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`SIXTH EDITION
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`ESSENTIAL
`IMMUNOLOGY
`
`Ivan M. Roitt
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`MA, DSc(Oxon), FRCPath, Hon MRCP (Lond), FRS
`Professo r and Head of
`Departm ents of Immunology and Rh euma tology Research
`Unive rsity College n11d Mirldlesex Scli ool of Medicine
`Univ e1:sity College
`London WlP 9PC
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`BLACKWELL SCIENTIFIC PUBLICATIONS
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`OXFORD LONDON EDINBURGH
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`BOSTON PALO ALTO MELBOURNE
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`Hopewell EX1044
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`vi
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`lmmun oglobulin classes and s ubclasses, 40
`Immunoglobulin G , 40
`Immunoglob ulin A, 40
`Immunoglobu lin M , 41
`Immunoglobulin D, 43
`Immunoglobulin E, 43
`lmmunoglobulin s ubclasses, 43
`The major histocompatibility complex (MHC), 43
`Class I and class II molecules are me mbrane-bound
`heterodimers, 43
`Gene map of the major histocompatibility complex, 44
`The genes of the MHC display remarkable polymorphism ,
`44
`Nomenclature, 46
`Inheritance of the MHC , 47
`The tissue distribution of MHC molecules, 47
`MHC functions , 47
`The T-cell receptor, 48
`The generation of diversity for antigen recognition, 49
`Multiple gene segments code for antibody, 49
`A similar pattern of genes codes for the T-cell receptor, 50
`The mechanisms which generate tremendous diversity from
`limited gene pools, 50
`Intrachain amplification of diversi ty, 50
`Interchain amplification, 52
`Somatic h ypermutation , 52
`Summary, 53
`Further reading, 54
`
`4 · THE RECOGNITION OF ANTIGEN
`I - Primary Interaction
`
`the bonu s effect of
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`What is an antigen?, 55
`Of epitopes and antigen determinants, 55
`Antigens and antibodi es interact by s patial comple mentarity
`not by covalent bonding, 56
`The forces binding ant igen to antibody beco me large as
`intermolecu lar distances beco m e small, 58
`The affinity or s trength of binding of antigen and ant ibody ,
`60
`The avid ity of ant ise rum for antige n -
`multivalency, 61
`The specificity of antigen recognition by ant ibody is not
`absolute, 63
`What th e T-cell sees, 64
`Haplotype restri ction revea ls the need for MHC
`participation, 64
`Do T-cell s see ' processed' antigen 7, 64
`Does s pecificity imply dua l T-cell rece ptors?, 66
`Do MHC and nomina l an ti gen interact positively to fo rm
`a complex 7, 66
`Features associated with an ti genicity, 67
`Summary, 68
`Further read ing, 68
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`5 · THE RECOGNITION OF ANTIGEN
`II - Detection and Application
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`Visualization of the preci pita ti on reaction in gels, 69
`Indirect precipitation of comp lexes, 73
`Agglutination by antibody, 74
`Purification of antige ns and antibod ies by affinity
`chromatography, 76
`Immunoassay of antigen a nd antibody with labelled
`reagents, 76
`A w ide variety of labels is available, 76
`Soluble phase immunoassays, 76
`Solid phase immunoassays, 76
`Immunoblotting (Weste rn blots), 78
`Immunohistochemistry -
`loca li za tion of antigens in cells
`and tissues, 79
`Immunofluorescence, 79
`Reaction with cell s urface antigens, 80
`Other labelled a ntibody methods, 81
`Cell separation techniqu es, 81
`Neutralization of biologi cal activity, 83
`Summary, 84
`Further reading, 84
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`6 · THE ACQUIRED IMMUNE
`RESPONSE
`I - Consequences of Antigen Recognition
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`Where does it all happen?-The anatomy of the immune
`response, 85
`Lymph node, 85
`B-cell areas, 86
`T-cell areas, 86
`Lymphocyte traffi c, 87
`Spleen , 87
`Mucosa I-associated lymphoid tissue, 87
`Bone marrow can be a major site of antibody synth es is, 87
`Where does antigen go?, 88
`The activation ofT-cells, 92
`T he su rface markers of immunocompetent T- and
`B-ly mphocytes, 92
`The acti va tion of T-cells req uires two signals, 94
`The activation of B-cells, 94
`B-cells res pond to three different types of antigen, 94
`1. Type 1 th ym us-ind epe nd e nt antigens, 94
`2. Type 2 thymus-indepe nd ent antigens, 95
`3. Thymus-dependent a ntige ns -
`the need for
`col laboration with T-helpe r cell s, 95
`The nature of B-cell activation, 96
`Clona l ex pan s ion is ac hi eved by T-cell solubl e factors , 98
`Furth er T-cell fa ctors bring about maturation of effector
`ce ll s, 98
`Summary, 99
`Furthe r reading, 100
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`7 · THE ACQUIRED IMMUNE
`. RESPONSE
`II - Production of Effectors
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`Precipitation , 69
`Th e classica l precipitin reacti on, 69
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`The synthesis of humoral antibody, 101
`De tection a nd enum eration of antibody-forming cells, 101
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`CONTENTS
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`this situation. These polymorphonuclear 'cousins'
`of the neutrophil have distinctive gran ul es which
`stain avidly with acid dyes (figure 1.3) and have a
`characteristic appearance in the electron microscope
`(figure 10.15). A major basic protein (MBP) is local(cid:173)
`ized in the core of the granules while an eosino(cid:173)
`philic cationic protein together with a peroxidase
`have been identified in the granule matrix. Other
`enzymes include arylsulphatase B, phospholipase D
`and histaminase. They have surface receptors for
`C3b and on activation produce a particularly im(cid:173)
`pressive respiratory burst with concomitant genera(cid:173)
`tion of active oxygen metabolites. As if that were
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`not e nough, it has recently been demonstrated that
`one of the granule proteins can produce a trans(cid:173)
`membrane plug in the target membrane like C9 and
`the NK perforin .
`the alternative
`Most helminths can activate
`complement pathway, but although resistant to C9
`attack, their coating with C3b allows adherence of
`eosinophils through their C3b receptors. Upon
`activation, the eosinophil launches its extracellular
`attack which includes the release of MBP and
`especially the cationic protein which damages the
`parasite membrane.
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`14
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`CHAPTER l
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