Immunodermatology

By 1940, immunological mechanisms had been proved to have fundamental influ­ ences on a great number and variety of skin reactions, and skin diseases had brought to light a great number of fundamental immunological mechanisms that were basic to a wide range of different diseases, dermatological and nondermato­ logical. The preeminence of dermatological research in the advancement of immu­ nological knowledge should not astonish anyone. For the skin is not only the most easily accessible tissue for producing and studying immunological reactions, it is also the great organ of protection that meets the first onslaughts of inimical environmental forces and agents-potential enemies, both living and dead. And protection is in essence what immunology is all about. To get an idea of the long-established role that testing the skin and the study of its many reactions has played in advancing general immunology, one need recall only smallpox vaccination; tuberculin testing; testing with fungal extracts; skin testing in hay fever, asthma, and serum sickness; skin tests with toxins and toxoids; the patch test; the passive transfer of skin-adhering antibodies (reagins); skin sensitization by simple chemicals; and similar dermatological procedures that have exerted their influence on medical and scientific disciplines far beyond dermatology.

1 Cell-Mediated Immunity.- 1. Introduction.- 2. Cellular Immune Function.- 2.1. T-Cell Immunity.- 2.2. The Primary Response.- 2.3. The Secondary Response.- 2.4. Lymphocyte Subpopulations.- 3. Lymphocyte Activation in Vitro.- 3.1. Parameters of Activation.- 3.2. Lymphocyte Stimulators.- 3.3. Process of Activation.- 3.4. Lymphocyte Mediators.- 4. References.- 2 Antigens and Immunogens.- 1. Introduction.- 2. Properties of Antigenic Determinants.- 2.1. Size.- 2.2. Specificity.- 2.3. Forces Binding Antigen to Antibody.- 2.4. Conformation.- 2.5. Cross-Reactions.- 3. Immunogens.- 3.1. Foreignness.- 3.2. Size.- 3.3. Requirement for Multivalence.- 3.4. Genetic Control.- 4. Allergens.- 5. Autoantigens.- 6. References.- 3 Humoral Immunity in Comprehensive Immunology.- 1. Introduction.- 2. Antibody Structure and Function.- 2.1. General Characteristics.- 2.2. Conformation of Immunoglobulins.- 3. Structure and Biological Function of the Antibodies.- 3.1. Immunoglobulin G.- 3.2. Immunoglobulin M.- 3.3. Immunoglobulin A.- 3.4. Immunoglobulin D.- 3.5. Immunoglobulin E.- 4. The B-Cell System.- 5. B-Cell Activation.- 6. Immunoglobulin Synthesis and Secretion.- 7. Evolution of the Immunoglobulins.- 8. References.- 4 The Complement System: Mechanisms of Action, Biology, and Participation in Dermatological Diseases.- 1. Introduction.- 2. Biochemistry of Complement: Activation Mechanisms.- 2.1. Classical Complement Reaction.- 2.2. Alternative and Amplification Pathways of Complement Activation.- 3. Roles of “Control” Proteins in the Complement System.- 3.1. Inhibitor of the Activated First Component (C?) of Complement (C?INH).- 3.2. The C3b Inactivator (C3bINA)—Control Protein of C3b and C4b.- 3.3. An Inactivator of the C3a and C5a Anaphylatoxins (AI).- 4. Biological Activity of Some Products of the Complement System.- 5. Evaluation of the Complement System.- 6. Laboratory Measurement of Complement.- 6.1. Collection of Samples.- 6.2. Functional Hemolytic Assays.- 6.3. Immunochemical Assays for Complement Proteins.- 6.4. Additional Complement Assays.- 7. Complement Abnormalities in Skin Diseases.- 8. Inborn Deficiencies of the Complement System.- 8.1. Deficiencies of Components.- 8.2. Deficiencies of Control Proteins.- 9. Acquired Abnormalities of the Complement System Associated with Skin Diseases.- 9.1. Angioedema and Urticaria.- 9.2. Complement Abnormalities in Cutaneous Vasculitis.- 9.3. Complement Abnormalities in Infectious Processes with Skin Manifestations.- 9.4. Uncommon Cutaneous Disorders Associated with Complement Abnormalities.- 9.5. Autoimmune Processes Involving the Skin Associated with Complement Abnormalities.- 9.6. Inflammatory Processes Involving the Skin Associated with Complement Abnormalities.- 10. Conclusions.- 11. References.- 5 Mechanisms of Nonspecific Host Resistance.- 1. Introduction.- 2. Methods for Measurement of Inflammatory Cell Accumulation and Chemotaxis.- 3. Chemotactic Factors.- 3.1. C-Derived Chemotactic Factors.- 3.2. Cell-Derived Chemotactic Factors.- 3.3. Bacterial Chemotactic Factors.- 4. Mechanisms of Chemotaxis.- 5. Phagocytosis.- 6. Summary.- 7. References.- 6 The HLA System and Dermatological Diseases.- 1. Introduction.- 2. HLA System.- 2.1. HLA-A, -B, -C.- 2.2. HLA-D and -DR.- 3. Genetics of HLA.- 4. HLA Genetic Linkage Group.- 5. HLA and Disease.- 5.1. Introduction.- 5.2. Statistical Considerations and Experimental Design.- 5.3. HLA and Dermatological Diseases.- 5.4. HLA-Linked Diseases.- 6. Conclusions.- 7. References.- 7 Natural Control over Immune Responses.- 1. Introduction.- 2. Immunological Enhancement.- 2.1. Role of Lymphocytes.- 2.2. Role of Monocytes and Macrophages.- 3. Suppressor Cells and Activities.- 3.1. Animal Models.- 3.2. Studies in Man.- 3.3. Soluble Suppressor Factors.- 4. Lymphokines.- 5. Immunological Memory.- 5.1. B-Cell Memory.- 5.2. T-Cell Memory.- 6. Immune Tolerance.- 6.1. B-Cell Tolerance.- 6.2. T-Cell Tolerance.- 6.3. Role of Other Cells in Tolerance.- 6.4. Role of Antibody and Antigen-Antibody Complexes in Tolerance.- 7. Summary.- 8. References.- 8 Mechanisms of Tissue Injuries and Repairs in Hypersensitivity.- 1. Introduction.- 2. Type I Reactions.- 2.1. Receptor Binding Phase.- 2.2. Activation Phase.- 2.3. Release of Mediators.- 2.4. Clinical Signs.- 3. Type II Reactions.- 3.1. Classes of Antibody.- 3.2. Mechanisms of Activation.- 3.3. Effects on Sensitized Cells.- 4. Type III Reactions.- 4.1. Mechanisms of Reaction.- 4.2. Serum Sickness.- 4.3. Arthus Reactions.- 4.4. Massive Complement Activation.- 5. Type IV Reactions.- 6. Differential Diagnosis and Cautions.- 7. References.- 9 Cyclic Nucleotides, Arachidonic Acid, and Polyamines in the Pathophysiology of Inflammatory Proliferative Skin Diseases.- 1. Introduction.- 2. Role of the Cyclic AMP System.- 3. Role of the Cyclic GMP System.- 4. Role of the Arachidonic Acid-Prostaglandin Transformation System.- 5. Role of the Cell Surface.- 6. Role of the Polyamines.- 7. Summary.- 8. References.- 10 Prostaglandins and Other Arachidonate Metabolites.- 1. Introduction.- 2. Biochemistry.- 3. Prostaglandins and Inflammation.- 3.1. Induction of Inflammation.- 3.2. Release during Inflammation.- 3.3. Effects of Antiinflammatory Drugs.- 3.4. Prostaglandins as Modulators of Inflammation.- 4. Prostaglandins and Immune Responses.- 4.1. Humoral Immune Response.- 4.2. Cell-Mediated Responses.- 5. Prostaglandins and Cutaneous Pathophysiology.- 5.1. Prostaglandins and Vitamin A.- 5.2. Prostaglandins and Pigmentation.- 6. Concluding Remarks.- 7. References.- 11 Role of Proteinases in Cutaneous Inflammation.- 1. Introduction.- 2. Epidermal Proteinases.- 2.1. Cathepsin D.- 2.2. Cathepsin Bl.- 2.3. Plasminogen Activator.- 3. Serine Proteinases Operable at Physiological pH.- 4. Role of Serine Proteinase as a Possible Messenger for Polymorphonuclear Leukocyte Accumulation.- 5. Chemotactic Proteinase in Psoriasis.- 6. Role of Proteinase in Pemphigus Vulgaris.- 7. Conclusion.- 8. References.- 12 Collagen Biosynthesis and Connective Tissue Abnormalities.- 1. Introduction.- 2. Collagen Structure and Amino Acid Sequence.- 3. Intracellular Biosynthesis.- 4. Extracellular Modifications.- 5. Collagen Degradation.- 6. Collagen and the Immune System.- 7. Conclusions.- 8. References.- 13 Vasculitis.- 1. Introduction.- 2. Leukocytoclastic Vasculitis (Hypersensitivity Angiitis or Allergic Vasculitis).- 2.1. Leukocytoclastic Vasculitis.- 2.2. Hypocomplementemic (Urticarial) Vasculitis.- 2.3. Essential Mixed Cryoglobulinemia.- 3. Rheumatic Vasculitis.- 3.1. Systemic Lupus Erythematosus.- 3.2. Rheumatoid Vasculitis.- 3.3. Dermatomyositis.- 3.4. Progressive Systemic Sclerosis (Scleroderma).- 4. Granulomatous Vasculitis.- 4.1. Allergic Granulomatous Angiitis (Churg-Strauss Syndrome).- 4.2. Wegener’s Granulomatosis.- 4.3. Lymphomatoid Granulomatosis.- 4.4. Granuloma Annulare, Necrobiosis Lipoidica Diabeticorum, and Rheumatoid Nodules.- 5. Polyarteritis Nodosa.- 5.1. Classic Type.- 5.2. Cutaneous Type.- 6. Giant-Cell Arteritis.- 6.1. Temporal Arteritis.- 6.2. Polymyalgia Rheumatica.- 6.3. Takayasu’s Disease.- 7. Immunological and Etiological Aspects.- 8. References.- 14 Adverse Drug Reactions.- 1. Introduction.- 2. Anaphylaxis.- 3. Urticaria.- 4. Bullous Reactions.- 4.1. Toxic Epidermal Necrolysis.- 4.2. Erythema Multiforme.- 4.3. Bullous Pemphigoid.- 4.4. Systemic Lupus Erythematosus.- 5. Specific Drugs.- 5.1. Silicone.- 5.2. Penicillin.- 5.3. Parabens.- 5.4. Trichloroethylene.- 5.5. Ethylene Oxide.- 5.6. Phenylbutazone.- 5.7. Salicylanilides, Bithionol, and Other Photosensitizers.- 5.8. Tetracycline.- 5.9. Dyes.- 5.10. Antihistamines.- 5.11. Phenothiazines.- 5.12. Sulfones.- 5.13. Neomycin.- 5.14. Gold.- 5.15. Isoniazid.- 5.16. Penicillamine.- 6. Treatment.- 7. References.- 15 The Graft-vs.-Host Reaction in Man: Genetics, Clinical Features, and Immunopathology.- 1. Introduction.- 2. Clinical Spectrum.- 2.1. GVHR in Children with Immune Deficiency.- 2.2. GVHR in Immunosuppressed Patients.- 2.3. GVHR Following Marrow Transplantation.- 3. Genetics of Transplantation.- 3.1. Allograft Reaction.- 3.2. Determinants Controlling GVHR.- 4. GVHR in Bone Marrow Transplant Patients.- 4.1. Treatment of Children with Severe Combined Immune Deficiency Disease.- 4.2. Patients with Aplastic Anemia and Leukemia.- 5. Pathogenesis of GVHR and Immunological Mechanisms.- 5.1. Experimental GVHR.- 5.2. Graft-vs.-Host Disease in Humans.- 6. Clinical Features of Graft-vs.-Host Disease.- 6.1. Acute GVHD.- 6.2. Chronic GVHD.- 7. Pathology of Cutaneous GVHD.- 7.1. Acute Cutaneous GVHR.- 7.2. Chronic Cutaneous GVHR.- 7.3. Pathogenesis and Results of Special Studies.- 8. Therapy of GVHD.- 8.1. Avoidance of GVHR in Susceptible Individuals: Use of Irradiated Blood Products.- 8.2. Prophylactic Treatment of GVHR in Marrow Transplant Patients.- 8.3. Treatment of Established GVHD.- 9. References.- 16 Allergic Contact Dermatitis, Photoallergic Contact Dermatitis, and Phototoxic Dermatitis.- 1. Introduction.- 2. Allergic Eczematous Contact Dermatitis.- 2.1. Clinical Changes.- 2.2. Histological Changes.- 2.3. Immunological Mechanisms.- 2.4. Antigens.- 2.5. In Vivo and in Vitro Tests.- 2.6. Genetic Factors.- 2.7. Specific Immunological Tolerance.- 2.8. “Systemic” Effects of Contact Allergens.- 2.9. Hyposensitization and Desensitization.- 3. Photoallergic Contact Dermatitis.- 3.1. Introduction.- 3.2. Clinical Manifestations.- 3.3. Histological Changes.- 3.4. Immunological Mechanisms.- 3.5. Mechanism of Persistent Light Reactivity.- 3.6. Photopatch Tests.- 4. Phototoxic Dermatitis.- 5. References.- 17 Urticaria/Angioedema: The Mast Cell, Its Diverse Mediators, and Its Role in Cutaneous Inflammation.- 1. Introduction and Definition.- 2. Epidemiology.- 3. Pathogenesis.- 3.1. The Mast Cell.- 3.2. Chemical Mediators.- 3.3. Mast Cell Activation in Vivo.- 4. Clinical Manifestations.- 4.1. IgE-Dependent Urticaria/Angioedema.- 4.2. Complement-Mediated Urticaria/Angioedema.- 4.3. Non immunological Urticaria/Angioedema.- 4.4. Idiopathic Urticaria/Angioedema.- 5. Laboratory Findings.- 6. Pathology.- 7. Diagnosis and Differential Diagnosis.- 8. Prevention and Treatment.- 9. References.- 18 Eosinophil in Skin Disorders.- 1. Introduction.- 2. Morphology and Function.- 3. Specific Properties.- 4. Eosinophilia in Dermatological Disorders.- 5. Conclusion.- 6. References.- 19 Atopic Dermatitis.- 1. General Considerations.- 1.1. Definition.- 1.2. History.- 1.3. Natural Course.- 1.4. Epidemiology and Inheritance.- 2. Immunological Associations.- 2.1. Reagenic Hypersensitivity.- 2.2. IgE in Atopic Dermatitis.- 2.3. Other Immunoglobulin Studies in Atopic Dermatitis.- 2.4. Dysfunctional Cellular Immune Mechanisms.- 2.5. Relationship to Immunodeficiency Diseases.- 3. Altered Physiological and Pharmacological Reactivity.- 3.1. Abnormal Cutaneous Responses.- 3.2. Investigations Relating to the ?-Adrenergic Blockade Theory.- 4. Canine Allergy: A Possible Animal Model of Atopic Dermatitis.- 5. References.- 20 Autoimmunity.- 1. Self-Tolerance and the Control of Autoimmune Reactions.- 2. Autoimmune Reactions in Man.- 3. Factors Which Influence the Expression of Autoimmunity.- 3.1. Genetic Constitution.- 3.2. Sex.- 3.3. Age.- 4. Innovative Therapeutic Approaches to Autoimmunity.- 5. References.- 21 Immunopathology and Pathogenesis of Cutaneous Lupus Erythematosus.- 1. Introduction.- 2. LE-Specific Skin Disease: Classification and Clinical Features.- 3. Pathological Features of Cutaneous LE.- 4. Immunopathology of Cutaneous LE.- 5. Experimental Models of LE Skin Disease.- 6. Relationship between Cutaneous and Systemic LE.- 7. Proposed Immunopathogenic Mechanism of Cutaneous LE.- 8. Summary and Conclusions.- 9. References.- 22 Other Disorders with Autoimmune Manifestations.- 1. Introduction.- 2. Rheumatoid Arthritis.- 3. Juvenile Rheumatoid Arthritis.- 4. Polymyositis and Dermatomyositis.- 5. Scleroderma.- 6. Sjogren’s Syndrome.- 7. “Mixed Connective Tissue Disease”.- 8. Relapsing Polychondritis.- 9. Lyme Arthritis.- 10. References.- 23 Recurrent Aphthous Stomatitis and Behçet’s Syndrome.- 1. Historical Perspective.- 2. Recurrent Aphthous Stomatitis.- 2.1. Clinical Characteristics.- 2.2. Epidemiological Characteristics.- 3. Behçet’s Syndrome.- 3.1. Clinical Characteristics.- 3.2. Epidemiological Characteristics.- 4. Evidence for an Immunopathogenesis of RAS and BS.- 4.1. Introduction.- 4.2. Disease Associations.- 4.3. Histocompatibility Antigen Associations.- 4.4. Response to Therapy.- 4.5. Pathological Observations.- 4.6. Absence of a Defined Microbiological Agent.- 4.7. Streptococcal Antigens.- 4.8. Oral Mucosal Antigens.- 5. Conclusion.- 6. References.- 24 Alopecia Areata.- 1. Introduction.- 2. Histopathology.- 3. Etiology and Pathogenesis.- 4. Association with Autoimmune Disorders.- 5. Association with Mongolism.- 6. Experimental Studies.- 7. Conclusion.- 8. References.- 25 Vesiculobullous Skin Diseases.- 1. Introduction.- 2. Pemphigus.- 3. Bullous Pemphigoid.- 4. Herpes Gestationis.- 5. Cicatricial Pemphigoid.- 6. Erythema Multiforme.- 7. Benign Chronic Bullous Dermatosis of Childhood.- 8. References.- 26 Dermatitis Herpetiformis.- 1. Introduction.- 2. Immunoglobulin and Complement Deposition in DH Skin.- 3. Serum Factors.- 4. Gastrointestinal Lesion in Dermatitis Herpetiformis.- 5. Effect of Gluten Withdrawal on the Skin Disease.- 6. Immunogenetic Aspects of Dermatitis Herpetiformis.- 7. Conclusions.- 8. References.- 27 Syndromes Resembling Scalding of the Skin.- 1. Introduction.- 2. Staphylococcal Epidermolytic Toxin Syndrome (SETS; Ritter von Rittershain).- 2.1. Clinical Observations.- 2.2. Histopathological Observations.- 2.3. Experimental SETS.- 2.4. Immunology of SETS.- 2.5. Epidermolysin in Bullous Impetigo.- 3. Toxic Epidermal Necrolysis (TEN; Lyell Syndrome).- 3.1. Clinical Observations of TEN.- 3.2. Histopathological Observations of TEN.- 3.3. Relation to GvH Disease.- 3.4. Relation to Erythema Multiforme.- 4. Conclusion.- 5. References.- 28 Primary Immunodeficiency Diseases of Man.- 1. Introduction.- 2. X-Linked Infantile Agammaglobulinemia.- 3. DiGeorge’s Syndrome.- 4. Severe Combined Immunodeficiencies (SCID, Swiss-Type Immunodeficiencies).- 5. Severe Combined Immunodeficiencies with Adenosine Deaminase Deficiency.- 6. Thymoma with Immunodeficiency.- 7. Common Variable Immunodeficiency (CVI).- 8. Selective Immunoglobulin Deficiency—Isolated Absence of IgA.- 9. Immunodeficiency with Wiskott-Aldrich and Ataxia-Telangiectasia Syndromes.- 10. Other Primary Immunodeficiencies.- 10.1. Deficiencies of Components of the Complement System.- 10.2. Deficiencies of Phagocytic Cells.- 10.3. Chronic Mucocutaneous Candidiasis.- 10.4. Other Manifestations of Primary Immunodeficiency.- 11. Conclusion.- 12. References.- 29 Deficiency of Phagocyte Function and Related Disorders.- 1. Introduction.- 2. Impaired Chemotaxis.- 2.1. Hyperimmunoglobulinemia E Syndrome.- 2.2. Atopic Dermatitis.- 2.3. Lazy Leukocyte Syndrome.- 2.4. Acrodermatitis Enteropathica.- 2.5. Ichthyosis.- 2.6. Mucocutaneous Candidiasis.- 2.7. Wiskott-Aldrich Syndrome.- 2.8. Measles.- 2.9. Mycosis Fungoides.- 2.10. Inhibitors of Chemotaxis.- 2.11. Impaired Generation of Chemotactic Factors.- 2.12. Augmented Chemotaxis.- 3. Impaired Phagocytic Microbial Killing.- 3.1. Chronic Granulomatous Disease.- 3.2. Chediak-Higashi Syndrome.- 3.3. Myeloperoxidase Deficiency.- 3.4. Glucose-6-Phosphate Dehydrogenase Deficiency.- 3.5. Leukocyte Alkaline Phosphatase Deficiency.- 4. Conclusion.- 5. References.- 30 Acrodermatitis Enteropathica and the Immunological Role of Zinc.- 1. Introduction.- 2. The Human Disorder.- 3. The Bovine Disease.- 4. Symptomatology.- 5. Biogeochemistry of Zinc.- 6. Sources of Zinc.- 7. Biochemistry of Zinc.- 8. Zinc and Nucleic Acids.- 9. Bioavailability and Biological Antagonism of Trace Metals.- 10. Zinc and Protein Metabolism.- 11. Zinc and Glutathione.- 12. Superoxide Dismutase.- 13. Physiology of Zinc.- 13.1. Ab...