Transcript Classes of effector CD4 + T cells Functions of Th1 cells

REQUIREMENTS AND CONSEQUENCES
OF T-LYMPHOCYTE ACTIVATION
Activation of naive and effector T cells by antigen
Cellular and Molecular Immunology, 7th ed., 2014 Elservier
ANTIGEN RECOGNITION ≠ CELL ACTIVATION
Activation of a naive T cell requires an antigen-specific
signal and a co-stimulatory signal
Co-stimulation is essential for priming of
naive T lymphocytes
The antigen-specific and the co-stimulatory signal has to
be induced in concert to induce T lymphocyte activation.
The antigen-specific and co-stimulatory signals can be
delivered simultaneously by professional antigen
presenting cells only.
The antigen-specific and the co-stimulatory signals
has to be delivered by the same professional antigen
presenting cell.
The B7 and CD28 families
Cellular and Molecular Immunology, 7th ed., 2014 Elservier
Protein-protein interactions in the area of contact between
a T cell and an antigen presenting cell form an ordered
structure called the immunological synapse
tcell.stanford.edu/projects/synapse.html
SMAC: supramolecular activation complex
Formation of the immunologic synapse
Phases of T cell responses
Cellular and Molecular Immunology, 7th ed., 2014 Elservier
Biologic actions of IL-2
Cellular and Molecular Immunology, 7th ed., 2014 Elservier
The role of IL-2 cytokine in helper T-cell activation
Antigen
β
γ
1
IL-2
IL-2
IL-2R
IL-2R
Resting T cell
Express a low affinity IL-2 receptor
( and  chains) and produce no IL-2
Signal 1
NFAT binds to the promoter
of the IL-2 receptor- chain gene.
Association of the -chain converts the IL-2R
to a high affinity form
that is expressed on the cell surface
Mechanism of co-stimulation in T cells
Costimulation
Antigen
Signal 2
1
2
Activates AP-1 and NF-kB to increase IL-2
gene transcription by 3 fold
Stabilises and thus increases the half-life of
IL-2 mRNA by 20-30 fold
IL-2
IL-2 production increased by 100 fold overall
IL-2R
Naive T cells that recognize self antigen alone
are prevented from responding to those antigens
Anergy
Antigen
Naïve
T cell
1
Signal 1 only
IL-2
IL-2R
Endothelial
cell
Self peptide epitopes presented
by a non-classical APC e.g. an
endohelial cell
The T cell is unable to produce IL-2 and therefore is
unable to proliferate or be clonally selected.
Unlike immunosupressive drugs that inhibit ALL
specificities of T cell, Signal 1 in the absence of
signal 2 causes T cell unresponsiveness to a specific
antigen
CYTOTOXIC T LYMPHOCYTES
The induction and effector phases of
cell-mediated immunity
Cellular and Molecular Immunology, 7th ed., 2014 Elservier
Clonal expansion of T cells
Cellular and Molecular Immunology, 7th ed., 2014 Elservier
It is estimated that more than 90% of the antigen-specific T cells that arise by
clonal expansion die by apoptosis as the antigen is cleared.
Activation of naive CD8+ T cells
Role of helper T cells in the differentiation of
CD8+ T lymphocytes
Cellular and Molecular Immunology, 7th ed., 2014 Elservier
Induction of T cell responses to virus-infected cells
Cellular and Molecular Immunology, 7th ed., 2014 Elservier
Induction of T cell responses to tumors
Cellular and Molecular Immunology, 7th ed., 2014 Elservier
Co-stimulatory signals are required for the activation
of naive T cells but not for the activation of effector T cells
CTLs kill infected cells by secretion of lytic granules and
focused delivery of cytotoxins onto the target cell surface
MTOC: microtubule-organizing center
GA: Golgi apparatus
LG: lytic granules
Time course of cytotoxin release after a cytotoxic T cell
encounters its target
Cytotoxic CD8 T cells can kill several infected target cells
in succession
Mechanisms of CTL-mediated killing of target cells I.
Mechanisms of CTL-mediated killing of target cells II.
CAD: caspase-acticated DNase
Mechanisms of Fas receptor – mediated
„activation-induced cell death”
In addition to direct cell killing,
CD8+ T cells secrete IFN-γ
Destruction of infected cells by CTLs is a cause of tissue
injury in some diseases
Liver cells
infected with
HBV
EFFECTOR FUNCTIONS OF HELPER
T-LYMPHOCYTES
Classes of effector CD4+ T cells
Differentiation of Th subsets from
naïve CD4+ T cells: general principles I.
• Different subsets develop from the same naïve CD4+ T cells.
• Cytokines produced at the site of antigen recognition drive
differentiation into one or the other subset.
• The cytokines that drive the development of CD4+ T cell
subsets are produced by APCs (primarily dendritic cells and
macrophages) and other immune cells (such as NK cells and
basophils or mast cells) present in the lymphoid organ where
the immune response is initiated.
Differentiation of Th subsets from
naïve CD4+ T cells: general principles II.
• Stimuli other than cytokines may also influence the pattern
of helper T cell differentiation.
• Differentiation of each subset is induced by the types of
microbes that the subset is best able to combat.
• Commitment to each subset is driven by transcription
factors.
• Each subset of differentiated effector cells produces
cytokines that promote its own development and may
suppress the development of the other subsets.
Classes of effector CD4 + T cells
Molecular events in follicular helper T cell generation
Diversity of follicular helper T cells (Tfh)
Sequence of events in the reactions of effector CD4+ T cells
in the peripheral tissues
Cellular and Molecular Immunology, 7th ed., 2014 Elservier
Classes of effector CD4 + T cells
Functions of Th1 cells
Cellular and Molecular Immunology, 8th ed., 2015 Elservier
Effector functions of Th1 cells
Activation
Killing
Proliferation
Feed back
Entry to tissue Recruitment
Macrophage activation by Th1 cells
Cellular and Molecular Immunology, 8th ed., 2015 Elservier
Classes of effector CD4 + T cells
Functions of Th2 cells
Cellular and Molecular Immunology, 8th ed., 2015 Elservier
Classical and alternative macrophage activation
Cellular and Molecular Immunology, 8th ed., 2015 Elservier
Classes of effector CD4 + T cells
Functions of Th17 cells
Cellular and Molecular Immunology, 8th ed., 2015 Elservier
Functional classes of effector CD4 T cells