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
Different lgs

Proliferation
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

No Proliferation

Add Antigen A

Proliferation

PROOF OF CLONAL SELECTION THEORY

IMMUNOGLOBULIN (Ig)
2 Fab
Hinge Region

Cleavage by
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 : , , 1 4 , 12,

IMMUNIGLOBULINS ARE NAMED AFTER ITS H CHAINS :

lgM, lgD, lg G, lg A, lg E

ORGANISATION OF IG GENES

L-CHAIN

L-CHAIN

L-CHAIN

MICE
HUMAN

L : Leader
(untranslated)
Signal for translation in ribosomes
bound to E.R. (membrane bound
& secreted proteins)

H-CHAIN

M : membrane
(only transcribed in membrane
bound lg)

GENE REARRANGEMENT
PRE-TRANSCRIPTIONAL PROCESSING
IMMUNOGLOBULIN LIGHT CHAIN
GERM LINE DNA

LYMPHOCYTE DNA

CELL DIFFERENTATION
( & GENE REARRANGEMENT)

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

lg M

CHAIN

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
SEQUENCE

CODONS
GENERATED

A.A.

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