Immunity to Protozoa
Martin Rollinghoff, University Erlangen-Nurnberg, Erlangen, Germany
Christian Bogdan, University Erlangen-Nurnberg, Erlangen, Germany
Andre Gessner, University Erlangen-Nurnberg, Erlangen, Germany
Michael Lohoff, University Erlangen-Nurnberg, Erlangen, Germany
Protozoan parasites that enter their host are often able to survive and multiply
since they are adapted to the hosts immune system.
Relative Role of B and T Cells in
Immunity to Protozoa
Parasites with complex life cycles often stimulate both
antibody- and cell-mediated defence mechanisms, whose
eectiveness depends on the particular parasite and the
stage of infection. Malaria, which is caused by dierent
species of plasmodia, ranks amongst the most common
and important parasitic diseases. Infection of humans is
initiated by the bite of an infected mosquito, resulting in the
injection of sporozoite stages. The sporozoite enters
hepatocytes where asexual reproduction (schizogony)
takes place. Rupture of the infected cells releases thou-
sands of merozoites, which then penetrate red blood cells to
initiate repeated erythrocytic cycles. Thus, the dierent
stages of the parasite occur inside cells that either express
(e.g. hepatocytes) or lack (e.g. erythrocytes) major
histocompatibility complex (MHC) class I or class II
molecules. Since T cells are able to recognize parasite
antigens only as processed peptides presented by appro-
priate MHC molecules, extracellular forms of the parasite,
or parasite stages in erythrocytes devoid of the presenta-
tion machinery, are controlled mainly by antibody-
dependent acquired immune eector mechanisms. How-
ever, the immunological control is only partial: complete
elimination of plasmodia is not achieved.
Role of antibodies
In both humans and mice, passive transfer of antibodies
from immune individuals to those suering from acute
malaria results in quick and marked reduction of
parasitaemia. In addition, infection with Plasmodium
berghei and P. yoelii cannot be controlled in mice from
which B cells have been removed by neonatal anti-m
treatment (Grun and Weidanz, 1981). The elimination of
parasites is also impaired in mice with targeted gene
deletions resulting in B-cell deciency (van der Heyde et al.,
1994; von der Weid et al., 1996). While immunoglobulin
(Ig) G2a is essential in the mouse model (White et al., 1991),
IgG1 and IgG3 (Groux and Gysin, 1990) appear to be most
eective in humans.
ENCYCLOPEDIA OF LIFE SCIENCES / & 2001 Nature Publishing Group / www.els.net
Secondary article
Article Contents
. Relative Role of B and T Cells in Immunity to Protozoa
. Protection Versus Susceptibility Mediated by T helper
Type 1 Versus Type 2 Cells
. Role of CD41 Versus CD81 T Cells
in the Control of Parasitic Diseases
. Pathological Consequences of the Immune Response:
Autoimmunity (Trypanosoma cruzi)
. Role of Antigenic Variation (African Trypanosomes)
. Summary
IgG1 and IgG3 in humans and IgG2a in mice are
cytophilic immunoglobulin isotypes that are able to
promote activation of monocytes and macrophages via
Fc receptors. The antibody-dependent killing of parasites
in vitro is dependent on the presence of either mouse
neutrophils or human monocytes. One mechanism possi-
bly involved in this antibody activity is the induction of
tumour necrosis factor (TNF) a secretion by monocytes,
leading to growth inhibition of intracellular parasites in
neighbouring cells.
Selective agglutination of infected erythrocytes is con-
sistently associated with reduced parasite density. Opso-
nizing and agglutinating antibodies recognize a group of
large proteins inserted in the red cell membrane by mature
asexual blood stage parasites. These proteins, which
interact with a variety of endothelial receptors such as
CD36, E-selectin, thrombospondin, vascular cell adhesion
molecule 1 and intercellular adhesion molecule 1, play a
critical role in the retention of infected erythrocytes in the
blood vessels and, thereby, protect the parasite from
sequestration in the spleen. Thus, an important function of
antimalaria antibodies may be the inhibition of endothe-
lial]blood cell interaction which ultimately promotes the
elimination of infected erythrocytes by phagocytes in the
spleen.
Role of T cells
Two stages of the malaria parasite are truly intracellular:
the sporozoites that infect the hepatocytes and the asexual
merozoite stage that resides in red blood cells. Infection
with plasmodia stimulates both CD41 and CD81 T cells
expressing an ab or a gd T-cell receptor (TCR). While mice
genetically decient for ab TCR T cells are very susceptible
to P. chabaudi chabaudi infection and die rapidly after
infection, there is no dierence between gd TCR-decient
mice and control mice (Langhorne et al., 1995; Sayles and
Rakhmilevich, 1996). CD81 T cells mediate killing of the
liver stage of plasmodia, possibly by producing cytokines
(interferon g (IFN-g), TNF) which induce the production
1
 Immunity to Protozoa
of nitric oxide by infected hepatocytes (Homan et al.,
1996).
The central role of CD41 T cells in the protective
immunity against the asexual blood stages of experimental
malaria has been shown by in vivo cell depletion analysis
and by cell transfer studies. Since transfer of puried
CD41 T cells or CD41 T-cell lines to severe combined
immunodecient or lethally irradiated mice clears the
infection only in the presence of B cells, T]B-cell
interaction is thought to be required for the establishment
of a fully protective immune response to malaria parasites.
In plasmodia-infected mice both T helper (TH) 1-type
and TH2-type CD4 T cells are involved in protective
immunity (Taylor-Robinson et al., 1993). However, the
relative contribution of these subsets changes during the
course of infection: TH1 cells predominate during the acute
phase, and TH2 cells are found primarily during later
phases of infection. The protective eect of transferred TH1
cells in mice infected with P. chabaudi chabaudi can be
blocked by inhibitors of inducible nitric oxide synthase
(iNOS), whereas resistance conferred by TH2 cells is not
aected (Taylor-Robinson et al., 1993). Even in the case of
TH1 cells, there appear also to be nitric oxide-independent
mechanisms of protection, as shown in P. yoelii-infected
mice (Amante and Good, 1997). Protective TH2 cell clones
specic for P. chabaudi chabaudi drive a strong protective
malaria-specic IgG1 response in vivo (see above), which is
promoted by interleukin (IL) 4.
Given the central protective role of CD41 T cells in
murine models of malaria, it is still puzzling that there is no
major eect of the human immunodeciency virus pan-
demic on the incidence or severity of human malaria as has
been observed for tuberculosis, toxoplasmosis and leish-
maniasis. It has been speculated that progression to
acquired immune deciency syndrome (AIDS) involves a
preferential depletion of TH1-type CD4 T cells and not
TH2-type cells, and that the latter might be sucient to
maintain a protective antibody-mediated immunity to
malaria.
Protection Versus Susceptibility
Mediated by T helper Type 1 Versus
Type 2 Cells
T cells can be subdivided on the basis of the expression of
the proteins CD4 and CD8 into the CD41 and CD81
subsets which have helper functions for other cells of the
immune system and cytolytic functions, respectively. After
description of these subsets, CD41 T cells with mutually
exclusive helper functions were identied: those that
stimulate antibody production and others that mediate
delayed-type hypersensitivity. In 1986, the basis for these
dierent functions was discovered by the description of
2 ENCYCLOPEDIA OF LIFE SCIENCES / & 2001 Nature Publishing Group / www.els.net
two types of T helper cells which diered by the pattern of
cytokines they produced. TH1 cells were dened as
producers of IL-2, IFNg and TNFb, whereas TH2 cells
produced IL-4, IL-5, IL-6, IL-9, IL-10 and IL-13. Later, it
was shown that TH1 and TH2 cells develop from identical
precursor cells under dierent stimulatory conditions
which include the presence of IL-12 (for TH1 cells) or
IL-4 (for TH2 cells).
The denition of TH1 and TH2 cells was originally
derived from results obtained from long-term in vitro
cultured T-cell clones. The rst model demonstrating that
similar patterns of coproduced cytokines were indeed
detectable in vivo was experimental mouse leishmaniasis,
which develops after subcutaneous inoculation of promas-
tigotes of the protozoan parasite species Leishmania major.
This parasite invades phagocytes (most notably macro-
phages) and replicates intracellularly in its amastigote
form. Only macrophages that have been activated by T
helper cells, especially by their product IFNg, are able to
kill the parasites by mechanisms that include the produc-
tion of nitric oxide. Interestingly, this disease may have
dramatically dierent outcomes depending on the mouse
strain infected. While resistant mice (such as C57BL/6)
develop a self-healing local lesion and acquire immunity to
reinfection, susceptible mice (e.g. BALB/c) suer from
systemic spreading of the parasites and nally die from
massive hepatosplenomegaly, immunosuppression and the
formation of immune complexes. In cell transfer experi-
ments, it was shown that both the protective and the
susceptible phenotype could be transferred into syngeneic
animals by puried CD41 T cells. (Liew et al., 1982).
Hence, these CD41 T cells taken from the dierent mouse
strains behave completely dierent. Not surprisingly, the
protective CD41 T cells were subsequently shown to
produce the TH1 pattern of cytokines, including the
macrophage-activating cytokine IFNg. Instead, CD41
T cells from susceptible mice produced a TH2 pattern of
cytokines, including the macrophage-deactivating product
IL-10 (Heinzel et al., 1989).
The reasons why such a dierential appearance of
CD41 T cells occurs in susceptible and resistant mice have
not yet been elucidated and are a matter of extensive
investigation. It is known that no single gene is responsible
for the phenotype. Rather, a cluster of possibly six dierent
genes appears to be involved (Demant et al., 1996). What is
known, and what leads back to the basic ndings on the
generation of TH1 and TH2 cells, is that BALB/c (but not
C57BL/6) mice produce IL-4 within hours after inocula-
tion of the parasites. If this early IL-4 is neutralized, the
mice develop a resistant phenotype. The cellular source of
the early IL-4 has been identied to reside within a
population of T cells that carry a TCR made up of the Va8
and Vb4 families (Launois et al., 1997). These T cells react
with a L. major protein termed Leishmania homologue of
receptors for activated kinase (LACK), and their depletion
creates a resistant phenotype in BALB/c mice (Julia et al.,

1996). However, this cell subset does not denitely explain
the susceptibility of BALB/c mice. First, it is at present
unclear whether or not C57BL/6 mice have a similar T-cell
subset and which cytokines the cells might produce.
Second, it is possible that the preponderance of IL-4
secretion found within this Va8/b4 T-cell subset in BALB/c
mice may already be the consequence of a dierent, more
proximal, alteration which is the real reason for the
phenotype. In turn, this alteration may have the important
consequence to lead to a bias of the Va8/b4 T cells to
produce IL-4.
Role of CD41 Versus CD81 T Cells
in the Control of Parasitic Diseases
Infections with Leishmania spp. and Toxoplasma gondii are
often cited as prototypic examples for parasitic diseases
controlled by dierent subpopulations of T lymphocytes.
As detailed above, the resolution of human and murine
cutaneous leishmaniasis (elicited, for example, by L. major
or L. mexicana) is critically dependent on the development
of CD41 type 1 T helper cells (TH1) which release IFNg
and activate macrophages for the killing of intracellular
Leishmania amastigotes. Conversely, a lack of TH1 cells
and/or the expansion of a dierent type of CD41 T cells
(TH2) is found during the nonhealing course of L. major
infection in certain inbred mouse strains (BALB/c,
DBA/2) or in humans with chronic progressive visceral
leishmaniasis which is caused by L. donovani or L. infantum
(Reiner and Locksley, 1995). In contrast to the essential
role of CD41 T cells for both protection and disease,
CD81 T cells appear to be dispensable for a protective
immune response towards Leishmania. Depletion of
CD81 T cells (by antibodies or via deletion of the
b-microglobulin or the CD8a chain gene) does not prevent
cure of infection with L. major in genetically resistant
mouse strains (Wang et al., 1993; Huber et al., 1998).
However, CD81 T cells are not without function in
murine and human leishmaniasis. They produce IFNg and
induce the production of nitric oxide, mediate resistance
against reinfection, and are cytotoxic for parasite-infected
macrophages (Muller et al., 1994; Brodskyn et al., 1997).
Whether the latter function is benecial to the host
organism or contributes to progressive tissue damage as
seen in chronic mucocutaneous leishmaniasis is currently
unclear.
Similar to Leishmania spp., T. gondii is also an
intracellular protozoan which undergoes stage conversion
after infection of mammalian host organisms. Unlike
Leishmania, which is usually taken up by macrophages via
classical and coiling phagocytosis, T. gondii tachyzoites
actively invade nearly all nucleated cells, including profes-
sional phagocytes, broblasts, endothelial and epithelial
cells, and astrocytes (Mauel, 1996). During the acute phase
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Immunity to Protozoa
of infection, T. gondii tachyzoites rapidly proliferate within
these cells. The replication process is nally controlled by
the immune system which leads to a chronic infection, in
which the parasites persist lifelong as slowly dividing
bradyzoites in tissue cysts.
In the past, a number of dierent mouse models was used
to analyse the relative contribution of CD41 and CD81
T cells during the various phases of the immune response to
T. gondii. Adoptive transfer studies showed that CD81 T
cells from immune mice are most potent in mediating
resistance to primary infection with virulent T. gondii in
immunocompetent naive recipients. Likewise, after vacci-
nation of mice with an attenuated T. gondii strain,
depletion of CD81 T cells partially reduces resistance to
infection with live virulent T. gondii, whereas anti-CD41
treatment does not aect the vaccine-induced resistance.
Total abrogation of resistance, however, is achieved by
combined treatment of the mice with anti-CD4, anti-CD8
and anti-IFNg before the challenge infection. In vitro,
CD81 T cells produce less IFNg (and no IL-2) in response
to T. gondii antigen, compared with CD41 T cells, but can
be induced to secrete IFNg when exposed to (CD41 T cell-
derived) IL-2.
Mice that are depleted of CD41 T cells before vaccina-
tion (with an attenuated T. gondii strain) or infection (with
an avirulent T. gondii strain) never develop resistance to
infection with a virulent strain of the parasite. Similarly,
when mice are orally infected with a lethal inoculum of
virulent T. gondii, CD41 T cells are required for long-
lasting survival of the mice after treatment with antipar-
asitic drugs (atovaquone or sulfadiazine); mice depleted of
CD41 T cells before infection rapidly succumb to
reactivated toxoplasmosis as soon as the drug treatment
is discontinued (Araujo, 1992).
In mice chronically infected with an avirulent strain of
T. gondii, the asymptomatic latent infection is fully
reactivated upon treatment with anti-IFNg or a combina-
tion of anti-CD4 plus anti-CD8 antibodies, whereas
application of either anti-CD4 or anti-CD8 alone fails to
enhance
brain pathology or mortality. Reactivation of latent
toxoplasmosis was also observed in a mouse model of
retrovirus-induced CD4 immunodeciency resembling
HI virus-induced AIDS in humans. Some mice survived
the reactivation, which was dependent on the presence of
both CD81 T lymphocytes and IFNg (Gazzinelli et al.,
1992).
Together, the summarized results point to a major
eector role of CD81 T cells in toxoplasmosis, whereas
CD41 T cells seem primarily to assume regulatory
(helper) functions essential for the generation of CD81
eectors. Both CD41 and CD81 T cells release IFNg,
which is the key cytokine for the induction of antimicrobial
activity in a wide variety of host cells. Known toxoplasmo-
static eector mechanisms are the generation of reactive
oxygen intermediates (by reduced nicotinamide]adenine
3
 Immunity to Protozoa
dinucleotide (NADPH) oxidase), the production of nitric
oxide (by iNOS) and the degradation of the tryptophan (by
the indolamine 2,3-dioxygenase), which is an essential
amino acid for T. gondii. Alternatively, CD8 1 (and
perhaps also CD41 ) T cells might also confer protection
through lysis of T. gondii-infected target cells (Montoya
et al., 1996). As target cell lysis does not lead to the death of
the intracellular T. gondii, the question arises as to how
tachyzoites are cleared in vivo. Possible eector mechan-
isms that might act against released tachyzoites in the
extracellular space include anti-Toxoplasma antibodies
plus complement, macrophages, natural killer cells and a
subpopulation of cytotoxic CD81 T cells, which were
reported to be directly toxoplasmacidal.
Pathological Consequences of the
Immune Response: Autoimmunity
(Trypanosoma cruzi)
Infection of humans with the protozoon Trypanosoma
cruzi results in American trypanosomiasis or Chagas
disease. The acute phase of Chagas disease is usually not
fatal, subsiding within 2]4 months, and is followed by a
chronic phase in which the parasites are controlled by the
immune response of the host. However, they are not fully
eliminated as they are able to persist lifelong in humans in
scarce numbers. Symptomatic chronic Chagas disease
develops in 20]30% of individuals infected with T. cruzi
within 10]20 years of infection. The heart is most
commonly aected. A T lymphocyte-rich inammatory
mononuclear inltrate is observed in the cardiac tissue
(Higuchi et al., 1997), often together with interstitial
brosis and atrophy of myocardial cells, resulting even-
tually in death by disturbances of the cardiac conducting
system or congestive heart failure. Some patients present
with serious pathological enlargement of the oesophagus
and/or colon (mega viscera) associated with dysphagia and
severe constipation.
Pathogenesis of Chagas disease
The pathogenesis of the chronic cardiac or intestinal
lesions is not fully understood, but an altered immune
response has repeatedly been implicated, suggesting that
cross-reacting autoimmune antigens deviate the parasite-
induced immune response towards the aected organs of
the host.
Autoimmunity
Such an autoimmune response could be induced either by
T. cruzi antigens that show molecular mimicry to heart
4 ENCYCLOPEDIA OF LIFE SCIENCES / & 2001 Nature Publishing Group / www.els.net
proteins or by heart proteins that are liberated from
cardiac cells during the course of the parasite-driven acute
myocarditis. Several investigators have found cross-
reactive antibodies in T. cruzi-infected patients, directed
mainly towards ubiquitous and evolutionary conserved
molecules. Many of these autoantibodies have been
shown to be of heterophilic nature (Petry and Eisen,
1989).
Characteristically, the lymphocytic inltrates are asso-
ciated with destruction of myocardial muscle cells. This
destruction could result from the local eects of lympho-
cytes against T. cruzi antigens, host antigens, or both.
Several T. cruzi antigens have been identied that show
molecular mimicry with host cellular components, includ-
ing a ribosomal protein termed phosphoprotein (PO) and
the cardiovascular b1-adrenergic receptor which trigger
the induction of autoantibodies, but only few of them seem
to be associated solely with Chagas disease (Ferrari et al.,
1995). Of special interest is the immunodominant T. cruzi
B13 antigen, which induces antibodies against the cardiac
myosin heavy chain and stimulates myosin heavy chain-
specic T cells present in all patients with chronic Chagas
cardiomyopathy (Cunha-Neto et al., 1996). The myosin
heavy chain is the most abundant heart protein (50% of
total protein by weight) and is recognized in many
conditions of heart-specic autoimmunity, such as rheu-
matoid heart disease and murine post-Coxsackie B3
autoimmune cardiomyopathy.
Most of the evidence, however, suggests the participa-
tion of T cells rather than of antibodies in heart
destruction. An analysis of the phenotype of the T cells
inltrating aected heart tissue suggests a 2 to 1
preponderance of CD81 cells over CD41 cells, many
of which express granzyme A as a marker for cytolytic
capability. A direct relationship has been observed
between the number of inltrating lymphocytes and the
propensity of the immune response against the local load of
parasites as well as the start of the tissue-destructive
lesions. This scenario suggests that the tissue destruction
of the heart tissue is the eect of an immune res-
ponse triggered by parasite-specic CD41 and CD81
T lymphocytes, which via cross-reactivity to host self
antigens augment the damaging process (Tarleton et al.,
1996). It remains to be shown whether the myosin-specic
T cells are able to initiate and support the cardial
inammation, or whether these cells are just passively
recruited to the inamed tissue. Macrophages seem to play,
if at all, only a minor role in cardiac lesions.
Experimental murine Chagas disease
In mice, T. cruzi reproducibly induces dierent mild
cardiomyopathy but does not lead to intestinal disease.
CD41 T cells from chronically infected mice were shown
to transfer the capacity for heart damage, which was taken

as evidence of a T cell-mediated autoimmune process
(Kierszenbaum, 1995).
Role of Antigenic Variation (African
Trypanosomes)
Antigenic variation describes the ability of a microorgan-
ism to change the antigenic make-up of its surface proteins,
and thereby to evade the deadly immune response of the
mammalian host and to cause a chronic infection.
In the early twentieth century, it was observed that
sleeping sickness, which is caused by African trypano-
somes, is associated with successive waves of parasitaemia.
It is now generally accepted that this wavelike mode is the
result of the continuous generation of trypanosome
variants exhibiting a distinct antigenic identity. The
trypanosomes are destroyed by host antibodies. However,
some trypanosomes have altered their antigenic surface
coat and are able to escape eradication. They start a
subsequent wave of multiplication and continue the
infection.
Antigenic variation can be detected by various immu-
nological methods. Binding of antibody to a given variant
antigenic type (VAT) can be measured by agglutination,
complement xation, immunouorescence or neutraliza-
tion of parasite infectivity.
Molecular basis of antigenic variation:
surface glycoprotein coat
The xation of antibodies to bloodstream trypanosomes
indicates the presence of antigenic material on the surface
of the parasite. This can be shown by electron microscopy
using labelled antisera which reveal a dense surface coat.
The coat covers the plasma membrane and consists
primarily of 5]10  106 molecules of a single variable
surface glycoprotein (VSG) (Cross, 1990). Trypanosomes
of dierent VAT dier with respect to their VSG. The VSG
has a molecular weight of about 60 kDa and comprises
about 10% of the dry weight of the parasite. Its major
biological function is to provide trypanosomes with a
physical shield, preventing potentially adverse host mole-
cules from interacting with the plasma membrane of the
parasite. The VSG coat is essential for survival of the
parasites in the blood of the host, because it is antiphago-
cytic, prevents complement-mediated lysis and provides
the basis for antigenic variation, which endows the parasite
population with the ability to survive despite recognition
and control by the host immune system and subsequent
immune elimination.
Trypanosomes of a given VAT exhibit only a single
VSG. Epitopes of this VSG are the target of VAT-specic
antibodies. Antigenic variation results in the exhibition of
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Immunity to Protozoa
a dierent VSG in the coat of a few parasites, thus
producing a distinct VAT, which is not aected by
antibodies against the previous VAT, and thereby guar-
antees continuation of the chronic infection. To allow for
ecient and lasting parasite transmission, it is of greater
advantage for trypanosomes to reside in the host for long
periods of time with a somewhat uctuating parasitaemia
than to multiply in an unlimited fashion and rapidly to kill
the host, or to maintain low levels of infection that may be
terminated by the immune response.
Structure of the variable surface
glycoprotein coat
The molecular structure of the VSG is well characterized
(Blum et al., 1993). VSG molecules are homodimers that
are inserted in the plasma membrane with a glycosylpho-
sphatidylinositol (GPI) anchor. The molecule is composed
of about 400]500 amino acids and consists of a highly
variable N-terminal domain and a rather conserved
C-terminal domain, both of which carry carbohydrate
side-chains. The variability of the N-terminal polypeptide
chain, which is exposed to the external surface of the
parasite, is responsible for the distinct antigenic specicity
of each VSG. The carbohydrate side-chains, primarily
those of the GPI anchor, represent structures that contain
cross-reacting epitopes. These epitopes are not exposed at
the surface of the intact parasite and therefore do not
contribute to antibody-mediated parasite elimination.
Genetic organization of the variable
surface glycoprotein
A single trypanosome can generate more than 100
antigenically dierent VSGs, but at a given time expresses
only one of the multiple ( 4 1000) VSG genes. The active
VSG gene is expressed from a telomeric expression site.
VSG variation is encoded by the rather complex trypano-
some genome. Each parasite carries the full VSG repertoire
of its strain. T. brucei parasites switch VSGs spontaneously
at a rate of 10 2 3 to 10 2 7 per division (Cross, 1990),
independent of the host antibodies.
Switching takes place by duplicate transposition of a
silent VSG gene into the active site or by activation of one
of the other known 20 telomeric expression sites. The
question why trypanosomes possess so many expression
sites is still not well understood.
The sequence in which VSG genes are expressed during
sleeping sickness is irregular, although not fully accidental.
This could be relevant for survival of the parasite, as an
orderly use of VSG genes would put the host in the position
to generate an antibody response against a VSG early
during the sequence of expression. The fortuitousness in
the production of VSG may be of importance for the
5
 Immunity to Protozoa
evolution of a host]parasite system with many donor
sequences and several hosts.
Antigenic variation is not a phenomenon unique to
trypanosomes. For example, the bacterium Borrelia
hermsii causes relapsing fever in humans and similar
diseases in other mammals. Borrelia survive in the host by
altering a surface protein, termed the variable major
protein.
Summary
Immunological control of the African trypanosome
growth is mediated by antibody responses to the VSG
molecule. Owing to the variation of these surface coat
molecules, the parasites are capable of evading destruction
by the immune system of the vertebrate host. Thus, despite
their relevance to the control of trypanosome growth VSG-
specic antibodies do not generate prolonged immune
protection.
To date, it is not known to what extent other parts of the
immune system contribute to control of the African
trypanosomes and to defence of the host from adverse
eects of the parasites. Interestingly, as a consequence of
infection with the parasites the immune response of the
host is greatly altered in that the production of specic
antibodies and the proliferation of T cells is signicantly
suppressed, whereas levels of CD51 B cells, known to
produce autoantibodies, are increased and macrophages
are activated.
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ENCYCLOPEDIA OF LIFE SCIENCES / & 2001 Nature Publishing Group / www.els.net
Immunity to Protozoa
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