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IMMUNOLOGY
FOR MEDICAL STUDENTS
NOTE TO INSTRUCTORS:
Contact your Elsevier Sales Representative for teach-
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IMMUNOLOGY
FOR MEDICAL STUDENTS
THIRD EDITION

MATTHEW HELBERT, MBChB, FRCP, FRCPath, PhD

Consultant Immunologist
Yorkshire, United Kingdom
1600 John F. Kennedy Blvd.
Ste 1800
Philadelphia, PA 19103-2899

IMMUNOLOGY FOR MEDICAL STUDENTS, THIRD EDITION ISBN: 978-0-7020-6801-0

Copyright © 2017 by Elsevier Limited. All rights reserved.

No part of this publication may be reproduced or transmitted in any form or by any means, electronic or
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This book and the individual contributions contained in it are protected under copyright by the Publisher (other
than as may be noted herein).

Notices

Knowledge and best practice in this field are constantly changing. As new research and experience broaden our
understanding, changes in research methods, professional practices, or medical treatment may become
necessary.
Practitioners and researchers must always rely on their own experience and knowledge in evaluating and
using any information, methods, compounds, or experiments described herein. In using such information or
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Previous editions copyrighted © 2007, 2002 by Mosby, an imprint of Elsevier, Inc.

Library of Congress Cataloging-in-Publication Data

Names: Helbert, Matthew, author. | Nairn, Roderick. Immunology for medical students. Preceded by (work):
Title: Immunology for medical students / Matthew Helbert.
Description: Third edition. | Philadelphia, PA : Elsevier, [2017] | Preceded by: Immunology for medical
students / Roderick Nairn, Matthew Helbert. 2nd ed. c2007. | Includes index.
Identifiers: LCCN 2016008040 | ISBN 9780702068010 (pbk. : alk. paper)
Subjects: | MESH: Immune System Phenomena
Classification: LCC QR181 | NLM QW 504 | DDC 616.07/9—dc23 LC record available at http://lccn.loc.gov/
2016008040

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Senior Content Development Specialist: Joanie Milnes
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Senior Project Manager: Carrie Stetz
Design Direction: Ryan Cook

Printed in China

Last digit is the print number: 9 8 7 6 5 4 3 2 1


■ PREFACE TO THE THIRD EDITION
This book continues to be focused on meeting the needs of
medical students. I have concentrated on a simple, straightfor-
ward treatment of immunology, reflecting an acknowledgment
of the time constraints in today’s curricula.
Immunology is one of the most rapidly developing medical
sciences and, to respond to this, considerable new material has
been added to this book, including regulation of the immune
system, T-cell subsets, and epigenetics. There is also new material
on some of the recent technical developments, notably vaccines,
biopharmaceuticals, and screening and diagnostic tests. These
technologies are already widely adopted, and some familiarity
will be important for all medical students. New clinical vignettes
have been added that focus on everyday clinical material. Mate-
rial that, over time, has lost some of its impact on clinical
practice has been reduced in this edition (eg, allelic exclusion,
gene rearrangement studies to diagnose lymphoma, tetramers).
Medical students face two specific problems with immunol-
ogy. First, the immune system is complex because it has evolved
to respond to a wide range of pathogens. Many students find
themselves bogged down in the complexities of the molecules
and cells of the immune system without having an understand-
ing of how these components work together to fight infection.
We begin our book with two overview chapters that explain
what the immune system does and then how the components
fit together. We recommend that students begin by reading these
chapters. Further on in the text, there are more short, integrating
overview chapters. These are not just for review, but to make
sure that students understand how the material that they have
read fits into the overall system. The second problem is that
medical students do not always immediately see the relevance of
immunology to day-to-day clinical practice. We have included
clinical correlations throughout the text that explain how under-
standing the science of immunology can translate into under-
standing real clinical problems.
2016 M.H.
■ PREFACE TO THE SECOND EDITION
In preparing this edition, we have made improvements through-
out to improve the clarity and accessibility of the material. We
have updated all the sections, particularly the material dealing
with Toll-like receptors, dendritic cells, regulatory T cells, and
HIV. We have also introduced a final chapter on therapeutic
PREFACE
immunomodulation, which is being increasingly utilized in
clinical practice. This chapter also aims to review what readers
will have learned about the immunopathogenesis of several dis-
eases covered in earlier chapters. In response to user feedback,
we have also enhanced the clinical vignettes, which form the
final pages of most chapters. Although some of these vignettes
describe rare diseases, we hope that this helps readers link their
studies of immunology with real clinical experience.
2007 R.N. & M.H.
■ PREFACE TO THE FIRST EDITION
We have recognized the need for an immunology book that is
primarily focused on the needs of medical students for as long
as we have been teachers of immunology. This book has been
written to fill this need. Immunology can fall into different
medical school courses or modules. Often, immunology is
taught in the Host Defense course, which integrates basic and
clinical immunology (including allergy, immunopathology, etc).
Some medical schools, however, teach basic immunology and
clinical immunology in two separate courses. This book should
be useful for either curriculum organization.
We have concentrated on a simple, straightforward treatment
of the subject. The book is relatively short and contains the
topics we considered important to understanding the human
immune system and its role in protecting us from disease. This
reflects our acknowledgment of the time constraints on today’s
medical student. With new topics and a growing amount of
information considered to be essential, there are increasing
demands on students. It is therefore important to have a concise,
readable textbook, and that has been our primary aim. Most
chapters contain the information needed for a typical 50-minute
large class or small-group teaching/learning session. This, of
course, means that details dear to the hearts of some immunolo-
gists are not covered!
We are aware of two specific problems that medical students
have with immunology. First, the immune system is complex
because it has evolved to respond to the wide range of patho-
gens. Many students find themselves bogged down in the com-
plexities of the molecules and cells of the immune system
without having an understanding of how these components
work together to fight infection. We begin our book with two
overview chapters that explain what the immune system does
and then how the components fit together. We recommend that
students begin by reading these chapters. Further on in the text,
v
PREFACE
there are more short, integrating overview chapters. These are
not just for revision, but are there to make sure that students
understand how the material that they have read fits into the
overall system. The second problem is that medical students do
not always immediately see the relevance of immunology to
day-to-day clinical practice. We have included clinical correla-
tions throughout the text that explain how understanding the
science of immunology can translate into understanding real
clinical problems.
The book is a concise description of the science of immunol-
ogy, a topic that defies a final complete description because there
is much still to be learned. Hopefully, we will have succeeded in
inducing an interest and appreciation of the relevance of immu-
nology to medical students, to form the basis for a lifetime of
vi
learning about the immune system and its potential for use in
improving the human condition. Most medical students today
could still be practicing medicine in 40 to 50 years. Approxi-
mately 50 years ago, immunology was still in its infancy. For
example, we did not know the chemical structure of antibody
molecules in any detail, and treatments such as organ transplan-
tation had not been carried out. The next 50 years will likely
bring equally important advances in the field. History suggests
that we would be foolish to try to predict what they will be. We
hope that you enjoy participating in these advances in immunol-
ogy and their application to human disease as much as we have
in those that we have been privileged to observe in our careers.
2002 R.N. & M.H.
 ACKNOWLEDGMENTS

I am grateful to the very helpful team at Elsevier. I thank

Antonio Benitez for his kindness and support, without which
writing this edition would have been impossible. My greatest
debt is to the patients who have informed and inspired me over
the last 30 years.

vii
HOW TO USE THIS BOOK
Immunology for Medical Students is organized to be read com-
prehensively. The flow of the book is from genes and molecules
to cells and organs, and finally to the immune system as an
integrated system protecting the body from infection and
helping to maintain the health of the body.
Section I introduces the basic concepts and is essential for an
understanding of the language of immunology.
Section II continues with a discussion of the antigen recogni-
tion molecules, that is, antibodies, T-cell receptors, and the
molecules encoded by the major histocompatibility complex.
Section III deals with immune physiology, the role of the
cells and organs of the immune system in the response to a
pathogen.
Section IV discusses the innate immune system and its con-
nections to the adaptive immune system.
Section V considers hypersensitivity, allergy and asthma,
autoimmunity, immunodeficiency, and transplantation and
includes a new chapter on therapeutic immunomodulation.
Throughout the book, the core knowledge objectives are
listed as Learning Points at the ends of chapters to aid in review.
There are also several integrating overview chapters (eg, “Review
of Antigen Recognition,” “Brief Review of Immune Physiology”)
that focus the student on the major points of the pertinent
topics. Each section is relatively freestanding. For example,
Section V, “Immune System in Health and Disease,” could be
used in a clinical correlations course, independent of the remain-
der of the book. Immunology for Medical Students will be most
useful in the comprehensive host defense–type courses that are
growing in popularity in medical schools.
viii
The icons used throughout are illustrated on the next page.
You should become familiar with them to fully understand the
illustrations. Several pathogens (listed on the next page) have
been selected to use throughout the book as examples. Some
basic aspects of the structure and mechanism of action of these
organisms are described. You should reacquaint yourself with
these organisms, which are commonly encountered in microbi-
ology and infectious disease courses, and use the figure as a
convenient reference as you encounter these pathogens in the
examples used in this book.
In general, boxes have been clustered at the end of chapters
to aid the flow of the text and understanding of the material.
Clinical Box
Clinical boxes throughout the text put immunology
into a clinical context. The clinical material selected is
current and relevant.
Technical Box
Technical boxes show how advances in the field have
expanded our knowledge of how the immune system
works and provided new means of preventing disease.
 ICONS

Icons in Immunology
Key molecules

DNA Signaling Cytokine, Receptor, MHC I MHC II Antigen T-cell receptor Immunoglobulin Complement
molecule chemokine, surface (TCR) (Ig) (C′)
etc. molecule,
ligand

Key cells Key colors

TH
Professional Neutrophil, Lymphocytes Adaptive Innate Antigen,
antigen-presenting eosinophil, immune response immune response microorganism,
cell (APC) mast cell tumor, etc.

Key complexes

Bone marrow Thymus Lymph node Other (peripheral) tissue In vitro Medical intervention

ix
MICROORGANISMS MENTIONED IN THIS BOOK

This table shows some of the different types of microorganisms

the immune system has to deal with. These microorganisms are
used throughout the book to illustrate the diverse range of
targets for the immune system. These select microorganisms
cause about 10 million deaths per year around the world.

Microorganism Type

HIV RNA Virus Small virus with a high mutation rate. Many different strains develop in one
infected person, allowing the virus to escape the immune response.

Influenza virus RNA virus Spreads easily from person to person. Mutates gradually but also can exchange
genes with other viruses.

Epstein-Barr virus (EBV) DNA virus Causes infectious mononucleosis. The EBV genome encodes proteins that help the
virus escape the immune system.

Hepatitis B virus DNA virus Lives in hepatocytes. The immune response to the virus causes liver damage.
Vaccination prevents infection.

Escherichia coli (E. coli) Bacterium One of many organisms normally living harmlessly in the gut. If it invades the body,
it may trigger septic shock.

Mycobacterium tuberculosis Bacterium Transmitted by airborne droplets. Able to survive inside phagocytes. If not
adequately controlled by the immune system, it causes tuberculosis.

Candida albicans Fungus Lives harmlessly on the skin but able to cause disease (“thrush”) if not controlled
by the immune system.

Plasmodium Protozoan Transmitted by insect bites and causes malaria. Has a complex life cycle that allows
it to evade the immune system. Effective vaccines are now being developed.

Schistoma Helminth Invasive worm that attacks the liver and urinary tract.

x
 CONTENTS

SECTION I Introduction 11. Lymphocyte Activation 69

Antigen Receptors, 69
1. Introduction to the Immune System 2 Signaling Events, 71
Amplification Through Signaling Pathways, 72
2. Basic Concepts and Components of Response, 74
the Immune System 7
Innate Immunity, 7 12. Hematopoiesis 77
Adaptive Immunity, 8 Three Major Stages of Hematopoiesis, 77
Components of the Immune System, 9 Lymphoid Cells, 78
Active and Passive Immunity, 9 Myeloid Cells, 79
Phases of an Immune Response, 9
Types of Immune Response, 9 13. Organs and Tissues of the Immune System 83
Primary and Secondary Lymphoid Organs, 83
Lymphocyte Trafficking, 88
SECTION II Antigen Recognition Molecules
14. B-Cell Development 94
3. Introduction to Antigen Recognition 15 Early B-Lymphocyte Development, 94
Antigen Recognition Molecules, 15 The Mature B Cell, 96
B-Cell and T-Cell Receptors, 16 Somatic Mutation and Class Switching in Germinal Centers, 97
Major Histocompatibility Complex Molecules, 16 Thymus-Independent Antigens, 98
B1 B Cells and Natural Antibodies, 99
4. Antigens and Antibody Structure 18
Antigens, 18 15. T-Cell Development 101
Antibodies, 19 The Thymus, 101
The Periphery: Naive T-Cell Activation by Antigen, 105
5. Antibody-Antigen Interaction 25
Antigen-Binding Sites of Antibodies, 25 16. T-Cell Interactions and T-Cell Help 111
Diagnostic Tests for Antibody or Antigen, 26 Generation of Stimulated, or Primed, B and T Cells, 111
Generation of Effector Cells, 113
6. Antibody Diversity 35 Providing the Most Appropriate Immune Response for
Immunoglobulin Genes, 35 a Given Pathogen, 113
Immunoglobulin Classes, 41
17. Immunologic Memory and Homeostasis 123
7. The T-Cell Receptor 44 Long-Term Immunologic Memory, 123
Structure of the T-Cell Receptor, 44 Lymphocyte Homeostasis, 126
Generation of Diversity of the T-Cell Receptor Genes, 45 Apoptosis, 126
Recognition of Antigen, 47
Other Accessory Molecules Involved in T-Cell Function, 47 18. Regulation of the Immune System 128
Tolerance, 128
8. Major Histocompatibility Complex 51
Genetic Organization, 51 19. Brief Review of Immune Physiology 134
Regulation of Gene Expression, 51 Integrated Immune System: Connections Between Adaptive and
Structure of the Major Histocompatibility Complex Innate Responses, 135
Gene Products, 52
Restriction of Antigen Recognition, 54 SECTION IV Innate Immunity
Population Advantages of Polymorphism in the Major
Histocompatibility Complex, 56 20. Constitutive Defenses Including Complement 139
Disease Correlations, 56
Barriers to Infection, 139
9. Review of Antigen Recognition 59 Extracellular Molecules of the Innate Immune System, 140
Important Structural Features, 59 21. Phagocytes 150
Generation of Diversity, 60
Phagocytic Cell Types, 150
Phagocyte Production, 152
SECTION III Physiology Phagocyte Recruitment, 152
Receptors on Phagocytes, 153
10. Antigen Processing and Presentation 63 Molecular Patterns, 153
Pathways of Antigen Processing, 64 Actions of Phagocytes, 154
Mechanisms of Antigen Processing, 64 Phagocyte Defects, 156
Evasion of Processing Pathways by Pathogens, 67 Molecular Recognition by the Innate and Adaptive Immune Systems, 157

xi
CONTENTS

22. Killing in the Immune System 162 29. Antibody-Mediated Hypersensitivity (Type II) 231
Response to Parasite Worms, 162 Immune-Mediated Hemolysis, 231
Mast Cells, 162 Type II Hypersensitivity and Antibodies That Affect
Natural Killer Cells, 166 Cell Function, 234
Intracellular Mechanisms of Apoptosis, 168
30. Immune Complex Disease
23. Inflammation 172 (Type III Hypersensitivity) 238
Types of Inflammation, 172 Antigens in Immune Complexes, 238
Cytokine Network in Inflammation, 173 Antibodies in Immune Complexes, 239
Tuberculosis, 174 Clearance of Immune Complexes, 239
Hepatitis B Infection, 176 Mechanisms of Inflammation in Immune Complex Disease, 240
“Overzealous” Inflammation, 177 Immune Complex Disease in the Kidney, 240
Treatment of Immune Complex Disease, 241
24. Cytokines in the Immune System 182
Overview, 182 31. Delayed Hypersensitivity (Type IV) and Review
Cytokine Receptors and Signaling Molecules, 183 of Hypersensitivity Reactions 245
Review of Some of the Roles of Cytokines in Immune Responses, 184 Delayed Hypersensitivity Reactions Are Driven by
Clinical Uses for Cytokines and Cytokine Blockade, 187 T-Helper 1 Cells, 245
Type IV Hypersensitivity Disease, 245
SECTION V Immune System in
32. Primary Immunodeficiency 252
Health and Disease
Infections Provide Clues to the Type of Immunodeficiency, 252
25. Infections and Vaccines 191 Causes of Primary Immunodeficiency, 253
Screening for Severe Combined Immune Deficiency, 255
How Organisms Evade the Immune Response, 191
Diagnosis of Primary Immunodeficiency, 256
Mechanisms of Immunity, 191
Treatment, 257
Types of Vaccines, 192
Vaccine Schedules, 194 33. Secondary Immunodeficiency 262
26. Hypersensitivity Reactions 200 HIV Infection, 262
Other Secondary Immunodeficiencies, 266
Types of Triggers for Hypersensitivity, 200
Types of Hypersensitivity Reaction, 201 34. Transplantation 270
Diagnosis and Treatment of Hypersensitivity, 202 Transplantation Terminology, 270
27. Immediate Hypersensitivity (Type I): Allergy 206 Solid Organ Transplantation, 270
Stem Cell Transplantation, 272
Definitions, 206
Tissue-Typing Techniques, 273
Allergen, 206
Immunosuppressive Drugs, 275
Degranulating Cells, 207
Xenotransplantation, 276
Antibody, 208
T-Helper 2 Cells, 208 35. Tumor Immunology 280
Predisposition to Allergy, 209 Lymphoid Tumors, 280
Mediators of Early Phase of Allergy, 210 Immunity to Tumors, 282
Mediators of Late Phase of Allergy, 211
Treatment, 211 36. Biopharmaceuticals 290
28. How Autoimmune Disease Develops 217 Monoclonal Antibodies, 291
Some Autoimmunity Is Normal, 217 Recombinant Cytokines, 294
Initiation of Autoimmune Disease, 218
T-Cell Tolerance, 218 Glossary 297
Breakdown of T-Cell Tolerance, 219
Tests for Autoimmune Disease, 221 Index 301

xii
SECTION I Introduction
 Introduction to the
CHAPTER
1 Immune System

INNATE ADAPTIVE
Barriers to primary infection Self vs. nonself
Phagocytosis Antigen recognition molecules
Complement Clonal selection
Inflammatory mediators Memory

Immune system associations

Vaccines
Immunity to microbes Autoimmunity
Successful transplantation Immunodeficiency
Monoclonal antibodies Allergy

SUCCESS FAILURE

We inhabit a world dominated by microbes, many of which can
cause harm (Box 1.1). The immune system is the body’s primary
defense system against invasion by microbes. This chapter briefly
introduces the major components of the human immune system,
what they do, and how they accomplish their host defense role.
As you will read later in this book, and as is illustrated in the
overview figure above, the immune system is organized into
innate and adaptive components. The innate immune system is
the first line of defense for the body, and it uses nonspecific cells,
such as phagocytes, and molecules, such as complement com-
ponents, to attempt to eliminate invading organisms. This
chapter first introduces the innate system and its characteristics.
This is followed by an introduction to the antigen-specific mech-
anisms used by the adaptive immune system, which include,
among others, antigen recognition molecules and specific sets of
lymphocytes. This chapter also introduces the reader to the
important ways in which manipulation of the immune response
can aid us in ensuring the health of people—for example,
through vaccination—and to the diseases caused by “failure” of
the immune system, such as in autoimmunity.
The human body has evolved natural barriers to prevent entry
by microbes (see also Chapter 20). For example, the skin and
mucous membranes are part of the innate, or nonadaptive,
immune system. However, if these barriers are broken, such as
after a cut, microbes and potential pathogens (harmful microbes)
can enter the body and can begin to multiply rapidly in the
warm, nutrient-rich systems, tissues, and organs.
One of the first features of the immune defense system that
a foreign organism encounters after being introduced through a
cut in the skin is the phagocytic white blood cells (leukocytes,
such as macrophages; Fig. 1.1), which congregate within minutes
and begin to attack the invading foreign microbes (Chapter 21).
Later, neutrophils are recruited into the area of infection. These
phagocytic cells bear molecules called pattern recognition receptors
that detect structures commonly found on the surface of bacteria
and other pathogens. Phagocytosis, the ingestion of particulate
matter into cells for degradation, is a fundamental defense mech-
anism against invading foreign microbes (Chapter 21).
Various other protein components of serum, including the
complement components (Chapter 20), may bind to the invader
organisms and facilitate their phagocytosis, thereby limiting the
source of infection and disease. Other small molecules known
as interferons mediate an early response to viral infection by the
innate system (Chapter 20).
The innate immune system is often sufficient to destroy
invading microbes. If it fails to clear infection rapidly, it activates
the adaptive or acquired immune response, which takes over.
Messenger molecules known as cytokines mediate the connection
between the two systems. The interferons are part of the cytokine
family (Chapter 24).

The effector cells of the adaptive immune defense system are
also white blood cells, the T and B lymphocytes (Chapters 2,
12, 14, and 15). The B and T cells of the adaptive immune
system are normally at rest, but they become activated (Chapters
2 and 11) on encountering an entity referred to as an antigen.
Most antigens are derived from invading pathogens, but when
things go wrong, an antigen can be a harmless foreign substance,
as in hypersensitivity, or even a molecule derived from the self,
as in autoimmunity. Adaptive immune responses are highly
effective but can take 7 to 10 days to mobilize completely. A
very important aspect of the adaptive immune response is the
molecular mechanism used to generate specificity in the response.
The immune system as a whole distinguishes self from nonself.
Fig 1.1 Confocal image of a human monocyte–derived macrophage
harboring live M1T1 streptococci (green) as assessed by staining with a
bacterial viability. (From Norrby-Teglund A, Johansson L. Beyond the
traditional immune response: bacterial interaction with phagocytic cells.
Int J Antimicrob Agents. 2013;42[suppl]:S13-S16.)
Large numbers of When antigen encounters a
B cells, each with B cell with the appropriate
a different immunoglobulin (Ig) Ig to bind the antigen,
on the cell surface the B cell proliferates
Fig 1.2 Clonal selection of B cells.
Cytokine,
MCH II chemokine,
etc.
Introduction • Introduction to the Immune System 1
It is able to cope with the great diversity in nonself structures
by anticipating these foreign antigens and creating a diverse
repertoire of antigen receptors or antigen recognition molecules.
These receptors bind to small areas of the molecular structures
of the foreign antigens called epitopes. The genetic mechanisms
used for generation of this diverse range of antigen recognition
molecules are described in Chapters 6, 7, 8, 14, and 15. Several
versions of these antigen receptors are used by the immune
system; these are antibodies (B-cell antigen receptors), T-cell
antigen receptors, and the protein products of a genetic region
referred to as the major histocompatibility complex (MHC). All
vertebrates appear to possess an MHC. The MHC genes of
humans are referred to as human leukocyte antigen (HLA) genes,
and their products are known as HLA molecules (Chapter 8).
In addition to being antigen receptors on B cells, antibodies
are also found as soluble antigen-recognizing molecules in the
blood (immunoglobulin or antibody). Both the B-cell and T-cell
antigen receptors are clonally distributed (for B cells and anti-
bodies; Fig. 1.2), which means that a unique antigen receptor is
found on each lymphocyte. When a foreign antigen enters the
body, it eventually encounters a lymphocyte with a matching
receptor. This lymphocyte divides and, in the case of B cells, the
daughter clones produce large amounts of soluble receptor. In
the case of T cells, large numbers of specific effector cells bearing
the appropriate receptor on their cell surface are generated. Dif-
ferent types of specialist T cells, such as T-helper (TH) cells, are
produced for specific situations (Chapter 16). For example, TH1
T cells are usually produced in response to viral infections, TH2
T cells are produced in response to worms, and TH17 cells
respond to fungi and extracellular bacteria.
B-cell and T-cell antigen receptors differ in one very impor-
tant way: B-cell antigen receptors can interact directly with
antigen, whereas T-cell antigen receptors recognize antigen only
when it is presented to them on the surface of another cell by
MHC molecules (Chapters 2, 7, and 8).
In addition to recognizing nonself antigens, the cells of the
immune system also recognize alterations of self that result from
certain disease processes—for example, modified self antigens
found on tumor cells—and may eliminate the tumor cell once
it has been recognized (Fig. 1.3; Chapter 35). The ability to
recognize unaltered self antigen can, if unregulated, lead to
The B cell divides Mature B cell (plasma cell)
to produce identical secreting immunoglobulin
daughter cells (clones) with specificity for the antigen
3
Complement Signaling
(C′) molecule
Introduction to Antigen
Recognition
Antigen
recognition
molecules
MHC
Immunoglobulin TCR Antigen
domain recognition
“building block”
Ig
As described in Chapters 1 and 2, two main systems allow
humans to identify foreign (nonself ) materials: the innate
immune system and the adaptive immune system.
The innate immune system is characterized by the presence
of phagocytic cells and blood proteins, which recognize invading
microbes using pattern recognition molecules. Mannan-binding
lectin (MBL) and Toll-like receptors (TLRs) are examples of
pattern recognition molecules. These recognize and bind types
of molecules present in microbes but not host cells. MBL, for
example, binds mannan on the surface of bacteria, viruses, and
fungi. Mannan is not present on the surface of healthy host cells
but is present on the surface of damaged cells. Thus MBL rec-
ognizes and binds both microbes and damaged host cells but
not normal cells. Although MBL is able to distinguish between
health and disease, it is described as being “nonspecific” because
it cannot distinguish bacteria from viruses, nor can it distinguish
different types of bacteria. This lack of specificity is the key
feature of the pattern recognition molecules of the innate
immune system.
The innate immune system relies on preexisting molecules
and cells that nonspecifically attack invaders; this system pro-
tects us well against a wide range of infections. In general, the
innate system protects against infection by removing the infec-
tious agent. However, it is unable to respond specifically to
3 CHAPTER
microbes or other foreign material (antigen). Microbes evolve
much more rapidly than vertebrates, thus enabling them to
evade nonadaptive defense systems by changing their structure.
This is one reason vertebrates developed an adaptive immune
system, which depends on gene rearrangement to generate a
large number of preexisting receptors (repertoire), expressed on
lymphocytes, that can identify essentially any antigen.
■ ANTIGEN RECOGNITION MOLECULES
Three groups of molecules specifically recognize foreign antigen
for the adaptive immune system. The first two are the cell
surface–located receptors found on B and T cells. The B-cell
receptor (BCR) is also secreted from differentiated B cells (plasma
cells) to create a soluble antigen receptor, known as antibody. The
third group of antigen receptors is encoded in the major histo-
compatibility complex (MHC). This cluster of genes is known
as human leukocyte antigen (HLA) in humans. The MHC mol-
ecules function to present antigenic peptides to T cells. T-cell
receptor (TCR), BCR, and MHC molecules have similar struc-
tures and are part of the family of protein molecules that uses
the immunoglobulin fold; this family is known as the immu-
noglobulin superfamily (Chapter 9). Figure 3.1 summarizes how
the three types of antigen receptor differ.
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were the guardians of that little flock which he, amid perils and
death, had gathered from the heathen waste of Ionic Asia, to the fold
of Christ. When he left it last, the raging wolves of persecution and
wrath,――the wild beasts of Ephesus,――were howling death and
destruction to the devoted believers of Christ, and they were still
environed with temptations and dangers, that threatened to
overwhelm these feeble ones, left thus early without the fostering
care of their apostolic shepherd. Passing on his way to the great
scene of his coming trials, he could not venture among them to give
them his parting counsels, and could now only intrust to their
constituted guardians, this dear charge, with renewed exhortations to
them to be faithful, as in the presence of their God, to those objects
of his labors, his cares, his prayers, and his daily tears. Amid the
sorrows of that long farewell, arose on the prophetic vision of the
apostle some gloomy foreshadowings of future woes to fall on that
Ephesian charge, and this deepened the melancholy feeling of his
heart almost to agony. This no doubt was the burden of his last
prayer, when with their elders, and for them, he kneeled down on the
shore and sent up in earnest petition to God, that voice which they
were doomed to hear no more forever.

Such passages as this in the life and words of Paul, constitute a

noble addition to the reader’s idea of his character. They show how
nobly were intermingled in the varied frame of his spirit, the
affectionate, the soft, and the winning traits, with the high, the stern,
and the bitter feelings that so often were called out by the
unparalleled trials of his situation. They show ♦that he truly felt and
acted out, to the life, that divine principle of Christian love which
inspired the most eloquent effort of his pen;――and that he trusted
not to the wonder-working powers that moved his lips, as with the
eloquence of men and angels,――not to the martyr-spirit, that,
sacrificing all earthly substance, devoted itself to the raging flames of
persecution, in the cause of God,――not to the genius whose
discursive glance searched all the mysteries of human and divine
knowledge,――but to that pure, exalted and exalting spirit of ardent
love for those for whom he lived like his Savior, and for whom he
was ready to die like him, also. This was the inspiration of his words,
his writings, and his actions,――the motive and spirit of his
devotion,――the energy of his being. Wherever he went and
whatever he did,――in spite of the frequent passionate outbreaks of
his rougher nature, this honest, fervent, animated spirit of
charity,――glowing not to inflame, but to melt,――softened the
austerities of his character, and kindled in all who truly knew him, a
deep and lasting affection for him, like that which was so strikingly
manifested on this occasion. Who can wonder that to a man thus
constituted, the lingering Ephesians still clung with such enthusiastic
attachment? In the fervid action of that oriental clime, they fell on his
neck and kissed him, sorrowing most of all for the words which he
said,――that they should see his face no more. Still loth to take their
last look at one so loved, they accompanied him to the ship, which
bore him away from them, to perils, sufferings and chains.

♦ duplicate word “that” removed

“Assos was a sea-port town, situated on the south-west part of the province of Troas,
and over against the island Lesbos. By land it is much nearer Troas than by sea, because of
a promontory that runs a great way into the sea, and must be doubled to come to Assos,
which was perhaps the reason that the apostle chose rather to walk it.” (Wells’s Geography
and Calmet’s Commentary.)

MYTELENE. Acts xx. 14.

 “Mitylene, (chapter xx. verse 14,) was one of the principal cities in the island of Lesbos,
situated on a peninsula with a commodious haven on each side; the whole island was also
called by that name, as well as Pentapolis, from the five cities in it, viz. Issa or Antissa,
Pyrrhe, Eressos, Arisba, and Mitylene. It is at present called Metelin. The island is one of
the largest in the Archipelago, and was renowned for the many eminent persons it
produced; such as Sappho, the inventress of Sapphic verses,――Alcaeus, a famous lyric
poet,――Pittacus, one of the seven wise men of Greece,――Theophrastus, the noble
physician and philosopher,――and Arion, the celebrated musician. It is now in the
possession of the Turks. As mentioned by St. Luke, it may be understood either the island
or the city itself.” (Wells’s Geography and Whitby’s Table.)

“Chios, (verse 15,) was an island in the Archipelago, next to Lesbos, both as to situation
and size. It lies over against Smyrna, and is not above four leagues distant from the Asiatic
continent. Horace and Martial celebrate it for the wine and figs that it produced. It is now
renowned for producing the best mastic in the world.

“Sir Paul Ricaut, in his ‘Present State of the Greek Church,’ tells us, that there is no
place in the Turkish dominions where Christians enjoy more freedom in their religion and
estates than in this island, to which they are entitled by an ancient capitulation made with
Sultan Mahomet II.” (Wells’s Geography.)

“Samos, (verse 15,) was another island of the Archipelago, lying south-east of Chios,
and about five miles from the Asiatic continent. It was famous among heathen writers for the
worship of Juno; for one of the Sibyls called Sibylla Samiana; for Pherecydes, who foretold
an earthquake that happened there, by drinking of the waters; and more especially for the
birth of Pythagoras. It was formerly a free commonwealth; at present, the Turks have
reduced it to a mean and depopulated condition; so that ever since the year 1676, no Turk
has ventured to live on it on account of its being frequented by pirates, who carry all whom
they take into captivity.” (Wells’s Geography and Whitby’s Table.)

“Trogyllium, (verse 15,) is a promontory at the foot of Mount Mycale, opposite to, and
five miles from Samos: there was also a town there of the same name, mentioned by Pliny,
Lib. v, c. 29. p. 295.” (Whitby’s Table.)

“Miletus, (verse 15,) a sea-port town on the continent of Asia Minor, and in the province
of Caria, memorable for being the birth-place of Thales, one of the seven wise men of
Greece, and father of the Ionic philosophy; of Anaximander, his scholar; Timotheus, the
musician; and Anaximenes, the philosopher. It is called now, by the Turks, Melas; and not
far distant from it is the true Meander.” (Whitby’s Table and Wells’s Geography.) [Williams
on Pearson. pp. 66, 67.]

Tearing himself thus from the embraces of his Ephesian brethren,

Paul sailed off to the southward, hurrying on to Jerusalem, in order
to reach there if possible, before the Pentecost. After leaving Miletus,
the apostolic company made a straight course to Coos, and then
rounding the great northwestern angle of Asia Minor, turned
eastwardly to Rhodes, and passing probably through the strait,
between that island and the continent, landed at Patara, a town on
the coast of Lycia, which was the destination of their first vessel.
They therefore at this place engaged a passage in a vessel bound to
Tyre, and holding on southeastward, came next in sight of Cyprus,
which they passed, leaving it on the left, and then steering straight
for the Syrian coast, landed at Tyre, where their vessel was to
unlade; so that they were detained here for a whole week, which
they passed in the company of some Christian brethren who
constituted a church there. These Tyrian disciples hearing of Paul’s
plan to visit Jerusalem, and knowing the dangers to which he would
there be exposed by the deadly hate of the Jews, were very urgent
with him against his journey; but he still resolutely held on his
course, as soon as a passage could be procured, and bade them
farewell, with prayer on the shore, to which the brethren
accompanied him with their women and children. Standing off from
the shore, they then sailed on south, to Ptolemais, where they spent
a day with the Christians in that place, and then re-embarking, and
passing round the promontory of Carmel, reached Caesarea, where
their sea-voyage terminated. Here they passed several days in the
house of Philip the evangelist, one of the seven deacons, who had
four daughters that were prophetesses. While they were resting
themselves in this truly religious family, from the fatigues of their long
voyage, they were visited by Agabus, a prophet from
Jerusalem,――the same who had formerly visited Antioch when
Paul was there, and who had then foretold the coming famine, which
threatened all the world. This remarkable man predicted to Paul the
misfortunes which awaited him in Jerusalem. In the solemnly
impressive dramatic action of the ancient prophets, he took Paul’s
girdle, and binding his own hands with it, said――“Thus says the
Holy Spirit, ‘So shall the Jews at Jerusalem, bind the man that owns
this girdle, and shall deliver him to the Gentiles.’” On hearing this
melancholy announcement, all the companions of Paul and the
Christians of Caesarea, united in beseeching Paul to give up his
purpose of visiting Jerusalem. But he, resolute against all entreaty,
declared himself ready not only to be bound, but to die in Jerusalem
for the Lord Jesus. And when they found that he would not be
persuaded, they all ceased to harass him with their supplications,
and resigned him to Providence, saying,――“The will of the Lord be
done.” They then all took carriages, and rode up to Jerusalem,
accompanied by some brethren from Caesarea, and by Mnason, an
old believer, formerly of Cyprus, but now of Jerusalem, who had
engaged them as his guests in that city.

“Coos, (chapter xxi. verse 1,) an island in the Aegean or Icarian sea, near Mnydos and
Cnidus, which had a city of the same name, from which Hippocrates, the celebrated
physician, and Apelles, the famous painter, were called Coi. Here was a large temple of
Aesculapius, and another of Juno. It abounded in rich wines, and is very often mentioned by
the classic poets.” (Whitby’s Alphabetic Table.)

Witsius very absurdly defines the situation of this island by saying that it is “near
Crete.”――“Coos, quae maris Mediterranei insula est prope Cretam.” It is in the Aegean
sea properly, and not in the Mediterranean; and can not be less than one hundred and
twenty miles from Crete, much farther off from it than is Rhodes,――the next island in
Paul’s route, and there are many islands between Coos and Crete, so that the statement
gives no just idea of the situation of the island. It would be as proper to say that Barbadoes
is near Cuba, or the isle of Man near France.

“Rhodes, (verse 1,) an island, supposed to have taken its name απο των Ροδων from the
many roses which were known to grow there. It lies south of the province of Caria, and it is
accounted next to Cyprus and Lesbos, for its dignity among the Asiatic islands. It was
remarkable among the ancients for the expertness of its inhabitants in navigation; for a
college, in which the students were eminent for eloquence and mathematics; and for the
clearness of its air, insomuch that there was not a day in which the sun did not shine upon
it; and more especially celebrated for its prodigious statue of brass, consecrated especially
to the sun, and called his Colossus. This statue was seventy cubits high, and every finger
as large as an ordinary sized man, and as it stood astride over the mouth of the harbor,
ships passed under its legs.” (Whitby’s Table and Wells’s Geography.) [Williams on
Pearson, pp. 67, 68.]

last visit to jerusalem.

Paul was now received in Jerusalem by the brethren with great

joy, and going, on the day after his arrival, to see James, now the
principal apostle resident in the Holy city, communicated to him and
all the elders a full account of all his various labors. Having heard his
very interesting communications, they were moved with gratitude to
God for this triumph of his grace; but knowing as they did, with what
rumors against Paul these events had been connected by common
fame, they desired to arrange his introduction to the temple in such a
manner, as would most effectually silence these prejudicial stories.
The plan proposed by them was, that he should, in the company of
four Jews of the Christian faith, who had a vow on them, go through
with all the usual forms of purification prescribed under such
circumstances for a Jew, on returning from the daily impurities to
which he was exposed by a residence among the Gentiles, to a
participation in the holy services of solemn worship in the temple.
The apostles and elders, however, in recommending this course,
declared to him, that they believed that the Gentiles ought not to be
bound to the performance of the Jewish rituals, but should be
exempt from all restrictions, except such as had formerly been
decided on, by the council of Jerusalem. Paul, always devout and
exact in the observance of the institutions of his national religion,
followed their advice accordingly, and went on quietly and
unpretendingly in the regular performance of the prescribed
ceremonies, waiting for the termination of the seven days of
purification, when the offering should be made for himself, and one
for each of his companions, after which, they were all to be admitted
of course, to the full honors of Mosaic purity, and the religious
privileges of conforming Jews. But these ritual observances were not
destined to save him from the calamities to which the hatred of his
enemies had devoted him. Near the close of the seven days allotted
by the Mosaic ritual for the purification of a regenerated Israelite,
some of the Asian Jews, who had known Paul in his missionary
journeys through their own country, and who had come to
Jerusalem, to attend the festival, seeing their old enemy in the midst
of the temple, against whose worship they had understood him to
have been preaching to the Gentiles,――instantly raised a great
outcry, and fell upon him, dragging him along, and shouting to the
multitude around, “Men of Israel! help! This is the man, that every
where teaches all men against the people, and the law, and this
place; and he has furthermore, brought Greeks into the temple, and
has polluted this holy place.” It seems they had seen Trophimus, one
of his Gentile companions from Ephesus, with him in the city, and
imagined also that Paul had brought him into the temple, within the
sanctuary, whose entrance was expressly forbidden to all Gentiles,
who were never allowed to pass beyond the outermost court. The
sanctuary or court of the Jews could not be crossed by an
uncircumcised Gentile, and the transgression of the holy limit was
punished with death. Within this holy court, the scene now described
took place; and as the whole sanctuary was then crowded with Jews,
who had come from all parts of the world to attend the festival in
Jerusalem, the outcry raised against Paul immediately drew
thronging thousands around him. Hearing the complaint that he was
a renegade Jew, who, in other countries, had used his utmost
endeavors to throw contempt on his own nation, and to bring their
holy worship into disrepute, and yet had now the impudence to show
himself in the sanctuary, which he had thus blasphemed,――and
had, moreover, even profaned it by introducing into the sacred
precincts one of those Gentiles for whose company he had forsaken
the fellowship of Israel,――they all joined in the rush upon him, and
dragged him out of the temple, the gates of which were immediately
shut by the Levites on duty, lest in the riot that was expected to
ensue, the consecrated pavement should be polluted with the blood
of the renegade. Not only those in the temple, but also all those in
the city, were called out by the disturbance, and came running
together to join in the mob against the profaner of the sanctuary, and
Paul now seemed in a fair way to win the bloody crown of
martyrdom.

The great noise made by the swarming multitudes who were

gathering around Paul, soon reached the ears of the Roman garrison
in castle Antonia, and the soldiers instantly hastened to tell the
commanding officer, that “the whole city was in an uproar.” The
tribune, Claudius Lysias, probably thinking of a rebellion against the
Romans, instantly ordered a detachment of several companies
under arms, and hurried down with them, in a few moments, to the
scene of the riot. The mob meanwhile were ♦diligently occupied in
beating Paul; but as soon as the military force made their way
among the crowd, the rioters left off beating him, and fell back. The
tribune coming near, and seeing Paul alone in the midst, who
seemed to be the object and occasion of all the disturbance, without
hesitation seized him, and putting him in chains, took him out of the
throng. He then demanded what all this riot meant. To his inquiry, the
whole mob replied with various accounts; some cried one thing and
some another; and the tribune finding it utterly impossible to learn
from the rioters who he was or what he had done, ordered him to be
taken up to the castle. Castle Antonia stood at the northwestern
angle of the temple, close by one of the great entrances to it, near
which the riot seems to have taken place. To this, Paul was now
taken, and was borne by the surrounding soldiers, to keep off the
multitude, who were raging for his blood, like hungry wolves after the
prey snatched from their jaws,――and they all pressed after him,
shouting, “kill him!” In this way Paul was carried up the stairs which
led to the high entrance of the castle, which of course the soldiers
would not allow the multitude to mount; and when he had reached
the top of the stairs, he was therefore perfectly protected from their
violence, though perfectly well situated for speaking to them so as to
be distinctly seen and heard. As they were taking him up the stairs,
he begged the attention of the tribune, saying, “May I speak to
thee?” The tribune hearing this, in some surprise asked, “Canst thou
speak Greek? Art thou not that Egyptian that raised a sedition some
time ago, and led away into the wilderness a band of four thousand
cut-throats?” This alarming revolt had been but lately put down with
great trouble, and was therefore fresh in the mind of Lysias, who had
been concerned in quelling it, along with the whole Roman force in
Palestine,――and from some of the outcries of the mob, he now
took up the notion that Paul was the very ringleader of that revolt,
and had now just returned from his place of refuge to make new
trouble, and had been detected by the multitude in the temple. Paul
answered the foolish accusation of the tribune, by saying, “I am a
Jewish citizen of Tarsus, in Cilicia, which is no mean city; and I beg
of thee, to let me speak to the people.” The tribune, quite glad to
have his unpleasant suspicions removed, as an atonement for the
unjust accusation immediately granted the permission as requested,
and Paul therefore turned to the raging multitude, waving his hand in
the usual gesture for requesting silence. The people, curious to hear
his account of himself, listened accordingly, and he therefore uplifted
his voice in a respectful request for their attention to his plea in his
own behalf. “Men! Brethren! and Fathers! Hear ye my defence which
I make to you!”

♦ “dilgently” replaced with “diligently”

Those words were spoken in the vernacular language of

Palestine, the true Hebraistic dialect of Jerusalem, and the multitude
were thereby immediately undeceived about his character, for they
had been as much mistaken about him, as the tribune was, though
their mistake was of a very opposite character; for they supposed
him to be entirely Greek in his habits and language, if not in his
origin; and the vast concourse was therefore hushed in profound
silence, to hear his address made in the true Jewish language.
Before this strange audience, Paul then stood up boldly, to declare
his character, his views, and his apostolic commission. On the top of
the lofty rampart of Castle Antonia,――with the dark iron forms of
the Roman soldiery around him, guarding the staircase from top to
bottom, against the raging mob,――and with the enormous mass of
the congregated thousands of Jerusalem, and of the strangers who
had come up to the festival, all straining their fierce eyes in wrath
and hate upon him, as a convicted renegade,――one feeble, slender
man, now stood, the object of the most painful attention to
all,――yet, less moved with passion and anxiety than any one
present. Thus stationed, he began, and gave to the curious multitude
an interesting account of the incidents connected with that great
change in his feelings and belief, which was the occasion of the
present difficulty. After giving them a complete statement of these
particulars, he was narrating the circumstance of a revelation made
to him in the temple, while in a devotional trance there, on his first
return to Jerusalem, after his conversion. In repeating the solemn
commission there confirmed to him by the voice of God, he repeated
the crowning sentence, with which the Lord removed his doubts
about engaging in the work of preaching the gospel, when his hands
were yet, as it were, red with the blood of the martyred
faithful,――“And he said to me, ‘Go: for I will send thee far hence,
unto the Gentiles.’” But when the listening multitude heard this clear
declaration of his having considered himself authorized to
communicate to the Gentiles those holy things which had been
especially consigned by God to his peculiar people,――they took it
as a clear confession of the charge of having desecrated and
degraded his national religion, and all interrupted him with the
ferocious cry, “Take him away from the earth! for such a fellow does
not deserve to live.” The tribune, finding that this discussion was not
likely to answer any good purpose, instantly put a stop to it, by
dragging him into the castle, and gave directions that he should be
examined by scourging, that they might make him confess truly who
he was, and what he had done to make the people cry out so against
him,――a very foolish way, it would seem, to find out the truth about
an unknown and abused person, to flog him until he should tell a
story that would please them. While the guard were binding him with
thongs, before they laid on the scourge, Paul spoke to the centurion,
who was superintending the operation, and said in a sententiously
inquiring way, “Is it lawful for you to scourge a Roman citizen without
legal condemnation?” This question put a stop to all proceedings at
once. The centurion immediately dropped the thongs, and ran to the
tribune, saying, “Take heed what thou doest, for this man is a Roman
citizen.” The tribune then came to Paul, in much trepidation, and with
great solemnity said――“Tell me truly, art thou a Roman citizen?”
Paul distinctly declared, “Yes.”

Desirous to learn the mode in which the prisoner had obtained this
most sacred and unimpeachable privilege, the tribune remarked of
himself, that he had obtained this right by the payment of a large
sum of money,――perhaps doubting whether a man of Paul’s poor
aspect could have ever been able to buy it; to which Paul boldly
replied――“But I was born free.” This clear declaration satisfied the
tribune that he had involved himself in a very serious difficulty, by
committing this illegal violence on a person thus entitled to all the
privileges of a subject of law. All the subordinate agents also, were
fully aware of the nature of the mistake, and all immediately let him
alone. Lysias now kept Paul with great care in the castle, as a place
of safety from his Jewish persecutors; and the next day, in order to
have a full investigation of his character and the charges against
him, he took him before the Sanhedrim, for examination. Paul there
opened his defence in a very appropriate and self-vindicating style.
“Men! Brethren! and Fathers! I have heretofore lived before God with
a good conscience.” At these words, Ananias the high priest,
provoked by Paul’s seeming assurance in thus vindicating himself,
when under the accusation of the heads of the Jewish religion,
commanded those that stood next to Paul to slap him on the mouth.
Paul, indignant at the high-handed tyranny of this outrageous attack
on him, answered in honest wrath――“God shall smite thee, thou
whited wall! For dost thou command me to be smitten contrary to the
law, when thou sittest as a judge over me?” The other by-standers,
enraged at his boldness, asked him, “Revilest thou God’s high
priest?” To which Paul, not having known the fact that Ananias then
held that office, which he had so disgraced by his infamous conduct,
replied――“I knew not, brethren, that he was the high priest; for it is
written, thou shalt not speak evil of the ruler of thy people.” Then,
perceiving the mixed character of the council, he determined to avail
himself of the mutual hatred of the two great sects, for his defense,
by making his own persecution a kind of party question; and
therefore called out to them――“I am a Pharisee, the son of a
Pharisee. Of the hope of the resurrection of the dead, I am called in
question.” These words had the expected effect. Instantly, all the
violent party feeling between these two sects broke out in full force,
and the whole council was divided and confused,――the scribes
who belonged to the Pharisaic order, arising, and declaring, “We find
no occasion of evil in this man. But if a spirit or an angel has spoken
to him, let us not fight against God.” This last remark, of course, was
throwing down the gauntlet at the opposite sect; for the Sadducees,
denying absolutely the existence of either angel or spirit, could of
course believe no part of Paul’s story about his vision and spiritual
summons. They all therefore broke out against the Pharisees, who
being thus involved, took Paul’s side very determinedly, and the
party strife grew so hot that Paul was like to be torn in pieces
between them. The tribune, seeing the pass to which matters had
come, then ordered out the castle-guard, and took him by force,
bringing him back to his former place of safety.

“The reason why St. Paul chose to speak in the Hebrew tongue, may be accounted for
thus. There were at this time two sorts of Jews, some called by Chrysostom οἱ βαθεις
Ἑβραιοι, profound Hebrews, who used no other language but the Hebrew, and would not
admit the Greek Bible into their assemblies, but only the Hebrew, with the Jerusalem
Targum and Paraphrase. The other sort spoke Greek, and used that translation of the
scriptures; these were called Hellenists. This was a cause of great dissension among these
two parties, even after they had embraced Christianity, (Acts vi. 1.) Of this latter sort was St.
Paul, because he always made use of the Greek translation of the Bible in his writings, so
that in this respect he might not be acceptable to the other party. Those of them who were
converted to Christianity, were much prejudiced against him, (Acts xxi. 21,) which is given
as a reason for his concealing his name in his Epistle to the Hebrews. And as for those who
were not converted, they could not so much as endure him: and this is the reason which
Chrysostom gives, why he preached to the Hellenists only. Acts ix. 28. Therefore, that he
might avert the great displeasure which the Jews had conceived against him, he accosted
them in their favorite language, and by his compliance in this respect, they were so far
pacified as to give him audience.” (Hammond’s Annotations.) [Williams’s Pearson, p. 70.]

“Scourging was a method of examination used by Romans and other nations, to force
such as were supposed guilty to confess what they had done, what were their motives, and
who were accessory to the fact. Thus Tacitus tells us of Herennius Gallus, that he received
several stripes, that it might be known for what price, and with what confederates, he had
betrayed the Roman army. It is to be observed, however, that the Romans were punished in
this wise, not by whips and scourges, but with rods only; and therefore it is that Cicero, in
his oration pro Rabirio, speaking against Labienus, tells his audience that the Porcian law
permitted a Roman to be whipped with rods, but he, like a good and merciful man,
(speaking ironically,) had done it with scourges; and still further, neither by whips nor rods
could a citizen of Rome be punished, until he were first adjudged to lose his privilege, to be
uncitizened, and to be declared an enemy to the commonwealth, then he might be
scourged or put to death. Cicero Oratio in Verres, says, ‘It is a foul fault for any praetor, &c.
to bind a citizen of Rome; a piacular offense to scourge him; a kind of parricide to kill him:
what shall I call the crucifying of such an one?’” (Williams’s notes on Pearson, pp. 70, 71.)

“Ananias, the son of Nebedaeus, was high priest at the time that Helena, queen of
Adiabene, supplied the Jews with corn from Egypt, (Josephus Antiquities, lib. xx. c. 5. § 2,)
during the famine which took place in the fourth year of Claudius, mentioned in the eleventh
chapter of the Acts. St. Paul, therefore, who took a journey to Jerusalem at that period,
(Acts xv.) could not have been ignorant of the elevation of Ananias to that dignity. Soon after
the holding of the first council, as it is called, at Jerusalem, Ananias was dispossessed of
his office, in consequence of certain acts of violence between the Samaritans and the Jews,
and sent prisoner to Rome, (Josephus, Antiquities, lib. xx. c. 6. § 2,) whence he was
afterwards released and returned to Jerusalem. Now from that period he could not be called
high priest, in the proper sense of the word, though Josephus (Antiquities, lib. xx. c. 9. § 2,
and Jewish War lib. ii. c. 17. § 9,) has sometimes given him the title of αρχιερευς, taken in
the more extensive meaning of a priest, who had a seat and voice in the Sanhedrim;
αρχιερεις in the plural number is frequently used in the New Testament, when allusion is
made to the Sanhedrim;) and Jonathan, though we are not acquainted with the
circumstances of his elevation, had been raised, in the mean time, to the supreme dignity in
the Jewish church. Between the death of Jonathan, who was murdered (Josephus
Antiquities of the Jews lib. xx. c. 8. § 5,) by order of Felix, and the high priesthood of Ismael,
who was invested with that office by Agrippa, (Josephus Antiquities lib. xx. c. 8. § 3,)
elapsed an interval in which this dignity continued vacant. Now it happened precisely in this
interval, that St. Paul was apprehended at Jerusalem; and, the Sanhedrim being destitute of
a president, he undertook of his own authority the discharge of that office, which he
executed with the greatest tyranny. (Josephus Antiquities lib. xx. c. 9. § 2.) It is possible
therefore that St. Paul, who had been only a few days at Jerusalem, might be ignorant that
Ananias, who had been dispossessed of the priesthood, had taken upon himself a trust to
which he was not entitled. He might therefore very naturally exclaim, ‘I wist not, brethren,
that he was the high priest!’ Admitting him on the other hand to have been acquainted with
the fact, the expression must be considered as an indirect reproof, and a tacit refusal to
recognize usurped authority.” (Michaelis, Vol. I. pp. 51, 56.)

“The prediction of St. Paul, verse 3, ‘God shall smite thee, thou whited wall,’ was,
according to Josephus, fulfilled in a short time. For when, in the government of Florus, his
son Eleazar set himself at the head of a party of mutineers, who, having made themselves
masters of the temple, would permit no sacrifices to be offered for the emperor; and being
joined by a company of assassins, compelled persons of the best quality to fly for their
safety and hide themselves in sinks and vaults;――Ananias and his brother Hezekias, were
both drawn out of one of these places, and murdered, (Josephus Jewish War lib. ii. c. 17,
18,) though Dr. Lightfoot will have it that he perished at the siege of Jerusalem!” (Whitby’s
Annotations.) [Williams on Pearson.]

During that night, the soul of Paul was comforted by a heavenly

vision, in which the Lord exhorted him to maintain the same high
spirit,――assuring him that as he had testified of him in Jerusalem,
even so he should bear witness in Rome. His dangers in Jerusalem,
however, were not yet over. The furious Jews, now cut off from all
possibility of doing any violence to Paul, under the sanction of legal
forms, determined to set all moderation aside, and forty of the most
desperate bound themselves by a solemn oath, neither to eat nor
drink, till they had slain Paul. In the arrangement of the mode in
which their abominable vow should be performed, it was settled
between them and the high-priest, that a request should be sent to
the tribune to bring down Paul before the council once more, as if for
the sake of putting some additional inquiries to him for their final and
perfect satisfaction; and then, that these desperadoes should station
themselves, where they could make a rush upon Paul, just as he
was entering the council-hall, and kill him before the guard could
bestir themselves in his defense, or seize the murderers; and even if
some of them should be caught and punished, it never need be
known, that the high priest was accessory to the assassination. But
while they were arranging this hopeful piece of wickedness, they did
not manage it so snugly as was necessary for the success of the
plot; for it somehow or other got to the ears of Paul’s nephew,――a
young man no where else mentioned in the New Testament, and of
whose character and situation, nothing whatever is known. He,
hearing of the plot, came instantly to his uncle, who sent him to
communicate the tidings to the tribune. Lysias, on receiving this
account of the utterly desperate character of the opposition to Paul,
determined not to risk his prisoner’s life any longer in Jerusalem,
even when guarded by the powerful defenses of castle Antonia. He
dismissed the young man with the strongest injunctions, to observe
the most profound secrecy, as to the fact of his having made this
communication to him; and immediately made preparations to send
off Paul, that very night, to Caesarea, designing to have him left
there with the governor of the province, as a prisoner of state, and
thus to rid himself of all responsibility about this very difficult and
perilous business. He ordered two centurions to draw out a
detachment, of such very remarkable strength, as shows the excess
of his fears for Paul. Two hundred heavy-armed soldiers, seventy
horsemen, and two hundred lancers, were detached as a guard for
Paul, and were all mounted for speed, to take him beyond the reach
of the Jerusalem desperadoes, that very night. He gave to that
portion of the detachment that was designed to go all the way to
Caesarea, a letter to be delivered to Felix the governor, giving a fair
and faithful account of all the circumstances connected with Paul’s
imprisonment and perils in Jerusalem.

return to caesarea.

The strong mounted detachment, numbering four hundred and

seventy full-armed Roman warriors, accordingly set out that night at
nine o’clock, and moving silently off from the castle, which stood
near one of the western gates of the city, passed out of Jerusalem
unnoticed in the darkness, and galloped away to the north-west.
After forty miles of hard riding, they reached Antipatris before day,
and as all danger of pursuit from the Jerusalem assassins was out of
the question there, the mounted infantry and the lancers returned to
Jerusalem, leaving Paul however, the very respectable military
attendance of the seventy horse-guards. With these, he journeyed to
Caesarea, only about twenty-five miles off, where he was presented
by the commander of the detachment to Felix, the Roman governor,
who always resided in Caesarea, the capital of his province. The
governor, on reading the letter and learning that Paul was of Cilicia,
deferred giving his case a full hearing, until his accusers had also
come; and committed him for safe keeping in the interval, to an
apartment in the great palace, built by Herod the Great, the royal
founder of Caesarea.

After a delay of five days, the high priest and the elders came
down to Caesarea, to prosecute their charges against Paul before
the governor. They brought with them, as their advocate, a speech-
maker named Tertullus, whose name shows him to have been of
Roman connections or education, and who, on account of his
acquaintance with the Latin forms of oratory and law, was no doubt
selected by Ananias and his coadjutors, as a person better qualified
than themselves to maintain their cause with effect, before the
governor. Tertullus accordingly opened the case, and when Paul had
been confronted with his accusers, began with a very tedious string
of formal compliments to Felix, and then set forth a complaint against
Paul in very bitter and abusive terms, stating his offense to be, the
attempt to profane the temple, for which the Jews would have
convicted and punished him, if Lysias had not violently hindered, and
put them to the trouble of bringing the whole business before the
governor, though a matter exclusively concerning their religious law.
To all his assertions the Jews testified.

This presentation of the accusation being made, Paul was then

called on for his defense, which he thereupon delivered in a tone
highly respectful to the governor, and maintained that he had been
guilty of none of the troublesome and riotous conduct of which he
was accused: but quietly, without any effort to make a commotion
among the people anywhere, had come into the city on a visit, after
many years absence, to bring alms and offerings; and that when he
was seized by the Asian Jews in the temple, he was going
blamelessly through the established ceremonies of purification. He
complained also, that his original accusers, the Asian Jews, were not
confronted with him, and challenged his present prosecutors to bring
any evidence against him. Felix, after this hearing of the case, on the
pretence of needing Lysias as a witness on the facts, deferred his
decision, and left both accusers and accused to the enjoyment of the
delays and “glorious uncertainties of the law.” Meanwhile he
committed Paul to the charge of a centurion, with directions that he
should be allowed all reasonable liberty, and should not be in any
particular restricted from the freest intercourse with his friends. The
imprisonment of Paul at Caesarea was merely nominal; and he must
have passed his time both pleasantly and profitably, with the
members of the church at Caesarea, with whom he had formerly
been acquainted, especially with Philip and his family. Besides
these, he was also favored with the company of several of his
assistants, who had been the companions of his toils in Europe and
Asia; and through them he could hold the freest correspondence with
any of the numerous churches of his apostolic charge throughout the
world. He resided here for two whole years at least, of Felix’s
administration; and during that time, was more than once sent for by
the governor, to hold conversations with him on the great objects of
his life, in some of which he expressed himself so forcibly on
righteousness, temperance and judgment to come, that the wicked
governor,――at that moment sitting in the presence of the apostle
with an adulterous paramour,――trembled at the view presented by
Paul of the consequences of those sins for which Felix was so
infamous. But his repentant tremors soon passed off, and he merely
dismissed the apostle with the vague promise, that at some more
convenient season he would send for him. He did indeed, often send
for him after this; but the motive of these renewals of intercourse
seems to have been of the basest order, for it is stated by the sacred
historian, that his real object was to induce Paul to offer him a bribe,
which he supposed could be easily raised by the contributions of his
devoted friends. But the hope was vain. It was no part of Paul’s plan
of action to hasten the decision of his movements by such means,
and the consequence was, that Felix found so little occasion to
befriend him, that when he went out of the office which he had
uniformly disgraced by tyranny, rapine, and murder, he thought it, on
the whole, worth while to gratify the late subjects of his hateful sway,
by leaving Paul still a prisoner.

“This Drusilla was the youngest daughter of Herod Agrippa. (Josephus lib. xix. c. 9. in.)
Josephus gives the following account of her marriage with Felix:――‘Agrippa, having
received this present from Caesar, (viz. Claudius,) gave his sister Drusilla in marriage to the
Azizus, king of the Emesenes, when he had consented to be circumcised. For Epiphanes,
the son of king Antiochus, had broken the contract with her, by refusing to embrace the
Jewish customs, although he had promised her father he would. But this marriage of
Drusilla with Azizus was dissolved in a short time, after this manner. When Felix was
procurator of Judaea, having had a sight of her, he was mightily taken with her; and indeed
she was the most beautiful of her sex. He therefore sent to her Simon, a Jew of Cyprus,
who was one of his friends, and pretended to magic, by whom he persuaded her to leave
her husband, and marry him; promising to make her perfectly happy, if she did not disdain
him. It was far from being a sufficient reason; but to avoid the envy of her sister Bernice,
who was continually doing her ill offices, because of her beauty, she was induced to
transgress the laws of her country, and marry Felix.’” (Lardner’s Credibility, 4to. Vol. I. p. 16,
17, edition, London, 1815.) [Williams on Pearson, p. 78.]

SYRACUSE. Acts xxviii. 12.

The successor of Felix in the government of Palestine, was

Porcius Festus, a man whose administration is by no means
characterized in the history of those times by a reputation for justice
or prudence; yet in the case of Paul, his conduct seems to have
been much more accordant with right and reason, than was that of
the truly infamous Felix. Visiting the religious capital of the Jews
soon after his first entrance into the province, he was there earnestly
petitioned by the ever-spiteful foes of Paul, to cause this prisoner to
be brought up to Jerusalem for trial, intending when Paul should
enter the city, to execute their old plan of assassination, which had
been formerly frustrated by the benevolent prudence and energy of
Claudius Lysias. But Festus, perhaps having received some
notification of this plot, from the friends of Paul, utterly refused to
bring the prisoner to Jerusalem, but required the presence of the
accusers in the proper seat of the supreme provincial administration
of justice at Caesarea. After a ten days’ stay in Jerusalem, he
returned to the civil capital, and with a commendable activity in his
judicial proceedings, on the very next day after his arrival in
Caesarea, summoned Paul and his accusers before him. The Jews
of course, told their old story, and brought out against Paul many
grievous complaints, which they could not prove. His only reply to all
this accusation without testimony was――“Neither against the law of
the Jews, nor against the temple, nor yet against Caesar, have I
offended in any particular.” But Festus having been in some way
influenced to favor the designs of the Jews, urged Paul to go up to
Jerusalem, there to be tried by the supreme religious court of his
own nation. Paul replied by a bold and distinct assertion of his rights,
as a Roman citizen, before the tribunal of his liege lord and sovran: “I
stand before Caesar’s judgment-seat, where I ought to be judged. To
the Jews I have done no wrong, as thou very well knowest. If I am
guilty of anything that deserves death, I refuse not to die; but if I
have done none of these things of which they accuse me, no man
can deliver me into their hands. I appeal to Caesar.” This solemn
concluding formula put him at once far beyond the reach of all
inferior tyranny; henceforth no governor in the world could direct the
fate of the appellant Roman citizen, throwing before himself the
adamantine aegis of Roman law. Festus himself, though evidently
displeased at this turn of events, could not resist the course of law;
but after a conference with this council, replied to Paul――“Dost
thou appeal to Caesar? To Caesar shalt thou go.”

While Paul was still detained at Caesarea, after this final reference
of his case to the highest judicial authority in the world, Festus was
visited at Caesarea, by Herod Agrippa II. king of Iturea, Trachonitis,
Abilene, and other northern regions of Palestine, the son of that
Herod Agrippa whose character and actions were connected with the
incidents of Peter’s life. He, passing through Judea with his sister
Bernice, stopped at Caesarea, to pay their compliments to the new
Roman governor. During their stay there, Festus, with a view to find
rational entertainment for his royal guests, bethought himself of
Paul’s case, as one that would be likely to interest them, connected
as the prisoner’s fate seemed to be, with the religious and legal
matters of that peculiar people to whom Agrippa himself belonged,
and in the minutiae of whose law and theology he had been so well
instructed, that his opinion on the case would be well worth having,
to one as little acquainted with these matters as the heathen
governor himself was. Festus therefore gave a very full account of
the whole case to Agrippa, in terms that sufficiently well exhibited the
perplexities in which he was involved, and in expressions which are
strikingly and almost amusingly characteristic,――complaining as he
does of the very abstruse and perplexing nature of the accusations
brought by the Jews, as being “certain questions of their own
religion, and of one Jesus, whom Paul affirmed to be alive.” Agrippa
was so much interested in the case that he expressed a wish to hear
the man in person; and Festus accordingly arranged that he should
the next day be gratified with the hearing.

“‘King Agrippa and Bernice.’ Acts. xxv. 13. This Agrippa was the son of Herod Agrippa;
St. Luke calls him king, which Josephus also does very often. (Antiquities lib. xx. c. viii. § 6,
et passim.) But St. Luke does not suppose him to be king of Judaea, for all the judicial
proceedings of that country relating to St. Paul, are transacted before Felix, and Festus his
successor; besides, he says, that ‘Agrippa came to Caesarea to salute Festus,’ to
compliment him on his arrival, &c. verse 1. When his father died, Claudius would have
immediately put him in possession of his father’s dominions, but he was advised not to do
so, on account of the son’s youth, then only seventeen; the emperor, therefore, ‘appointed
Cuspius Fadus praefect of Judea and the whole kingdom, (Josephus Antiquities lib. xix. c.
9, ad fin.) who was succeeded by Tiberius, Alexander, Cumanus, Felix, and Festus, though
these did not possess the province in the same extent that Fadus did.’ (Antiquities xx.
Jewish War lib. ii.)

“Agrippa had, notwithstanding, at this time, considerable territories. ‘Herod, brother of

king Agrippa the Great, died in the eighth year of the reign of Claudius. Claudius then gave
his government to the young Agrippa.’ (Josephus Antiquities xx. p. 887.) This is the Agrippa
mentioned in this twenty-fifth chapter. ‘The twelfth year of his reign being completed,
Claudius gave to Agrippa the tetrarchy of Philip and Batanea, adding also Trachonitis with
Abila. This had been the tetrarchy of Lysanias. But he took away from him Chalcis, after he
had governed it four years.’ (Josephus Antiquities xx. p. 890, v. 25, &c.) ‘After this, he sent
Felix, the brother of Pallas, to be procurator of Judea, Galilee, Samaria, and Peraea; and
promoted Agrippa from Chalcis to a greater kingdom, giving him the tetrarchy which had
been Philip’s. (This is Batanea, and Trachonitis, and Gaulonitis;) and he added, moreover,
the kingdom of Lysanias, and the province that had been Varus’s.’ (Josephus War of the
Jews lib. ii. c. 12. fin.) ‘Nero, in the first year of his reign, gave Agrippa a certain part of
Galilee, ordering Tiberias and Tarichaea to be subject to him. He gave him also Julias, a city
of Peraea, and fourteen towns in the neighborhood of it.’ (Antiquities xx. c. 7. § 4.) St. Luke
is therefore fully justified in styling this Agrippa king at this time.” (Lardner’s Credibility, 4to.
Vol. I. pp. 17, 18.) [Williams’s Pearson, p. 81, 82.]

On the next day, preparations were made for this audience, with a
solemnity of display most honorable to the subject of it. The great
hall of the palace was arrayed in grand order for the occasion, and,
in due time, king Agrippa, with his royal sister, and the Roman
governor, entered it with great pomp, followed by a train composed
of all the great military and civil dignitaries of the vice-imperial court
of Palestine. Before all this stately array, the apostolic prisoner was
now set, and a solemn annunciation was made by Festus, of the
circumstances of the prisoner’s previous accusation, trial, and
appeal; all which were now summarily recapitulated in public, for the
sake of form, although they had before been communicated in
private, to Agrippa. The king, as the highest authority present, having
graciously invited Paul to speak for himself, the apostle stretched
forth his hand and began, in that respectful style of elaborately
elegant compliment, which characterizes the exordiums of so many
of his addresses to the great. After having, with most admirable skill,
conciliated the attention and kind regard of the king, by expressing
his happiness in being called to speak in his own defense before one
so learned in Hebrew law, he went on; and in a speech which is well
known for its noble eloquence, so resplendent, even through the
disguise of a quaint translation, presented not merely his own case,