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1. Introduction. The role of the immune system. Components of the immune system. Morphology of lymphoid organs . Basic definitions. The structure of antibodies, generation of diversity.

4. Topics 12. Classes of immunoglobulins and biological activities (two light-chain subtypes, λ 4 subtypes, five heavy-chains isotypes/classes, subisotypes/subclasses, Immunoglobulin superfamily of receptors 14. Secreted immunoglobulins (sIg), membrane-bound immunoglobulins (mIg), carboxyl-terminal domain ( extracellular hydrophilic “spacer” sequence , hydrophobic transmembrane sequenc e, cytoplasmic tail ) 16. Immunoglobulin genes 17. Generation of diversity ( combinatorial V-D-J joining , junctional diversity, hyper mutations) 18. Clinical application of antibody-based therapeutics (IVIg)

5. Overview of the immune respone

6. BLOOD CELLS Pluripotent haemopoietic stem cell Red blood cells 5x10 12 /l (5x10 6 /mm 3 ) 120 days Platelets 200x10 9 /l (2x10 5 /mm 3 ) 8-12 days White blood cells 5x10 9 /l (2x10 3 /mm3) <hours – years Neutrophils 50-70% Lymphocytes 20-40% Monocytes 1-6% Eosinophils 1-3% Basophils <1% BLOOD PLASMA Clotting factors Proteins of innate and adaptive immunity

7. Blood cells Human red blood cells ( red ), activated platelets ( purple ) white blood cells - monocyte ( green ) T lymphocyte ( orange ). Colorized - SEM (scanning electron micrograph) Magnification: - 1200x -- (Based on an image size of 1 inch in the narrow dimension) ©Dennis Kunkel Microscopy, Inc., www.DennisKunkel.com

8. WHITE BLOOD CELLS Basophil mast cell Eosinophil phagocyte Neutrophil phagocyte Monocyte macrophage phagocyte Langerhans / dendritic cell family Natural killer cell B lymphocyte T lymphocyte

9. Neutrophils - phagocytes that form first line of defence against bacteria that proliferate in the extracellular fluids Deficiency in numbers or quality of neutrophils:- Skin infections Abscess formation (staphylococci) Invasive bacterial infections (rapidly dividing extracellularly replicating) Septicaemia Invasive fungal infection Death within 1-2 weeks if no neutrophils

22. Monoclonal antobodies and their derivatives. Immunological tests and techniques employing monoclonal antibodies. Monoclonal antiodies in therapy. Structure and function of T cell receptor . Seminar 2

29. Monoclonal antibodies approved for therapeutic use in the USA Multiple sclerosis Receptor binding and antagonism; inhibition of leukocyte adhesion to their counter receptors α4-Subunit of α4β1-integrin And α4β7-integrin Humanized IgG4 Tysabri; natalizumab Persistent asthma Ligand binding and receptor antagonism; reduction in release of allergic-response mediators from mast cells and basophils IgE Humanized IgG1 Xolair; omalizumab Prophylaxis against RSV infection in children at high risk Binding and neutralization of RSV; inhibition of viral fusion and replication RSV gpF Humanized IgG1 Synagis; palivizumab Rheumatoid and psoriatic arthritis Ligand binding and receptor antagonism; induction of CDC TNF Human IgG1 Humira; adalimumab Plaque psoriasis Receptor binding and antagonism; inhibition of leukocyte adhesion to other cells CD11a Humanized IgG1 Raptiva; efalizumab Rattle snake antidote Toxin binding and neutralization Snake venom Ovine Fab CroFab Digoxin overdose Drug binding and neutralization Digoxin Ovine Fab DigiFab Prevention of plateletmediated clots in coronary angioplasty Receptor binding and antagonism; inhibition of platelet aggregation gpIIb–gpIIIa and αvβ3-Integrin Chimeric Fab ReoPro; abciximab Crohn’s disease, rheumatoid and psoriatic arthritis, Ulcerative colitis and ankylosing spondylitis Ligand binding and receptor antagonism TNF Chimeric IgG1 Remicade; infliximab Non-Hodgkin’s lymphoma and rheumatoid arthritis Sensitization of cells to chemotherapy; induction of apoptosis, ADCC and CDC CD20 Chimeric IgG1 Rituxan, MabThera; rituximab Non-Hodgkin’s lymphoma Induction of cell death by radiation; induction of apoptosis, ADCC and CDC CD20 Mouse IgG2a, 131I-labelled Bexxar; 131I-tositumomab Non-Hodgkin’s lymphoma Induction of cell death by radiation; induction of apoptosis CD20 Mouse IgG1, 90Y-labelled Zevalin ibritumomab tiuxetan Acute myeloid leukaemia that expresses CD33 Induction of double-stranded DNA breaks and cell death (caused by calicheamicin) CD33 Humanized IgG4, Calicheamicin conjugated Mylotarg; Gemtuzumab ozogamicin B-cell chronic lymphocytic leukaemia Induction of ADCC and CDC CD52 Humanized IgG1 Campath; alemtuzumab Metastatic colorectal cancer Ligand binding and receptor antagonism; inhibition of angiogenesis and metastatic disease progression VEGF Humanized IgG1 Avastin; bevacizumab Metastatic colorectal cancer, and head and neck cancer Receptor binding and antagonism; inhibition of cell proliferation; induction of apoptosis; sensitization of cells to chemotherapy and radiotherapy; inhibition of angiogenesis, invasion and metastasis; induction of ADCC EGFR Chimeric IgG1 Erbitux cetuximab Metastatic breast cancer that overexpresses ERBB2 Sensitization of cells to chemotherapy; inhibition of angiogenesis and proliferation, induction of ADCC ERBB2 Humanized IgG1 Herceptin trastuzumab Prophylaxis of acute kidney-transplant rejection Receptor binding and antagonism CD25 Chimeric IgG1 Simulect basiliximab Prophylaxis of acute kidney-transplant rejection Receptor binding and antagonism CD25 Humanized IgG1 Zenapax daclizumab Prophylaxis of acute kidney-transplant rejection Blocking of function of T-cell expressed CD3; reversal of graft rejection CD3 Mouse IgG2a Orthoclone OKT3 muromonab-CD3 Approved indication Mechanisms of action Antigen Product type Product name / antibody name

31. Immune response, its induction and development. Lymphocyte activation. Subpopulations of lymphocytes. Seminar 4

34. Cytokines-functions and clinical applications. Regulation of the immune response . Effector mechanisms of the immune response. Mechanisms of cytotoxicity . Seminar 5

36. Generation of the immune response

37. Effector mechanisms of the immune system

38. Th1/Th2 ballance

42. The effector functions of antibodies

59. Innate immunity. The complement system. The phagocytic system. Interferons-role and clinical applications. Immunity to infectious diseases. Seminar 7

61. Complement activation

77. Transplantation immunology. Mechanisms of allogeneic transplant rejection, induction of transplantation tolerance Seminar 11

78. Types of transplants syngeneic = autograft cells/tissue/organ transferred from one part of the body to another in the same individual allogeneic = allograft cells/tissue/organ transferred between genetically different members of the same species xenotransplant = xenograft cells/tissue/organ transferred between members of different species isogeneic = isograft cells/tissue/organ transplanted between genetically identical individuals

79. Types of rejection antibodies, immune complexes, cellular reaction, recurrence of disease months/years Chronic primary activation of T cells days/weeks Acute reactivation of sensitized T cells days Accelerated preformed anti-donor antibodies minutes/hours Hyperacute CAUSE TIME TEKEN TYPE OF REJECTION

81. Acute rejection – direct and indirect presentation

84. Crossmatch measuring cell lysis suspension of donor lymphocytes recipient’s seru m complement

91. Hypersensitivity types. Atopic diseases – pathogenesis and current treatment, immunotherapy. Seminar 12

93. HYPERSENSITIVITY NON-SELF ANTIGEN AUTOIMMUNITY SELF ANTIGEN IMMUNE RESPONSE TOLERANCE

97. Type IV hypersensitivity

98. Major histocompatibility complex. Antigen presentation and recognition. Seminar 4

101. Cytosolic pathway

102. Endocytic pathway

103. Introduction to tumor biology. Immunology and immunothrapy of tumors. Seminar 12

108. Cancer pathways

109. Cancer screening

110. Cancer therapeutic agents

111. Tolerance, autoimmunity, mechanisms preventing autoimmune response. Prospects for specific therapies. Seminar 13

122. Primary and secondary immunodeficiencies. Prospects for treatment and prevention of AIDS Seminar 15