Dr. Fadwa AlGhalib Immunology 2nd year 2010
Cell surface receptors
T-Lymphocytes Surface Markers
Hematopoietic Stem Cells
Divide into:
1. Lymphoid Lineage – give rise to B-cell, T-cell, NK
2. Myeloid Lineage– give rise to MÆ, dendritic cells
Granulocytes (neutrophils, basophils, eosinophils) & mast cells
3. Erythroid Lineage ===== give rise to blood cells
Lymphoid Lineage
- Lymphocytes range in size from 6-10 um in diameter
- 109 lymphocytes are produced /day
- The average adult has about 1012 total lymphocyte
- Lymphocytes comprise 20% of all leukocytes
- Lymphoid Tissue accounts for about 2% of body weigh
- Relatively indistinguishable under light microscopey
- Can be distinguished by different protein markers on their surfaces
- These markers are called CD (cluster of differentiation)
CD Nomenclature
l CD (Cluster designation)
Refers to groups (clusters) of monoclonal Antibodies (mAb) binding a particular molecule.
l The CD nomenclature for cell-surface proteins of leucocytes gives each cell surface a unique number but does not reflect its structure or function in any way.
Molecular Markers
Are defined according to the information they offer about the cell:
1. Lineage markers identify a specific lineage
e.g. CD3, found only on T cells.
2. Maturation Markers, are transiently expressed during differentiation
e.g. CD1 present on developing thymocytes but not on mature T cells
A maturation marker for one lineage is sometimes an activation marker for the same lineage.
e.g. CD10 present on immature B cells , is lost on mature B cells, but reappears on activation
3. Activation Markers, is only expressed when cells are stimulated by antigens or mitogens. e.g.- CD25
e.g. -MHC class II expressed more on monocytes following activation by IFN-gamma
Families of Cell Markers
1. The Immunolglobulin superfamily:
Comprises molecules structurally similar to those of Immunoglobulins
e.g.- CD2, CD3, CD4, CD8, CD28, MHC class I and II.
T-Cell Receptor
– The T-cell receptor have much in common with the immunoglobulins
– They have similar structure as Igs
– Highly variable and diverse in their antigen specificity
– Is a membrane-bound glycoprotein
– TCR generally only binds peptide antigens presented on MHC
– TCR is not secreted from the T cell
– Each TCR has a single binding site for antigen,
2. The Integrin Family:
Comprise a major group of adhesion molecules present on many cells, including leucocytes.
l Heterodimeric molecules with a & b
l All share a common b chains, but each has a unique a chain.
l Three subfamilies: a- b1-integrins
b- b2-integrins
c- b 3-integrins
l Integrins are receptor proteins which are of crucial importance
l are involved in a variety of cellular functions such as wound healing, cell differentiation, homing of tumor cells and apoptosis.
Subfamilies of Integrins
The b1 Integrins:
are involved in binding of cells to extracellular matrix.
The b2 Integrins: are involved in binding of cells to leucocyte adhesion to endothelium or to other immune cells.
The b3 Integrins; (cytoadhesions): are involved in the interactions of platelets and neutrophils at inflammatory sites or sites of vascular damage.
b1-integrins:
l has CD29, includes VLA ( very late activation markers).
l Found on : T Cell, B Cell, NK cell, Granulocyte, Monocyte/macrophage
b 2- integrins:
l Uses CD18 as the b-chain, which can be associated with:
l CD11a® LFA-1 (Lymphocyte Function antigen)
l CD11b ®Mac-1(CR3) (membrane attack complex)
l CD11c ® p150,95
l ad ® adb2
l They are all common found on leucocytes.
l CD11a/CD18 (LFA-1) (Lymphocyte Function-Associated Antigen-1) is critical in neutrophil transmigration, and important in transmigration of other leukocyte subtypes.
l increase adherence of leukocytes to the surfaces of endothelial cells, thereby allowing the leukocytes to crawl to the gaps between endothelial cells and transmigrate to the extravascular space.
3- SELECTIN FAMILY
l Selectins are a family of "sticky" molecules (Adhesion molecules) that are expressed on the surface of the cells lining the inside of blood and lymph vessels.
l Selectins and other adhesion molecules act as hooks to capture white blood cells (Leucocytes) and bring them to the site of an infection.
l Are carbohydrate-binding lectins;
Consist of three adhesion molecules;
1. P-selectin (CD62P), found on activated endothelial & platelets.
2. E-selectin ( CD62E), on activated endothelial cells.
3. L-selectin ( CD62L), on T cell, granulocytes & monocytes/macrophages.
They have a single C-type lectin domain (L) at their extracellular amino termini,
- followed by an epidermal growth factor (EGF)-like domain (E),
- several complement regulatory domains (C),
- transmembrane domain
- and short cytoplasmic tail
4- Proteoglycan family: (CD44)
§ Have a number of glycosaminoglycan (GAG) binding sites,
§ binds to extracellular matrix components.
5- Other families: include:
v TNF
v NGF (nerve growth factor)
v C-type lectin family(calcium-dependent)
v Seven transmembrane segments (tm7)
v Four membrane spanning-segment (tm4) e.g. CD20
Function of the Marker Molecules
v Allow the Lymphocyte to communicate with their environment.
v The Key of cell-cell and cell-matrix interactions
v Cell trafficking
v Adhesion
v Activation
Types of Lymphocytes
l B- Cells ª Natural Killer Cells (NK) § T cells
Types of T-Cells
1- Cytotoxic T cells (Tc) 2- Helper T Cells (Th)
l Cytotoxic T cells:
Lyse cells that produce foreign Anitgens
Are identified by presence of CD8 marker
Also called cytolytic T cells or CD8+ cells
l Helper T-Cell
o Identified by the presence of CD4 marker,
o Also called Cd4+ cells
o Secrete cytokines that help proliferation and differentiation of T cells, B cells, & MÆ
o Their cytokines help in recruiting and activating inflammatory leukocytes
o Further subdivided into: Th1, and Th2
Naive T Cell (Th0) Activation by Antigen:
l Priming the T-cell:
The initial encounter of T cells with antigen.
When CD4+ T (TH0) cell is activated ... Differentiate into one of two helper cells subsets:
TH1 and TH2
Depending on the cytokines present in the environment of the cell
R If APCs are responding to infection by microbes and releasing IL-12, the TH1 population of CD4+ T cells predominates.
R If the environment enriched in IL-4 (i.e. IL-4 released from mast cells on encountering a parasitic worm or allergen), ...They stimulate the production of TH2 subset.
v T helper 1 Cells (Th1):
Are called inflammatory helper cells
Produce : Il-2 = for T-cell proliferation
-a- IFN- g : antiviral, macrophage activation, ----- inhibits the generation of TH-2 cells.
b-TNF- b : activation of macrophage, enhances MHC-1 production
TH1 : are dominant in response to microbial infection
v T helper 2 cells (Th2):
Are called helper cells
Produce IL-4 = for B-cell activation, differentiation, -- inhibits the generation of TH1
IL-5 = eosinophil growth and differentiation.
IL-6 = B cell differentiation
IL10 = inhibition of cytokine synthesis of Th 1 cells
& TGF- b (transforming growth factor)
All these cytokines promote Ab synthesis by B cells
TH2 : are dominant in parasitic infection.
l Lymphocytes & other leucocytes express a large number of different molecules on their surfaces.
l These cell markers can now be identified by specific Monoclonal Antibodies (mAb).
l MonoclonalAntibodies:
Are antibodies of a single specific type coming from a clone of identical B-lymphocytes, therefore they are identical in structure and antigen specificity
l *CD8+ T-Cell (Cytotoxic T cells):
CD8+ T cells are activated to become effector cells EITHER by:
1- encounter Ag on APC + receiving activation signals from both MHC-1 & co-stimulatory molecules (e.g.B7)
OR
2- encountering Ag on non-APC target cells + receiving “second signal” from cytokines released by CD4+ T-helper cells
MHC-1 is found on all nucleated cells.
l Cytotoxic T cells:
Ø Lyse cells that produce foreign Anitgens
Ø Are identified by presence of CD8 marker
Ø Also called cytolytic T cells or CD8+ cells
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