Clinical Immunology

Front cover
	Half title
	Full title
	Copyright
	Dedication
CONTENTS
Contributors
Preface
Acknowledgment
Chapter 1 - The immune system
	Introduction
	Humoral and cellular immunity
	Lymphocytes and their specific receptors
	Memory
	Self-tolerance
	Cells of the immune system
		Granulocytes
		Monocytes/macrophages
		Antigen-presenting cells
		Dendritic cells (DCs)
		Lymphocytes
	Primary lymphoid organs
	Secondary lymphoid organs
	Innate immunity
		Recognition of microbes in the context of innate immune system
		Cellular component of innate immunity
		Humoral components of innate immunity
	Major histocompatibility complex (MHC) and antigen presentation
		The phenomenon of MHC restriction
		MHC structure
			MHC I structure
			MHC II structure
		MHC presentation
			MHC I processing and presentation pathway
			MHC II processing and presentation pathway
		Cross-presentation
	B lymphocytes
		B lymphocyte development
		B cell subsets
		B cell activation
		Plasma cell differentiation
		Memory B cell
		Effector functions of antibodies
	T lymphocytes
		T cell development
		T cell activation
		CD4+ T cells effector functions
		CD8+ T cells effector functions
		γδ T cells
		NKT cells
		MAIT cells
	Mechanisms of tolerance
		T cell tolerance
		B cell tolerance
	Apoptosis
	References
Chapter 2 - Asthma and Allergy
	Introduction
	Asthma
		Definition and classifications
		Epidemiology and risk factors
		Etiology and pathogenesis
			Etiology
				Genetics
				Epigenetics
				Viral infections
			Pathogenesis
				Inflammation
				Tissue remodeling
				IgE
				Mast cells
				Eosinophils
				Epithelium
		Clinical features
			History
			Clinical findings
		Diagnosis
		Differential diagnosis
		Treatment
			GINA guidelines
				Patients >11 years old
				Patients between 6 and 11 years old
			Novel therapies
			Non-pharmacological treatments
			Severe and difficult to treat asthma cases
			Management of asthma exacerbations
	Allergic rhinitis
		Definition
		Epidemiology and risk factors
		Pathogenesis
		Clinical features
		Diagnosis
		Differential diagnosis
		Treatment
	Allergic conjunctivitis
		Definition
		Epidemiology
		Pathogenesis
		Clinical features
		Diagnosis
		Treatment
	Urticaria and angioedema
		Definition and classification
			Definition
			Classification
				Acute urticaria
				Chronic spontaneous urticaria (CSU)
				Chronic inducible urticaria (CInU)
				Acquired angioedema (AAE)
					Idiopathic histaminergic acquired angioedema (IH-AAE)
					Idiopathic non-histaminergic acquired angioedema (InH-AAE)
					Acquired angioedema related to angiotensin-converting enzyme inhibitors (ACEI-AAE)
				Acquired angioedema with C1 inhibitor deficiency (C1-INH-AAE)
				Hereditary angioedema (HAE)
					Hereditary angioedema with C1 inhibitor deficiency (C1-INH─HAE)
					Hereditary angioedema with normal C1 inhibitor and factor XII mutation (FXII-HAE) and of unknown origin (U-HAE)
		Epidemiology
		Etiology and pathogenesis
		Diagnosis
		Differential diagnosis
		Treatment
	Atopic dermatitis and allergic contact dermatitis
		Definition of atopic dermatitis
		History of atopic dermatitis
		Epidemiology and risk factors of atopic dermatitis
		Etiology and pathogenesis of atopic dermatitis
		Clinical features of atopic dermatitis
		Diagnosis of atopic dermatitis
		Differential diagnosis of atopic dermatitis
		Treatment of atopic dermatitis
		Definition of allergic contact dermatitis
		Epidemiology of allergic contact dermatitis
		Pathogenesis of allergic contact dermatitis
		Clinical features of allergic contact dermatitis
		Diagnosis of allergic contact dermatitis
		Treatment of allergic contact dermatitis
	Food allergy and gastrointestinal syndromes
		Definition
		Epidemiology and risk factors
		Etiology and pathogenesis
		Clinical features
		Diagnosis
		Treatment
		Prevention
	Drug allergy
		Definition
		Epidemiology and risk factors
		Etiology and pathogenesis
		Clinical features
		Diagnosis
		Specific drugs
			Non-Steroidal anti-inflammatory drugs (NSAIDs)
			β-Lactam antibiotics
			Angiotensin-converting enzyme inhibitors (ACE-I)
			Radiocontrast media (RCM)
			Biological drugs
		Treatment
	Anaphylaxis
		Definition
		Epidemiology and risk factors
		Pathogenesis
		Clinical features
		Diagnosis
		Differential diagnosis
		Treatment
	References
Chapter 3 - Autoimmune diseases
	Introduction
	Immune cells and immune responses
		Innate immune activation
		Central and peripheral tolerance
		Adaptive immune activation and regulatory lymphocytes
		Defective suppression of immune activation
		Tissue damage
	Initiation and facilitation of autoimmunity
		Noninfectious environmental triggers
		Diet and gut microbiome
		Infectious triggers
		Genetics and epigenetics
	Multisystem autoimmune diseases
		Systemic lupus erythematosus
		Rheumatoid arthritis
		Juvenile idiopathic arthritis
		Systemic sclerosis
		Spondyloarthropathies
		Sjogren’s disease
		Autoimmune myopathies
		Antiphospholipid syndrome
		Immunoglobulin G4-related disease
	System-specific autoimmune diseases
		Nervous system
			Multiple sclerosis
			Myasthenia gravis
			Guillain barre´ syndrome
		Endocrine system
			Autoimmune thyroiditis
			Graves’ disease
			Autoimmune diabetes
		Gastrointestinal system
			Autoimmune gastritis and pernicious anemia
			Autoimmune hepatitis
		Blood disorders
			Autoimmune hemolytic anemia
			Immune thrombocytopenia
		Cardiovascular system
			Rheumatic fever and rheumatic heart disease
	Future perspectives and concluding remarks
	References
Chapter 4 - Tumor immunology
	Introduction
	Cancer immunoediting
	Immune profiles in malignancy
	Cancer antigens and cancer antigen presentation
		Antigen presentation machinery
		Cancer cell antigenicity
		Cancer antigen categories
	Immunity to cancer
		T cells
			Basic immunobiology of T cells
			Activation, recruitment and the effector functions of T cells in tumor setting
		B cell and immunoglobulin
		NK cells
		Macrophages
	The interaction of immune system with other components of TME
	Evading immune destruction and immune escape mechanisms
	Immune regulation of cancer progression and metastasis
	Immunolopathology and immunotherapy of hematologic malignancies
		Immunopathology
			Lymphoma
			Leukemia
			Multiple myeloma (MM)
		Immunotherapies
			Immune checkpoint inhibitors (ICIs)
			Chimeric antigen receptor T-cell therapies
			Bispecific T cell engagers
			Cancer vaccines
		Antibodies against clusters of differentiation
		Future perspective
	Immunolopathology and immunotherapy of central nervous system tumors
		Immunopathology
		Immunotherapies
			Immune checkpoint inhibitors (ICIs)
			Cancer vaccines
			Other immunotherapies
		Future perspective
	Immunolopathology and immunotherapy of head and neck cancers
		Immunopathology
		Immunotherapies
			Immune checkpoint inhibitors (ICIs)
			Other immunotherapies
		Future perspective
	Immunolopathology and immunotherapy of respiratory system cancer
		Immunopathology
		Immunotherapies for non-small cell lung cancer
			Immune checkpoint inhibitors (ICIs)
			Other immunotherapies
		Immunotherapies for small cell lung cancer
			Immune checkpoint inhibitors (ICIs)
			Other therapies
		Immunotherapies for mesothelioma
			Immune checkpoint inhibitors (ICIs)
			Other immunotherapies
	Immunolopathology and immunotherapy of breast cancer
		Immunopathology
		Immunotherapies
			Immune checkpoint inhibitors (ICIs)
			Other immunotherapies
		Future prospective
	Immunolopathology and immunotherapy of gastrointestinal system cancers
		Immunopathology
			Esophageal cancers
			Gastric cancer
			Colorectal and anal cancer
			Hepatobiliary and pancreatic cancers
		Immunotherapies for esophageal and gastric cancers
			Immune checkpoint inhibitors (ICIs)
			Other immunotherapies
		Immunotherapies for colorectal cancers
			Immune checkpoint inhibitors (ICIs)
			Other immunotherapies
		Immunotherapies for hepatocellular carcinoma
			Immune checkpoint inhibitors (ICIs)
			Other immunotherapies
		Immunotherapies for pancreatic cancers
			Immune checkpoint inhibitors (ICIs)
			Vaccine therapies
			Other immunotherapies
	Immunolopathology and immunotherapy of endocrine system cancers
		Immunopathology
		Immunotherapies for thyroid cancers
		Future perspective
	Immunolopathology and immunotherapy of urinary system cancers
		Immunopathology
			Kidney cancer
			Bladder cancer
		Immunotherapies for renal cell carcinoma
			Immune checkpoint inhibitors (ICIs)
			Future perspective
		Immunotherapies for bladder cancer
			Immune checkpoint inhibitors (ICIs)
			Future perspective
	Immunolopathology and immunotherapy of skin cancers
		Immunopathology
		Immunotherapies
			Immune checkpoint inhibitors (ICIs)
			Oncolytic viruses
			Interferon-α
			Interleukins
			Other immunotherapies
		Future perspective
	Immunolopathology and immunology of soft tissue and bone cancers
		Immunopathology
		Immunotherapies
			Immune checkpoint inhibitors (ICIs)
			Cancer vaccines
			Adoptive cell therapy
			Other immunotherapies
		Future perspective
	Immunolopathology and immunotherapy of cancers of men reproductive system
		Immunopathology
		Immunotherapies for prostate cancer
			Immune checkpoint inhibitors (ICIs)
			Vaccines
		Immunotherapies for testicular cancer
		Future perspective
	Immunolopathology and immunotherapy of cancers of women reproductive system
		Immunopathology
		Immunotherapies for ovarian cancer
			Immune checkpoint inhibitors (ICIs)
			Other immunotherapies
		Immunotherapies for cervical cancer
			Immune checkpoint inhibitors (ICIs)
			Cancer vaccines
			Adaptive cell therapies
		Future perspective
	Immunotherapy in combination with other therapeutic approaches
	Tumor immune microenvironment (TIME) after other therapeutic approaches
		TIME Post-Chemotherapy
		TIME post-radiation therapy
	Immune regulation of therapeutic-resistance
		Chemo-resistance
			Role of macrophages in environment-mediated drug resistance
		Radio-resistance
	Immune regulation of therapeutic-induced relapse
		Therapy induces a dual tumor-host inflammatory response
		Loco-Regional relapse
			Angiogenesis
			Immune escape and proliferation
		Distant relapse
			At the primary site
			At distant sites
	References
Chapter 5 - Immunodeficiencies
	Introduction
	Initial screening of patients with immunodeficiencies
	Inborn errors of immunity (IEIs)
	Humoral immunodeficiencies
		X-linked agammaglobulinemia (XLA)
			Definition
			Clinical manifestations and diagnosis
			Treatment
		Autosomal recessive agammaglobulinemia
		Hyper IgM syndrome (HIGM)
			Definition
			Classification
				Type I hyper IgM (HIgM1)
				Hyper IgM due to the NEMO mutation
				Type II hyper IgM (HIgM2)
				Type III hyper IgM (HIgM3)
				Type IV hyper igm (HIgM4)
				Type V hyper igm (HIgM5)
			Treatment
		Selective IgA deficiency
			Definition
			Clinical manifestations and diagnosis
			Treatment
		Selective IgG deficiency
			Definition
			Clinical manifestations and diagnosis
			Treatment
		Common variable immunodeficiency (CVID)
			Definition
			Clinical manifestations and diagnosis
			Treatment
		Laboratory assays for humoral immunity deficiencies
	Cellular immunodeficiencies and combined immunodeficiencies
		Di george syndrome
			Definition
			Clinical manifestations and diagnosis
			Treatment
		Severe combined immunodeficiencies (SCID)
			SCID caused by gamma chain mutation
			SCID caused by defects in adenosine deaminase (ADA)
			SCID caused by defects in purine nucleoside phosphorylase (PNP)
			SCID caused by mutation in RAG1 and RAG2
			SCID caused by defects in interleukin-7 receptor a (IL-7Ra)
			SCID caused by defects in CD45
			SCID caused by defects in CD3σ, CD3ε, and CD3ζ
			SCID caused by defects in ZAP70
			SCID caused by defects in JAK3
			SCID caused by defects in ORAI1 and STIM1
			SCID caused by defects in adenylate kinase 2 (Reticular dysgenesis)
			Treatment
		Wiskott-aldrich syndrome
			Definition
			Clinical manifestations and diagnosis
			Treatment
		Ataxia-telangiectasia
			Definition
			Clinical manifestations and diagnosis
			Treatment
		X-linked lymphoproliferative syndrome (XLP)
			Definition
			Clinical manifestations and diagnosis
			Treatment
		Familial homophagocytosis lymphohistocytosis syndrome (FHL)
			Definition
				Clinical manifestations and diagnosis
				Treatment
		Autoimmune lymphoproliferative syndrome (ALPS)
			Definition
			Clinical manifestations and diagnosis
			Treatment
		Immune dysregulation- Polyendocrinopathy-enteropathy-x-linked syndrome (IPEX)
			Definition
			Clinical manifestations and diagnosis
			Treatment
		Bare lymphocyte syndrome
			Definition
			Clinical manifestations and diagnosis
			Treatment
		Laboratory assays for cellular immunity deficiencies
	Innate immunity immunodeficiencies
		Leukocyte adhesion deficiency (LAD)
			Definition
				Leukocyte adhesion deficiency i (LADI)
				Leukocyte adhesion deficiency ii (LADII)
				Leukocyte adhesion deficiency III (LADIII)
			Clinical manifestations and diagnosis
			Treatment
		Chronic granulomatosis disease (CGD)
			Definition
			Clinical manifestations and diagnosis
			Treatment
		Chediak-higashi syndrome
			Definition
			Clinical manifestations and diagnosis
			Treatment
		Neutropenia
			Definition
			Classification
				Cyclic neutropenia
				Treatment
				Severe congenital neutropenia (SCN)
				Treatment
					Shwachman-diamond syndrome
					Dyskeratosis congenita
				Treatment
					Neutropenia caused by infections
					Drug-induced neutropenia
				Treatment
			Clinical manifestations and diagnosis
		Hyper-IgE syndrome
			Definition
			Clinical manifestations and diagnosis
			Treatment
		Defects in toll-like receptor (TLR) signaling pathway
			Definition
			Classification
				IRAK-4 and myd88 deficiency
				Treatment
				IκBα and NEMO (IKKγ) deficiency
				Treatment
					HOIL-1 deficiency
					Deficiency in TLR3 signaling and UNC-93B
				Treatment
		Defects in IFN-γ/IL-12 pathway
			Definition
			Treatment
		Defects in complement system
			Definition
			Clinical manifestations and diagnosis
			Treatment
	References
Chapter 6 - Infection and Immunity
	Introduction
	Bacterial infections
		Definition
		Mechanisms
			Innate immunity
				Inflammasomes
					An overview of inflammasomes
					NLRP3
					Other NLRPs: NLRP1b, NLRP6, NLRP7, NLRP10, and NLRP12
					NLRC4
					Absent in melanoma 2 (AIM2)
				TLRs
				Other mechanisms
					Immune evasion by bacteria after invasion
			Adaptive immunity
				Cellular immunity
				Humoral immunity
				Other mechanisms
					Sepsis
					Central nervous system infections
					MicroRNAs
		Diagnosis
			Helicobacter pylori
			Yersinia
			Salmonella
			Shigella
			Campylobacter
		Treatment
			Targeting innate immune receptors
				TLR modulating therapies
				NOD-like receptors modulating therapies
			Targeting immune checkpoints
				Programmed cell death protein (PD)-1
				T cell immunoglobulin and mucin domain-containing protein 3 (Tim-3)
			Cytokine modulation therapies
			mAbs
	Fungal infections
		Definition
			Respiratory allergy
			Skin diseases
			Recurrent vulvovaginal candidiasis
			Inflammatory bowel disease (IBD)
			Invasive fungal infections
		Mechanisms
			Innate immunity
				Inflammasomes
				TLRs
				CLRs
			Adaptive immunity
				Cellular immunity
				Humoral immunity
			Other mechanisms
				Interconnecting the innate and adaptive immunity
		Diagnosis
			Candidiasis
			Blastomycosis
			Coccidiomycosis
			Histoplasmosis
			Paracoccidioidomycosis
			Penicillinosis
			Mucormycosis
		Treatment
			Adoptive T-cell therapy
			Chimeric antigen receptor (CAR) T-cells
			Granulocyte transfusion
			DCs therapy
			NK cell therapy
			Granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF)
			Cytokine therapy
	Parasitic infections
		Definition
		Mechanisms
			Innate immunity
				Inflammasomes
				TLRs
				Other mechanisms
					Other innate immune receptors
			Adaptive immunity
				Cellular immunity
				Humoral immunity
			Immune escape mechanisms
				Passive
				Active
		Diagnosis
			Falcon assay screening test-elisa (FAST-ELISA)
			Dot-ELISA
			Rapid diagnostic tests (RDTs)
			Luciferase immunoprecipitation system (LIPS)
		Treatment
			Leishmaniasis
			Cryptosporidiosis
			Malaria
			Trypanosomiasis
			Toxoplasmosis
			Trichomoniasis
			Schistosomiasis
	Viral infections
		Definition
		Mechanisms
			Innate immunity
				Inflammasomes
					NLRP3
					NLRP1
					AIM2
					TLRs
			Adaptive immunity
				Cellular immunity
				Humoral immunity
		Diagnosis
			Advanced serological immunoassays
			ELISA-based detection
			Immunofluorescence-based immunodetection
			mAb-based immunodetection
			Hemagglutination inhibition (HI) assay
		Treatment
			Interferons
			Cellular therapies
			Vaccines
	References
Chapter 7 - Transplantation
	Introduction
	Solid organ transplantation (SOT)
		Sources
			Autologous/allogeneic
			Deceased/live donor
		Kidney transplantation
		Liver transplantation
		Heart transplantation
		Lung transplantation
		Other
	Hematopoietic stem cell transplantation (HSCT)
		Indications
			Adults
				Acute myeloid leukemia (AML)
				Acute lymphoblastic leukemia (ALL)
				Chronic myeloid leukemia (CML)
				Myeloproliferative disorders other than CML
				Myelodysplastic syndromes (MDS)
				Chronic lymphocytic leukemia (CLL)
				Lymphomas
				Diffuse large B cell lymphoma (DLBCL)
				Follicular lymphoma
				Waldenström’s macroglobulinemia (lymphoplasmacytic lymphoma with IgM gammopathy; WM)
				Mantle cell lymphoma (MCL)
				T cell lymphomas
				Hodgkin lymphoma
				Multiple myeloma (MM)
				Systemic immunoglobulin-light-chain amyloidosis
				Acquired severe aplastic anemia
				Constitutional severe aplastic anemia
				Solid tumors
				Autoimmune diseases
			Children and adolescents
				Acute myeloid leukemia (AML)
				Acute lymphoblastic leukemia (ALL)
				Chronic myeloid leukemia (CML)
				MDS and juvenile myelomonocytic leukemia
				Lymphoma
				Inherited diseases
					Primary immunodeficiencies (PID)
					Metabolic diseases
					Hemoglobinopathies
					Osteopetrosis
					Acquired severe aplastic anemia and inherited bone marrow failure syndromes
					Solid tumors
					Autoimmune diseases
		Sources
			Autologous/allogeneic/syngeneic
			Peripheral blood/bone marrow/umbilical cord blood/amniotic fluid
		Establishment process
			Homing/engraftment/repopulation/reconstitution
	Transplantation immunopathogenesis
		The role of cellular immunity
			T cell expansion and repertoire formation
			Notch signaling
			Treg activation
			Memory T cells
			Natural killer T cells
		The role of humoral immunity
			Innate B cells/natural Abs
			Donor specific antibodies (DSA)
			Anti-donor memory B cells
		The role of NK cells, DCs, neutrophils, macrophages, and toll-like receptors
		The role of complement activation
		The role of cytokine level and polymorphisms
	Matching
		HLA compatibility
		Desensitization
		Tolerance induction
	Pre-transplantation conditioning
		Hematopoietic stem cell transplantation
			High-dose conditioning regimens
			Reduced-intensity and non-myeloablative conditioning regimens
				Common reduced-intensity conditioning regimens
				Common non-myeloablative regimens
			Radioimmunotherapy-based regimens
	Complications
		Graft failure
		Graft rejection
			Antibody-mediated rejection (AMR)
			T cell-mediated rejection (TCMR)
		GVHD
		Change in immunosurveillance
			Malignancies
			Lymphoproliferative disease (LPD)
		Infections
		Autoimmune diseases
		Organ-dependent complications
			Kidney transplantation
			Liver transplantation
			Heart transplantation
		Allergies
		Other complications
	Post-transplantation therapy
		Maintenance therapy
		Prophylaxis
	Future directions and concluding remarks
	References
Index
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