:
Leukocidins
Lyse phagocytes:
Membrane attack
complex
Streptococcus pyogenes, S.
pneumoniae
Escape phagosome
Shigella
Prevent phagosomelysosome fusion
Survive in
phagolysosome
Staphylococcus aureus
Listeriamonocytogenes
HIV
Coxiella burnetti
Phagocytosis and Evasion of Phagocytosis
ANIMATION Phagocytosis: Overview
ANIMATION Phagocytosis: Mechanism
ANIMATION Virulence Factors: Hiding From Host Defenses
ANIMATION Virulence Factors: Inactivating Host Defenses
ANIMATION Phagocytosis: Microbes That Evade It
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Inflammation
Tissue damage leads to inflammatory response
Purpose:
 Destroy pathogen
 limit spread of infection
 pave way for tissue repair
4 cardinal signs:?
Acute-phase proteins (Chemical mediators)
activated:
 Complement proteins
 Cytokines
 Specialized proteins such as fibrinogen and
bradykinin
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The Three Stages of Inflammation
1. Vasodilation and increased vessel permeability
due to histamine (and other cytokine) release 
edema
2. Phagocyte migration and phagocytosis
 Margination and diapedesis (emigration)
 Chemotaxis(due to various cytokines and
components of complement system)
 Pus formation
 Factors challenging effectiveness of
phagocytosis
3. Tissue repair and regeneration depends on type
of tissue
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Inflammatory Process
Margination
Diapedesis
Compare to Fig 16.8
Treatment of abscess?
Fever: Abnormally High Body Temperature
 Hypothalamus acts as body’s thermostat
 Endotoxin causes phagocytes to release
interleukin–1 (IL–1). IL-1 is an endogenous
pyrogen
 Hypothalamus releases
prostaglandins that reset the
thermostat
 Body reacts to raise the
temperature. How?
 When no more IL–1, body
temperature falls (crisis).
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Beneficial effects of moderate fever:
Inhibited pathogen growth
Increased cellular metabolism  e.g.:
 Increased transferrin production
 Increased IL–1 activity  T cell production 
 Faster repair mechanisms
Problematic effects of high fever:
> 40.7C (105F) can be dangerous (Tachycardia,
acidosis, dehydration)
Death at temp. > 44 - 46C
Antimicrobial Substances
1. The complement system
2. Interferons
3. Transferrins: bind serum iron
4. Antimicrobial peptides: cause bacterial
cell lysis. Produced by mucous
membrane cells and phagocytes.
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The
Complement
System
Compare to
Foundation
Fig 16.9
Complement System Summary
Series of  30 plasma (serum) proteins,
activated in a cascade
Three effects of complement system:
1. Enhances inflammatory response, e.g.:
attracts phagocytes
2. Increases phagocytosis through
opsonization or immune adherence
3. Creates Membrane Attack Complexes (MACs)
 Cytolysis
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Opsonins (complement proteins or
antibodies) coat bacteria and promote
attachment of micro-organism to phagocyte 
Opsonization
Classical Pathway
Fig 16.12
Alternative Pathway
Does not require a
specific antibody to
get started
Fig 16.13
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Some Bacteria Evade Complement
 Capsules prevent Complement activation.
 Surface lipid-carbohydrates of some Gramnegatives prevent MAC formation.
 Enzymatic digestion of C5a by Grampositives.
ANIMATION Complement System: Overview
ANIMATION Complement System: Activation
ANIMATION Complement System: Results
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Interferons (IFNs)
 Family of glycoproteins
 Host-cell-specific but not virus-specific
 -IFN and -IFN: Produced by virus infected cells.
Mode of action is to induce uninfected cells to produce
antiviral proteins (AVPs) that inhibit viral replication.
 -IFN: Produced by lymphocytes. Causes
neutrophils and macrophages to phagocytize
bacteria. Also involved in tumor immunology.
 Recombinant interferons have been produced. However
short-acting and many side-effects. No effect on already
infected cells.
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Interferons (IFNs)
Fig 16.15
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Unnumbered
Figure 16.1a
Applications of
Microbiology:
Serum Collection
Unnumbered
Figure 16.1b