PURNOMO SURYOHUDOYO

DEPT. OF BIOCHEMISTRY
SCHOOL OF MEDICINE
AIRLANGGA UNIVERSITY
 IMMUNITY
INNATE (NATURAL) IMMUNITY
Nonspecific
Does not depend on antigen – antibody interaction
First line defence, acts before acquired (adaptive) immunity
Present in plants, invertebrates and vertebrates
Always present

ACQUIRED (ADAPTIVE) IMMUNITY

Specific
Depends on antigen – antibody interactions
Only present in vertebrates takes time to develop
ADAPTIVE
IMMUNORESPONSE
1. HUMORAL
B LYMPHOCYTES

2. CELLULAR
T LYMPHOCYTES
Tc (Cytotoxic) CD8+
TH (Helper) CD4+
TR (Regulator) CD4+

T Cell Receptor (TCR)

Major Histocompatibility
Complex proteins (MHC)
MHC I ( HLA I)
MHC II (HLA II)
CLONAL SELECTION THEORY

Antigen

Antigen bind
to complementary lg
B Lymphocytes
Displaying Proliferation
Different lgs
B Lymphocytes
displaying same lg

differentation

lg secreted
Plasma Cells
 Lymphocytes suspension from
unimmunised animal

Antigen (A) imbedded in gelatin

wash

Digest with enzyme and resuspend

Place in culture medium & observe

under microscope

Add Antigen B Add Antigen A

No Proliferation Proliferation

PROOF OF CLONAL SELECTION THEORY

IMMUNOGLOBULIN (Ig)

2 Fab

Cleavage by
Hinge Region Papain

2 Fc

H : heavy dhain V : variable domain

L : light chain C : constant domain
CHO : carbohydrate
: disuliphide link
Fab. : antibody binding fragment
Fc. : crystralline fragment
(does not bind Ab)
L Chain :  (lambda0 or  ( kappa)
H Chain : , δ, 1  4 , α1α2, έ
IMMUNIGLOBULINS ARE NAMED AFTER ITS H CHAINS :
lgM, lgD, lg G, lg A, lg E
ORGANISATION OF IG GENES
 L-CHAIN

 L-CHAIN

H L-CHAIN

MICE

HUMAN

C H-CHAIN
L : Leader
(untranslated) M : membrane
Signal for translation in ribosomes bound (only transcribed in membrane
to E.R. (membrane bound bound lg)
& secreted proteins)
 GENE REARRANGEMENT
PRE-TRANSCRIPTIONAL PROCESSING
IMMUNOGLOBULIN LIGHT CHAIN
GERM LINE DNA

CELL DIFFERENTATION
( & GENE REARRANGEMENT)
LYMPHOCYTE DNA

IMMUNOGLOBULIN
LIGHT CHAIN

IMMUNOGLOBULIN SYNTHESIS IN B LYMPHOCYTES

Y : GENES FOR VARIABLE REGION
J : GENES FOR JOINING SEGMENTS
C : GENE FOR CONSTANT REGION
H-CHAIN GENE REARRANGEMENT
ALLELIC EXCLUSION (1)

IMMUNOGLOBULIN GENES
H – CHAIN : CHR 14
 L - CHAIN : CHR 6
 L - CHAIN : CHR 16

H CHAIN  CHAIN  CHAIN

   
 
† lg M lg M †
ALLELIC EXCLUSION (2)
SWITCHING
(BIFUNCTIONAL LYMPHOCYTE)

SWITCHING
(MONOFUNCTIONAL LYMPHOCYTE)
MEMBRANE & SECRETED I.G.
GENETIC BASIS FOR ANTIBODY DIVERSITY
VARIABILITY DUE TO
VJ & VDJ JOINING

JUNCTION CODONS A.A.

SEQUENCE GENERATED

FRAME-SHIFT DUE TO
VJ & VDJ JOINING

FRAME-SHIFT WILL RESULT IN A NON-FUNCTIONAL

REARRENGED GENE  CELL DIES
B CELL SIGNALING

FURTHER
EFFECT
T CELL RECEPTOR ( TCR)

TCR CHAINS

TCR GENES
MHC I & II
MAJOR HISTOCOMPTABILITY COMPLEX CLASS I & II

MHC I is found on most cell

MHC II is only found on B-Lymphocytes, activated lymphocytes,
macrophages vascular endothelium & some types of
epithelial cells
 T – LYMPHOCYTE DIFFERENTIATON

CORTEX

MEDULLA

PERIPHERY
 ANTIGEN PROCESSING & PRESENTATION
Cytoplasmic
Viral protein
Nucleated
Tissue Cell

MHC - I

B-LYMPHOCYTE

MHC - II

MACROPHAGES
ANTIGEN PRESENTING
CELL (APC)
MHC - II
T CELLS INTERACTIONS
 Tc INTERACTION
TARGET
CELL

CELL DIES BY
APOPTOSIS

Tc PROLIFERATION
CELL DIES BY NECROSIS

TARGET CELL
T HELPER INTERACTION

CELL MEDIATED IMMUNITY

(DTH) HUMORAL IMMUNITY
T HELPER (T CD4+) INTERACTION
REGULATORY T CELL (TR)
B CELL INTERACTION (1)
T CELL INDEPENDENT ANTIGEN *

* ALSO CALLED : THYMUS INDEPENDENT ANTIGEN

B CELL INTERACTION (2)
T CELL DEPENDENT ANTIGEN *
T CELL SIGNALING