IMMUNOGLOBULINS

STRUCTURE AND FUNCTION

IMMUNOGLOBULINS

Definition

Glycoprotein molecules that are

present on B cells (BCR) or
produced by plasma cells (usually
referred to as antibodies) in
response to an immunogen
 Antibodies production is the sole
function of the B cells

Not toxic or destructive, bind the

pathogen tightly and target destructive
components of the immune system

Antibodies are useful in the defense

against extracellular pathogens

Antibodies are secreted in the secondary

lymphoid organs and in bone marrow and
find their way to the extracellular spaces

During the course of an infection

antibody effectiveness improves steadily
PHASES OF B CELL RESPONSE !
 IMMUNOGLOBULIN STRUCTURE !
2x Heavy chain (light blue)

2x light chain (dark blue)

Variable regions antigen binding

disulfide bond

Constant regions carbohydrate

CL
VL

CH CH2 CH3

VH 1
hinge region
Ribbon structure of IgG
 BCR (B cell receptor) Antibody
!!

Transmembrane
Associated chains domain
for signaling

Cytoplasmic
domain SOLUBLE (freely circulating)
MEMBRANE BOUND! Antigen recognition and effector
Antigen recognition and B cell functions.
activation Produced by plasma cells
ANTIBODY DOMAINS AND THEIR FUNCTIONS

Antigen recognition
!!
antignkts VH
VL
CH1
Variable
varibilisdomnek
CL
domain
ss
ss
Constant domain
konstansdomnek CH2ss s
s

effektorfunkcik CH3ss s
s

Effector
functions
 mIg = BCR !

Associated chains providing

signaling capacity
 B CELL ACTIVATION !

B cell

BCR oligomerization results in B cell

activation, proliferation and differentiation
FLEXIBILITY OF ANTIBODIES
FEATURES OF ANTIBODY-ANTIGEN INTERACTION

Valency: numbers of antigen

epitopes an antibody binds

Affinity: the strength of

interaction between a specific
antigen and one binding site
of the antibody

Avidity: The overall strength

of binding at multiple sites in
an antibody
 ANTIGEN BINDING

Antigen Binding
Fragment (Fab)

Complement binding site

Constant fragment (Fc)
Binding to Fc receptors Placental transfer
on phagocytic cells
 VARIABILITY IN DIFFERENT REGIONS OF THE Ig
DETERMINES Ig SPECIFICITY OR CLASS

isotype

Idiotype

Sequence variability of H/L-

chain constant regions

Sequence variability of H/L-

chain variable regions
DIFFERENT VARIABLE REGIONS
DIFFERENT ANTIGEN-BINDING SITES
DIFFERENT SPECIFICITIES
 ANTIGEN BINDING FRAGMENT (Fab)
CONTAINS HYPERVARIABLE REGIONS

DNA recombination of gene

segments encoding these
regions (variable heavy and
light polypeptide chains) gives
a huge number of variability
during B cell development in
the bone marrow.

Aka. Somatic recombination

COMPLEMENTARY DETERMINING REGIONS (CDR)

Light
CDR2 chain
CDR1 CDR3

Epitope

CDR1 CDR3
CDR2

Heavy
chain
 VARIABILITY IN DIFFERENT REGIONS OF THE Ig
DETERMINES Ig SPECIFICITY OR CLASS

Isotype

Sequence variability of H/L-

chain constant regions

Sequence variability of H/L-

chain constant regions
 HUMAN IMMUNOGLOBULIN CLASSES !
ENCODED BY DIFFERENT STRUCTURAL GENE SEGMENTS (ISOTYPES)

Heavy chain types:

IgG - gamma () heavy chains
IgM - mu () heavy chains
IgA - alpha () heavy chains
IgD - delta () heavy chains
IgE - epsilon () heavy chains

Light chain types:

kappa ()
lambda ()
ISOTYPE SWITCHING
PHASES OF B CELL RESPONSE !
MAIN CHARACTERISTICS OF ANTIBODY ISOTYPES
Ig isotype Serum Characteristics, functions
concentration
Major isotype of secondary
(memory) immune response
12-14 mg/ml Complexed with antigen activates
effector functions (Fc-receptor
binding, complement activation
The first isotype in B-lymphocyte
Trace membrane
amounts Function in serum is not known

Major isotype in protection against

parasites
Trace Mediator of allergic reactions (binds
amounts to basophils and mast cells)

Major isotype of secretions (saliva,

tear, milk)
3-3,5 mg/ml Protection of mucosal surfaces

Major isotype of primary immune

responses
Complexed with antigen activates
complement
1-2 mg/ml Agglutinates microbes
The monomeric form is expressed in
B-lymphocyte membrane as antigen
binding receptor
MAIN CHARACTERISTICS OF ANTIBODY ISOTYPES
 ANTIBODY PRODUCTION DURING THE
PRIMARY AND THE SECONDARY IMMUNE RESPONSES

Ig . C oofn cantibodies
Level e n tra tio n
secondary response against
Santigen
z e k u n d Ae r la s y e c o n d a r y re s p o

Primary response
p rim eantigen
against r re s p oAn se Ig G
Ig A
Ig E
Ig M Ig M
primary response
against antigen B

5 10 15 20 25 30
nnapok
apok
Days
A a n tig An
Antigen A s B
Antigen A and
a n tig n B
 ANTIBODY PRODUCTION DURING THE
PRIMARY AND THE SECONDARY IMMUNE RESPONSE !
 !!
EFFECTOR FUNCTIONS OF ANTIBODIES

Antibody-mediated immune responses

NEUTRALIZATION
OPSONIZATION
ADCC
MAST CELL DEGRANULATION
COMPLEMENT FIXATION
 NEUTRALIZATION
Covering of the pathogens surface
prevents replication and growth
Antigen binding

Complement binding site

Binding to Fc receptors
Placental transfer
OPSONIZATION
Flagging a pathogen

Antigen binding portion (Fab)

binds the pathogen, the Fc
region binds phagocytic cells
Fc-receptors speeding up the
process of phagocytosis
Antibody Dependent Cellular Cytotoxicity
(ADCC)
 MAST CELL DEGRANULATION

FcRI
+
IgEs

(A) High-affinity FcRs on the surface of the cell bind monomeric

Ig before it binds to antigen. (mast cell)
(B) Low-affinity FcRs bind multiple Igs that have already bound to
a multivalent antigen. (macrophage, NK cell)
Antigen binding

Complement binding site

Binding to Fc receptors
Placental transfer
 COMPLEMENT FIXATION
IgM and IgGs activate the classical pathway of
the complement system
 OPSONIZATION BY C3b

C3b Bacterium
Complementreceptor

Macrophage
IMMUNOGLOBULIN ISOTYPES HAVE EACH
THEIR SPECIFIC CAPABILITIES
Antigen binding

Complement binding site

Binding to Fc receptors
Placental transfer

FcRn on the placenta

facilitate the transfer of
maternal IgG to the fetuss
circulation
 PRODUCTION OF IMMUNOGLOBULINS
B E F O R E B IR T H A F T E R B IR T H
b r e a s t m i lk
Ig A
100% Ig M
( a d u lt)
m a te r n a l I g G
Ig G

Ig A

0 3 6 9 1 2 3 4 5 a d u lt
m o n th year
IgG transport is so efficient that at birth babies have as high a level of IgG in
their plasma as their mothers

These transfers are a form of passive immunization. The babies protection by

IgG and IgA is against those pathogen that the mother has mounted

At the first year (esp.3-12m) maternal IgGs are catabolized and breast feeding
diminishes so babies become most susceptible/vulnerable to infections
Pathological consequences of placental
transport of IgG
(hemolytic disease of the newborn)

anti-Rh
IgM

Passive anti-D IgG

 DIMERIC IgA

(Transcytosis)

IgA dimers are in the highly vulnerable mucosal epithelia lining the
GI, respiratory, urinary and genital tracts, the eyes, nose and throat