Mucosal Immunology and Virology

217 Pages·2006·4.86 MB·English

by  Vandana Madkan M.D.

Mucosal Immunology and Virology
Stephen K. Tyring (Ed.)
Mucosal Immunology
and Virology
Stephen K.Tyring
Departments of Dermatology,Microbiology &
Molecular Genetics and Internal Medicine
The University of Texas Health Science Center
Houston,TX
USA
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Preface
Mucosal immunity plays a very promi- immunological memory, thus providing
nent role in protection against viruses protection against reinfection.
and other infectious agents in the gas- Public health measures are ofprimary
trointestinal tract, in the eyes, in the importance in preventing the immune
anogenital mucosa and in the respiratory system from being overwhelmed with
tract. Because the gastrointestinal (GI) infectious organisms. Such measures
tract is the largest and most complex of include sanitation, hand washing, use
these systems, the greatest attention in of masks, gloves and condoms, blood
this text has been given to the GI testing,discouraging sharing of needles,
tract. Therefore, separate chapters are etc.Since 1797 vaccines have also played
devoted to the virology and the mucosal an important role in prevention of viral
immunology ofthe gastrointestinal tract. infection/disease. Interestingly, some
A third chapter focuses on the proximal vaccines against mucosal infection
end of the gastrointestinal tract (i.e.the appear to work when administered via
oral cavity). The mucosal immunology injection or by direct exposure to MALT.
and virology of the distal end of the For example, both intranasal and
gastrointestinal tract is covered in the injectable influenza vaccines are avail-
chapter on the anogenital mucosa. able,as are both oral and injectable forms
Mucosa-associated lymphoid tissue ofthe polio vaccine.Other vaccines given
(MALT) plays a role in protection against by the nasal,oral or anogenital mucosal
all viral (and other) infections except routes are under study.Not only can the
those that enter the body via a bite (e.g. route of administration be critical in
yellow fever or dengue from a mosquito maximum induction of the mucosal
or rabies from a dog) or an injection or immune response,the adjuvant also plays
transfusion (e.g. HIV, Hepatitis B). In an important role, as was seen in the
these cases where a break in the skin is marked difference in efficacy between
necessary for viral entry, peripheral protective and non-protective herpes
(i.e. systemic) immunity plays a greater simplex virus vaccines.
role. Peripheral immunity is primarily Three vaccines were recently approved
controlled by the bone marrow, lymph by the United States Food and Drug
nodes and spleen. Both systems involve Administration. Two of these vaccines,
humoral and cell mediated immunity,but RotaTeq and Gardasil,stimulate mucosal
their immune functions also can be immunity.RotaTeq is an oral pentavalent
divided into innate and adaptive immu- vaccine approved for prevention of
nity. Innate immunity provides a rapid rotavirus infection, the most important
response to a new antigen and sets the cause of severe infantile gastroenteritis
stage for the adaptive response; innate worldwide. Gardasil is a quadrivalent
immunity is pathogen nonspecific and (injectable) vaccine approved for preven-
has no recall.On the other hand,adaptive tion of human papillomavirus (HPV)
immunity is organism/antigen-specific, types 16 and 18, the leading causes of
is involved in disease recovery, has cervical cancer worldwide,as well as for
v
vi Preface
prevention of HPV types 6 and 11, the that infected the patient decades earlier.
leading causes of condyloma acumina- Future vaccines will be designed to safely
tum.The third,recently-approved vaccine boost mucosal immunity using innova-
is Zostavax which will be used for the pre- tive routes, adjuvants and carriers (e.g.
vention ofherpes zoster and postherpetic fruits and vegetables) and may include
neuralgia.Therefore,this vaccine will not new therapeutic as well as prophylactic
be used in the classic sense as a prophy- vaccines.
lactic vaccine,but rather will be given to
prevent the clinical reappearance ofvirus Stephen K.Tyring
Contents
List ofContributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ix
1 The Role ofMucosal Immunity in Protection against Viral Diseases
Vandana Madkan,Karan Sra,and Stephen K.Tyring . . . . . . . . . . . . . . 1
2 Anogenital Mucosal Immunology and Virology
Anthony Simmons . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
3 Gastrointestinal Mucosal Immunology
David A.Bland,Carlos A.Barrera,and Victor E.Reyes . . . . . . . . . . . . . 23
4 Virology ofthe Gastrointestinal Tract
Richard L.Ward,Xi Jiang,Tibor Farkas,and Dorsey M.Bass . . . . . . . . . 55
5 Oral Manifestations ofViral Diseases
Denis P.Lynch . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 99
6 Common Respiratory Viruses and Pulmonary Mucosal Immunology
David B.Huang . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 157
7 Ophthalmic Manifestations ofViral Diseases
Steven Yeh and Mitchell P.Weikert . . . . . . . . . . . . . . . . . . . . . . . . 179
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 207
vii
List of Contributors
Carlos A.Barrera,Ph.D. Victor V.Reyes,Ph.D.
Department of Pathology Departments of Pediatrics and
University of Texas Medical Branch Microbiology and Immunology
Galveston,TX,USA University of Texas Medical Branch
Galveston,TX,USA
Dorsey M.Bass,M.D.
Department of Pediatrics Anthony Simmons,M.D.,Ph.D.
Stanford University Department of Pediatrics
Palo Alto,CA,USA University of Texas Medical Branch
Galveston,TX,USA
David A.Bland,B.S.,M.S.
Microbiology and Immunology Karan Sra,M.D.
University of Texas Medical Branch Center for Clinical Studies
Galveston,TX,USA Houston,TX,USA
Tibor Farkas,D.V.M.,Ph.D. Stephen K.Tyring,M.D.,Ph.D.,M.B.A.
Division of Infectious Diseases Departments of Dermatology,
Cincinnati Children’s Hospital Medical Microbiology & Molecular Genetics
Center and Internal Medicine
Cincinnati,OH,USA University of Texas Health Science
Center
David B.Huang,M.D.,Ph.D.,M.P.H. Houston,TX,USA
Division of Infectious Diseases
Department of Medicine Richard L.Ward,Ph.D.
Baylor College of Medicine Division of Infectious Diseases
Houston,TX,USA Cincinnati Children’s Hospital Medical
Center
Xi Jiang,Ph.D. Cincinnati,OH,USA
Division of Infectious Diseases
Cincinnati Children’s Hospital Medical Mitchell P.Weikert,M.D.,M.S.
Center Department of Ophthalmology
Cincinnati,OH,USA Cullen Eye Institute
Houston,TX,USA
Vandana Madkan,M.D.
Center for Clinical Studies Steven Yeh,M.D.
Houston,TX,USA Department of Ophthalmology
Cullen Eye Institute
Denis P.Lynch,D.D.S.,Ph.D. Houston,TX,USA
Department of Surgical Sciences
Marquette University School of
Dentistry
Milwaukee,Wisconsin,USA
ix
1
The Role of Mucosal Immunity in Protection against
Viral Diseases
Vandana Madkan,Karan Sra,and Stephen K.Tyring
The study of mucosal immunity has provided once thought to be non-infectious,such as some
incredible insight into the human body’s cancers,have now been shown to have an infec-
complex and intricate system of battling the tious etiology. Cervical cancer, for example, is
many viruses and other pathogens it encounters one ofthe most common cancers among women
on a daily basis.Mucosal surfaces,which collec- in the developing world.It is now known to be
tively form an area larger than one and one half associated with human papillomavirus infec-
football fields (1,2),are mucus-secreting mem- tion, a disease spread through infection of the
branes lining all body cavities or passages that mucosa of the anogenital tract (1).
communicate with the exterior.They are located Surprisingly, despite the fact that the over-
primarily in the gastrointestinal,urogenital,and whelmingly majority of infectious agents pene-
respiratory tracts and are portals of entry for trate the human body at these mucosal surfaces,
disease-causing organisms. In fact, the great most vaccines developed thus far were designed
majority ofpathogens enter via the mucosa,with to target the peripheral immune system.As the
few exceptions such as infections that are intro- counterpart to the mucosal immune system,
duced via arthropod or other bites,injections,or the peripheral immune system is made up ofthe
blood transfusions (1). The body is dependent bone marrow, lymph nodes, and spleen and
on immune cells and antibodies present in the relies on presentation of foreign antigens to
mucosal lining to protect it against the onslaught lymph nodes via the lymph fluid. Peripheral
oforganisms to which it is exposed;therefore,it immunity is known to fight an infection once it
comes as no surprise that the human gastroin- has entered the body and stops the infection
testinal tract contains more lymphocytes than from causing disease. The mucosal immune
all other lymphoid organs (components of the system, however, defeats the pathogen at the
peripheral immune system) combined (3). mucosal barrier and prevents infection from
Many ofthe world’s most devastating diseases occurring (5).Although several vaccines,includ-
are spread via mucosal infection.According to ing all traditionally recommended childhood
the World Health Report of 2004 conducted by vaccines, are injectable and therefore would
WHO,more than 90% ofthe world’s deaths from likely stimulate the peripheral immune system,
infectious diseases are caused by the following it is unclear if they provide adequate mucosal
six disease processes: lower respiratory infec- immunity as measured by secretory IgA,etc.(6).
tions, HIV/AIDS, diarrheal diseases, tuberculo- For instance, studies conducted comparing
sis, malaria and measles. Combined, they kill the immune response to inactive poliovirus
greater than 13 million persons yearly (4). Of vaccine (IPV) and oral poliovirus vaccine (OPV)
these six diseases, five are primarily spread by revealed that IPV alone could not induce a suffi-
mucosal infection,with malaria being the only cient mucosal immune response;however,ifthe
significant exception (3). Even certain diseases IPV was given in individuals already “primed”
1
2 Mucosal Immunology and Virology
with the oral vaccine, a sufficient mucosal rently available oral cholera vaccines have been
response was generated (7).With both natural shown to be effective and may even provide
infection and OPV,secretory IgA is seen at the community protection (10). The most com-
mucosal surfaces of exposed individuals. IPV monly employed vaccine (Dukoral) is made ofa
has been shown to produce a strong IgA recombinant toxin subunit and inactive whole
response in recipients,but only in those persons cholera cells. The vaccine has been shown to
who have previously had a natural infection or stimulate IgA production in the intestinal
oral vaccination.If there was no previous infec- mucosa (9).
tion, IPV vaccinees would remain susceptible Rotavirus is noted to be the most common
to mucosal infection with the polio virus. If cause of infectious diarrhea worldwide and is
exposed and infected,they may remain asymp- noted to be responsible for 20% ofdeaths due to
tomatic,but still able to spread disease to others infectious diarrhea (8). The virus kills almost
who are not fully vaccinated.The overall signif- half a million children globally each year (9).
icance of this finding is incredibly important In the United States, its peak incidence is the
if mankind is to truly eradicate poliomyelitis. winter months.Two new oral vaccines are being
In communities where IPV recipients,who can developed in attempt to decrease the number of
contribute to the transmission of the virus, people afflicted each year.RotaRix and RotaTeq
remain in contact with those with low vaccine are both attenuated oral viruses shown to be effi-
rates,and therefore have no mucosal or periph- cacious in certain populations and are currently
eral protection against the disease,epidemics of undergoing further clinical trials (9).
poliovirus could ravage human life. This very Enteric infections are the second deadliest
situation has been observed in the Netherlands infections in children worldwide, behind only
in small religious communities in 1978 and 1992 respiratory infections. Perhaps the most well
that were not vaccinated,but still in contact with known etiology of lower respiratory infections
those populations who were (7).Since an entirely is the influenza virus,whose natural variability
oral vaccination series may carry its own mor- and genomic mutations can cause epidemics
bidity,a suitable solution may be to initially vac- and even pandemics,killing millions each year.
cinate with OPV and use IPV boosters (7). Statistics cite 20,000 deaths annually in the US
As more insight is gained regarding the alone and tens of thousands hospitalized (11)
immune system and its complex pattern of with a large financial burden placed upon even
response with regard to the interplay between industrialized countries. Standard vaccinations
peripheral and mucosal immunity, research is against the influenza virus have been adminis-
leading to improved vaccines.Due to the knowl- tered for years in the United States,with prefer-
edge that mucosal defense can provide an advan- ence given to those individuals most likely to
tage over peripheral immunity in preventing suffer significant morbidity and mortality from
infection and that traditional vaccines may not the disease, e.g. people over the age of 65 or
provide mucosal immunity,several new vaccines those with chronic medical conditions, etc.
targeting mucosal response are being studied. The influenza vaccine used more commonly
As mentioned above, enteric infections cause within the United States is an injectable vaccine
impressive morbidity and mortality, especially targeting the peripheral immune system which
in the developing world, and are spread by produces a serum IgG antibody response. An
mucosal transmission. Each year, 2 million occasional mucosal protective effect has also
children worldwide die from enteric infections been documented (9) but this also includes
with 400 ofthose deaths occurring in the United more mucosal IgG than IgA. However, the
States (8). Possible etiologic agents include newly licensed,more readily dispensed vaccine,
viruses such as rotavirus and noroviruses as well FluMist, is intranasally administered and is
as invasive bacteria such as E.coli and shigella, shown to provide immunity more comparable to
or toxic bacteria including Cholera species.The immunity gained from a natural infection.
injectable cholera vaccine, which was designed Natural infection is more likely to provide long
to prevent infection with V.cholerae,was judged term immunity,with an IgA response noted in
largely ineffective (9).However,as this virulent nasal washings and an IgG response in the lower
pathogen is responsible for severe outbreaks and respiratory tract.It protects against reinfection
occasional epidemics of diarrhea, attempts to of the offending virus as well as against anti-
develop a mucosal vaccine were launched.Cur- genically similar strains (11).Similarly,live virus