CLASSIFICATION
Lymphocyte | - | Human body contain 1012 lymphocyte out of which 109 are renewed daily. Mature B and T cells before they encounter antigen are called naive cells. |
1. T. lymphocyte
- Thymus derived lymphocyte, constitute 60-70% of peripheral lymphocyte.
- Found in paracortical area of lymphnodes and periarteriolar sheaths of spleen.
- Antigen binds to TCR [T cell receptor] which is responsible for signal 1.
- Demonstration of TCR gene by southern blot analysis is a molecular marker of T lineage cell.
- All T-lymphocyte contain CD-3 molecule which are involved in transduction of signal 1.
- Other surface molecules or co-receptors include CD 2, CD 4 or CD 8, CD 11a, CD 28 (Binds to B 7-1 and B 7-2 of antigen presenting cells and provide signal 2), CD 40.
- CD 4 is expressed on 60% of T cells, while 30% expressed CD 8.
2. B. Lymphocyte
- 10 - 20% of peripheral lymphocyte.
- Responsible for humoral immunity.
- Present in Bone Marrow, peripheral lymphoid tissue eg. lymph node (superficial cortex), spleen (white pulp), tonsils and extralymphatic organs eg. GIT.
- In spleen and lymph node it form lymphoid follicles.
- Unlike T cell, it responds to free Ag.
- B cell act as Antigen presenting cells.
- Antigenic binding component of B cell receptor is surface IgM. Thus presence of rearranged Ig genes in lymphoid cell is used as molecular marker of B cell lineage.
- Other molecules are complement receptor, Fc receptors, CD 21 (receptor of EBV), CD 40 (essential for interaction of T and B cell which cause B cell maturation so mutation in CD 40 ligand cause immunodeficiency called X-linked hyper - IgM syndrome).
Differentiation of T and B cells | ||
---|---|---|
T cells | B cells | |
a. Ag binding site | Ag receptor (= TCR with CD. 3) | Surface Ig |
b. Fc receptor | Absent | Present |
c. Complement receptor | Absent | Present |
d. EAC rosette (C 3 receptor CR 2; EBV receptor) | Absent | Present |
e. E/SRBC rosette (CD 2; measles receptor) | + | – |
f. Microvilli on surface | – | + |
g. Thymus specific Ag | + | – |
h. Blast transformation | Occurs by anti CD-3, Phytohemagglutinin Concanavalin | Occurs by anti Ig Endotoxin S. aureus (cowan I strain) EBV |
3. Null Cell/Large Granular Lymphocyte (LGL)
- Do not bear TCR or surface Ig and are non adherent, non-phagocytic.
- They together with macrophage form innate immunity in comparison of adaptive immunity by lymphocytes.
- Constitute 5 - 10% of peripheral lymphocytes
- They are classified as :
- ADCC lymphocyte
- LGL express :
- Receptor for Fc portion of IgG (CD-16) which is used for ADCC (antibody dependent cell mediated cytotoxicity).
- Receptor for NCAM-I (CD 56).
- Many LGL express some T lineage markers particularly CD-8, CD-2.
- Usually CD-3 negative but subset of NK cell are CD-3 positive called NK/T cell.
- Some NK proliferate in the presence of IL-2 called as LAK cells.
- LGL can arise in both bone marrow and thymic microenvironment.
- Target cell killing by NK cell is :
- Inversely related to target cell expression of MHC class I molecule.
- So, it kills the cell that express little or no HLA class I molecule (provide immunosurveillance) such as virus infected cells, certain tumour cells and allogenic cells.
- Non-immune i.e. without previous sensitization, MHC unrestricted and non-antibody mediated.
- It kill host cell infected with intracellular bacteria eg. Mycobacteria, TB, listeria monocytogens.
- Not kill cells which express class I MHC (all normal nucleated cell express it).
- Receptors
- NK has two receptors - Killer cell inhibitory receptors (KIRs) which recognized classic MHC-I and -CD 94/NKG- 2 receptor which recognized MHCIb or HLA - E.
- NK cell secrete
- TNF α, GMCSF, IFN - γ, Cytolytic factors (perforin).
- Also secrete IL-4 to recruit TH.2 T cell; IgG1, IgE.
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4. Phagocytic cells
It is of two types :
- Mononuclear Macrophages of blood and tissues :
- Blood macrophages (monocytes) are largest of lymphoid cells.
- Tissue macrophages (histiocytes) are :
- Microglia in CNS
- Kupffer in liver
- Alveolar macrophage in lung
- Osteoclast in bone
- Sinus histiocyte - spleen, lymph node.
- Half life of blood monocyte is about 1d while life span of tissue macrophage is several months.
- Have role in chronic inflammation in the form of activated macrophages, fusion giant cell and epitheloid cell of granulomatous lesion.
- It is obligatory for induction of Cell mediated immunity since it is required to process and present antigen to immuno competent T cell.
- Like other Ag presenting / processing cell, it has both class of MHC I and II (more).
- Also important for effector phase of humoral immunity.
- Microphages which are polymorphonuclear leucocytes of blood-neutrophil, eosinophil and basophil. They do not have any role in specific immune processes.
5. Dendritic Cells
- These are Antigen presenting cells to T cell during primary immune response.
- They are bone marrow derived cells of lineage different from macrophages and T or B cell.
- They possess MHC I and II (more).
- They have little or no phagocytic activity.
- It is of following types -
- Interdigitating dendritic (= Dendritic) cells - Found in lymphoid tissue and interstitium of non-lymphoid organs eg. heart and lung. Possess costimulatory molecules like B 7-1 and B 7-2.Most potent antigen presenting cell for naive T cell (ideally CD - 4).
- Langerhans cell - They process and present antigens which reach the dermis.
- Follicular dendritic cells - Bear Fc receptor for IgG. Hence can trap antigen bound to antibodies. They are present in germinal centers of lymphoid follicles in spleen and lymph nodes.
MAJOR HISTOCOMPATIBILITY COMPLEX (MHC)
- Located on short arm of chromosome six which codes for Histocompatibility (transplantation) antigen.
- Main function of Histocompatibility (MHC) molecule is to bind peptide fragments of foreign protein for presentation to appropriate antigen specific T cells.
- MHC gene products are classified as :
- Class I antigens
- Are glycoprotein expressed on all nucleated cells and platelets.
- Cells with class I antigen presents antigen to CD - 8.
- It is the principal antigen involved in graft rejection and cell mediated cytolysis.
- Locus of class I gene - A, B, C.
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- Glycoprotein, restricted to antigen presenting cells (macrophage, dendritic cell, B cell) to CD - 4.
- Locus - D region.
- Responsible for graft versus host response and mixed leucocyte reaction (MLR).
- Class III
- Soluble protein of complement system; (C2 and C4 of classical pathway; properdin factor B of alternative pathway); heat shock protein; TNF alpha and beta.
COMPLEMENT SYSTEM
Consist of heat labile factor called alexine or complement (Serum proteins).
Fixation of Complement is not influenced by nature of antigens but only by class of Ig.
- IgM > IgG3 > IgG1 > IgG2 – Classic pathway activators
- IgA1, IgA2, IgD, IgG4 – Alternative pathway activators
- Classic C3 convertase
Classic C5 convertase- C4b2b
- C4b2b3b
- Alternate C3 convertase
Alternate C5 convertase- C3bBb
- C3bBb3b
- Role of complement derived factors in inflammation :
- C3b and C3bi - act as opsonin so cause phagocytosis.
- C3a + C5a [ = Anaphylatoxin] - ↑ vascular permeability, vasodilation.
- C5a - activate lipoxygenase pathway, chemotaxis, activation and adhesion.
- C5b-9 (= Membrane attack complex) - Lysis of cell.