Immune%20Receptors%20%20and%20Signal%20Transduction

1
Immune Receptors andSignal
Transduction

• Chapter 7

2
(No Transcript)
3

• The idea that cells may have specific surface
  receptors that can be triggered by external
  ligands came from one of the founders of modern
  immunology. Paul Ehrlich, in his side chain
  theory, published in 1897, conceived of
  antibodies on the surface of immune cells that
  recognize antigens and instruct the immune cell
  to secrete more of the same antibody. Cell
  surface receptors for hormones were discovered
  many decades later in the second half of the 20th
  century but well before the identification of
  antigen receptors on lymphocytes in the early
  1980s

4

• Cell surface receptors serve two major functions
• the induction of intracellular signaling and
• the adhesion of one cell to another or to the
  extracellular matrix
• Signaling initiated by these receptors typically
  involves an initial cytosolic phase when the
  receptor or proteins that interact with the
  receptor may be post-translationally modified.
  This often leads to the activation or nuclear
  translocation of transcription factors that are
  silent in resting cells, followed by a nuclear
  phase when transcription factors orchestrate
  changes in gene expression
• Signal transduction result in a number of
  different consequences for a cell, including
  acquisition of new functions, induction of
  differentiation, commitment to a specific
  lineage, protection from cell death, initiation
  of proliferative and growth responses, and
  induction of cell cycle arrest or of death by
  apoptosis

5
(No Transcript)
6
Signaling from the cell surface involves
cytosolic and nuclear phases
7

• AN OVERVIEW OF SIGNAL TRANSDUCTION

8

• The initiation of signaling from a cell surface
  receptor may require ligand-induced clustering of
  the receptor, known as receptor cross-linking, or
  may involve a conformational alteration of the
  receptor that is induced by its association with
  ligand
• The enzymes that add phosphate groups onto amino
  acid side chains are called protein kinases
  (protein tyrosine kinases)
• Other protein are serine/ threonine kinases,
• Some enzymes activated downstream of signaling
  receptors phosphorylate lipid substrates they
  are therefore known as lipid kinases
• specific phosphatase,

9

• Cellular receptors are grouped into several
  categories based on the signaling mechanisms they
  use and the intracellular biochemical pathways
  they activate

10
Modular Signaling Proteins and Adaptors
11
The modular structure of tyrosine kinases that
influence lymphocyte activation
12

• THE IMMUNE RECEPTOR FAMILY

13
Immunoglobulin (Ig) superfamily
14
(No Transcript)
15
T Cell Receptor Complex and T Cell Signaling
16
(No Transcript)
17
(No Transcript)
18
Ligand-receptor pairs involved in T cell
activation
19
Co-receptors
20
Immunologic Synapse
21
Early tyrosine phosphorylation events in T cell
activation
22
(No Transcript)
23
(No Transcript)
24

• Activation of Transcription Factors That Regulate
  T Cell Gene Expression

25
(No Transcript)
26
Co-stimulatory and Inhibitory Receptors of the
CD28 Family

• CD28 is a membrane protein that transduces
  signals that function together with signals
  delivered by the TCR complex to activate naive T
  cells
• In the case of T cells, binding of peptide-MHC
  complexes to the TCR (and to the CD4 or CD8
  coreceptor) provides signal 1. The second signal
  for T cell activation is provided by molecules
  that are collectively called costimulators
• Best defined costimulators for T lymphocytes are
  a pair of related proteins, called B7-1 (CD80)
  and B7-2 (CD86), that are expressed on dendritic
  cells, macrophages, and B lymphocytes

27
Costimulatory Receptors of T Cells
28

• Structure of the B Cell Receptor for Antigen

29
Metabolic changes during T cell activation
30
(No Transcript)
31
(No Transcript)
32
(No Transcript)
33

• THE ATTENUATION OF IMMUNE RECEPTOR SIGNALING

34
Inhibitory signaling in lymphocytes
35
E3 Ubiquitin Ligases and the Degradation of
Signaling Proteins
36

• The prototypical inhibitory receptor of the CD28
  family, CTLA-4 (also called CD152), has the
  ability to inhibit T cell responses induced on
  activated T cells and has a higher affinity than
  CD28 for B7 proteins. CTLA-4 is involved in the
  maintenance of unresponsiveness (tolerance) to
  self antigens
• Another inhibitory receptor of the same family is
  called PD-1 (programmed death 1)
• CTLA-4 contains a tyrosine-containing motif in
  its tail that may be inhibitory PD-1 contains
  cytosolic ITIM (Immunoreceptor tyrosine-based
  inhibition motif) and ITSM (Immunoreceptor
  tyrosine-based switch motif) motifs, and its
  cytosolic tail is critical for the initiation of
  inhibitory signals
• The key inhibitory receptors in B cells include
  Fc?RIIB and CD22/ Siglec-2

37

• CYTOKINE RECEPTORS AND SIGNALING

38
Classes of Cytokine Receptors
39
(No Transcript)
40
JAK-STAT Signaling
41
(No Transcript)
42
(No Transcript)