Case Studies in Infectious Disease - 1st Edition
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Peter M. Lydyard
Michael F. Cole
John Holton
William L. Irving
Nino Porakishvili
Pradhib Venkatesan
Katherine N. Ward
This edition published in the Taylor & Francis e-Library, 2010. Peter M. Lydyard, Emeritus Professor of
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Professor of Immunology, School of
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©2010 by Garland Science, Taylor & Francis Group, LLC
College London Hospital Foundation Trust,
London, UK. William L. Irving, Professor
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Senior Lecturer, School of Biosciences,
responsibility for the validity of all materials or for the consequences of
University of Westminster, London, UK
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and Honorary Professor, Javakhishvili
copyright heron may be reproduced or used in any format in any form
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Infectious Diseases, Nottingham University
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drug doses in this book are correct. Readers must check up to date
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ISBN 0-203-85687-2 Master e-book ISBN
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Library of Congress Cataloging-in-Publication Data
Case studies in infectious disease / Peter M Lydyard ... [et al.].
p. ; cm.
Includes bibliographical references.
SBN 978-0-8153-4142-0
1. Communicable diseases--Case studies. I. Lydyard, Peter M.
[DNLM: 1. Communicable Diseases--Case Reports. 2. Bacterial
Infections--Case Reports. 3. Mycoses--Case Reports. 4. Parasitic Diseases--
Case Reports. 5. Virus Diseases--Case Reports. WC 100 C337 2009]
RC112.C37 2009
616.9--dc22
2009004968
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Preface
The idea for this book came from a successful course in a medical school
setting. Each of the forty cases has been selected by the authors as being
those that cause the most morbidity and mortality worldwide. The cases
themselves follow the natural history of infection from point of entry of
the pathogen through pathogenesis, clinical presentation, diagnosis, and
treatment. We believe that this approach provides the reader with a logi-
cal basis for understanding these diverse medically-important organisms.
Following the description of a case history, the same five sets of core ques-
tions are asked to encourage the student to think about infections in a
common sequence. The initial set concerns the nature of the infectious
agent, how it gains access to the body, what cells are infected, and how the
organism spreads; the second set asks about host defense mechanisms
against the agent and how disease is caused; the third set enquires about
the clinical manifestations of the infection and the complications that can
occur; the fourth set is related to how the infection is diagnosed, and what
is the differential diagnosis, and the final set asks how the infection is man-
aged, and what preventative measures can be taken to avoid the infection.
In order to facilitate the learning process, each case includes summary bul-
let points, a reference list, a further reading list and some relevant reliable
websites. Some of the websites contain images that are referred to in the
text. Each chapter concludes with multiple-choice questions for self-test-
ing with the answers given in the back of the book.
In the contents section, diseases are listed alphabetically under the
causative agent. A separate table categorizes the pathogens as bacterial,
viral, protozoal/worm/fungal and acts as a guide to the relative involve-
ment of each body system affected. Finally, there is a comprehensive glos-
sary to allow rapid access to microbiology and medical terms highlighted
in bold in the text. All figures are available in JPEG and PowerPoint® for-
mat at www.garlandscience.com/gs_textbooks.asp
We believe that this book would be an excellent textbook for any course in
microbiology and in particular for medical students who need instant
access to key information about specific infections.
Happy learning!!
The authors
March, 2009
Acknowledgments
In writing this book we have benefited greatly from the advice of many microbiologists and immunologists. We would like to thank the
following for their suggestions in preparing this edition.
William R. Abrams (New York University College of Dentistry, University Medical Center, USA); Awewura Kwara (Warren
USA); Abhijit M. Bal (Crosshouse Hospital, UK); Keith Alpert Medical School of Brown University, USA); Jerika T.
Bodger (University of Liverpool, UK); Carolyn Hovde Bohach Lam (Loma Linda University, USA); Robert A. Lamb
(University of Idaho, USA); Robert H. Bonneau (The (Northwestern University, USA); Audrey Lenhart (Liverpool
Pennsylvania State University College of Medicine, USA); School of Tropical Medicine, UK); Michael D. Libman
Dov L. Boros (Wayne State University, USA); Thomas J. (McGill University, Canada); David Lindsay (Virginia
Braciale (University of Virginia Health Systems, USA); Technical University, USA); Dennis Linton (University of
Stephen M. Brecher (VA Boston Healthcare System USA); Manchester, UK); Martin Llewelyn (Brighton and Sussex
Patrick J. Brennan (Colorado State University, USA); Christine Medical School, UK); Diana Lockwood (London School of
M. Budke (Texas A&M University, USA); Neal R. Chamberlain Hygiene & Tropical Medicine, UK); Francesco A. Mauri
(A.T. Still University of Health Sciences/KCOM, USA); (Imperial College, UK); Don McManus (Queensland Institute
Dorothy H. Crawford (University of Edinburgh, UK); Jeremy of Medical Research, Australia); Keith R. Matthews (University
Derrick (University of Manchester, UK); Joanne Dobbins of Edinburgh, UK); Ernest Alan Meyer (Oregon Health and
(Bellarmine University, USA); Michael P. Doyle (University of Science University, USA); Manuel H. Moro (National
Georgia, USA); Sean Doyle (National University of Ireland); Institutes of Health, USA); Kristy Murray (The University of
Gary A. Dykes (Food Science Australia); Stacey Efstathiou Texas Health Science Center, USA); Tim Paget (The
(University of Cambridge, UK); Roger Evans (Raigmore Universities of Kent and Greenwich at Medway, UK); Andrew
Hospital, UK); Ferric C. Fang (University of Washington Pekosz (Johns Hopkins University, USA); Lennart Philipson
School of Medicine, USA); Robert William Finberg (Karolinska Institute, Sweden); Gordon Ramage (University of
(University of Massachusetts Medical School, USA); Joanne Glasgow, UK); Julie A. Ribes (University of Kentucky, USA);
Flynn (University of Pittsburgh School of Medicine, USA); Alan Bernard Rickinson (University of Birmingham, UK);
Scott G. Franzblau (University of Illinois at Chicago, USA); Adam P. Roberts (University College London, UK); Nina
Caroline Attardo Genco (Boston University School of Salama (Fred Hutchinson Cancer Research Center and
Medicine, USA); Geraldo Gileno de Sá Oliveira (Oswaldo University of Washington, USA); John W. Sixbey (Louisiana
Cruz Foundation, Brazil); John W. Gow (Glasgow Caledonian State University Health Sciences Center-Shreveport, USA);
University, UK); Carlos A. Guerra (University of Oxford, UK); Deborah F. Smith (York Medical School University of York,
Paul Hagan (University of Glasgow, UK); Anders P. Hakansson UK); John S. Spencer (Colorado State University, USA);
(SUNY at Buffalo, USA); Tim J. Harrison (University College Richard Stabler (London School of Hygiene & Tropical
London, UK); Robert S. Heyderman (Liverpool School of Medicine, UK); Catherine H. Strohbehn (Iowa State
Tropical Medicine, UK); Geoff Hide (University of Salford, University, USA); Sankar Swaminathan (University of Florida
UK); Stuart Hill (Northern Illinois University, USA); Stephen Shands Cancer Center, USA); Clive Sweet (University of
Hogg (University of Newcastle, UK); Malcolm J. Horsburgh Birmingham, UK); Clarence C. Tam (London School of
(University of Liverpool, UK); Michael Hudson (University of Hygiene & Tropical Medicine, UK); Mark J. Taylor (Liverpool
North Carolina at Charlotte, USA); Karsten Hueffer School of Tropical Medicine, UK); Yasmin Thanavala (Roswell
(University of Alaska Fairbanks, USA); Paul Humphreys Park Cancer Institute, USA); Christian Tschudi (Yale
(University of Huddersfield, UK); Ruth Frances Itzhaki University, USA); Mathew Upton (University of Manchester,
(University of Manchester, UK); Aras Kadioglu (University of UK); Juerg Utzinger (Swiss Tropical Institute, Switzerland);
Leicester, UK); A. V. Karlyshev (Kingston University, UK); Julio A. Vázquez (National Institute of Microbiology, Institute
Ruth A. Karron (Johns Hopkins University, USA); Stephanie of Health Carlos III, Spain); Joseph M. Vinetz (University of
M. Karst (Louisiana State University Health Sciences Center, California, San Diego, USA); J. Scott Weese (University of
USA); C. M. Anjam Khan (University of Newcastle, UK); Guelph, Canada); Lee Wetzler (Boston University School of
Peter G.E. Kennedy (University of Glasgow, UK); Martin Medicine, USA); Peter Williams (University of Leicester, UK);
Kenny (University of Bristol, UK); H. Nina Kim (University of Robert Paul Yeo (Durham University, UK); Qijing Zhang
Washington, USA); George Kinghorn (Royal Hallamshire (Iowa State University, USA); Shanta M. Zimmer (Emory
Hospital, UK); Michael Klemba (Virginia Polytechnic Institute University School of Medicine, USA); Prof G. Janossy
and State University, USA); Brent E. Korba (Georgetown (University College, London, UK).
vii
Table of Contents
Case 1 Aspergillus fumigatus 1 Case 24 Neisseria gonorrhoeae 303
Case 2 Borrelia burgdorferi and related species 19 Case 25 Neisseria meningitidis 315
Case 3 Campylobacter jejuni 33 Case 26 Norovirus 329
Case 4 Chlamydia trachomatis 41 Case 27 Parvovirus 339
Case 5 Clostridium difficile 63 Case 28 Plasmodium spp. 347
Case 6 Coxiella burnetti 73 Case 29 Respiratory syncytial virus 361
Case 7 Coxsackie B virus 99 Case 30 Rickettsia spp. 371
Case 8 Echinococcus spp. 107 Case 31 Salmonella typhi 383
Case 9 Epstein-Barr virus 115 Case 32 Schistosoma spp. 393
Case 10 Escherichia coli 129 Case 33 Staphylococcus aureus 403
Case 11 Giardia lamblia 139 Case 34 Streptococcus mitis 419
Case 12 Helicobacter pylori 149 Case 35 Streptococcus pneumoniae 429
Case 13 Hepatitis B virus 161 Case 36 Streptococcus pyogenes 439
Case 14 Herpes simplex virus 1 177 Case 37 Toxoplasma gondii 453
Case 15 Herpes simplex virus 2 187 Case 38 Trypanosoma spp. 463
Case 16 Histoplasma capsulatum 197 Case 39 Varicella-zoster virus 475
Case 17 Human immunodeficiency virus 217 Case 40 Wuchereria bancrofti 485
Case 18 Influenza virus 235
Case 19 Leishmania spp. 249
Case 20 Leptospira spp. 261 Glossary 495
Case 21 Listeria monocytogenes 269 Answers to Multiple Choice Questions 513
Case 22 Mycobacterium leprae 277 Figure Acknowledgments 566
Case 23 Mycobacterium tuberculosis 291 Index 573
viii
Pathogens by type and body systems affected
Guide to the relative involvement of each body system affected by the infectious organisms
described in this book: the organisms are categorized into bacteria, viruses, and
protozoa/fungi/worms.
Organism Resp MS GI H/B GU CNS CV Skin Syst L/H
Bacteria
Borrelia burgdorferi 4+ 1+ 1+
Campylobacter jejuni 4+ 2+
Chlamydia trachomatis 2+ 4+ 2+
Clostridium difficile 4+
Coxiella burnetti 4+ 4+
Escherichia coli 4+ 4+ 4+ 4+
Helicobacter pylori 4+
Leptospira spp. 4+ 4+ 4+
Listeria monocytogenes 2+ 4+ 2+ 4+
Mycobacterium leprae 2+ 4+
Mycobacterium tuberculosis 4+ 2+
Neisseria gonorrhoeae 4+ 2+
Neisseria meningitidis 4+ 4+
Rickettsia spp. 4+ 4+ 4+
Salmonella typhi 4+ 4+
Staphylococcus aureus 1+ 1+ 2+ 1+ 4+ 1+
Streptococcus mitis 1+ 4+
Streptococcus pneumoniae 4+ 4+
Streptococcus pyogenes 3+ 4+ 3+
Viruses
Coxsackie B virus 1+ 1+ 4+ 1+
Epstein-Barr virus 2+ 4+
Hepatitis B virus 4+
Herpes simplex virus 1 2+ 4+ 4+
Herpes simplex virus 2 4+ 2+ 4+
Human immunodeficiency virus 2+ 2+ 4+
Influenza virus 4+ 1+ 1+
Norovirus 4+
Parvovirus 2+ 3+ 4+ 2+
Respiratory syncytial virus 4+
Varicella-zoster virus 2+ 2+ 4+
INFECTIOUS ORGANISMS BY BODY SYSTEM ix
Protozoa/Fungi/Worms
Aspergillus fumigatus 4+ 1+ 2+
Echinococcus spp. 2+ 4+
Giardia lamblia 4+
Histoplasma capsulatum 3+ 1+ 4+
Leishmania spp. 4+ 4+
Plasmodium spp. 4+ 4+
Schistosoma spp. 4+ 4+ 4+
Toxoplasma gondii 2+ 4+
Trypanosoma spp. 4+ 4+ 4+
Wuchereria bancrofti 4+
The rating system (+4 the strongest, +1 the weakest) indicates the greater to lesser involvement of the body system.
KEY:
Resp = Respiratory: MS = Musculoskeletal: GI = Gastrointestinal
H/B = Hepatobiliary: GU = Genitourinary: CNS = Central Nervous System
Skin = Dermatological: Syst = Systemic: L/H = Lymphatic-Hematological
Case 1
Aspergillus fumigatus
A 68-year-old Caucasian man was diagnosed with B-cell
chronic lymphocytic leukemia (B-CLL) and received
various regimens of chemotherapy. As a patient with
chronic leukemia he attended the CLL clinic regularly. Ten
years later the patient presented with pneumonia
symptoms and was examined by chest CT scan. The
results were suggestive of aspergillosis and additional
laboratory tests were done. Positive Aspergillus serology
allowed the doctors in the clinic to give a diagnosis of
A. fumigatus pneumonia. The patient was not neutropenic
and his condition improved following an 8-month course
of itraconazole followed by voriconazole for 6 months.
Two years later the patient was diagnosed with
pulmonary aspergillosis. The diagnosis was based on a CT
scan, cytology results, and a history of prior infection
(Figure 1). He was treated with amphotericin B, monitored
by radiography, followed by caspofungin for 9 days, but he Figure 1. Chest X-ray showing that the fungus has
died 2 days later of drug discontinuation. An autopsy was invaded the lung tissue. There is a large cavity in the upper
performed and the diagnosis of invasive pulmonary left lobe of the lung, with a fungus ball within the cavity.
aspergillosis was confirmed.
1. What is the causative agent, how does it enter the body and
how does it spread a) within the body and b) from person to
person?
Causative agent
Aspergillosis is caused by Aspergillus, a saprophytic, filamentous fungus
found in soil, decaying vegetation, hay, stored grain, compost piles,
mulches, sewage facilities, and bird excreta. It is also found in water stor-
age tanks (for example in hospitals), fire-proofing materials, bedding, pil-
lows, ventilation and air conditioning, and computer fans. It is a frequent
contaminant of laboratory media and clinical specimens, and can even
grow in disinfectants!
Although Aspergillus is not the most abundant fungus in the world, it is one
of the most ubiquitous. There are more than 100 species of Aspergillus.
Although about 10 000 genes have been identified in the Aspergillus
genome, none of the gene sets is shared with other fungal pathogens.
The cell wall of A. fumigatus contains various polysaccharides (Figure 2).
Newly synthesized b(1-3)-glucans are modified and associated to the other
cell wall polysaccharides (chitin, galactomannan, and b(1-3)-, b(1-4)-glucan)
2 CASE 1 • ASPERGILLUS FUMIGATUS
Figure 2. Three-dimensional schematic
representation of the Aspergillus
fumigatus cell wall.
100 nm
GPI β1-3-glucans amorphous chitin protein transmembrane
anchored polysaccharide (antigen) enzyme
protein (α1,3 glucan, (glucan-,
galactomannan) chitin synthase)
leading to the establishment of a rigid cell wall. Glycosyltransferases bound
to the membrane by a glycosylphosphatidyl inositol (GPI) anchor play a
major role in the biosynthesis of the cell wall. Fungal cell composition affects
its virulence and susceptibility to immune responses.
Of over 100 species of Aspergillus only a few are pathogenic, most of all
A. fumigatus, but other species, including A. niger, A. terreus, A. flavus,
A. clavatus, and A. nidulans, have also been implicated in pulmonary aller-
gic disorders. However, other than A. fumigatus, Aspergillus species do not
normally grow at temperatures higher than 37∞C, and therefore do not
cause invasive disease (see Section 3). A. nidulans can cause occasional
infections in children with chronic granulomatous disease.
A. fumigatus is a primary pathogen of man and animals. It is characterized
by thermotolerance: ability to grow at temperatures ranging from 15∞C to
55∞C, it can even survive temperatures of up to 75∞C. This is a key feature
for A. fumigatus, which allows it to grow over other aspergilli species and
within the mammalian respiratory system.
A. fumigatus is a fast grower. It reproduces by tiny spores formed on spe-
cialized conidiophores. A. fumigatus sporulates abundantly, with every
conidial head producing thousands of conidia. The conidia released into
the atmosphere range from 2.5 to 3.0 mm in diameter and are small enough
to fit in the lung alveoli. The spores are easily airborne both indoors and
outdoors since their small size makes them buoyant. There is no special
CASE 1 • ASPERGILLUS FUMIGATUS 3
mechanism for releasing the conidia, it is simply due to the disturbances of
the environment and air currents. When inhaled the spores are deposited
in the lower respiratory tract (see below, Section 2).
A. fumigatus can be identified by the morphology of the conidia and coni-
diophores. The organism has green-blue echinulate conidia produced in
chains basipetally from greenish phialides (Figure 3). A few isolates are
nonpigmented and produce white conidia. A. fumigatus strains with col-
ored conidia indicate the presence of accumulated metabolites and are
more virulent than nonpigmented strains since they give the fungus an
advantage to adapt to its environment. Figure 3. Microscopic morphology of
Aspergillus fumigatus showing typical
In the past A. fumigatus was considered as an “asexual” fungus. Recent conidial heads. Conidiophores are short,
studies, however, have indicated the existence of a fully-functional sexual smooth-walled, and have conical shaped
reproductive cycle. terminal vesicles, which support a single
row of phialides. Conidia are produced in
basipetal succession forming long chains.
Entry and spread within the body
They are green and rough-walled to
We normally inhale 100–200 Aspergillus conidial spores daily, but only sus- echinulate. Chains of spores can be seen
ceptible individuals develop a clinical condition. The spores enter the body emerging from phialides surrounding
via the respiratory tract and lodge in the lungs or sinuses. Once inhaled, the head.
spores can reach distal areas of the lung due to their small size. Very rarely
other sites of primary infection have been described such as the skin, peri-
toneum, kidneys, bones, eyes, and gastrointestinal tract, but these are not
clinically important. Usually the invasion of other organs by A. fumigatus
is secondary and follows its spread from the respiratory tract.
When Aspergillus spores enter the human respiratory system at body tem-
perature they develop into a different form, thread-like hyphae, which
absorb nutrients required for the growth of the fungus. Some enzymes,
particularly proteases, are essential for this fungal pathogen to invade the
host tissue. Proteases are involved in the digestion of the lung matrix com-
posed of elastin and collagen. In the case of infection of respiratory tissues,
this contributes to the pathogenesis (see Section 3). Together the hyphae
can form a dense mycelium in the lungs. However, in the case of healthy
immunocompetent individuals the spores are prevented from reaching this
stage due to optimal immune responses (see Section 2), and there is some
colonization but limited pathology.
Aspergillus species are essentially ubiquitous in the environment world-
wide, and no geographic preference of the exposure to airborne conidia or
spores has been reported.
Person to person spread
This organism is not spread from person to person.
Until recently, A. fumigatus was considered a causative factor of mainly
allergic conditions such as farmer’s lung. However, over the past 20 years,
due to the increase in aggressive immunosuppressive therapies and the AIDS
pandemic, the number of immunocompromised patients developing
aspergillosis has grown significantly. Thus severe and often fatal invasive
infections with A. fumigatus have increased several times in developed coun-
tries and it has become the dominant airborne fungal pathogen.
4 CASE 1 • ASPERGILLUS FUMIGATUS
2. What is the host response to the infection and what is the
disease pathogenesis?
When the fungi colonize the respiratory tract the clinical manifestation
and the severity of the disease depend on the efficiency of the immune
responses. In susceptible hosts, Aspergillus conidia germinate to form
swollen conidia and then progress to hyphae, its invasive form. The main
goal of the immune system is to recognize and kill Aspergillus conidia and
to prevent its transition to the hyphal form.
Mechanical barriers and innate immunity
In immunocompetent hosts, innate immunity to the inhaled spores begins
with the mucous layer and the ciliated epithelium of the respiratory tract. The
majority of the conidia are normally removed from the lungs through the
ciliary action. However, A. fumigatus can produce toxic metabolites such as
gliotoxin, which inhibit ciliary activity, and proteases which can damage the
epithelial tissue.
Because of the site of the infection by A. fumigatus, bronchoalveolar
macrophages – the resident phagocytic cells of the lung, together with
recruited neutrophils, are the major cells involved in the phagocytosis of
A. fumigatus. While macrophages mostly attack conidia, neutrophils are
more important for elimination of developing hyphae.
Bronchoalveolar macrophages sense A. fumigatus through pathogen-
associated membrane patterns (PAMPs) on the conidia via their Toll-
like receptors TLR2 and TLR4, followed by engulfment and phagocyto-
sis. Inhaled conidia via galactomannan bind some soluble receptors such as
pentraxin-3 and lung surfactant protein D. This enhances phagocytosis
and inflammatory responses. Phagosomes containing conidia fuse with
endosomes followed by activation of NADPH oxidase-dependent
killing. Nonoxidative mechanisms are also essential for the digestion of
phagocytosed conidia by macrophages. Swelling of the conidia inside the
macrophage appears to be a prerequisite for fungal killing. Conidial
swelling inside macrophages or in the bronchoalveolar space alters cell
wall composition and exposes fungal b-glucan. This further triggers fun-
gicidal responses via mammalian b-glucan receptor dectin-1. However, the
killing is delayed and quite slow and a total distruction of inhaled conidia
by alveolar macrophages has never been reported. A. fumigatus is often
able to block phagocytosis by producing hydrophobic pigments – melanins
such as conidial dihydroxynaphthalene-melanin. Melanins are expressed
on the conidial surface and protect the pathogen by quenching reactive
oxygen species (ROS).
In the cases when resident bronchoalveolar macrophages fail to control the
fungus, conidia germinate into hyphae. Neutrophils and monocytes are
then recruited from the circulation to phagocytose and kill hyphae.
Neutrophils adhere to the surface of the hyphae, since hyphae are too large
to be engulfed. They are often seen clustered around fungal hyphae. This
triggers a respiratory burst, secretion of ROS, release of lysozyme,
neutrophil cationic peptides, and degranulation of neutrophils. NADPH
CASE 1 • ASPERGILLUS FUMIGATUS 5
oxidase-independent killing through the release of lactoferrin, an iron-
sequestering molecule, is important. In contrast to the slow and sub-
efficient killing of conidia by macrophages, hyphal damage by neutrophils
is rapid, possibly through a release of fungal cell wall glycoproteins with
the help of polysaccharide hydrolases produced by the neutrophils.
Defensins may also play a role in responses to A. fumigatus hyphae. A
defense mechanism of the pathogen is that it produces oxidoreductases,
which could neutralize phagocytic ROS.
The importance of neutrophils in protection against Aspergillus is illus-
trated by a development of invasive aspergillosis in immunodeficient
patients with chemotherapy-induced neutropenia. Corticosteroid-based
treatment, purine analogs (fludarabine) and some monoclonal antibody
treatment (Campath 1H – anti-CD52) and immunosuppression lead to
neutropenia and/or neutrophil dysfunction. Corticosteroids reduce the
oxidative burst and superoxide anion release by neutrophils, thereby
inhibiting hyphal killing.
Platelets also play some role in protection against Aspergillus. They attach to
the cell walls of invasive hyphae and become activated, thus enhancing direct
cell wall damage of A. fumigatus and neutrophil-mediated fungicidal effect.
Hence thrombocytopenia, which is associated with prolonged neutropenia
during chemotherapy, increases the risk of infection by A. fumigatus.
Invasion with A. fumigatus enhances the levels of serum fibrinogen,
C-reactive protein, and other acute-phase proteins. Resting conidia acti-
vate the alternative complement pathway, and induce neutrophil chemo-
taxis and deposition of complement components on the fungal surface. To
combat this, A. fumigatus produces a specific lipophilic inhibitor of the
alternative complement pathway and enhances proteolytic cleavage of C3
complement component bound to conidia by molecules present in the
outer wall.
Antigen-presenting dendritic cells (DCs) exposed to hyphae in the lung
migrate to the spleen and draining lymph nodes where they launch periph-
eral T helper (Th)-cell responses.
Adaptive immunity
T-cell responses
T-cell responses against A. fumigatus are mostly confined to the CD4+
T cells. To a certain extent their efficiency resides in the ability of Th1
cells to further enhance neutrophil-mediated killing. A Th1 response,
associated with a strong cellular immune component and increased levels
of IFN-gg, granulocyte and granulocyte-macrophage colony-stimulating
factors (G-CSF and GM-CSF), TNF-a a, interleukin-1 (IL-1), IL-6,
IL-12, and IL-18, provides resistance to mycotic disease. Th1
proinflammatory signals recruit neutrophils into sites of infection. TNF-a
enhances the capacity of neutrophils to damage hyphae; G-CSF, GM-CSF,
and especially IFN-g enhance monocyte and neutrophil activity against
hyphae; while IL-15 enhances hyphal damage and IL-8 release by
neutrophils. IL-8 recruits more neutrophils to sites of inflammation and
mediates release of antimicrobial peptides.
