Chapter 15: The Innate Immune Response

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Chapter 15The InnateImmune Response
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Important Point
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Immunity

• From a microorganisms standpoint, the tissues
  and fluids of the human body are much like a warm
  culture flask filled with a nutrient-rich
  solution.
• Considering this, it may be surprising that the
  interior of the body--including blood, muscles,
  bones, and organs--is generally sterile.
• If this were not the case, microbes would simply
  degrade our tissues, just as they readily
  decompose the carcass of a dead animal.
• The immunity that keeps us from decomposing like
  said carcass can be differentiated into an Innate
  Immunity and an Adaptive Immunity.
• This chapter will concentrate on Innate Immunity.

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Immunity

• From a microorganisms standpoint, the tissues
  and fluids of the human body are much like a warm
  culture flask filled with a nutrient-rich
  solution.
• Considering this, it may be surprising that the
  interior of the body--including blood, muscles,
  bones, and organs--is generally sterile.
• If this were not the case, microbes would simply
  degrade our tissues, just as they readily
  decompose the carcass of a dead animal.
• The immunity that keeps us from decomposing like
  said carcass can be differentiated into an Innate
  Immunity and an Adaptive Immunity.
• This chapter will concentrate on Innate Immunity.

Recall that Sterile means absence of life,
though here we mean absence of microorganisms.
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The Bodys Surfaces(from a microbes persepctive)
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First-Line Defense
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First-Line Defenses

• The skin is the most difficult surface to
  penetrate.
• Mucous on mucous membranes helps wash away
  microbes, in some cases via active propulsion
  such as via the lungs mucocilliary escalator.
• Lysozyme, an enzyme that destroys particularly
  Gram-positive cell walls, is found in various
  body fluids, secretions, and defensive cells.
• Lactoferrin sequesters iron within the body iron
  is a key nutrient required for bacterial growth.
• Defensins are small proteins that create pores in
  bacterial membranes (killing the bacteria).
• Free Fatty Acids essentially are soap.
• Normal flora occupies space, utilizes nutrients,
  and produces antimicrobial substances that
  together can prevent pathogen colonization of
  body surfaces.

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Cells of the Immune System
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Leukocytes White Blood Cells
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Phagocytic Leukocytes
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PMNs
Polymorphonuclear Neutrophilic Leukocytes,
a.k.a., PMNs. They are shorter lived than
macrophages but have greater killing power.
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Non-Phagocytic Granulocytes
Eosinophils are involved in allergic responses,
inflammation, and release of Histamine Histamine
is released by Basophils.
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Mediators of Adaptive Immunity
These are mostly considered in chapter 16.
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Toll-Like Receptors
Including phagocyte-attracting citokines.
Danger, Im infected! signal.
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Complement
2. Complement proteins are activated by various
mechanisms.
1. Inactive complement proteins are in constant
circulation.
3. These are the consequences...
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Complement Activation
Lets just worry about Classical and Alternative
Pathways...
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Complement Cascade
Lets just worry about C3a, C3b, and C5a.
Note, typo!
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Complement Action
Note, typo!
Opsonization signals phagocytes to engulf
materials including bacterial cells.
C3b serves as an Opsonin.
C3b binds to all cells but is actively removed
from body cells.
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Phagocytosis
It is the toll-like receptors on macrophages
that enable them to sense that the material is
microbial in origin, and must therefore be
eliminated quickly.
Chemotaxis movement toward infections.
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Inflammation

• Inflammation gives rise to localized reddening,
  swelling, increased temperatures, and pain.
• The function of inflammation is to localize
  tissue damage, localize responses, and then to
  restore tissue function.
• The action of localized leukocytes is augmented
  (i.e., enhanced) via the attraction of
  neutrophils and monocytes normally found in
  circulation.
• Microbial materials such as LPS, flagellin
  (making up bacterial flagella), activated
  complement, and even bacterial DNA serve as
  indicators of infection which in turn activates
  the production of pro-inflammatory cytokines
  (immune-system activating chemicals).
• In addition to the cell-to-cell interactions
  underlying inflammation, the inflammatory
  response involves localized increases in blood
  flow, leakage of blood vessels, and attraction of
  leukocytes from the blood.

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Inflammation
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Inflammation
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Fever

• Inflammation is a great tool, unless it becomes
  chronic or non-localized.
• Chronic inflammation typically has an underlying
  cause (e.g., ongoing infection).
• Non-localized inflammatory responses gives rise
  to body-wide vessel dilation and leakage,
  resulting in precipitous drops in blood pressure
  called Shock.
• Endotoxin signals inflammatory responses and
  systemic infections with Gram-negative bacteria
  can give rise to a very dangerous condition known
  as Septic Shock.
• Fever is the preferred systemic response to
  bacterial infection.
• Fevers are elevated body temperatures induced
  either by pathogen molecules or by body molecules
  produced in response to pathogen molecules.
• Fever results in temperatures that, ideally,
  inhibit microbes while enhancing body defenses.

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Interferon An Antiviral
dsRNA normally is not present in cells.
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