Dental Microbiology

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Dental Microbiology 211IMMUNOLOGY2006 Lecture
4The Antibodies and the Complement System
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Antibodies are also called Immunoglobulins
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Topics

• The structure of Immunoglobulins
• Classes of Immunoglobulins
• Biological properties of Immunoglobulins
• The Complement system and its functions

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The Antibodies
Antibodies are synthesized by B lymphocytes in 2
forms soluble and cell bound. The cell-bound
form is the BCR. The soluble form is released
into the circulation as antibodies Each B cell
produces Ab of a single specificity and expresses
on the cell surface only one BCR specificity
The specificity of the Ab produced by a B cell
is the same as of its BCR
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The Antibodies Fig 1
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Antibodies are also called Immunoglobulins
Immunoglobulins (Ig) are divided into 5
classes IgG IgM IgA IgD IgE Ig are
glycoproteins They differ in size, amount of CHO
and biologic functions
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Ig structure Fig 2
The prototypic Ig molecule is IgG. It is made up
of 4 polypeptide chains held together by
disulfide bonds Two Light (L) and two Heavy (H)
chains form the letter Y in which the two arms
and the stem are linked by a Hinge region L
chain 212-213 amino acids long H chain 440 amino
acids The chains are held together by disulfide
bonds
S-S
Hinge
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Variable and Constant regions Fig 3
V
The first 110 amino acids in each chain are
variable (V regions) blue and purple The
remaining 110 aa in the L chain and the remaining
330 aa in the H chain are constant (C regions)
(green and yellow) The V regions contact the
antigen. The C regions are involved in biological
functions
V
VL
CH
CL
C
C
CH
C
C
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Ig Domains
Each segment of about 110 amino acids is tightly
packed and forms a domain. Each Ab molecule has
therefore 4 V domains (one in each H and one in
each L chain), one C domain in each L chain and
either 3 or 4 C domains in each H chain. Each IgG
H chain has 3 C domains but IgM and IgE H chains
each has 4 C domains.
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Ig Fragments Fig 4
The IgG molecule can be dissected by proteolytic
enzymes Papain? 2 Fab and 1 Fc
fragment. Pepsin? 1 large F(ab)2 and several
small fragments from the Fc segment
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The function of the Ig segments
The distinct Ig segments are involved in
different functions The Fab binds Ag The Fc is
involved in Transplacental passage of
Ab Enhanced phagocytosis by macrophages and PMN
(opsonization) Activation of Complement Kills
foreign cells, triggers inflammatory reactions.
Enhances phagocytosis
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Ag-binding function Fig 5
Antibodies bind Ag in pockets or grooves defined
by the V regions of the H and L chains.
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Ig Classes Structure Fig 6
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Ig classes and their functions

• All Ig classes bind Ag in the same way via their
  Variable regions
• Distinct classes have different Fc segments and
  thus perform distinct biologic functions
• IgG
• Neutralizes toxins and prevents viral entry into
  cells
• Crosses the placenta from mother to fetus.
• Activates the Complement cascade.
• Enhances phagocytosis (opsonization)

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IgM Neutralizes toxins and viruses Activates
the Complement cascade IgA Crosses secretory
epithelia. Neutralizes toxins and viruses Clears
pathogens in secretions saliva, nasal, bronchial
secretions, seminal fluid, etc. IgE Releases
pharmacologic mediators from basophils and mast
cells and triggers allergic reactions (Hay fever)
IgD Function unknown
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Polymeric Ig (Fig. 7)
All immunoglobulins are constructed from a basic
unit of two H and two L chains, but IgM and IgA
form polymers
In order to form the polymers, both IgM and IgA
have an additional polypeptide chain, called the
J chain, that helps to hold the subunits together
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sIgA Fig 8
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The Complement System

• The complement system (Abbr. C)
• A group of proteins present in the plasma of all
• individuals. Part of the innate immune system.
• A major biological effector system of both the
• innate and the adaptive immune responses.
• The C components are present in the plasma in
• an inactive state.
• Upon activation most C components become
• proteolytic enzymes and act in sequence to cleave
  
• the next C component into active fragments.

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• There are 9 complement proteins (C1 to C9)
• The C facilitates and amplifies inflammatory
  responses in several ways
• Increases vascular permeability
• Destroys cell membranes of pathogens and thus
  induce cell death through lysis
• Enhances phagocytosis (opsonization).

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The three C activation pathways Fig 9
Adaptive Innate Innate
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In the adaptive immune response, the classical C
pathway becomes activated when either IgM or IgG
Ab binds to specific Ag. The binding of Ab to Ag
exposes a site on the Fc segment of the Ig H
chain which in turn binds to and triggers the
activation of the first C component (C1).
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Activation of the C cascade Fig 10
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Activation of the C cascade. Fig 11
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The Membrane Attack Complex
The activation of the first C component called C1
starts the sequential enzymatic activity that
becomes progressively amplified (C
cascade). Each component splits the next one
into a large and a small fragment. The large
fragments become attached to the target cell
membrane and end up by forming the Membrane
Attack Complex (MAC).
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MAC Fig 12
The MAC terminates with multiple copies of the
last C component called C9 which generate pores
in the target cell membrane thus inducing cell
lysis
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Role of the small C fragments Fig 13
The small fragments called anaphylatoxins induce
powerful inflammatory reactions, by increasing
vascular permeability and thus allowing passage
of inflammatory cells from the blood vessels into
the surrounding tissue (diapedesis).
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END