Complement Monday, September 29, 2003

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ComplementMonday, September 29, 2003

• Reading-
• Anatomy and Physiology- Neutrophils, etc. (pp 6-7)

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Definition of Inflammation
Inflammation is a process of vascularized
tissues, whereby fluid and white blood cells
accumulate at the site of injury.   Overall
biological significance of inflammation is that
of a host defense mechanism.


Neutrophilia Margination and
diapedesis
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Definition of Inflammation (Contd)


Vasodilation with exudation- outpouring of
fluid into the alveolar spaces
Neutrophilic exudate of an acute abscessing
pneumonia
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Changes in Vascular Flow
1. There is transient vasoconstriction of
arterioles.   --it last from a few seconds to
several minutes.   2. Next and fundamental event
is vasodilatation.   --results in opening of new
microvascular beds.   --Increased blood flow
is the hallmark of early hemodynamic changes in
acute inflammation, and causes heat and redness.
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Changes in Vascular Flow (contd)
3. Slowing of the circulation, brought about by
increased permeability of the microvasculature. --
outpouring of protein-rich fluid in the
extravasculature. 4. Orientation of leukocytes
(neutrophils) along the vascular endothelium, a
process termed leukocyte margination.
--leukocytes stick to the endothelium, soon
after they migrate through the vascular wall into
the interstitial tissue, the latter process being
called diapedesis. Increased vascular
permeability is seen clinically as edema.
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Dilation Mediators
Histamine (first phase mediator)   Permeability
factors (second phase mediators)   --Complement
components (C3a and C5a)   --Prostaglandins,
fatty acids derivatives of arachadonic acid
(prostaglandin E2 and thromboxane
A2).   --Leukotrienes (leukotriene E4), are from
leukocytes, derived from arachadonic acid.
  --Released when leukocytes arrive at the
injury.
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Edema
   






Erythema and edema Edema in
friction blister
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Acute Inflammation
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Acute Inflammation
Neutrophil ingestion of bacteria in lungs
Abscess, which is a localized collection of
PMN's here in the myocardium
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Acute Inflammation Components
Physiology Symptoms
Release of soluble mediators Vasodilation Increa
sed blood flow Extravasation of fluid
(permeability) Cellular influx
(chemotaxis) Elevated cellular metabolism
heat (calore) redness (tubor) swelling
(tumor) pain (dolore)
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Acute Inflammation Components
Physiology Symptoms
Release of soluble mediators Vasodilation Increa
sed blood flow Extravasation of fluid
(permeability) Cellular influx
(chemotaxis) Elevated cellular metabolism
heat (calore) redness (tubor) swelling
(tumor) pain (dolore)
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Acute Inflammation Components
Physiology Symptoms
Release of soluble mediators Vasodilation Increa
sed blood flow Extravasation of fluid
(permeability) Cellular influx
(chemotaxis) Elevated cellular metabolism
heat (calore) redness (tubor) swelling
(tumor) pain (dolore)
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Acute Inflammation Components
Physiology Symptoms
Release of soluble mediators Vasodilation Increa
sed blood flow Extravasation of fluid
(permeability) Cellular influx
(chemotaxis) Elevated cellular metabolism
heat (calore) redness (tubor) swelling
(tumor) pain (dolore)
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Acute Inflammation Components
Physiology Symptoms
Release of soluble mediators Vasodilation Increa
sed blood flow Extravasation of fluid
(permeability) Cellular influx
(chemotaxis) Elevated cellular metabolism
heat (calore) redness (tubor) swelling
(tumor) pain (dolore)
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Complement
Synthesis and attachment of specific antibody to
invading microorganisms does not directly lead to
destruction.   It is a "label" that identifies
them as targets for destruction.   Microorganisms
coated with IgG antibody are more susceptible to
phagocytosis by neutrophils and
macrophages.   Complement consists of a series
of blood proteins, which when activated, lead to
lysis of target cells.
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Three Major Biological Activities of Complement
Complement
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The Complement System
Complement is the term applied to a plasma
effector system --direct mediation of acute
inflammatory reactions --destruction of many
kinds of cells, bacteria and viruses. Complement
factors has some hormone-like properties   --re
cruit other humoral and cellular
effectors   --induces directed neutrophil
migration   --triggers histamine release from
mast cells   --stimulates release of lysosomal
enzymes from PMN's.
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Complement Pathway(s)
C1q-C1r-C1s
C3

B
C4 D
C2
properdin
C3 C5
C6, C7, C8

C9
Antigen-antibody complex
Bacteria, yeast, virus, or tumor cell
recognition unit (C1q-C1r-C1s)
activation unit (C4, C2, C3)
membrane attack (C5-C9)
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Membrane Attack Complex (MAC) of Complement
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A Different View of Complement Activation
C3
C3b
Opsonizing (coating)
C5 - C9 Terminal Sequence
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Opsonization by C3b
Opsonin binding
C3b coatings of cells   --facilitate adherence
of bacteria, viruses and other m'organisms to
neutrophils, monocytes and macrophages   --facili
tate ingestion of certain bacteria by neutrophils
and monocytes   --aids ingestion by activated
macrophages   --facilitates IgG-induced
phagocytosis and cell cytotoxicity.
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Actions of Complement
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