Lymphocytes PDF

Lymphocytes Presented by :  Dr. RADWA EL- SHARABY Assistant prof of clinical pathology department  Tanta university Objectives: By the end of the lecture, you will be able to: Enumerate the types of lymphocytes. Describe different type of lymphocy...

Lymphocytes Presented by :  Dr. RADWA EL- SHARABY Assistant prof of clinical pathology department  Tanta university Objectives: By the end of the lecture, you will be able to: Enumerate the types of lymphocytes. Describe different type of lymphocytes. Discuss the function of B- lymphocytes, T-lymphocytes and natural killer cells. Lymphocytes, are type of white blood cells and the are unique cells of adaptive immunity. CD ( cluster of differentiation) molecules  Cell surface molecules a.Expressed on all immune cells & have numbers :  b- Each type immune cell has  a particular number e.g  ∎ T cells : CD3  Th : CD4 Tc : CD8  B lymphocytes :CD19 Types of Lymphocytes B lymphocytes  Origin and maturation: B Lymphocytes develop from bone marrow stem cells, mature in the generative lymphoid organs i.e., bone marrow and then circulate through the blood to complete their maturation in secondary lymphoid organs. Subtypes: Pre-B cells lack surface immunoglobulins, but they express IgM heavy chains mu in their cytoplasm. Immature B cells express IgM receptors on the surface. Mature B cells express lgM and IgD molecules on their surface that serve as receptors for antigens. Memory B cells express IgG or IgA or IgE on the surface. Percentage, life span and location 01 02 03 B cells form Short i.e., They are found in the about 15 % of germinal center of the days or lymph nodes, in the white the recirculating weeks. pulp of the spleen and in pool of small the gut associated lymphocytes lymphoid tissue, awaiting the arrival of specific antigens. Function: 1. B cells are important antigen presenting cells. 2.Mature B cells differentiate on antigen stimulation to plasma cells that synthesize and secrete antibodies. quiz A child with a genetic disorder shows a lack of mature B cells in the blood. Where do B cells mature in the human body? A. Thymus B. Bone marrow C. Spleen D. Lymph nodes Correct Answer: B T lymphocytes  T lymphocytes development I- Origin of T lymphocytes From lymphoid stem cells in bone marrow Immature thymocytes Circulate in blood with no surface markers Origin and maturation: T Lymphocytes develop from bone marrow stem cells, mature in the thymus, and then circulate through the blood to secondary lymphoid organs. Naive lymphocytes may respond to foreign antigens in these secondary lymphoid tissues or return by lymphatic drainage to the blood and recirculate through other secondary lymphoid organs.  T lymphocyte receptor (TCR) recognizes only  processed protein Ag (epitope)  in association with MHC molecule  on the surface of APC  II-Maturation of T lymphocyte in thymus  Structure of thymus  1-Formed of an outer cortex & inner medulla.  2-Contains thymic epithelial cells ,  dendritic cells (DCs) & macrophages (MQ)  Stages of maturation  1-Double -ve immature thymoytes ( in cortex)  Don’t express CD4 or CD8 molecules  2 - Double +ve immature thymocytes ( in cortex)  Express TCR complex , CD4 & CD8  3 - Expression of TCR /CD3 complex ❑ Structure & functions  a.TCR : Formed of α &β polypeptide chains having :  i.C (constant) region  ii. V (variable) region recognizes APC  Specific peptide Ag(epitope) Part of MHC mol  (Complementary to it) Specific peptide  b.CD3 : Associated with TCR Recognition of Ag in LNs CD3  Transmits intracellular activation signal T cell ❑ Diversity  Each T cell clone expresses TCR specific for 1 peptide Ag (epitope)  Millions of T cells clones (differ in Vα and Vβ) that can react with millions of different peptide Ags Recognize Recognize epitope A epitope X Clone 1 Clone 2  QUIZ  Which of the following molecules transmits intracellular activation signal in T cells ? a. TCR &  chain b. CD4 c. CD3 d. CD8 e. CD2 4 - Single +ve mature T lymphocytes a. T cells whose TCR recognizes MHC class I on thymic epithelial cells loose the expression of CD4 & preserve the expression of CD8 ( coreceptor for class I) Become T cytotoxic CD8+ cells b. T cells whose TCR recognizes MHC class II on thymic epithelial cells loose the expression of CD8 & preserve the expression of CD4 ( coreceptor for class II) Become T helper CD4+ cells  5 - Negative selection : ensures self-tolerance  T cells expressing TCR that recognizes  self-peptide (self-reactive clones)  are deleted by apoptosis  Tolerance to self-peptides (self-tolerance)  No autoimmune reaction Subtypes: 1. T cytotoxic (Tc) or killer cells 2. T regulatory (Treg) cells 3. T helper (Th) cells (Th1 and Th-2) 4. T- Memory cells Percentage, life span and location Life span: Percentage: relatively long i.e., Location: months or years. T cells constitute T helper cells 65-80% (Th cells predominate in the 65% while Tc cells thymic medulla, constitute 35%). tonsils, and blood.  Main Functions: A. T helper cells (CD4): Th cells are the principal orchestrators of the immune response though cytokines secretion, results in: 1. Activation, proliferation, and differentiation of B-cells. 2. Proliferation of T- cells. 3. Proliferation of macrophages  Main Functions: B. T cytotoxic cells (CD8): They specifically kill cells infected with intracellular organisms or abnormal host cells as graft cells and tumour cells through the release of cytolytic proteins e.g., perforins and granzymes (cell mediated immunity).  N.B: In most tissues the ratio of CD4 to CD8 is about 2/1 Main Functions: C. T regulatory cells (Treg): They are responsible for terminating the immune response by suppressing the functions of activated immune cells. They express CD25. D. T memory cells: They have learned how to overcome the antigen by „remembering‟. At the second exposure with the same antigen, the T memory cells reproduce secondary immune response which is faster and stronger than the primary one. A patient with an autoimmune disease shows increased activity of T regulatory cells. What is the primary function of T regulatory cells?  A. Activating B cells  B. Enhancing cytokine production  C. Suppressing the functions of activated immune cells  D. Directly killing infected cells  Correct Answer: C Natural killer cells Origin, receptors and percentages: Origin: The lymphoid stem cells in the bone marrow. Important Percentage: receptors: They comprise CD56, CD16 5-10% of the (receptor for Fc peripheral portion of Ig G) lymphocytes.  Main functions: 1. They have spontaneous non-specific cytotoxic activity on virus infected cells, tumor cells and graft cells (Innate). 2. Production of cytokines e.g., INF-γ, TNF α and GM-CSF (Granulocytes monocytes colony stimulating factor).  Main functions: 3. LAK cells (IL-2 Lymphokine activated Natural killer cells) with killing effect more efficient than NK alone with promising results in metastatic cancer therapy.  Main functions: 4. ADCC (Antibody-dependent cellular cytotoxicity )through receptor for Fc portion of IgG, it can interact with and kill IgG coated cells. (Acquired)  A patient undergoing immunotherapy for cancer shows increased activity of a specific lymphocyte subtype that kills tumor cells non-specifically. Which lymphocyte is involved? A. B cells B. T helper cells C. T regulatory cells D. Natural killer cells Correct Answer: D References: Abbas A.K. and Lichtman A.H.: Basic Immunology, 5th edition, 2015, El Servier Sanders. Abbas A.K. eta/.: Cellular and Molecular Immunology, 9th edition, 2017, El Servier Sanders. Abla M. El/Mishad: Manual of Medical Microbiology and Immunology, vol.II, 9th edition, 2019, El-Ahram Press, Egypt. Thank you