Antibody : Structure & Function.

The recognition of Ag is the hallmark of the specific adaptive immune responses

Humoral immunity Ig (Abs) CMI TCR

Ag
(Yoes Prijatna Dachlan, 2010)

Ag

Electrophoretic profiles of the serum

Yoes Prijatna Dachlan, 2010

(Stewart,2004)

(Yoes Prijatna Dachlan, 2011)

Clonal selection theory

(Yoes Prijatna Dachlan, 2010)

Ag receptor of B lymphocytes

(Yoes Prijatna Dachlan, 2012)

Schematic representation of the primary and secondary structure of a human IgG

(Yoes Prijatna Dachlan, 2011)

(Virella G., 2007)

Four-polypeptide Structure of Immunoglobulin Monomers

(Rodney Porter, Gerald Edelman)

(Yoes Prijatna Dachlan, 2013)

(Roitts Essential Immunology, 2011)

The structure : 4 polypeptide chains ~ 2 identical H chains ~ 2 identical L chains Arranged to span

3 structural units

2 identical Fab units bind Ag

binds effector molecules to trigger Ag elimination The 3rd unit (Fc) to mediate functions such as maternal-fetal transport
(Yoes Prijatna Dachlan, 2013)

(Roitts Essential Immunology, 2011)

The neonatal receptor for IgG

(Roitts Essential Immunology, 2011)

(Yoes Prijatna Dachlan, 2013)

ANTIBODY SINGLE ACTION

(Gregory Stewart, the Immune System,2004)

(Yoes Prijatna Dachlan, 2011)

HIV Life Cycle

(Abbas, 2012)

(Yoes Prijatna Dachlan, 2012)

Model for neutralization of HIV by antibody (Ivan Roitt, Ess Immunol, 2011)
(Yoes Prijatna Dachlan, 2012)

Opsonization of bacteria

(Yoes Prijatna Dachlan, 2011)

S. pneumoniae

CRO CDN

C1q

C3b CRP

SAP

Opsonization

S. pneumoniae

FcR

C3bR Receptor for CRP SAP

Phagocytosis

(Yoes Prijatna Dachlan, 2013)

Opsonization of bacteria

(Yoes Prijatna Dachlan, 2011)

Antibody-dependent cellular cytotoxicity (ADCC)

(Yoes Prijatna Dachlan, 2010)

Ig protein domain = Ig fold

(Janeway, CA., 2001) (Yoes Prijatna Dachlan, 2010)

Antigen binding site

(Yoes Prijatna Dachlan, 2010)

Ag can bind in pockets or grooves or on extended surfaces in the binding sites of Abs

(Janeway, CA., 2001) (Yoes Prijatna Dachlan, 2010)

(Janeway, CA., 2001)

(Yoes Prijatna Dachlan, 2010)

(Stevens, CD.,2010)

(Yoes Prijatna Dachlan, 2010)

CDRs bind antigen

CDR : Complementarity-determining region; hypervariable region

(Infectious Disease : Shetty N, 2009) (Yoes Prijatna Dachlan, 2010)

(Yoes Prijatna Dachlan, 2010)

(Kuby, 2006)

(Kuby, 2006)

(Yoes Prijatna Dachlan, 2010)

IgM

(Janeway, CA., 2001)

(Yoes Prijatna Dachlan, 2010)

(Yoes Prijatna Dachlan, 2011)

(Gregory Stewart, the Immune System,2004)

Structural changes in IgM associated with complement activation

(Electron micrographs, Drs A. Feinstein & E. A. Munn)

IgA

(Janeway, CA., 2001)

(Gabriel Virella, 2007, Med Immunol, 6th ed., p55) (Yoes Prijatna Dachlan, 2010)

(Kuby, 2006)

(Yoes Prijatna Dachlan, 2010)

IMMUNOGLOBULIN SUPERFAMILY

(Yoes Prijatna Dachlan, 2010)

(Stewart,2004) (Yoes Prijatna Dachlan, 2011)

Interaction between B and Th cells

Th cell
C

B cell
CD80/CD86
CD40 D

CD28
CD40L

TCR

*
CD4

MHC Class II
ICAM-1 ICAM-3 LFA-3

LFA-1 CD2

mIg B

(Yoes Prijatna Dachlan,2011)

Signaling functions between Th B cell interaction A : TCR signal transduction B : Activation and proliferation of the B cell C : Co-stimulatory signals to the responding T cells D : Helps to drive B cells into cell cycle E : Receive signals from the T cells for division and differentiation
(Yoes Prijatna Dachlan,2010)

(Yoes Prijatna Dachlan, 2010)

Ab synthesis : IgM to IgG

(Yoes Prijatna Dachlan, 2010)

Mechanisms of Ab synthesis
Ehrlichs side chain hypothesis : is close to to the present view of clonal selection Dreyer & Bennett : one gene, one polypeptide dogma untenable Proved D & B hypothesis; somatic recombination
(Yoes Prijatna Dachlan, 2010)

(Yoes Prijatna Dachlan, 2010)

(Janeways.ImmBiol., 2008)

(Janeways.ImmBiol., 2008)

(Yoes Prijatna Dachlan, 2010)

Antibody diversity A vast antigen receptor repertoir in human

H-chain gene recombination: the germline, on chrom 14, V gene segments 38 to 46 23 D gene segments 6 J gene segments L-chain genes, on chrom 2, V gene segments 31 to 35, 5 Jgenes L-chain genes, on chrom 22 V gene segments 29 to 33, 7 11 J gene segments

(Yoes Prijatna Dachlan, 2010)

(Stevens, CD.,2010)

(Yoes Prijatna Dachlan, 2010)

Mechanisms for the generation of Ab diversity

1. 2. 3. 4. 5. 6. 7. Multiple germline V genes VJ and VDJ recombinations N-nucleotide addition Gene conversion Recombinational inaccuracies Somatic point mutation Assorted heavy and light chain

Chromosomal locations of Ig genes in human and mouse

GENE Light chain Light chain Heavy chain

Chromosome H M 22 16 2 6 14 12

(Yoes Prijatna Dachlan, 2010)

Isotype switching

(Yoes Prijatna Dachlan, 2010)

Chimeric and hybrid monoclonal antibodies engineered by recombinant DNA technology