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Chapter 8: T Cell-Mediated Immunity

Terms in this set (16)

(i) The CD3 subunits y, 8, and £ associated with the
antigen-binding T- cell receptor help transmit the
signal from the T- cell receptor-peptide-MHC
interaction at the cell surface into the interior of
the cell through immunoreceptor tyrosine-based
activation motifs (ITAMs) present on their cyto plasmic
tails. These are phosphorylated by asso ciated
protein tyrosine kinases, such as Fyn, when
the antigen receptor is activated, and in turn activate
further molecules of the signaling pathway.
(ii) Lck associates with the tails of the CD4 and
CD8 co -receptors. When these participate in
binding to peptide :MHC complexes, Lck is activated
and phosphorylates ZAP- 70, a cytoplasmic
protein tyrosine kinase.
(iii) CD45 is a cell- surface
protein phosphatase that helps activate Lck and
other kinases by removing inhibitory phosphate
group s from their tails.
(iv) When ZAP- 70 is pho s phorylated
it binds to the phosphorylated ITAMs
(v) the s chain, which initiates the signal trans duction
cascade by activating phospholipase C-y
(PLC -y) and guanine- exchange factors.
(vi) IP3,
which is produced by the action of PLC -y on
membrane inositol phospholipids, causes an
increase in intracellular Ca2+ levels, which leads
to the activation of the protein calcineurin.
Calcineurin activates the transcription factor
NFAT by removing an inhibitory phosphate
group. Activated NFAT enters the nucleus, and
together with the transcription factors NFKB and
AP- 1 will initiate the transcription of genes that
lead to T- cell proliferation and differentiation.
A. Many bacteria are surrounded by a polysaccharide
capsule. In some cases, antibodies against
the capsular polysaccharides give protective
immunity against the pathogen. Antibodies pro duced
against polysaccharide antigens are generally
restricted to the IgM isotype, because the
help needed to switch isotypes to IgG is provided
by T cells, which recognize only peptide antigens.
Adult humans make effective immune responses
to polysaccharides alone and thus can be protected
by subunit vaccines made from the capsular
polysaccharides of encapsulated bacteria.
Their antibody responses are polysaccharide specific,
T- cell independent, and involve antibodies
of the IgM isotype. In contrast, children do not
make effective immune responses to polysaccharides
alone and thus cannot be immunized with
such vaccines.
However, if the polysaccharide is conjugated to
a protein, peptides from the protein part of the
molecule can activate specific T H2 cells. B cells
specific for polysaccharide will bind and internalize
the whole antigen via their antigen receptors,
process it, and then present peptides from
the protein part on their surface. T cells specific
for these peptides will interact with the B cell,
delivering the necessary cytokines (such as IL-4)
and the CD40-CD40 -ligand signal required for
isotype switching. The B cell will then pro duce
IgG anti-polysaccharide antibodies. This type of
vaccine can be used to immunize children so as
to induce protective anti- polysaccharide antigens.

B. A vaccine of this type has been pro duced against
Haemophilus influenzae B (HiBC) , which can
cause pneumonia and meningitis. The conjugate
vaccine is composed of a capsular polysaccharide
of H. influenzae conjugated to tetanus or diphtheria
toxoid (a protein) . The antibody response
is polysaccharide - specific, T- cell dependent, and
comprises IgG that protects children from the
meningitis caused by this microorganism.