Immunochemistry - Cell-mediated immunity

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Immunochemistry Cell-mediated Immunity
R. C. Gupta Professor and Head Dept. of
Biochemistry National Institute of Medical
Sciences Jaipur, India
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Cell-mediated immunity operates against those
pathogens/antigens that have entered some
self-cell
E M B - R C G
Cell-mediated immunity is the function of T
lymphocytes
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E M B - R C G
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TCR is a protein made up of an a chain and a b
chain joined by a disulphide bond
E M B - R C G
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EMB-RCG
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T cell receptor
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TCR diversity
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E M B - R C G
EMB-RCG
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E M B - R C G
EMB-RCG
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E M B - R C G
EMB-RCG
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• MHC proteins and MHC genes

E M B - R C G
EMB-RCG
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EMB-RCG
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MHC genes
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E M B - R C G
EMB-RCG
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E M B - R C G
EMB-RCG
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• MHC proteins

E M B - R C G
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Endogenous peptides bound to MHC proteins are
ignored by the immune system
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If a T cell finds a foreign peptide bound to
an MHC protein, cell-mediated immunity comes
into operation
EMB-RCG
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E M B - R C G
EMB-RCG
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The a1 and a2 domains form the peptide
binding cleft
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??? Peptide
MHC I protein View from above
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E M B - R C G
EMB-RCG
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? Peptide
MHC II protein View from above
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E M B - R C G
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Newly synthesized MHC II proteins bind peptide
fragments, and go to the cell membrane

MHC II proteins get inserted in the cell
membrane, displaying the bound peptide on the
surface of the cell
Cell membrane
a2
b2
MHC Class II Protein
b1
Antigen fragment
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Function of cytotoxic T cells
E M B - R C G
EMB-RCG
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E M B - R C G
EMB-RCG
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E M B - R C G
EMB-RCG
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E M B - R C G
EMB-RCG
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The cytoplasmic tail of CD8 is associated with
Lck, a cytosolic tyrosine kinase
E M B - R C G
The cytoplasmic tail of T cell receptor is
associated with a trans-membrane protein, CD3
complex
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CD3 complex consists of a g chain, a d
chain, two e chains and two x chains
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Cytoplasmic portions of these chains have
immunoreceptor tyrosine-based activation motifs
(ITAMs)
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On binding of T cell receptor and CD8 to MHC I
protein and antigen fragment, Lck becomes active
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Active Lck phosphorylates the ITAMs of CD3 complex
Phosphorylated ITAMs act as a docking site for
ZAP-70 (zeta associated protein of 70 kD)
EMB-RCG
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ZAP-70 phosphorylates the tyrosine residues of
some target proteins in the cytotoxic T
cell
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This results in release of stored granules from
the cytotoxic T cell targeted at the
infected cell
The granules contain perforin, granzyme and
granulysin
EMB-RCG
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Action of cytotoxic T cell
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E M B - R C G
EMB-RCG
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E M B - R C G
EMB-RCG
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E M B - R C G
EMB-RCG
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Function of helper T cells
Helper T cells share some common features with
cytotoxic T cells
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But they also differ in some
respects

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E M B - R C G
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D1
D2
Four domains in CD4 protein
D3
D4
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E M B - R C G
EMB-RCG
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Antigen-presenting cells
Macrophage
Dendritic cell
B lymphocyte
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E M B - R C G
EMB-RCG
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E M B - R C G
EMB-RCG
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E M B - R C G
EMB-RCG
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Action of helper T cell
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Actions of lymphokines
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Continued
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Continued
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Continued
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E M B - R C G
EMB-RCG
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E M B - R C G
EMB-RCG
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E M B - R C G
EMB-RCG
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E M B - R C G
EMB-RCG
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• Function of suppressor T cells

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EMB-RCG
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EMB-RCG
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Functions of memory T cells
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EMB-RCG
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• Integrated immune response

E M B - R C G
EMB-RCG
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Self-tolerance
EMB-RCG
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EMB-RCG
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Processing of T cells
E M B - R C G
EMB-RCG
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Positive selection
E M B - R C G
EMB-RCG
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E M B - R C G
EMB-RCG
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Negative selection
E M B - R C G
EMB-RCG
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Processing of B cells
E M B - R C G
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EMB-RCG
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Multivalent antigen
Antigen
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EMB-RCG
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EMB-RCG
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Antigen of low valency
Antigen
Epitope
Epitope
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EMB-RCG
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Immunologically privileged sites
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EMB-RCG
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EMB-RCG
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E M B - R C G
EMB-RCG
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E M B - R C G
EMB-RCG
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Immunodeficiency
E M B - R C G
EMB-RCG
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Examples of immunodeficiency diseases
Type of immunity Example
Humoral Agammaglobulinaemia
Cell-mediated DiGeorge syndrome
Both humoral and cell- mediated Severe combined immuno-deficiency disease
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Acquired immunodeficiency
E M B - R C G
EMB-RCG
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HIV and AIDS
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Structure of HIV
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Genome of HIV
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HIV infection and immunodeficiency
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HIV and helper T cell
gp 120 of HIV binds avidly to CD4 of helper T
cells
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E M B - R C G
Multiplication of HIV inside helper T cells leads
to rupture of cells
EMB-RCG
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E M B - R C G
EMB-RCG
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