Immunological Aspects of

Parasitic Diseases in
Immunocompromised Individuals

Taniawati Supali & Heri Wibowo

Department of Parasitology

Immunocompromised
Having an immune system that has
been impaired by disease or medical
treatment
Immunodeficiency : Is state in which
the immune systems ability to fight
infections disease is compromised
Opportunistic infections : An infections
that occurs because of weakened
immune system

Acquired immunodeficiencies
Most cases, Immunodeficiency are aquired.
( some people are born with defect in their immune
system Primary immunodeficiency)

Two main types of pathogenic mechanisms:

Immunosuppression may occur as a biologic
complication of another disease process.
Humoral immunodeficiency Hypogammaglobulin
T cell deficiency AIDs HIV

Iatrogenic immunodeficiencies may develop as

complications of therapy for other diseases.

HIV Infection
CD4 was a viral
receptor
destruction of CD4
T cells in HIV
infected inviduals.

HIV Infection
Infecting CD4 T
lymphocyte, macrophages,
& dendritic cells

Dysfunction of the
immune system
Inducing opportunistic
infection

Iatrogenic immunodeficiencies
Due to some drugs either for the
treatment of inflammatory diseases or to
prevent rejection of tissues allografts
e.g. corticosteroids, cyclosporine
The drugs cause cytotoxic both mature
and developing lymphocyte as well as
granulocyte and monocyte precursors.

Strongyloides stercoralis

Strongyloidiasis
Exposure to contaminated faeces can result
in transmission of this disease.
The worm has an autoinfective cycle that
allows infection to persist in the host
indefinitely without the need for an
external enviroment
Transformation
of rhabditiform larvae into invasive
filariform larvae in the gut of human host

Strongyloidiasis
Increase number of larvae completing the
autoinfectious cycle
large numbers of
worms can enter the systemic circulation
hyperinfection syndrome.

Concept of hyperinfection and

autoinfection

Hyper infection syndrome

Immunosuppression caused by:
Iatrogenic: use of systemic corticosteroids)
Intercurrent illness
HTLV-1/Human T
cell Lymphotropic Virus-1, HIV infection,
organ transplantation
High risk of hyper infection syndrome in
patients with strongyloidiasis

Corticosteroid hyper infection

syndrome in patients with
strongyloidiasis Strongilodiasis
Corticosteroids
Increase
ecdysteroid like
substances in
wall&
intestinal
Molting eggs
Rhabditifor
Number Filariform

Th2 cell apoptosis

Eosinophil count
Mast cell response

Immune response
to helminth

S. stercoralis Hyper Infections

Syndrome

Immunosuppression by Corticosteroid

Mucosal Immunity against Strongyloides sp.

Humoral and cell mediated immunity
Rodent models: Induction of goblet cells and
intestinal mastocytosis by IL-13 secreted by Th2
cells
expulsion of worm from GI tract
Human: Lack of cell activation in the mucosa
no change in jejunal morphology, different T cell
subset numbers, mast cells, eosinophils and goblet
cells, BUT a decrease of mature macrophages and
dividing enterocytes in the crypts of intestinal walls
may preserve the architecture of mucosa and
absence of immune mediated diarrhea

Th2 role in strongyloidiasis

IL-4: important regulator of IgE production & mast
cell activation
Il-5: innate immunity (induce eosinophil production,
differentiation, maturation, survival) and adaptive
immunity (IgM production by plasma cells)
B cells: important role in subsequent challenge
infections (increased parasite-spesific IgM)
Specific IgE against filariform larvae: Protective role
not clear, maybe useful for immunodiagnosis?
ADCC (IgE activation of eosinophils & IgG activation
of neutrophils) in strongyloidiasis: not effective
against larvae?

In severe strongyloidiasis:
Compared to asymtomatic or mildly
symptomatic: lower levels of IgA, IgG,
IgM.
IgM specific for primary infective
filariform larvae is not effective against
autoinfective filariform larvae (have
different surface antigens)

In severe strongyloidiasis:
Eosinophils can cause destruction of
helminth larvae esp.host-adopted
filariform larvae, BUT not sufficient
for complete protection
Lower eosinophil counts in severe
strongyloidiasis: suppression of
eosinophils esp. in disseminated
infections

Diagnosis
Stool culture for larvae
Serology test (ELISA)

Treatment
Albendazole
Ivermectin not registered for human use
in Indonesia

Cryptosporidium parvum

Cryptosporidiosis
Transmission occurs by the fecal-oral spread of
oocysts.
Fecal contamination of drinking water sources can
serve as a vehicle for transmission of oocysts and
is a subtantial public health concern

Outbreak

Cryptosporidiosis
Oocyts retain viability, and therefore
infectivity, under moist and cool conditions
for several months.
Oocyts lose infectivity when undergoing heat
treatment above 65 C
pasteurization,
sterilization for food, ozone or exposure to
UV for water (chlorination is not effective).

Oocyts are ingested by the host,

then excyst to be sporozoites which
attach to epithelial cells of small
intestine. They become enveloped
by the host apical cell membrane,
resulting a parasitophorous vacuole
with membrane components from
both the host & Cryptosporidium, and
differentiate into the trophozoites
which resides intracellularly but
outside of the cytoplasm.
During maturation of trophozoite,
asexual multiplication occurs
resulting in the formation of a type 1
schizont contains 6-8 merozoites.
Rupture of the schizont results in
the release of merozoites which can
invade adjacent host epithelial cells
then develop subsequently into type 1
or type 2 schizonts.

Life cycle includes both

asexual multiplication and
sexual reproduction.

Life cycle
Type 1 schizonts contain merozoites important in asexual
multiplication.
Type 2 schizonts initiate sexual reproduction
(gametogony) by differentiating into male microgamonts or
female macrogamonts.
Male microgamonts release microgametes that can fertilize
the macrogametes inside the female macrogamont. The
oocysts that are generated then sporulate.
There are two types of oocysts, thin-walled oocyts and
thick-walled oocyts.
Thin-walled oocyts excyst and reinfect the host
(autoinfection)
Thick-walled oocyts exit the intestinal tract and can
infect a new host.

Immune responses to C. parvum

C. Parvum + Epithelial cells
Blocking antibody to IL-18

IL-18
Th1 (IFN)
Immunity to primary infection
Susceptibility

Host responses
The parasite resides at the apical surface of
intestinal epithelial cells and does not invade
deeper layers of the human gasrointestinal
mucosa.
Moderate to severe infection with this
intraepithelial parasite is characterized by
mucosal inflammation with neutrophils and
macrophages in the lamina propria underlying
epithelial cell.

Host responses
After infection, increased epithelial Interleukin 8
(IL-8) and GRO production (potent neutrophil
chemoattractants) could attract inflammatory
cells into the mucosa.
The infection in the intestinal epithelial cells also
rapidly upregulate the production of IFN
(proinflammatory cytokine)
important for
host innate and reacuired immunity to clearance
the infection but the mechanism has not defined
yet

Host responses
In addition, increased mucosal prostaglandine
production (PGE2) following infection with
enteroinvasive bacteria can inhibit neutral NaCL
absorption and result in secretory diarrhea.
PGE2 can downregulate inflammatory cytokine
production by macrophages
explaining why diarrhea
can develop during C. parvum infection in the absence
of significant mucosal inflammation.

Host responses
In mice model, Humoral immunity is not an absolute requirement for clearing infection.
The ability to clear acute and chronic parasite in human correlates with host CD4 T-cell
levels.
CD4+ T cells play the dominant role in resistance to C. Parvum.
In addition to CD4+ T cells, Th1 cytokine (IFN as innate response) play a major role to
prevent initiation as well as limit the extent of infection

Clinical symptoms
Diarrhoea is the most common symptom of C.
parvum infection, followed by abdominal pain
and vomiting.
In immunocompromised individuals, the
disease may be much more severe and
persistent, with invasion of other organ
systems including the lungs and the bile duct,
and it is life threatening.

Diagnosis
Finding oocysts in stool specimens by
light microscopy.
PCR

to detect the DNA of parasite

Oocyst

Treatment
Trimethoprim-sulfamethoxazole.
In AIDS patients without antiretroviral therapy,
AZT therapy should be started
In these
patients, a relationship between disease severity
and CD4+ count has been documented
Patients with AIDS may need higher doses and
long-term maintenance treatment.

Mucosal inflammation
Attachment of parasites to enterocytes (epithelial
cells in small intestine & colon with the function for
digestion & secretory) induce host immunity.
Mucosal inflammation accompanied by alternation in
intestinal motility is CD4 Tcell subset Th2
dependent.
The presence of IL-4 and IL-13 in muscularis
externa layer cause intestinal mucle
hypercontractility
Expulsion of the worms

Mucosal inflammation

Goblet cells reside in the small & large intestine

main soure of mucin.
Th2 induces goblet cells hyperplasia
enchancing
mucus secretion:
changes the environment of gut from neutral to acid
trapping the parasites/enveloping the parasites,
inhibition of parasite motility & feeding capacity

Expulsion of the worms

Mucosal inflammation
Entero endocrine (EE) cells located GI mucosa and acts as
specialized sensory nerve system, capable of transmitting
signals to activate the enteric nervous system.

Releasing secretin, serotonin, cholecystokinin,chromogranin

Intrinsic & extrinsic neural pathway

Affecting gut physiology (secretion, motility)