Lymphocyte Interactions
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Transcript of Lymphocyte Interactions
Lymphocyte Interactions
• Both the activation and functions of lymphocytes require them to interact with each other and with other cell types.
• The opportunities for lymphocyte interactions are maximized by the recirculation of lymphocytes through out the body and by their homing to secondary lymphoid tissues.
The Surface molecules of The Mature B Cell• Antigen-binding molecules : surface immunoglobulin
( sIg ,前章節已介紹)。– 於成熟 B 細胞才表現,可利用偵測此分子而將 B 細胞由混合淋巴球
細胞群中純化出。• Signal transduction molecules :
1. Igα ( CD79a )、 Igβ ( CD79b )– 進行 Signal transduction : the kinases associated with Igαand
Igβ phosphorylate several cellular proteins. Phosphorylation of these proteins leads to the transcription of different genes in the B cell and to B-cell activation 。
2. Additional signal transduction molecules : CD19 、 CD20 、 CD21
– To play coreceptor role for B cell receptor ( immunoglobulin )。– To play a similar signal transduction role as the CD3 complex in T cell 。
• CD40 : involved in isotype switching – The molecule accepts the soluble factors ( cytokines ) releas
ed by T cell 。• Antigen presentation molecule : MHC class II molecul
es1. MHC class II molecule expression is found on all cells of the B-c
ell lineage, starting with the pre-B cell 。2. B-cell expression of MHC class II molecules is constitutive ( al
ways expressed )。3. The expression of MHC class II molecules can be further increas
ed by exposure to certain cytokines 。• Costimulatory molecule : B7 ( B7-1 ( CD80 )、 B7-
2 ( CD86 ))
The Surface molecules of The Mature B Cell
1. To interact with surface molecules on T cell to send crucial positive signal to the T cell during antigen-specific stimulation 。
2. Resting B cells are poor APCs and express low levels of costimuatory molecules 。
3. Activated B cells express high levels of costimuatory molecules and very efficient APCs 。
• Fc receptor ( FcR ): CD32– CD32 is believed to play a role in "antibody feedback," the inactivati
on of B cell by antigen on the presence of antibody 。• Complement receptor : CD21(CR2), CD35 (CR1)
– CD21 involved in B-cell activation and is a receptor for a complement component, C3d 。
– CD35 involved in B-cell activation and is a receptor for a complement component, C3b 。
• Cytokine receptor
The Surface molecules of The Mature B Cell
Overview of surface molecules of B cell
The Surface molecules of The Mature T Cell
• TCR complex (含 TCR 、 CD3 complex ,前章節已介紹)。
• Co-receptor ( accessory ) molecules : CD4 、 CD8
1. Co-receptor molecule expression divides the αβ+ T cell population into two major subsets 。
2. To act as adhesion molecular that help to tighten the binding of T cell to antigen-presenting cells 。
3. They also act as signal transduction molecules, sending signals into T cell 。
(55 kDa, glycoprotein)
(30-38 kDa, glycoprotein)
Or αα homodimer
• CD451. It is a large ( 180-220 kDa ) cell surface molecule expressed by
all leukocytes, including T cell 。2. Its cytoplasmic domain has tyrosine phosphatase activity.3. T cells that lack CD45R cannot respond to antigen , even though t
hey express normal levels of TCR.• Molecules interacting with CD40 : CD40L ( CD40 ligand,
gp39 )1. It is a 30-39 kDa glycoprotein expressed on actived T cells 。2. It interact with CD40 on B cell surface to induce antibody class sw
itch 。• Adhesion molecule : CD2 、 LFA-1 ( leukocyte function
associated antigen-1 , CD11aCD18 )1. CD2 plays a role in adhesion to enhance the bindung of T cells to
other cells, and its ligand is CD58 ( LFA-3 ) found on many cells’ surface 。
The Surface molecules of The Mature T Cell
2. CD2 is the one of the first T-cell-specific molecules expressed, and it is expressed throughout the life of the T cell 。
3. LFA-1 bind to CD58 ( intercellular adhesion molecule-1 , ICAM-1 ) on other cells to enhance the bindung of T cells to other cells 。
• Molecules interacting with costimulatory molecule : CD28 、 CTLA-4
The Surface molecules of The Mature T Cell
1. They involve the interaction of molecules on the APC and T cell surface 。
2. CD28, a transmenbrane protein and a member of Ig supergene family, interacts with B7 on the surface of APC, and this interaction appears to be crucial in generation of IL-2 following the stimulation of resting, unprimed T cells 。
3. CTLA-4 has the same interaction as CD28, but this interaction may be a negative signal to activate T cell, serving to turn off the production of IL-2 and thus limiting the extent of the immune response 。
The Surface molecules of The Mature T Cell
Overview of surface molecules of T cell
The Surface molecules of The Antigen Presenting Cell
• MHC molecules : Class I 、 Class II• Costimulatory molecule : B7 ( B7-1 ( CD80 )、 B
7-2 ( CD86 ))• Adhesion molecule : CD58 ( LFA-3 )、 CD54 ( int
ercellular adhesion molecule-1 , ICAM-1 )
CD4+/CD8+T-APC Cell Interaction• In CD4+ T cells, TCR interacts with the peptide-MHC class II comple
x ( antigen-specific activation ) , and this recognition is crucial in initiating the series of events that results in T cell activation 。– The interaction between TCR and peptide-MHC class II ( class I ) co
mplex is increased by CD4 ( CD8 ) on T cell surface.• Adhesion pairs, such as CD2/ CD58 ( LFA-3 )、 LFA-1 /ICAM-1, fu
rther enhance T-cell-APC interaction 。• Costimulatory pair, such as CD28/B7, is required to complete the
process of T-cell activation ( to be vital in activating unprimed, resting T cell )。– Interaction of the costimulatory pairs is crucial for production of the I
L-2 by T cells 。– Not all MHC class II+ APCs are effective, that is, costimulatory molecul
e expression correlates with their relative effectiveness as APC 。
Affinity of interaction: TCR + adhesion molecules + growth factor receptors (costimulatory molecule)
Affinity of interaction: TCR + adhesion molecules + growth factor receptors (costimulatory molecule)
B-T Cell Interaction
• Costimulatory pair, such as CD28/B7Induction of B7 expression enhances the ability of the B cell to a
ct as an effective antigen-presenting cell 。• Adhesion pairs, such as CD2/ CD58 ( LFA-3 )、 LFA-1
/ICAM-1, further strengthen T-B cell interaction 。• CD40-CD40L binding promotes B cell proliferation and
is required for the B cell to switch the class of antibody that it can synthesis ( the absence of this interaction, only IgM is made )。
• Cytokine receptor-T cell derived cytokines binding also is required for the B cell to switch the class of antibody 。
1. IL-4 B cell will switch to produced IgE 。2. IFN-γ B cell will switch to produced IgG subtypes 。
Interaction between B and T Cell
B-T Cell Cooperation in Antibody Production
• Thymus-dependent ( TD ) antigens enhance CD4+ T cell to cooperate with B cells in the production of antibody
• The production of antibody to thymus-dependent antigen requires that both B and T cells be activated and interact 。
1. Many of the cytokines secreted by the activated T cell to activate B cells 。
2. The phenomenon of T-B cell cooperativity is known as linked recognition 。
3. In primary response, T-cell activation results in IL-2 synthesis, which appears to be necessary for B-cell activation and proliferation and results in B-cell secretion of IgM ; in secondary response, IgG, IgA, and IgE antibodies are produced 。
No T-cell Help in Antibody Production• The thymus-independent ( TI ) antigen do not us
e T-cell help, do not induce memory B cell and B cell cannot switch from IgM isotype 。– The thymus-independent ( TI ) antigens’ co
mmom properties :( 1 ) are large polymeric molecules with multiple, repeatin
g, antigenic determinants( 2 ) have some poorly defined mitogenic properties ( po
lyclonal activators ) : at high concentrations they are able to activate B-cell clones to poliferate and to produce antibody 。
Activation of Help T Lymphocytes• Help T cell activation occurs early in an immune resp
onse, and requires 2 signal :1. Signal I is provided by binding of TCR to peptide-MHC comple
x and is transmitted through the CD3 complex 。2. Signal II is costimulatory signal 。
• The signals induce help T cell to begin secreting IL-2 and also to begin expressing specific high-affinity IL-2 receptors on its surface 。
Activation of Help T Lymphocytes1. IL-2 has a very short half-life outside the cell and so act only ov
er extremely short distances 。2. IL-2 exerts its greatest effects on the cell from which it is secret
ed, called as autocrine effect 。 That is, T cell will not begin to proliferate in the absence of IL-2 or if its own surface IL-2 receptors are blocked 。
3. The IL-2 can also act on cell in immediate vicinity, called as paracrine effect
Activation of Help T Lymphocytes
• APC may begin to release IL-1 to act primarily in an autocrinemanner on itself 。– IL-1 function :
( 1 ) To increase the expression of MHC class II and various adhesion molecules on APCs 。
( 2 ) To strenghten binding of TH cell and APCs 。( 3 ) To enhance antigen presentation of APCs 。( 4 ) To be in paracrine manner on the TH cell to promote IL-2 s
ecretion and IL-2 receptor expression 。( 5 ) To potentiate the TH cell poliferative response 。
– There are TNF ( tumor necrosis factor ) and IL-6, produced by macrophages, that can mimic with IL-1 activity 。
Activation of TC Cell by TH Cell• Activation of TC cell
– Two signals are necessary for TC cell activation :( 1 ) Signal I alone induces high-affinity IL-2 receptors on the TC ce
ll 。( 2 ) Signal II is finished by IL-2 secreted from a nearby activated T
H cell 。– On receiving both signals, the activated TC cell acquires cytotoxic acti
vity ( by releasing specific toxins or inducing target cell suicide )
Activation of B Cell by TH Cell• Activation of B cell
– By direct contact with TH cell。– Cytokine activation: helper cell factor: IL-2、 IL-4、 IL-
5。
The induction of immune responses by cellular interaction