Immunopharmacology

1 Definition and History.- 2 The Immune System — A Short Introduction to its Structure and Function.- 2.1 The cells of the immune system.- 2.1.1 T- and B-lymphocytes.- 2.1.1.1 Lymphocyte receptors.- 2.1.1.2 Immunological memory.- 2.1.1.3 Generation of receptor diversity in lymphocytes.- 2.1.1.4 Effector functions of T-cells.- 2.1.1.5 Transplantation reactions and MHC antigens.- 2.1.2 Macrophages.- 2.1.3 Neutrophils.- 2.1.4 Eosinophilic granulocytes.- 2.1.5 Mast cells and basophils.- 2.1.6 NK- and K-cells.- 2.2 Humoral components of the immune system.- 2.2.1 The structure and function of antibodies.- 2.2.1.1 Antibody diversity.- 2.2.1.2 Physico-chemical aspects of antibody binding.- 2.2.2 Lymphokines and cytokines.- 2.2.2.1 Interferons (see also Chapter 6).- 2.2.2.2 The interleukin family.- 2.2.2.3 The tumour necrosis factor family.- 2.2.2.4 Chemotactic factor family or ‘small inducible gene’ family.- 2.2.2.5 The chromosome 5 linkage group.- 2.2.2.6 Individual cytokines with no close relatives.- 2.2.3 The complement system.- 2.3 Synopsis.- 3 Antibodies as Immunopharmacological Agents.- 3.1 Polyclonal animal immunoglobulins.- 3.1.1 Anti-lymphocyte (ALG) and anti-thymocyte (ATG) globulins.- 3.1.2 ATG/ALG can suppress transplantation immunity.- 3.1.3 ALG/ATG can facilitate hematopoietic recovery in patients with aplastic anemia.- 3.1.4 ALG/ATG can cause serum sickness.- 3.2 Polyclonal human immunoglobulins.- 3.2.1 Human IgG preparations.- 3.2.1.1 Standard ?-globulin (SGG).- 3.2.2 Intravenously applicable IgG preparations (IGIV).- 3.2.2.1 Enzymatically split immunoglobulin preparations.- 3.2.2.2 Chemically modified ?-globulins.- 3.2.2.3 Largely intact immunoglobulins.- 3.2.3 The subclass composition of IgG preparations.- 3.2.4 Contaminants of IgG preparations which can cause adverse reactions.- 3.3 Therapeutic applications of human immunoglobulins.- 3.3.1 Animal experiments with ?-globulins in infections.- 3.3.2 Clinical applications of human ?-globulins.- 3.3.2.1 Prophylaxis.- 3.3.2.2 Replacement of immunoglobulin.- 3.3.2.3 Therapy.- 3.3.2.4 Morbus hemolyticus neonatorum is largely prevented by anti-D IgG prophylaxis.- 3.3.2.4 IgG in the treatment of diseases caused by autoantibodies.- 3.4 Monoclonal antibodies.- 3.4.1 Methods of monoclonal antibody production.- 3.4.2 The use of monoclonal antibodies in neoplastic diseases.- 3.4.2.1 Tumour-associated antigens.- 3.4.2.2 Strategies for the use of antibodies in cancer treatment.- 3.4.2.2.1 In vivo use of unmodified antibodies.- 3.4.2.2.2 In vivo use of modified antibodies.- 3.4.2.2.3 In vitro use of unmodified or modified antibodies.- 3.4.2.3 Prospects of cancer therapy with monoclonal antibodies.- 3.4.3 Other therapeutic uses of monoclonal antibodies.- 4 Immunosuppression.- 4.1 What is an immunosuppressive?.- 4.1.1 Blocking the immune response.- 4.1.2 Strategies leading to the induction of tolerance.- 4.2 Azathioprine.- 4.2.1 Chemistry, history.- 4.2.2 Pharmacokinetics.- 4.2.3 Mechanism of action.- 4.2.4 Immunopharmacological effect of azathioprine.- 4.2.5 Clinical use.- 4.3 Glucocorticoids.- 4.3.1 Cellular mechanism of action.- 4.3.2 Pharmacological effects.- 4.3.2.1 Effect on the distribution of blood cells.- 4.3.2.2 Inhibition of lymphocyte activation.- 4.3.2.3 Lytic effects on lymphocytes.- 4.3.2.4 Phospholipase A2 inhibitors.- 4.4 Cyclosporin A.- 4.4.1 Chemistry.- 4.4.2 Immunosuppressive properties.- 4.4.3 Mechanism of action.- 4.4.4 Absorption, pharmacokinetics.- 4.4.5 Side effects.- 4.4.6 Clinical use.- 4.5 FK 506.- 4.5.1 Pharmacology.- 4.5.2 Toxicity.- 4.6 Orthoclone T3 (OKT3).- 4.6.1 Physical properties.- 4.6.2 Immunological actions.- 4.6.3 Therapeutic applications of OKT3.- 4.7 Immunotoxins.- 4.7.1 Mechanism of action.- 5 Substances with an Antiallergic Effect.- 5.1 Immediate-type hypersensitivity reactions.- 5.1.1 Histamine.- 5.1.2 Further primary and secondary mediators.- 5.1.3 IgE antibodies.- 5.1.3.1 Regulation of IgE synthesis in rodents (according to K. Ishizaka).- 5.1.3.2 Regulation of IgE synthesis (according to D. Katz).- 5.1.3.3 IgE regulation in human cell systems.- 5.1.3.4 Desensitization and IgE regulation.- 5.1.4 Degranulation of mast cells.- 5.1.4.1 Phospholipid metabolism.- 5.1.4.2 Cyclic nucleotides.- 5.1.4.3 Prostaglandins and leukotrienes.- 5.1.4.4 The biological role of prostaglandins and leukotrienes in immediate-type hypersensitivity.- 5.1.5 Antiallergic agents.- 5.1.5.1 Antihistamines.- 5.1.5.2 Cromolyn sodium.- 5.1.5.3 Ketotifen.- 5.1.5.4 Oxatomide.- 6 Immunostimulation.- 6.1 Possible therapeutic strategies.- 6.2 Endogenous substances.- 6.2.1 The role of gene cloning in the characterization and production of lymphokines and other endogenous proteins.- 6.2.2 Interferons.- 6.2.2.1 Definition and history.- 6.2.2.2 Classification.- 6.2.2.3 Properties.- 6.2.2.4 The interferon receptors.- 6.2.2.5 Biochemical and molecular changes induced by interferons.- 6.2.2.6 Physiological role of the interferons.- 6.2.2.7 Clinical uses of interferons.- 6.2.2.8 Synopsis, prospects.- 6.2.2.9 Interferon inducers.- 6.2.3 Interleukin 2.- 6.2.3.1 Definition and history.- 6.2.3.2 Properties.- 6.2.3.3 Mechanism of action.- 6.2.3.4 Changes in Il-2 production in vivo.- 6.2.3.5 Therapeutic uses of Il-2.- 6.2.4 Colony stimulating factors.- 6.2.4.1 GM-CSF.- 6.2.4.2 G-CSF.- 6.2.4.3 Interleukin 3.- 6.2.4.4 M-CSF.- 6.2.5 Thymic hormones.- 6.2.5.1 Definition and history.- 6.2.5.2 Thymosins and related peptides.- 6.2.5.3 Immunological effects of thymosin.- 6.2.5.4 Clinical findings with thymosin.- 6.2.5.5 Other thymic hormones.- 6.2.6 Transfer factor.- 6.2.7 Tuftsin.- 6.3 Substances of microbial origin.- 6.3.1 Patterns of macrophage activation.- 6.3.2 Corynebacterium parvum and BCG.- 6.3.3 Muramyl dipeptides.- 6.3.4 Beta 1,3-D-glucan.- 6.3.5 Coenzyme Q (ubiquinones).- 6.3.6 Bestatin.- 6.4 Synthetic substances.- 6.4.1 Levamisole.- 6.4.1.1 Pharmacokinetics.- 6.4.1.2 Mechanism of action.- 6.4.1.3 Immunopharmacological effects.- 6.4.1.4 Clinical use.- 6.4.1.5 Side effects.- 6.4.2 Cimetidine.- 6.4.2.1 Pharmacokinetics.- 6.4.2.2 Immunopharmacological effects.- 6.4.2.3 Clinical findings.- 6.4.2.4 Side effects.- 6.4.3 Isoprinosine.- 6.4.3.1 Pharmacokinetics.- 6.4.3.2 Clinical uses.- 6.4.3.3 Mechanism of action.- 6.4.3.4 Side effects.- 6.4.4 Other synthetic immunostimulants.- 7 Clinical Assessment and Perspectives.- 7.1 Immunosubstitution — antibodies.- 7.2 Immunosuppression.- 7.3 Antiallergic substances — suppression of the acute-type hypersensitivity reaction.- 7.4 Antiinflammatory substances.- 7.5 Immunostimulation — biological response modifiers.- General literature.- References.