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