Immunology for Life Scientists, 2nd Edition

Preface.

Preface to the 1st Edition.

Glossary.

1 Cells and tissues of the immune system.

1.1 Cells involved in the immune response.

1.1.1 Cellular origins – the pluripotent stem cell.

1.1.2 Cells principally involved in the innate immune response.

Polymorphonuclear leukocytes.

Neutrophils.

Eosinophils.

Basophils and mast cells.

Megakaryocytes and platelets.

1.1.3 Antigen presenting cells and large granular lymphocytes.

Monocytes and macrophages.

Dendritic cells.

Large granular lymphocytes.

1.1.4 Cells involved in the specific immune response.

Lymphocytes.

T cells.

B cells.

Key points for review.

1.2 Lymphoid tissues.

1.2.1 Primary lymphoid tissues.

The thymus.

Mammalian "bursa equivalents".

B cell development in the bone marrow.

1.2.2 Secondary lymphoid tissues.

The lymphatic system.

Lymph nodes.

Spleen.

1.2.3 Tertiary lymphoid tissues.

Mucosa-associated lymphoid tissue.

Intraepithelial lymphocytes.

Key points for review.

Bibliography.

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2 Antigens and their receptors.

2.1 Characteristics of antigens and immunogens.

2.1.1 Factors affecting immunogenicity.

Foreignness.

Size.

Chemical complexity.

Route of administration.

Dose.

Host genetic make-up.

Approaches used to increase immunogenicity.

Key points for review.

2.2 The major histocompatibility factor.

2.2.1 Class I MHC molecules.

2.2.2 Class II MHC molecules.

2.2.3 Non-classical HLA molecules.

Key points for review.

2.3 Antigen receptors on cells.

2.3.1 The B cell antigen receptor.

Immunoglobulins.

Antibody structure.

Isotypes.

Allotypes.

Idiotypes.

2.3.2 Antibody classes.

Immunoglobulin G.

Immunoglobulin M.

Immunoglobulin A.

Immunoglobulin D.

Immunoglobulin E.

2.3.3 Antibody function.

2.3.4 Fc receptors.

2.3.5 The T cell antigen receptor.

g d T cells.

The CD3 complex.

Function of the TCR–CD3 complex.

2.3.6 The natural killer cell receptor.

Key points for review.

2.4 Generation of antigen receptor diversity.

2.4.1 Theories concerning antibody diversity.

2.4.2 The genetic basis of antibody diversity

V, D and J region heavy chain genes.

The light chain V and J genes.

2.4.3 Generation of antibody diversity.

Combinatorial and junctional diversity.

Control of VDJ gene rearrangement.

Mechanisms of V(D)J rearrangement.

Diversity due to somatic mutation.

2.4.4 Antibody maturation.

2.4.5 Genetic basis of T cell antigen receptor diversity.

"Similarity to self rule" – limited diversity.

Diverse TCR repertoire.

Genomic organisation – the TCRa chain.

Genomic organisation – the TCRb chain.

Genomic organisation – the TCRg chain.

Genomic organisation – the TCRd chain.

2.4.6 Generation of T cell antigen receptor diversity.

Size of the T cell repertoire.

Key points for review.

Bibliography.

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3 The innate immune response.

3.1 The complement cascades.

3.1.1 The classical complement pathway.

C1.

C4.

C2.

C3.

3.1.2 The alternative complement pathway.

3.1.3 The lectin pathway.

3.1.4 The membrane attack complex.

3.1.5 Regulation of complement activation.

C1 inhibitor (C1INH).

Regulators of complement activation (RCA) family.

Regulators of the membrane attack complex.

Key points for review.

3.2 Phagocytosis.

3.2.1 Pattern recognition receptors.

Complement receptor 3 (CR3).

CD14.

Toll-like receptors.

Macrophage scavenger receptors.

3.2.2 Opsonisation.

3.2.3 Ingestion.

3.2.4 Digestion.

3.2.5 The respiratory burst.

3.2.6 Other antimicrobial activities of lysosomes.

Defensins.

Key points for review.

3.3 Inflammation.

3.3.1 Inflammatory mediators.

3.3.2 Cellular responses in inflammation.

3.3.3 Chemokines.

Key points for review.

3.4 Haemostasis and thrombosis.

3.4.1 Regulation of coagulation.

3.4.2 The fibrinolytic system.

Key points for review.

Bibliography.

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4 The adaptive immune response.

4.1 Antigen processing and presentation by MHC gene products.

4.1.1 Generation of peptides presented by MHC Class I molecules.

Assembly and intracellular transport of MHC Class I molecules.

4.1.2 Generation of peptides presented by MHC Class II molecules.

Assembly and intracellular transport of MHC Class II molecules.

Key points for review.

4.2 Antigen processing and presentation by CD1.

4.2.1 Structure of CD1.

4.2.2 Antigen presentation by CD1.

Key points for review.

4.3 Cell-mediated immunity.

4.3.1 Antigen-specific T cell stimulation.

T cell responses to antigen stimulation.

Th₀, Th₁ and Th₂ cells.

4.3.2 Other cells in cell-mediated immunity.

Mechanisms of target cell death.

Cytotoxic T cells.

Macrophages.

NK cells.

Key points for review.

4.4 Cell adaptive immunity.

4.4.1 B cell differentiation and antibody production.

Class switching.

Key points for review.

4.5 Lymphocyte memory.

Key points for review.

4.6 The mucosal immune response.

4.6.1 Structure of the mucosal immune system.

Organised mucosal lymphoid tissue.

Intraepithelial cells.

Leukocytes in the lamina propria.

4.6.2 Immunoglobulins and mucosal immunity.

Production of other immunoglobulins in the mucosa.

4.6.3 The mucosae and their role in immunity.

Key points for review.

4.7 Tolerance.

4.7.1 Lymphocyte tolerance.

Induction time.

Antigen dose.

Antigen persistence.

Specificity.

Duration.

Route of administration.

Tissue specificity.

4.7.2 Mechanisms of tolerance induction.

Clonal deletion.

Clonal anergy.

Clonal exhaustion.

Clonal abortion.

Antibody forming cell (AFC) blockade.

4.7.3 Maintenance of tolerance.

Regulatory T cells.

Antibody-induced tolerance.

4.7.4 Mechanisms involved in the development of incomplete tolerance.

Key points for review.

Bibliography.

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5 Abnormalities of the immune system.

5.1 Hypersensitivity.

5.1.1 Hypersensitivity reactions.

5.1.2 Type I hypersensitivity.

Regulation of Type I hypersensitivity.

Humoral events in allergy.

5.1.3 Type II hypersensitivity.

5.1.4 Type III hypersensitivity.

5.1.5 Type IV hypersensitivity.

Tuberculin-type DTH.

Granuloma formation.

Contact hypersensitivity.

Key points for review.

5.2 Autoimmunity and autoimmune diseases.

5.2.1 Causes of autoimmunity.

Genetic factors in autoimmune disease.

Sex-linked factors in autoimmune disease.

Stress and neurochemicals in autoimmune disease.

Chemicals and pharmaceuticals in autoimmune disease.

Viruses in autoimmune disease.

Antigen mimicry.

5.2.2 Classification of autoimmune disease.

5.2.3 Immunopathology of autoimmune diseases.

5.2.4 The immunology of autoimmune disease.

Target antigens.

Non-specific immunity in autoimmune disease.

Mononuclear phagocytes in non-specific immunity.

Mononuclear phagocytes in specific immunity.

Dendritic cells in autoimmune disease.

Role of T cells in autoimmune disease.

B cells in autoimmune disease.

Cytokine defects.

Chemokines in autoimmune disease.

Key points for review.

5.3 Immunodeficiency diseases.

5.3.1 Classification of immunodeficiency diseases.

5.3.2 Primary immunodeficiency diseases.

5.3.3 B cell abnormalities.

Selective immunoglobulin A deficiency.

X-linked agammaglobulinaemia (XLA).

CD40 ligand deficiency.

X-linked lymphoproliferative disease (Duncan’s syndrome).

5.3.4 T cell abnormalities.

Congenital thymic aplasia (Di George syndrome).

Wiskott–Aldrich syndrome.

5.3.5 T and B cell abnormalities.

Severe combined immunodeficiency disease (SCID).

X-linked severe combined immunodeficiency disease (XSCID).

SCID with adenosine deaminase deficiency (ADA-SCID).

The bare lymphocyte syndrome.

5.3.6 Abnormalities associated with phagocytic cells.

Chediak–Higashi syndrome (CHS).

Chronic granulomatous disease (CGD).

5.3.7 Abnormalities of the complement pathway.

Deficiencies of complement components.

The alternative pathway.

The classical pathway.

C1INH deficiency – hereditary angioedema (HAE).

5.3.8 Acquired immunodeficiencies.

Iatrogenic immunodeficiencies.

5.3.9 The acquired immunodeficiency syndrome (AIDS).

The human immunodeficiency virus (HIV).

Key points for review.

Bibliography.

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6 Infection, immunity, immunopathogenesis.

6.1 The innate immune system in infection.

6.1.1 The skin.

6.1.2 The mucosae.

6.1.3 Protective chemicals.

Lysozyme.

Alimentary fluids.

Complement.

Defensins.

Natural antibodies.

6.1.4 The role of normal body flora.

Key points for review.

6.2 Infection – the role of the innate immune system.

6.2.1 Attachment.

6.2.2 The body’s response to invasion – fever.

6.2.3 Cells involved in innate immunity in infection.

Phagocytic cells.

Natural killer cells.

Platelets.

6.2.4 Inflammation and immunopathology.

Endotoxin.

Endotoxin-induced injury.

Key points for review.

6.3 Infection – the role of the specific immune response.

6.3.1 Intracellular pathogens and fungi.

6.3.2 Parasitic infections.

6.3.3 The role of antibody in immunity to infection.

Opsonisation.

Complement activation.

Inhibition of adherence.

Toxin neutralisation.

Virus neutralisation.

Inhibition of microbial enzyme activity.

Inhibition of microbial growth.

6.3.4 Pathology due to specific antibody.

Polyclonal B cell activation.

Immune complex formation.

6.3.5 T cell-mediated immunity.

Parasitic infections.

Viral infections.

Th₁ and Th₂ cells.

Cytotoxic T cell activity.

Cytolytic mechanisms.

6.3.6 Pathology caused by the cell-mediated immune response.

Key points for review.

6.4 Cytokines in immunity to infection.

Key points for review.

Bibliography.

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7 Immunity and the MHC.

7.1 Transplantation.

7.1.1 Tissue typing.

7.1.2 Cross-matching.

7.1.3 Rejection.

Direct allorecognition.

Indirect allorecognition.

Mechanisms involved in hyperacute rejection.

Mechanisms involved in acute rejection.

Mechanisms involved in chronic rejection.

The role of the graft endothelium in rejection.

7.1.4 Kidney transplantation.

Pre-sensitisation.

Cadaveric kidney transplantation.

7.1.5 Liver transplantation.

Procedure.

Primary non-function and rejection.

7.1.6 Heart transplantation.

Rejection.

7.1.7 Bone marrow transplantation.

7.1.8 Pancreas transplantation.

7.1.9 Xenotransplantation.

Choice of donor.

Barriers to xenotransplantation.

Key points for review.

7.2 The immunology of reproduction.

7.2.1 The development of maternal and foetal tissues.

7.2.2 Female reproductive immunology.

7.2.3 Maternal–foetal exchange.

7.2.4 Effect of pregnancy on the maternal immune response.

Peripheral immunity.

Foetal–uterine immunity.

7.2.5 Cytokine–endocrine relationship in pregnancy.

Oestrogen and progesterone.

Human chorionic gonadotrophin.

7.2.6 Immunity to infection in pregnancy.

7.2.7 Immunocompetent cells in the decidua.

Large granular lymphocytes.

Macrophages.

Decidual antigen presenting cells.

T lymphocytes.

7.2.8 Recurrent, spontaneous, abortion

7.2.9 The immunology of male reproduction.

The blood–testis barrier.

Sperm-specific antigens.

Immunologically active cells in semen.

Key points for review.

Bibliography.

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8 Other diseases.

8.1 Atherosclerosis.

8.1.1 Normal arterial wall.

8.1.2 Extracellular matrix.

8.1.3 Pathogenesis of atherosclerosis.

Role of lipoproteins in atherosclerosis.

8.1.4 Plaque development.

8.1.5 Mononuclear cells in atherosclerosis – macrophages and dendritic cells.

8.1.6 Mononuclear cells in atherosclerosis – T cells.

8.1.7 Mononuclear cells in atherosclerosis – B cells.

8.1.8 Other immune cells in atherosclerotic plaques.

8.1.9 Cytokines in atherosclerosis.

8.1.10 Is atherosclerosis an autoimmune disease?

Potential autoantigens.

8.1.11 Infection and atherosclerosis.

Key points for review.

8.2 Tumour immunology.

8.2.1 The nature of malignant disease.

8.2.2 Causes of malignancy.

Physical carcinogens.

Chemical carcinogens.

Viral carcinogens.

Oncogenes.

8.2.3 Tumour antigens.

Melanoma–melanocyte differentiation antigens (MMDAs).

Cancer testes antigens (CTAs).

Renal carcinoma antigen.

Non-mutated shared antigens.

Mutated antigens.

8.2.4 Tumour suppressor gene – oncogene networks.

8.2.5 Tumour immunology.

Innate immunity.

Inflammation and the development of cancer.

Specific immunity.

Tumour cell evasion of the immune response.

8.2.6 Cancer biotherapy.

Anti-tumour vaccines.

Anti-idiotypic antibodies.

Biological response modifiers (BRM).

Key points for review.

Bibliography

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Index.