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CELLLULAR AND
MOLECULAR BASIS OF
IMMUNITY

MUHAMMAD JUNAID
07-Arid-1657

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 Structure Of Antibodies

 Antibodies are proteins produced by B cell and

plasma cells.
 B cell incorporate antibody molecule into their
plasma membrane where they serve as antigen
receptor.
 Where as plasma cells secrete these proteins into
blood and other body fluids.

Contd… 3
 Structure Of Antibodies

 Antibodies are globular proteins called

immunoglobulins.
 These are built of two types of chains.
 A larger heavy chains (50,000-70,000 daltons)
 And a smaller light chains (23,000 daltons)
 These are linked by disulfide bond.

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 Antibody Structure

 Domains comprising a constant region are indicated

by C.
 Domains comprising the variable are V.
 Each heavy chains contain three C regions (C 1 , C
2, C 3) one V regions and N-terminus of polypeptide.
 Each light chains contain one C L regions one V
regions at its N terminus.
 The V regions forms the antigen combining site.

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 Variation In The Antibody

 Half of each light chains has a variable region V.

 One quarter of each heavy chain is variable V.
 The remaining three regions are constant .
 The variable portion of light and heavy chains
contain subregions called hypervariable regions.
 Hypervariable regions play a prominent role in
forming antigen combining site.
 Variation in amino acid sequence of these regions
result in great diversity of antibody specificity.
Contd… 9
 Variation In The Antibody

 The combining site has a complementary portion

of the antigen which is called epitope.
 Because of their close fit ,antibodies and antigen
forms stable complexes

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 DNA Rearrangement Of Genes
Encoding B-and T- Cell Antigen
Receptors
 Each Ig molecule consist of light and heavy
chains.
 Both have a variable portions V.
 Whose amino sequence varies from one antibody
to another.
 The constant region C remain the same in both
classes.

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 What is the genetic basis for the
synthesis of polypeptide having a
combination of share and unique
amino acid sequences?

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 One gene one polypeptide hypothesis

 In 1965 William Dreyer and J Claude gave one

gene one polypeptide hypothesis.
 They proposed that each antibody is encoded by
two separate genes C gene and V gene. That
combine to form one gene.
 In 1976 Susumu Tonegawa provided evidence in
favour of DNA rearrangement.

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 DNA rearrangement lead to the
formation of a functional gene that
encodes an immunoglobulin chain

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 Mechanism of rearrangement

 The variable region of each immunoglobulin heavy or

light chain is encoded in several pieces known as gene
segments.
 These segments are called variable (V), diversity (D)
and joining (J) segments.
 V, D and J segments are found in Ig heavy chains, but
only V and J segments are found in Ig light chain.
 Developing B cell will assemble an immunoglobulin
variable region by randomly selecting and combining
one V, one D and one J gene segment

Contd… 16
 Mechanism of rearrangement

 As there are multiple copies of each type of gene

segment
 Different combinations of gene segments can be
used to generate each immunoglobulin variable
region
 This process generates a huge number of
antibodies, each with different paratopes and
thus different antigen specificities.

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 Class switching
 Once a cell is committed to form a specific antibody it can
switch the class of Ig it produces. By changing the heavy
chain in the cell.
 This is known as class switch. Occurs without changing
the combining site of antibody synthesized.
 Class switching allows different daughter cells from the
same activated B cell to produce antibodies of different
isotypes.
 Thus the progeny of a single B cell can produce
antibodies, all specific for the same antigen.
 It is initiated by cytokines secreted by T cells. During B
cell interactions.
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 Membrane Bound Antigen Receptor
Complexes
 The recognition of antigen of B and T cell occurs
at cell surface.
 B cell receptor combine epitope.
 T cell receptor combine with a fragment of
antigen.
 Both receptor are involved in signalling pathway.
 Which activate both the cells.

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 Pathway of activation of TCR

 TCR is phosphorylated by src Family of

Lck & Fyn
 Which recruit zap-70. to TCR.
 Map kinase cascade is initiated.
 The CD45 protein tyrosine phosphates
activates Lck and Fyn required for TCR
activation.

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 Pathway Of Activation Of BCR
 Reversible tyrosine phosphorylation plays an
important role in regulating B cell.
 Antigen binding promotes protein tyrosine
kinase.
 Phosphorylation increases.
 Src family PTKs are activated initially and serve
to phosphorylate CD79a and CD79b thereby
creating phosphotyrosine motifs.
 BCR complex leads to the recruitment and
activation of the PTK Syk, which in turn
promotes phosphorylation of PLCg, Shc and Vav
Contd… 23
 Pathway Of Activation Of BCR
 Tec,btk recruited to p.membrane Plcg activated.
 SLP-65/BLINK recruites effector proteins.
 After BCR activation numerous second
messenger PPI3 IP 3. DAG activate Pkc.
 IP3 promote Ca ions
 Ras, Rap also activated.Map kinase is also
actavated. Including Erk Jnk and p38.
 Several transcription factor activated which
initiate gene transcription.
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 Major Histocompatibility Complex

 T cells activated by APC.

 Small fragment of antigen are held in MHC.
 MHC interacts with TCR.
 This interaction is further strengthens by
coreceptor CD 4, CD 8.

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 Classes of MHC

 Two classes of MHC display antigen which

may be endogenous or exogenous.
 Class I endogenous.
 Class II exogenous.

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 Inhibition of TCR
 The phosphorylation of Lck by Csk inhibits T cell
receptor signaling and inhibits T cell activation.
 Csk activity is regulated in T cells by PKA, the
cAMP-dependent protein kinase activated by the
second messenger cAMP.
 The activity of csk depend on CBP.
 T cell receptor complex are localized. CBP also
directly activates Csk.

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 Distinguishing Self from Nonself

T Cells are recognized by their receptors which

are coded by transcription factors called AIRE.
 T Cells whose TCRs have high affinity for bodies
on protien are destroyed this process is negative
selection gradely reduces the chance of attack on
self.

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 Summary

 Genes are rearranged to form B and T cell and

antigen receptors.
V D J undergo recombination to produce many
types of antibodies.

TCells are activated by MHCs which are on the

APCs.
Contd… 33
 Summary

T Cells are activated through different Map

Kinase.

T Cells are recognized by their own system

through their receptors.

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Quote:

Don’t screw up the best things in your life just

because you don’t know who you really are

By: Zig Zagler

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 References
 www.wiley.com/college
 www.biocartta.com
 www.wikipedia.com
 www.immunitysec.com

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Thanks for you Patience

Any Questions:

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