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E-raamat: Essential Immunology for Surgeons

Edited by (Lead Clinician for Breast Services, Director of Research and Development, United Lincolnshire Hospitals NHS Trust; Clinical Director, Trent Comprehensive Local Research Network, Nottingham University Hospitals NHS Trust; and Special Prof), Edited by
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  • ISBN-13: 9780191621062
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There has been a huge increase in the knowledge and understanding of the immunological processes involved in surgical practice in recent years. Anaesthesiologists and intensive care physicians are increasingly recognising the significant derangements of immune function in the critically ill patient and the possible therapeutic approaches to manage such patients (including new approaches in transplantation rejections, novel vaccination strategies in cancer treatment, as well as a better understanding of the beneficial effects of standard chemotherapy).Written by recognised experts in their field from both the UK and the US, and extensively referenced for further reading, Essential Immunology for Surgeons provides a concise, up-to-date, and readable account of immunology in general and its translation into key areas of clinical practice. It provides the necessary foundation for a critical understanding of this essential and rapidly expanding area of biological science that underpins and explains the modern concepts of a range of diseases and conditions, encompassing autoimmunity, infection, trauma, cancer, nutrition, organ transplantation, and various forms of therapy.Previously published as Immunological Basis for Surgical Science and Practice, this fully-updated textbook is aimed predominantly at the surgical trainee, but will also be of value to undergraduate and postgraduate clinicians of any discipline who wish to have a better understanding and knowledge of the subject, as well as to researchers studying the various core topics discussed in the book.
List of contributors
xxvii
Abbreviations and acronyms xxix
1 Basic immunology
1(160)
Herb Sewell
Introduction
5(3)
Overview of immunology
8(47)
Introduction
8(1)
Innate and adaptive immunity
8(1)
Innate immunity
8(8)
Innate-adaptive immune interactions
16(2)
Adaptive immunity
18(5)
Dendritic cells
23(3)
Natural killer cells
26(3)
Clusters of differentiation and monoclonal antibodies
29(1)
Introduction
29(1)
Common CD antigens
29(4)
Cytokines, chemokines, and signalling
33(1)
Cytokines
33(1)
Chemokines
34(5)
Cytokines and signalling
39(1)
Central and peripheral lymphoid organs; lymphocyte recirculation
40(1)
Introduction
40(4)
Thymus
44(2)
Bursa equivalents
46(1)
Secondary lymphoid organs
47(1)
Lymphatic network; recirculation pathways
47(2)
Clonal selection
49(2)
Immunogens, antigens, and adjuvants
51(1)
Antigens and immunogens
51(1)
Concept of complementarity
52(1)
T cell requirement for optimal B cell response
52(1)
Tailor-made antigens
53(1)
Adjuvants
53(2)
Recognition elements, cells, and receptors in adaptive immunity
55(25)
Major histocompatibility complex
55(1)
Structure, location, and function
55(4)
MHC and disease associations
59(1)
Antigen processing and presentation: adhesion molecules and costimulation
60(1)
Introduction
60(1)
Extracellular pathogens and antigens
61(1)
Intracellular pathogens and antigens
62(1)
B cell recognition
63(1)
Essential signalling (1, 2, and 3)
63(2)
Costimulation and adhesion molecules
65(3)
T cells, receptors, and effectors: CD4+ Th1, Th2 and Th17; CD4+ Tregs and CD8+ CTLs
68(1)
T cell receptors
68(1)
T cell effectors: CD4+/CD8+ subsets
69(4)
T cell effectors: CD4+ Tregs
73(1)
B cells, receptors, and antibodies
73(1)
B cells and receptors
73(3)
Immunoglobulins and antibodies
76(3)
Primary and secondary antibody responses
79(1)
Recognition events and functionality of the integrated immune system in vivo
80(8)
Introduction
80(1)
Antigen entry and responses via the natural portal of the GIT
80(1)
GIT innate defences
80(2)
Dendritic cells
82(1)
Mucosal-associated lymphoid tissue
83(1)
Introduction
83(1)
MALT and GIT diseases
84(2)
Parental injection of antigen
86(1)
Superantigen
87(1)
T cell activation
87(1)
B cell activation
88(1)
Physiological benefits of the effector immune response
88(20)
Introduction
88(1)
Complement system of proteins
89(6)
Effector cells and receptors
95(1)
CD4+ and CD8+ T cell effectors
95(5)
NK cells
100(1)
NK T cells
101(1)
γδ T cells
102(1)
Mast cells and basophils
102(2)
Vaccination
104(1)
Introduction
104(3)
Vaccines at the extremes of life
107(1)
Immune regulation and modulation
108(21)
Introduction
108(1)
Immune regulation and innate immunity
109(2)
Apoptosis and autophagy
111(1)
Apoptosis
111(4)
Autophagy
115(1)
Immune tolerance: central and peripheral tolerance
116(1)
Introduction
116(1)
Central tolerance for T and B lymphocytes
117(1)
Peripheral tolerance for T and B lymphocytes
118(1)
Activation-induced cell death
118(1)
Autoimmunity
119(1)
Genetic factors in autoimmunity
119(4)
Hormonal and environmental factors in autoimmunity
123(1)
Hormonal factors
123(1)
Environmental factors
123(1)
Autoimmunity and epigenomics
124(1)
Immune modulation
125(1)
Autoimmunity: re-establishing homeostatic regulation
125(1)
Neuroimmunology: integration and interactivity
126(2)
Neuroimmunology: pathological disturbances
128(1)
Psychoneuroimmunology
128(1)
Immunopathology and tissue damage, immune deficiency and immunotherapeutics
129(10)
Immunopathological processes: hypersensitivity (types I-IV) and tissue damage
129(1)
Mechanisms underlying the hypersensitivity reactions
129(1)
Type I hypersensitivity
129(2)
Type II hypersensitivity
131(1)
Type III hypersensitivity
132(1)
Type IV hypersensitivity
133(1)
Case study of latex allergy
134(1)
Drug allergy
135(2)
Allergy, immunotherapy, and new vaccines
137(2)
Primary (congenital) and secondary (acquired) immune deficiencies (including HIV/AIDS)
139(2)
Innate and adaptive immune systems
139(2)
Acquired (secondary) immune deficiencies
141(1)
HIV, AIDS, and the surgeon
141(10)
Aetiopathology
141(4)
Epidemiology and transmission of HIV infection and treatment strategies
145(2)
Immunology of HIV/AIDS
147(1)
Serum antibodies in HIV/AIDS
148(1)
HIV/AIDS and surgical practice
148(2)
Antiviral therapy
150(1)
Vaccines for HIV
151(1)
Monoclonals and other biological therapies (including immunoglobulin replacement)
151(10)
Monoclonal antibodies
151(4)
Fusion proteins
155(1)
Soluble receptor constructs
155(1)
Recombinant cytokines
155(1)
Polyclonal immunoglobulin replacement therapy
156(1)
References and further reading
157(4)
2 Trauma and tissue injury
161(38)
John C. Eun
Ernest E. Moore
Winston P. Choi
James H. Wood
Christopher Silliman
Anirban Banerjee
Host defences and the metabolic response to injury
161(6)
Trauma background
161(1)
Trauma and multiple organ failure
162(2)
Multiple organ failure and mesenteric lymph
164(3)
Host defences and the critical care setting
167(6)
Background
167(1)
Epidemiology
167(1)
Inflammatory mediators
168(1)
Signalling molecules
169(1)
Pattern recognition receptors
170(1)
Cellular immunity
171(1)
Conclusion
172(1)
Trauma and coagulation
173(5)
Haemostasis and fibrinolysis
173(1)
Acute coagulopathy of trauma
174(1)
Coagulation and the immune system
175(2)
Transfusion-related acute lung injury
177(1)
Host defences and the metabolic response to injury in children
178(3)
Background
178(1)
Development of the immune system
179(1)
Injury-induced inflammation in children
180(1)
Therapeutic modulation of host defences
181(3)
Decreasing inflammation
181(1)
Hyperosmolar therapy
181(1)
Steroids
182(1)
Enhancement of the immune system
183(1)
Interferon-γ
183(1)
Human recombinant granulocyte colony-stimulating factor (rh-G-CSF)
183(1)
Oestrogen
183(1)
Gut modulation
184(1)
Immunonutrition
184(1)
Summary and conclusions
184(1)
References
185(14)
3 Transplantation immunology
199(38)
Eleanor M. Bolton
J. Andrew Bradley
Background
200(1)
Introduction and historical perspective
200(1)
Terminology
201(1)
Tissues and histocompatibility
201(8)
Introduction
201(3)
Immunological considerations in organ transplantation
204(1)
The HLA system
204(3)
HLA matching
207(1)
Tissue typing
207(2)
Immunology of transplant rejection
209(10)
Introduction
209(1)
Contribution of innate immunity
209(2)
Allorecognition: direct and indirect pathways
211(4)
Initiation and amplification of the alloimmune response
215(1)
Effector mechanisms: cellular and humoral responses
216(2)
Privileged sites, immunoisolation
218(1)
Clinical patterns of rejection
219(3)
Introduction
219(1)
Hyperacute rejection
219(2)
Acute cellular and humoral rejection
221(1)
Chronic rejection
221(1)
Immunosuppressive therapy
222(5)
Introduction
222(1)
Calcineurin blockers: ciclosporin and tacrolimus
222(1)
Antiproliferative agents: azathioprine and mycophenolate mofetil
223(1)
Corticosteroids
224(1)
mTOR inhibitors: sirolimus and everolimus
224(1)
Biological agents: anti-CD3, anti-CD25, anti-CD20
225(2)
Induction and maintenance immunosuppression; treatment of acute rejection
227(1)
Complications of nonspecific immunosuppression
227(2)
Introduction
227(1)
Infection
227(1)
Malignancy
228(1)
Cardiovascular disease and diabetes
228(1)
Desensitization
229(1)
Future prospects
230(3)
Introduction
230(1)
Transplant tolerance
231(2)
Xenotransplantation
233(1)
Summary and conclusions
233(1)
References
234(3)
4 Cancer and the immune response
237(66)
Mark Aloysius
Leslie Walker
Oleg Eremin
Introduction
240(1)
Immune surveillance and host responses in cancer
241(16)
The `danger' hypothesis
241(1)
Immune surveillance
242(1)
Mouse models
242(1)
Spontaneous tumour development in immunodeficient mice
242(2)
Inflammation and carcinogenesis
244(1)
Experimental carcinogenesis in immunodeficient mice
245(3)
Human tumours
248(1)
Tumour-infiltrating lymphocytes and role of T regulatory cells
248(1)
Tumour-infiltrating macrophages
249(2)
Multiple myeloma; natural progression
251(1)
Paraneoplastic syndromes
251(1)
Immunocompromised patients
252(1)
The modern concept of immunoediting
252(1)
Introduction
252(1)
Elimination
253(1)
Equilibrium
253(1)
Escape
254(1)
Failure of cancer immune editing and immune escape
254(1)
Tumour resistance to host defences and growth promotion
254(1)
Reduced/absent immunogenicity of the tumour
255(1)
Impairment of anticancer host defences by the tumour
256(1)
Tumour microenvironment: role of TGF-β
256(1)
Introduction
256(1)
Neutrophils
257(1)
NK cells and DCs
257(1)
TIMs and MDSCs
257(1)
CD4+ and CD8+ T cells
257(1)
Tumour antigens
257(3)
Introduction
257(1)
Repertoire of tumour antigens
258(1)
Products of mutated oncogenes and tumour suppressor genes
258(1)
Tumour-specific expressed cellular proteins
258(1)
Tumour antigens produced by oncogenic viruses
258(1)
Oncofoetal antigens
259(1)
Altered cell surface glycolipids and glycoproteins
259(1)
Cell-type-specific differentiation antigens
259(1)
Cancer and cellular immune mechanisms: innate and adaptive
260(7)
Introduction
260(1)
Dendritic cells
261(1)
Antigen-specific T cells (human vaccination)
262(1)
NK cells
262(4)
NK T cells
266(1)
γδ T cells
266(1)
Cancer and humoral immune mechanisms
267(3)
Immunoglobulins
267(1)
Complement
268(1)
Cytokines
268(1)
Chemokines
269(1)
Tumour metastasis
270(4)
Introduction
270(1)
TAMs, migration, and invasion
271(1)
Angiogenesis
272(1)
Metastatic tumour bed
272(2)
Nonsurgical treatment and host defences
274(1)
Introduction
274(1)
Chemotherapy
274(1)
Radiotherapy
274(1)
Biological agents
275(1)
Immunotherapy in malignant disease
275(6)
Introduction
275(1)
Passive immunotherapy
275(1)
Adoptive cellular transfer
275(1)
Monoclonal antibodies
276(1)
Active immunotherapy
276(1)
Introduction
276(1)
Vaccine adjuvants
277(1)
Peptide vaccines
278(1)
Protein vaccines
278(1)
Recombinant live viral vectors for gene transfer
279(1)
DNA and RNA plasmid vaccines
279(1)
Tumour cell vaccines
279(1)
DC-based vaccines
280(1)
Cancer cachexia
281(2)
What is cachexia?
281(1)
Role of cytokines
281(1)
Role of hormones (leptin)
282(1)
Potential therapies
282(1)
Agents affecting appetite
282(1)
Agents affecting cachectic mediators or signalling pathways
282(1)
Psychoneuroimmunological aspects of cancer
283(3)
Psychosocial and psychiatric morbidity
283(1)
Effects of stress on the immune system
283(1)
Effects of psychosocial and related interventions on host defences
284(1)
Overview
285(1)
Summary and conclusions
286(1)
References
286(17)
5 Sepsis and the immune response
303(40)
Rajan K. Thakkar
Xin Huang
Joanne Lomas-Neira
Daithi Heffernan
Alfred Ayala
Background and basic concepts in sepsis
304(2)
Innate immunity and sepsis
306(11)
Introduction
306(1)
Innate immune response in sepsis
307(1)
PPRs and SIRS
307(1)
Compensatory anti-inflammatory response syndrome
307(1)
Pro- and anti-inflammatory mediators in sepsis
308(1)
Cytokines and chemokines
308(2)
Complement and coagulation cascade
310(1)
Defensins and antimicrobial peptides
311(1)
Lipid mediators
311(1)
Reactive oxygen species and reactive nitrogen species
311(1)
Small molecules
312(1)
Cellular components of innate immune response in sepsis
312(1)
Monocytes and macrophages
312(2)
Neutrophils
314(1)
Dendritic cells
315(1)
NK cells
315(1)
Innate regulatory γδ T and NK T cells
315(2)
Nonprofessional immune cell effectors
317(1)
Adaptive immune response in sepsis
317(3)
CD4+/CD8+ T and B cells
317(2)
T regulatory cells
319(1)
Pathogenesis of septic shock and multiple organ failure
320(3)
Introduction
320(1)
Multiple organ failure and mortality as a result of hyperinflammation
321(1)
Multiple organ failure and mortality as a result of hypoinflammation
321(1)
Multiple organ failure and mortality as a result of dysfunctional regulation of apoptosis
321(1)
Predispositional components
322(1)
Haemodynamic and vascular dysfunction in sepsis
323(1)
Disseminated intravascular coagulation
323(1)
Endothelial interface
324(1)
Neuroimmune regulation of the septic response
324(2)
Neuroendocrine-immune regulation
324(2)
Inflammatory reflex
326(1)
Experimental models of sepsis (acute versus chronic)
326(2)
Introduction
326(1)
Endotoxin and superantigen (exotoxin) challenge
326(1)
Monospecific microbial challenge
327(1)
Peritoneal cavity inoculation with faecal material
327(1)
Pulmonary infection and sepsis
327(1)
Caecal ligation and puncture
327(1)
GIT or colon ascendens stent peritonitis (CASP)
328(1)
Treatment strategies for sepsis
328(5)
Historical background
328(1)
Source control
328(1)
Antibiotics
329(1)
Steroids
329(1)
Anticytokine therapies
330(1)
Activated protein C
331(1)
Unintentional immunomodulation of other ICU care and medications
332(1)
Opioids
332(1)
Statins
332(1)
Summary and conclusions
333(1)
Acknowledgements
333(1)
References
333(10)
6 Nutrition and immunity
343(36)
Steven D. Heys
Manuel Garcia-Caballero
Klaus W.J. Wahle
Protein-energy malnutrition and the immune system
344(1)
Obesity and the immune system
345(1)
Probiotics and prebiotics
346(2)
Probiotics
346(2)
Prebiotics
348(1)
Micronutrients
348(4)
Zinc
348(1)
Selenium
349(1)
Copper
350(1)
Magnesium
350(1)
Iron
351(1)
Amino acids
352(5)
L-Glutamine
352(1)
L-Arginine
353(2)
Branched chain amino acids
355(1)
Methionine and cysteine (sulphur amino acids)
356(1)
Other amino acids
357(1)
Fatty acids
357(10)
Saturated fatty acids
360(1)
ω-9 fatty acids
361(1)
ω-6 fatty acids
362(3)
ω-3 fatty acids
365(1)
Nutritional support
366(1)
Alcohol
367(1)
Vitamins
368(4)
Introduction
368(1)
Vitamin A
368(1)
Innate immunity
368(1)
Adaptive immunity
368(1)
Vitamin E
369(1)
Vitamin D
370(1)
Introduction
370(1)
Innate immunity
370(1)
Adaptive immunity
370(1)
Vitamin C
371(1)
Clinical implications
372(1)
Summary and conclusions
372(1)
References
373(6)
7 Therapy and host defences
379(24)
Mark Aloysius
Chandan Verma
Oleg Eremin
Introduction
380(1)
Surgery and anaesthesia
381(5)
Immunosuppressive aspects of surgery
381(1)
Stress response to surgery
381(1)
Lymphadenectomy
382(1)
Splenectomy
383(1)
Thymectomy
384(1)
Immunosuppressive aspects of blood transfusion
384(1)
Immunosuppressive aspects of anaesthetic agents and drugs
384(1)
General anaesthetic agents
384(1)
Neutrophil dysfunction
384(1)
Monocyte and macrophage dysfunction
385(1)
Natural killer cell dysfunction
385(1)
T and B lymphocyte dysfunction
385(1)
Regional and local anaesthetic agents
386(1)
Opioids
386(1)
Chemotherapy, corticosteroids, radiotherapy, and hormonal therapy
386(4)
Introduction
386(1)
Immune modulation by chemotherapy
386(2)
Immune modulation by corticosteroids
388(1)
Immune modulation by radiotherapy
389(1)
Immune modulation by hormonal therapy
390(1)
Immune-enhancing cytokine therapy
390(1)
Introduction
390(1)
Interleukin-2
390(1)
Tumour necrosis factor-alpha
391(1)
Interferon-alpha
391(1)
Gene therapy
391(2)
Immunotherapy
393(2)
Vaccination
393(1)
Monoclonal antibodies and small molecule inhibitors
394(1)
Summary and conclusions
395(1)
References
395(8)
8 Autoimmune disease and inflammatory disorders
403(26)
Herb Sewell
Introduction
404(1)
Organ-specific autoimmunity
405(3)
Thyroid autoimmunity
406(2)
Gastric autoimmunity and pernicious anaemia
408(1)
Systemic (non-organ-specific) autoimmunity
408(9)
Rheumatoid arthritis and seronegative arthritides
409(1)
Systemic lupus erythematosus and antiphospholipid syndrome
410(2)
Paediatric chronic arthritis
412(1)
Antiphospholipid antibody syndrome
412(1)
Wegener's granulomatous disease and Churg-Strauss syndrome
413(1)
Overview of autoantibodies in clinical practice
414(3)
Paraneoplastic syndromes and autoimmunity
417(1)
Gastrointestinal and inflammatory diseases
417(6)
Coeliac disease
417(3)
Crohn's disease and ulcerative colitis
420(3)
Autoinflammatory diseases
423(2)
Surgical interventions and autoimmune inflammation
425(1)
Summary and conclusions
426(1)
Further reading
427(2)
9 Principles of immunological assays and molecular technologies
429(44)
Herb Sewell
Paddy Tighe
Adrian Robins
Introduction
430(1)
Tumour markers
430(6)
Background
430(1)
Principles of techniques and monoclonal antibodies
431(1)
Immunohistochemical techniques
431(2)
ELISA and RIA techniques
433(2)
Flow cytometry
435(1)
Tumour marker assays in laboratory practice
435(1)
Assessment of immune responsiveness
436(20)
Cellular immunity (adaptive and innate)
439(1)
Quantitative and qualitative analysis
439(1)
In vitro functional assays
439(3)
In vivo assays of CMI-DTH skin test
442(1)
Assessment of neutrophils and monocytes
442(1)
Assays of phagocyte cell function
442(2)
Assays of chemotaxis
444(1)
Killing of bacteria
444(1)
Humoral immunity
444(1)
Qualitative and quantitative immunoglobulin assays
444(1)
Qualitative investigations
445(1)
Quantitative investigations
446(1)
Functional antibody tests
446(1)
Antibodies to microorganisms
447(1)
Antibodies to nonreplicating antigens detected in allergy
447(1)
Assessment of complement
448(1)
Assessment of cytokines
448(1)
Introduction
448(1)
Cytokine assays
449(2)
Flow cytometry: current practice and future developments
451(5)
Detection of autoantibodies
456(6)
Introduction
456(1)
Immunofluorescence techniques
456(1)
Direct
456(1)
Indirect
457(1)
Agglutination assays
457(1)
ELISA assays
458(1)
Multiplex and planar assays
458(1)
Introduction
458(1)
Line immunoassays
458(1)
Bead immunoassays
459(2)
Antibodies and protein microarrays
461(1)
Postgenomic technologies
462(4)
Introduction
462(1)
Transcriptomics
463(1)
Proteomics
464(1)
Metabolomics
465(1)
Principles of newer molecular technologies and therapeutic approaches
466(5)
Genome-wide association studies
466(1)
Bioinformatics and systems biology in medicine
467(2)
Gene therapy
469(1)
Stem cell therapy
470(1)
Summary and conclusions
471(1)
References
472(1)
Glossary 473(16)
Index 489
Professor Oleg Eremin graduated from the University of Melbourne, Australia, in 1964, before training in surgery at the Royal Melbourne Hospital and in Papua New Guinea. He moved to the UK in 1972, becoming Research Assistant at the University of Cambridge, between 1974 and 1980, undertaking research into tumour immunology and anti-cancer defences. In 1981 he became Senior Lecturer at the University of Edinburgh and Honorary Consultant Surgeon at the Edinburgh Royal Infirmary, and from 1985 to 1998 he was Regius Professor of Surgery at University of Aberdeen, and Honorary Consultant Surgeon at Aberdeen Royal Infirmary, before taking up his current posts. Professor Eremin has over 200 publications in peer-reviewed journals, 25 chapters in books, and is the editor of four textbooks. His recent research interests include tumour cell resistance and proteomics, and immunotherapy in advanced cancer with dendritic cells and hTERT.

Professor Herb Sewell studied at Birmingham University gaining BDS Hons1 in 1973. Following further studies and research in immunology, he gained an MSc in 1975 and PhD in 1978. He subsequently pursued professional training and accreditation in clinical immunology and qualified in Medicine (MB ChB in 1983). He was appointed Senior Lecturer/Honorary Consultant in Immunology at the University of Aberdeen 1985 and subsequently moved to the University of Nottingham as Professor and Honorary Consultant in Immunology in 1990. In 2002 he was appointed a Pro Vice Chancellor/Vice President of Research at the University of Nottingham (2002-2007). His research interests focus primarily on the immunology of allergic disease and in particular on immunomodulation of the allergic response by the biological properties of allergens and by molecularly engineered antibodies. He has published over 120 peer reviewed original papers and reviews.