Id-1b 7jan Ab Mkdu & s3 2012 Ypd
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Transcript of Id-1b 7jan Ab Mkdu & s3 2012 Ypd
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Antibody : Structure & Function.
The recognition of Ag is the
hallmark of the specific adaptive
immune responses
CMITCR
Ag
Humoral immunityIg (Abs)
Ag
(Yoes Prijatna Dachlan, 2010)
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Electrophoretic profiles of the serum
Yoes Prijatna Dachlan, 2010
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(Stewart,2004)
(Yoes Prijatna Dachlan, 2011)
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Clonal selection theory
(Yoes Prijatna Dachlan, 2010)
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Ag receptor of B lymphocytes
(Yoes Prijatna Dachlan, 2012)
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Schematic representation of the primary and secondary structure of a
human IgG
(Virella G., 2007)
(Yoes Prijatna Dachlan, 2011)
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Four-polypeptide Structure of Immunoglobulin Monomers
(Rodney Porter, Gerald Edelman)
(Roitts Essential
Immunology, 2011)(Yoes Prijatna Dachlan, 2013)
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The structure : 4 polypeptide chains
~ 2 identical H chains
~ 2 identical L chains
3 structural units
2 identical Fab units bind Ag
The 3rd unit (Fc)
binds effector
molecules to trigger
Ag elimination
to mediate functions
such as maternal-fetal
transport
Arranged to span
(Roitts EssentialImmunology, 2011)(Yoes Prijatna Dachlan, 2013)
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(Roitts EssentialImmunology, 2011)
(Yoes Prijatna Dachlan, 2013)
The neonatal receptor for IgG
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(Gregory Stewart, the Immune System,2004)
(Yoes Prijatna Dachlan, 2011)
ANTIBODY SINGLE ACTION
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(Abbas, 2012) (Yoes Prijatna Dachlan, 2012)
HIV Life Cycle
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Model for neutralization of HIV by antibody (Ivan Roitt, Ess Immunol, 2011)(Yoes Prijatna Dachlan, 2012)
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Opsonization of bacteria
(Yoes Prijatna Dachlan, 2011)
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S. pneumoniae
OpsonizationC3b
CRO CDN
C1q CRP SAP
Phagocytosis
Receptor for
CRP SAP
C3bRFcR
S. pneumoniae
(Yoes Prijatna Dachlan, 2013)
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Opsonization of bacteria
(Yoes Prijatna Dachlan, 2011)
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Antibody-dependent cellular cytotoxicity
(ADCC)
(Yoes Prijatna Dachlan, 2010)
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Ig protein domain = Ig fold
(Yoes Prijatna Dachlan, 2010)(Janeway, CA., 2001)
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Antigen binding site
(Yoes Prijatna Dachlan, 2010)
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Ag can bind in pocketsor groovesor on
extended surfacesin the binding sites of
Abs
(Yoes Prijatna Dachlan, 2010)(Janeway, CA., 2001)(Janeway, CA., 2001)
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(Janeway, CA., 2001)
(Yoes Prijatna Dachlan, 2010)
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(Stevens, CD.,2010)
(Yoes Prijatna Dachlan, 2010)
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CDRs bind antigen
CDR : Complementarity-determining region; hypervariable region
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(Infectious Disease : Shetty N, 2009)
(Yoes Prijatna Dachlan, 2010)
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(Kuby, 2006)(Yoes Prijatna Dachlan, 2010)
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(Kuby, 2006)
(Yoes Prijatna Dachlan, 2010)
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(Yoes Prijatna Dachlan, 2010)
IgM
(Janeway, CA., 2001)
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(Gregory Stewart, the Immune System,2004)(Yoes Prijatna Dachlan, 2011)
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(Electron micrographs, Drs A. Feinstein & E. A. Munn)
Structural changes in IgM associated with complement activation
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IgA
(Janeway, CA., 2001)
(Yoes Prijatna Dachlan, 2010)
(Gabriel Virella, 2007, Med Immunol, 6th ed., p55)
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IMMUNOGLOBULIN SUPERFAMILY
(Yoes Prijatna Dachlan, 2010)
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(Stewart,2004)(Yoes Prijatna Dachlan, 2011)
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Interaction between B and Th
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B cell
CD28
CD40CD40L
MHC Class II*TCR
ICAM-1
ICAM-3
LFA-1
LFA-3CD2
mIg
Th cell
CD80/CD86
*CD4
A
B
C
D
E
(Yoes PrijatnaDachlan,2011
Interaction between B and Th
cells
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Signaling functions between ThB cell
interaction
A: TCR signal transduction
B: Activation and proliferation of the B cell
C: Co-stimulatory signals to the responding Tcells
D: Helps to drive B cells into cell cycle
E: Receive signals from the T cells for divisionand differentiation
(Yoes PrijatnaDachlan,2010
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Ab synthesis : IgM to IgG
(Yoes Prijatna Dachlan, 2010)
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Mechanisms of Ab synthesis
Ehrlichs side chain hypothesis :is close to to the present view of clonal
selection
Dreyer & Bennett : one gene, one
polypeptidedogma untenable
Proved D & B hypothesis; somatic
recombination
(Yoes Prijatna Dachlan, 2010)
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(Yoes Prijatna Dachlan, 2010) (Janeways.ImmBiol., 2008)
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(Yoes Prijatna Dachlan, 2010)
(Janeways.ImmBiol., 2008)
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(Stevens, CD.,2010)
(Yoes Prijatna Dachlan, 2010)
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Mechanisms for the generation of Ab
diversity
1. Multiple germline V genes
2. VJ and VDJ recombinations
3. N-nucleotide addition4. Gene conversion
5. Recombinational inaccuracies
6. Somatic point mutation7. Assorted heavy and light chain
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GENE Chromosome
H M
Light chain 22 16
Light chain 2 6
Heavy chain 14 12
Chromosomal locations of
Ig genes
in human and mouse
(Yoes Prijatna Dachlan, 2010)
I t it hi
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Isotype switching
(Yoes Prijatna Dachlan, 2010)
Chimeric and hybrid
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Chimeric and hybrid
monoclonal antibodies
engineered by
recombinant DNA
technology