NAJRAN UNIVERSITY College of Medicine

1. NAJRAN UNIVERSITY College of Medicine Microbiology &Immunology Course Lecture No. 15 By Dr. Ahmed MoradAsaad Associate Professor of Microbiology

2. Cells of the immune system ‑ The lymphocyte is the dominant cell of the lymphoid system: Central lymphoid tissuesPeripheral lymphoid tissues Bone marrow &ThymusLymph nodes, spleen, tonsils ‑ The common lymphoid progenitor cell has the potential to differentiate into two lymphocyte populations: ‑ B-lymphocytes ‑ T-lymphocytes: are dependent on the thymus gland for differentiation. -Natural killer (NK) cells: a third population of large granular lymphocytes.

3. Lymphocyte selection Selection means two processes, 1- in the first B and T cells that respond to the self antigens are eliminated and killed during the embryonic life (Clonal selection). 2- in the second stage the native T lymphocytes will acquire either CD4 or CD8 receptor which is called programming of lymphocytes. T cell selection occurs totally in the thymus while B cell selection occurs first in the bone marrow and then acquiring B Ig receptor occurs in the peripheral lymphoid tissue (tonsils, lymph nodes and spleen).

4. B-LYMPHOCYTES • ‑ These constitute 15‑30% of the total peripheral lymphocytes. • ‑ Are mostly restricted to lymphoid tissues. ‑ Life span is short (5 ‑7 days) • On antigen stimulation : B lymphocytes differentiate, proliferate and maturate into plasma cells (large lymphocytes) that synthesize specific immunoglobulins. • Some large lymphocytes can revert to small B lymphocytes called memory cells and are involved in the secondary immune response. • B‑cells stimulation requires the cooperation of T‑cells and macrophages.

5. T lymphocytes • - They originate also from precursor cells of the bone marrow but maturate in the thymus under the influence of thymic hormones. • - Several subsets of the T cells arise during this maturation process; each has a specific function. • - These cells have long life span (months or years). • - They constitute about 55-75% of the total peripheral lymphocytes. • -T lymphocytes are responsible for various immune reactions called "cell mediated immune response".

6. - T‑cellsubpopulations express on their surface glycoprotein molecules or receptors, e.g. CD3, CD4, CD8, etc... • - All T‑cells have CD3 protein receptors. • - Mature T‑cells have either CD4 or CD8 protein receptors. • T‑cellsare subdivided into 2 major categories: • CD4 T-cells (T helper cells) • CD8 T-cells (T cytotoxic and T supressor cells)

7. CD4 T helper lymphocytes (TH) • - These constitute 65% of peripheral T‑cells and predominate in the thymus medulla, tonsils and blood. • - THlymphocytes recognize antigen on the surface of antigen presenting cells (APC). • They are the cells affected by the HIV virus (causing AIDS). • - THcells are the principal orchestrators of the immune response, as they are needed for the activation of the major effector cells in the response, i.e. cytotoxic T cells and antibody producing B‑cells.

8. The main functions of TH are: a. They help B‑cells to develop into antibody producing plasma cells. b. They help CD8T‑cytotoxic (Tc) cells to exhibit cytotoxic effects. c. They interact with CD8T suppressor T cells to induce suppressor activity. d. They release different soluble factors, i.e. lymphokines that have several stimulatory and proliferative effects on B‑cells, T‑cells, NK cells and macrophages.

9. TH0, TH1, TH2 • The virgin, non stimulated T cells termed TH0 after stimulation by specific antigen , T cells secrete stimulatory cytokines as IFN, IL-2, TNF and thus evoke effective CMI, at this stage they are known as TH1. • In some diseases this stage is followed by stage of suppression of these cytokines, T cells in this stage mainly produce inhibitory cytokines IL-10, IL-4, IL-5, IL-9 and are known as TH2. At this stage there is high titre of antibodies e.g. HBV, HCV and tuberculosis.

10. CD8 lymphocytes - These predominate in human bone marrow and gut lymphoid tissue. - They constitute 35% of peripheral T‑ cells. ‑ They include 2 main subpopulations; cytotoxic (Tc) and suppressor (Ts) cells. 1. Tc cells recognize antigen. They directly kill virus‑infected cells, tumor cells and graft cells.­ 2. Ts cells suppress B cell and T‑cell activities. They play an important role in regulation of the immune response.

11. NATURAL KILLER (NK) CELLS ‑ Large granular lymphocytes, lack most surface markers of B and T‑cells. ‑ Have spontaneous cytotoxic activity on tumour cells & virus ‑infected cells. ‑ Their activity is increased by interferon and interleukin 2 (IL‑2). ‑ They have Fc receptors and are also capable of killing antibody coated cells, i.e. antibody dependent cellular cytotoxicity (ADCC).

12. MACROPHAGES: • ‑ They exist: • Free in the blood, e.g. monocytes • Fixed in tissues, e.g. Kupffer cells of the liver. • ‑ Macrophages are activated and attracted to the site of foreign material by the action of different cytokines (including gamma interferon). • ‑ Fractions released on complement activation, e.g. C5a, C3a also attract macrophages to the site of inflammation.

13. The main functions of macrophages are: 1. Phagocytosis and opsonization. 2. They are important antigen presenting cells (APC). They ingest foreign material, process it and fragments of antigen are presented. 3. Macrophages may kill antibody coated infected cells or tumor cells (ADCC). 4. They synthesize and secrete: ‑Soluble mediators called monokines, e.g. interleukin‑l (activates T‑cell proliferation), interferon, colony stimulating factor (CSF) and tumour necrosis factor (TNF). ‑Prostaglandins and complement components.

14. POLYMORPHONUCLEAR NEUTROPHILS : • They are phagocytic cells • They play a role in the inflammatory reactions. • MAST CELLS AND BASOPHILS : • They possess receptors for the Fc fragment of IgE. • They are involved in type I hypersensitivity (anaphylaxis and atopy) by releasing histamine and other chemical mediators from their granules (i.e. by their degranulation). • EOSINOPHILS : • They have anti‑parasitic and anti ‑inflammatory activities. • - Their number increases in the circulation in allergic and parasitic diseases.