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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
• Constant regions
hinge region
carbohydrate
disulfide bond
CH
1
VL
CL
VH
CH2 CH3
!
Ribbon structure of IgG
Antibody
BCR (B cell receptor)
!!
MEMBRANE BOUND!
Associated chains
for signaling
Transmembrane
domain
Cytoplasmic
domain
Antigen recognition and B cell
activation
SOLUBLE (freely circulating)
Antigen recognition and effector
functions.
Produced by plasma cells
s
s
s
s
s
s
s
s
s s
s s
CH2
CH3
s
s
s
s
s
s
s
s
s
s
VL
VH
CL
CH1
s
s
s
s
s
s
s
s
s
s
effektor funkciók
konstans domének
antigénkötés
variábilis dom ének
ANTIBODY DOMAINS AND THEIR FUNCTIONS
!
!
Constant domain
Effector functions
Antigen recognition
Variable domain
mIg = BCR
Associated chains providing
signaling capacity
!
B cell
B CELL ACTIVATION
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
Placental transfer
Constant fragment (Fc)
Binding to Fc receptors
on phagocytic cells
Sequence variability of H/L-
chain constant regions
VARIABILITY IN DIFFERENT REGIONS OF THE Ig
DETERMINES Ig SPECIFICITY OR CLASS
isotype
Sequence variability of H/L-
chain variable regions
Idiotype
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)
Epitope
CDR1
CDR2
CDR3
CDR1
CDR2
CDR3
Light
chain
Heavy
chain
Sequence variability of H/L-
chain constant regions
VARIABILITY IN DIFFERENT REGIONS OF THE Ig
DETERMINES Ig SPECIFICITY OR CLASS
Sequence variability of H/L-
chain constant regions
Isotype
• IgG - gamma (γ) heavy chains
• IgM - mu (μ) heavy chains
• IgA - alpha (α) heavy chains
• IgD - delta (δ) heavy chains
• IgE - epsilon (ε) heavy chains
HUMAN IMMUNOGLOBULIN CLASSES
ENCODED BY DIFFERENT STRUCTURAL GENE SEGMENTS (ISOTYPES)
• kappa (κ)
• lambda (λ)
Heavy chain types:
Light chain types:
!
ISOTYPE SWITCHING
PHASES OF B CELL RESPONSE !
Ig isotype Serum
concentration
Characteristics, functions
12-14 mg/ml
 Major isotype of secondary
(memory) immune response
 Complexed with antigen activates
effector functions (Fc-receptor
binding, complement activation
Trace
amounts
 The first isotype in B-lymphocyte
membrane
 Function in serum is not known
Trace
amounts
 Major isotype in protection against
parasites
 Mediator of allergic reactions (binds
to basophils and mast cells)
3-3,5 mg/ml
 Major isotype of secretions (saliva,
tear, milk)
 Protection of mucosal surfaces
1-2 mg/ml
 Major isotype of primary immune
responses
 Complexed with antigen activates
complement
 Agglutinates microbes
 The monomeric form is expressed in
B-lymphocyte membrane as antigen
binding receptor
MAIN CHARACTERISTICS OF ANTIBODY ISOTYPES
MAIN CHARACTERISTICS OF ANTIBODY ISOTYPES
Ig. Concentration
napok
primer response
„A
” antig n
é
IgM
IgG
IgA
IgE
Szekunder ’lasyecondary respo
„A
” és
antigén
„B
”
5 10 15 20 25 30
IgM
secondary response against
antigen A
Primary response
against antigen A
Level of antibodies
napok
primary response
against antigen B
Antigen A
Days
Antigen A and B
ANTIBODY PRODUCTION DURING THE
PRIMARY AND THE SECONDARY IMMUNE RESPONSES
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 pathogen’s surface
prevents replication and growth
Antigen binding
Complement binding site
Placental transfer
Binding to Fc receptors
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)
(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)
MAST CELL DEGRANULATION
FcεRI
+
IgEs
Antigen binding
Complement binding site
Placental transfer
Binding to Fc receptors
COMPLEMENT FIXATION
IgM and IgGs activate the classical pathway of
the complement system
Bacterium
Complement receptor
Macrophage
OPSONIZATION BY C3b
C3b
IMMUNOGLOBULIN ISOTYPES HAVE EACH
THEIR SPECIFIC CAPABILITIES
Antigen binding
Complement binding site
Placental transfer
Binding to Fc receptors
FcRn on the placenta
facilitate the transfer of
maternal IgG to the fetus’s
circulation
IgG
IgM
IgA
AFTER BIRTH
breast milk
IgA
0
100%
( adult)
3 3
year
2 5
4
6 adult
9 1
month
maternal IgG
BEFORE BIRTH
PRODUCTION OF IMMUNOGLOBULINS
 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)
Passive anti-D IgG
anti-Rh
IgM
DIMERIC IgA
IgA dimers are in the highly vulnerable mucosal epithelia lining the
GI, respiratory, urinary and genital tracts, the eyes, nose and throat
(Transcytosis)

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IMMUNOGLOBULINS.ppt

  • 2. 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
  • 3.  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
  • 4. PHASES OF B CELL RESPONSE !
  • 5. IMMUNOGLOBULIN STRUCTURE • 2x Heavy chain (light blue) • 2x light chain (dark blue) • Variable regions  antigen binding • Constant regions hinge region carbohydrate disulfide bond CH 1 VL CL VH CH2 CH3 !
  • 7. Antibody BCR (B cell receptor) !! MEMBRANE BOUND! Associated chains for signaling Transmembrane domain Cytoplasmic domain Antigen recognition and B cell activation SOLUBLE (freely circulating) Antigen recognition and effector functions. Produced by plasma cells
  • 8. s s s s s s s s s s s s CH2 CH3 s s s s s s s s s s VL VH CL CH1 s s s s s s s s s s effektor funkciók konstans domének antigénkötés variábilis dom ének ANTIBODY DOMAINS AND THEIR FUNCTIONS ! ! Constant domain Effector functions Antigen recognition Variable domain
  • 9. mIg = BCR Associated chains providing signaling capacity !
  • 10. B cell B CELL ACTIVATION BCR oligomerization results in B cell activation, proliferation and differentiation !
  • 12. 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
  • 13. ANTIGEN BINDING Antigen Binding Fragment (Fab) Complement binding site Placental transfer Constant fragment (Fc) Binding to Fc receptors on phagocytic cells
  • 14. Sequence variability of H/L- chain constant regions VARIABILITY IN DIFFERENT REGIONS OF THE Ig DETERMINES Ig SPECIFICITY OR CLASS isotype Sequence variability of H/L- chain variable regions Idiotype
  • 15. DIFFERENT VARIABLE REGIONS  DIFFERENT ANTIGEN-BINDING SITES  DIFFERENT SPECIFICITIES
  • 16. 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
  • 17. COMPLEMENTARY DETERMINING REGIONS (CDR) Epitope CDR1 CDR2 CDR3 CDR1 CDR2 CDR3 Light chain Heavy chain
  • 18. Sequence variability of H/L- chain constant regions VARIABILITY IN DIFFERENT REGIONS OF THE Ig DETERMINES Ig SPECIFICITY OR CLASS Sequence variability of H/L- chain constant regions Isotype
  • 19. • IgG - gamma (γ) heavy chains • IgM - mu (μ) heavy chains • IgA - alpha (α) heavy chains • IgD - delta (δ) heavy chains • IgE - epsilon (ε) heavy chains HUMAN IMMUNOGLOBULIN CLASSES ENCODED BY DIFFERENT STRUCTURAL GENE SEGMENTS (ISOTYPES) • kappa (κ) • lambda (λ) Heavy chain types: Light chain types: !
  • 21. PHASES OF B CELL RESPONSE !
  • 22. Ig isotype Serum concentration Characteristics, functions 12-14 mg/ml  Major isotype of secondary (memory) immune response  Complexed with antigen activates effector functions (Fc-receptor binding, complement activation Trace amounts  The first isotype in B-lymphocyte membrane  Function in serum is not known Trace amounts  Major isotype in protection against parasites  Mediator of allergic reactions (binds to basophils and mast cells) 3-3,5 mg/ml  Major isotype of secretions (saliva, tear, milk)  Protection of mucosal surfaces 1-2 mg/ml  Major isotype of primary immune responses  Complexed with antigen activates complement  Agglutinates microbes  The monomeric form is expressed in B-lymphocyte membrane as antigen binding receptor MAIN CHARACTERISTICS OF ANTIBODY ISOTYPES
  • 23. MAIN CHARACTERISTICS OF ANTIBODY ISOTYPES
  • 24. Ig. Concentration napok primer response „A ” antig n é IgM IgG IgA IgE Szekunder ’lasyecondary respo „A ” és antigén „B ” 5 10 15 20 25 30 IgM secondary response against antigen A Primary response against antigen A Level of antibodies napok primary response against antigen B Antigen A Days Antigen A and B ANTIBODY PRODUCTION DURING THE PRIMARY AND THE SECONDARY IMMUNE RESPONSES
  • 25. ANTIBODY PRODUCTION DURING THE PRIMARY AND THE SECONDARY IMMUNE RESPONSE !
  • 26. EFFECTOR FUNCTIONS OF ANTIBODIES Antibody-mediated immune responses • NEUTRALIZATION • OPSONIZATION ADCC MAST CELL DEGRANULATION • COMPLEMENT FIXATION ! !
  • 27. NEUTRALIZATION Covering of the pathogen’s surface prevents replication and growth
  • 28. Antigen binding Complement binding site Placental transfer Binding to Fc receptors
  • 29. 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
  • 30. Antibody Dependent Cellular Cytotoxicity (ADCC)
  • 31. (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) MAST CELL DEGRANULATION FcεRI + IgEs
  • 32. Antigen binding Complement binding site Placental transfer Binding to Fc receptors
  • 33. COMPLEMENT FIXATION IgM and IgGs activate the classical pathway of the complement system
  • 35. IMMUNOGLOBULIN ISOTYPES HAVE EACH THEIR SPECIFIC CAPABILITIES
  • 36. Antigen binding Complement binding site Placental transfer Binding to Fc receptors FcRn on the placenta facilitate the transfer of maternal IgG to the fetus’s circulation
  • 37. IgG IgM IgA AFTER BIRTH breast milk IgA 0 100% ( adult) 3 3 year 2 5 4 6 adult 9 1 month maternal IgG BEFORE BIRTH PRODUCTION OF IMMUNOGLOBULINS  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
  • 38. Pathological consequences of placental transport of IgG (hemolytic disease of the newborn) Passive anti-D IgG anti-Rh IgM
  • 39. DIMERIC IgA IgA dimers are in the highly vulnerable mucosal epithelia lining the GI, respiratory, urinary and genital tracts, the eyes, nose and throat (Transcytosis)