antigen

secretion of antibodies

clonal expansion

Harvard-MIT Division of Health Sciences and TechnologyHST.176: Cellular and Molecular ImmunologyCourse Director: Dr. Shiv Pillai

Serum Electrophoresis

+ _ A l b u m i n G l o b u l i n s

α β

γ

Fab Fragment

Fc fragment

CDR1 CDR2

CDR3

Hinge

VH

VL

CL

CH1

CH2

CH3

N

CC

N

N

C

Papain cleavage

N

Y

Y

YYYYYYYY

Neutralization

Functions of Antibodies Agglutination

Complement fixation

YYYC

YYY Opsonization

YYY Antibody dependent cellular cytotoxicity

IgG IgD

IgE

J chain

Pentameric IgM

J chain Dimeric IgA

Different Ig isotypes mediate distinct functions

1. Complement fixation- (IgM, IgG1, and IgG3)

2. Opsonization- (IgG1 and IgG3)

3. Placental transfer- (IgG2 and IgG4)

4. Mucosal immunity - (IgA1, IgA2, and IgM)

5. Immediate type hypersensitivity - (IgE)

6. Antibody Dependent Cellular Cytotoxicity

Y

YY

YY

YY

Poly Ig receptor Y YY

Y Y Y

Y Y

J chain Y

Dimeric IgA

IgA SECRETING PLASMA CELL

secretory IgA

Generation of secretory IgA

Secretory component YY

IMMEDIATE TYPE HYPERSENSITIVITY

Crosslinking antigen

IgE Y Y YYFcεRI

MAST CELL

N N

Primary structure

Secondary structures

alpha - helix

beta-strand

C

C

N N C NC

NCN C

Tertiary structure Quaternary structure

C

Complementarity determining regions = CDRs = HVRs See Immunobiology, by Janeway,C., Travers, P.,Walport, M. and Capra, J., Garland Publishing, 5th edition, 2001 & Cellular and Molecular Immunology by

Abbas, A., Pober, J., and Lichtman, A., W B Saunders; 4th edition.

Isotypes

Allotypes

Anti -mannose Anti-glucose

IgG IgG

IgGIgD

IgG IgG

Idiotypes

secreted membrane form form

K V

K V

13 aa 26

aa

3aa

K K

Poly A sites

Cµ1 Cµ2 Cµ3 Cµ4 µM1 µM2

AAAA Choice of first polyadenylation site

AAAA Choice of second polyadenylation site

AAAA µs mRNA

AAAA µm mRNA

µVDJL

Hapten Polyvalent antigen

polysaccharidemonosaccharide

antigen receptor

NO SIGNAL SIGNAL TRANSDUCTION

Haptens, Antigens, Immunogens

• Haptens are small molecules or moieties. They are antigens but not immunogens

• All immunogens are antigens

• All antigens are not immunogens

Igs and the secretory pathway

Y

Y

Y

Y

Y

Y

Y

Y

Y

Y

ER

Golgi

Endocytosis, recycling, and lysosomes

Early endosomes

Late

ER

Golgi

Lysosomes

endosomes

Vesiculo-Tubular Compartment

Proteins are endocytosed after

Monovalent small molecule

Polyvalent biopolymer

biopolymer/

Y NO SIGNAL

they are seen by the BCR

Hapten

YYSIGNAL

ENDOCYTOSED FOR

Y

T-independent antigen

“Monovalent” Y ANTIGEN PRESENTATIONprotein

Viral envelope protein

MHC class I-peptide complex

T

T cell receptor

Antibodies -missing the forest for the trees?

α1 α2

α3 β 2-microg lobu l in

Transmembrane domain

Cytoplasmic tail

peptide

Heavy chain

peptide

α1 β1

β2α2

activated T TCR CD4

gp 39/CD40L

Y CD40BCR

MHC class II

(loaded)

Y B

HELPER T CELL

Nucleus

Endoplasmic reticulum

T cell receptor

CD4

MHC class II

membrane immunoglobulin

protein antigen

CLIPPeptide -CLIP exchange mediated by HLA-DM

Invariant chain

i

B cell epitope or hapten

linear peptides presented to T cells ("carrier determ nant")

H a p t e n-p r o t e in conjugate

(T dependent immunogen) WILL NOT CROSSLINK RECEPTOR

YYY

Y NO SIGNAL

SIGNAL

Y ENDOCYTOSED FOR ANTIGEN PRESENTATION

Hapten

T-independent antigen

T-dependent antigen