





Name the innate immune mechanisms in combating
parasitic infections.
Describe the acquired (humoral and cellular) immune
mechanisms in combating parasitic infections.
Describe immune response to protozoal and
helminthes infections
Describe how parasites can evade immune
mechanisms of the host.
Differentiate between the role of Macrophage, NK
cells, and Eosinophil in the protective immune response
to parasitic infections.





Parasitic infection refers to infection with animal
parasites, such as protozoa, helminths, and
ectoparasites (e.g., arthropods, such as ticks and
mites).
It is estimated that about 30 percent of the world's
population suffers from parasitic infestations.
Malaria alone affects almost 250 million people
worldwide, with about 1 to 2 million deaths annually.
Schistosoma 200 million with about 60000 deaths
annually.
Most parasites go through complex life cycles, part of
which is in humans





Weak innate immunity.
The ability of parasites to evade or resist elimination by
specific immune responses.
Many anti-parasite drugs are toxic or relatively ineffective
or both.
The persistence of parasites in human hosts also leads to
immunologic reactions that are chronic and may result in
pathologic tissue injury as well as abnormalities in
immune regulation.
Therefore, some of the clinicopathologic consequences of
parasitic infestations are due to the host response and not
the infection itself.
Hepatic granulomatous inflammation in
response to Schistosoma egg

Complexity of parasite structure.

Complexity of parasite metabolism.

Complexity of parasite life cycle.

Immune evasion.
Excretory/Secretory
antigens
Surface antigens
Internal antigens
Shed surface antigens
1- The skin: forms an important barrier against
penetration e.g. Schistosoma and Ancylostoma
2- Body secretions:
- Intestinal secretions wash away luminal
parasites e.g. Trichinella spiralis.
- Mucus prevents invasion mucosa by helminths
and protozoa.
3- Serum factors: high-density lipoproteins
(naturally present in serum) may kill parasites as
Trypanosoma.
When a parasite enters the human body an immune response
is initiated by antigen presenting cells
Parasite
Peptide
IFN-γ
TC
Th1
NK
MHC
class 2
Cellmediated
immunity
Mac
Th2
Humoral
B cell
IgE immunity
IL4
Eosinophils + mast cells
MHC class1
Release toxic molecules
Lysis
Tc cells identify infected cell (target cell) expressing
parasite Ag associated with MHC class I.
Tc cells release toxic molecules that induce pore formation
in cell membrane of infected cell resulting in cell lysis.
Cell lysis
Enzymes + toxic granules
Cell lysis
ADCC
NK cell attacks parasite infected cell directly or by the
help of antibody then release toxic products that cause
lysis of the target cell.

Antigen presenting cell:
Degrading parasite Ag into simple peptides and present
them on its surface associated with MHC class 2
molecules.
Intracellular killing of microparasites:
Phagocytosing the parasite then
killing it inside the phagolysosome.


Extracellular killing of macroparasites:
Releasing toxic products onto the
parasite.
IFNγ
Play an essential role against helminths
High or moderate eosinophilia:
seen with helminths that are invasive and
cause inflammation of tissues
e.g. Schistosoma and Fasciola.
Little or no eosinophilia:
IgE
seen with helminths that remain localized
to the intestinal tract e.g. Enterobius. Release
mediators
No eosinophilia:
seen in infections with protozoa e.g.
malaria, amoebiasis, toxoplasmosis,
leishmaniasis and trypanosomiasis.
IgG
B cells develop into Plasma cells produce Antibodies
Secretory IgA
Direct killing of
parasite
Prevent cell invasion
A- Direct action of antibodies
Inactivation of
parasite products
Complement activation
Opsonization
Complement
activation
Cell lysis
IgM and IgG activate
complement in the classical
pathway leading to cell lysis
e.g. red cells infected with
malaria parasite
Antibodies coat the
parasite making it more
easily phagocytosed
macrophage
neutrophil
platelet
Mast cell
NK cell
eosinophil
Immunoglobulin molecules act as a link between parasite and effector
cells. These cells become activated and release toxic products to
digest the parasite (ADCC)
Immunity to Malaria Infections
Red cell structure factor:
 Absence of Duffy antigen: provides resistance to P.vivax
infection.

Haemoglobin S: provides resistance to P. falciparum infection.
This type of haemoglobin is not suitable for the parasite

Deficiency of G6PD: provides resistance to P.falciparum
infection. The parasite needs this enzyme for its development.
1- Specific antibodies to surface proteins of
sporozoites and merozoites can prevent penetration of
host cells.
-However, the immune response is inefficient: Malaria induces a polyclonal
B-cell activation, with dramatic synthesis of especially IgG and IgM, only 6%
-11% of which is specifically against malarial antigens.
- IgG and IgE levels differ markedly in uncomplicated and severe falciparum
malaria. Both total IgG and antiplasmodial IgG were higher in patients with
uncomplicated malaria, while IgE was highest in the group with severe
disease, suggesting that IgG may play a role in reducing severity, while IgE
may contribute to pathogenesis
2- There is evidence that immunity to parasite sometimes
is mediated by an antibody-dependent, cell-mediated
cytotoxicity (ADCC).
3- At least part of sporozoite-induced immunity depends
on the killing of infected liver cells by cytotoxic T
lymphocytes.
Protective immunity to malaria is primarily a premunition, that
is, a resistance to superinfection, while the host’s immune
response controls numbers of parasites remaining in its body.
Premunition is effective only as long as a residual population of
parasites is present; if a person is completely cured, susceptibility
returns.
Protective immunity apparently has some components
that are species, strain, and variant specific, but thereis
now evidence that existing infection with P. vivax can
provide some protection against infection with P.
falciparum or, at least, prevent severe symptoms

It has been noted that some persons who have been
treated and seemingly recovered relapse back into the
disease weeks, months, or even years after the apparent
cure. Relapses up to eight years after initial infection
was doccumented.

The discovery of preerythrocytic schizogony in the
liver seemed to have solved the mystery

Preerythrocytic merozoites simply reinfected other
hepatocytes, with subsequent reinvasion of red blood
cells. This explain why relapse occurred after
erythrocytic forms were eliminated by erythrocytic
schizontocides, such as quinine and chloroquine.

not all species of Plasmodium cause relapse.

Only P. vivax and P. ovale cause true relapse. P. vivax,
P. ovale, and have hypnozoites, but they have not been
found in any species that does not cause relapse.


Recrudescences of the disease the recurrence
of symptoms after a period of remission. It may follow
remissions of up to a year, occasionally up to two or
three years, after initial infection, apparently because
small populations of the parasites remain in red blood
cells.
It can occur in all types of Plasmodium infection,
mainly due to drug resistance.
Immunity to Helminths Infections
Immunity to Helminths Infections ……..cont




Defense against many helminthic infections is mediated by
IgE antibodies and eosinophils.
This is a special type of antibody-dependent cellular
cytotoxicity (ADCC), in which IgE antibodies bind to the
surface of the helminth.
Eosinophils then attach via Fcε receptors, and the eosinophils
are activated to secrete granule enzymes (Major basic protein,
MBP) that destroy the parasites.
So, production of specific IgE antibody and eosinophilia are
frequently observed in infections by helminths.
Immunity to Helminths Infections ……cont
 These responses are attributed to Th2 subset of CD4+
helper T cells, which secrete IL-4 and IL-5.
◦ IL-4 stimulates the production of IgE.
◦ IL-5 stimulates the development and activation of
eosinophils.
 Also Th1 response play important role against some
helminthic parasites by activation of macrophage extracellular
killing mechanisms.
 Specific immune responses to parasites can also contribute to
tissue injury.
◦ Some parasites and their products induce granulomatous
responses with concomitant fibrosis.

Role of Macrophages and Eosinophils in parasitic infections
Eosinophils
•Play an essential role against
helminths.
•High or moderate eosinophilia: in
•Cause Intracellular killing of helminths that are invasive.
•Little or no eosinophilia: in
microparasites.
helminths that remain localized in
•Cause Extracellular killing of the intestinal tract.
macroparasites.
•No eosinophilia: against Protozoa.
Macrophages
•Act as antigen presenting
cell.


the immune response progresses through at least three
phases. In the first 3–5 weeks, during which the host is
exposed to migrating immature parasites, the dominant
response is T helper 1 (TH1)-like.
As the parasites mature, mate and begin to produce
eggs at weeks 5–6, the response alters markedly; the
TH1 component decreases and this is associated with
the emergence of a strong TH2 response. This response
is induced primarily by egg antigens.

During the chronic phase of infection the TH2 response
is modulated through the action of IL-10 and
granulomas that form around newly deposited eggs are
smaller than at earlier times during infection.

TH2-cell-mediated granulomas seem to protect
hepatocytes, but allow the development of fibrosis.

TH2 responses are also strongly implicated in naturally
acquired resistance to reinfection with schistosomes.

In Schistosoma mansoni and Schistosoma japonicum infections, the
liver is the principal site that is affected, because many of the eggs are
carried by the blood flow into this organ, the sinusoids of which are too
small for the eggs to traverse. This is a dead-end for the eggs, which
eventually die within the tissue.

The CD4+ T-cell response that is induced by egg antigens orchestrates
the development of granulomatous lesions — which are composed of
collagen fibres and cells, including macrophages, eosinophils and
CD4+ T cells — around the individual eggs. As the eggs die, the
granulomas resolve, leaving fibrotic plaques. Severe consequences of
infection with S. mansoni and S. japonicum are the result of an
increase in portal blood pressure as the liver becomes fibrotic,
congested and harder to perfuse

The main TH2 cytokine that is responsible for fibrosis
is IL-13. So, schistosome infected mice in which IL-13
is either absent, ineffective or neutralized by treatment
with soluble IL-13Rα2–Fc fail to develop the severe
hepatic fibrosis that normally occurs during infection,
which leads to prolonged survival of these mice.



The ability of parasites to survive in vertebrate hosts reflects
evolutionary adaptations that permit these organisms to evade
or resist immune effector mechanisms.
Different parasites have developed effective ways of resisting
specific immunity.
The most important of these ways fall into two categories:
◦ 1- Parasites can reduce or alter their own
antigenicity.
◦ 2- They can actively inhibit host immune
responses.

1- Anatomic sequestration is commonly observed
with protozoa.
◦ Some (e.g., malaria parasites and Toxoplasma) survive and
replicate inside cells.
◦ others (like Entamoeba) develop cysts that are resistant to
immune effectors.
◦ Some helminthic parasites reside in intestinal lumens and are
far from cell-mediated immune effector mechanisms.

2- Antigen masking is an important phenomenon in
which a parasite, during its residence within a host,
acquires on its surface a coat of host proteins.
◦ Larvae of Schistosoma mansoni coat it self by ABO blood
group glycolipids and MHC molecules derived from the host.

3- Parasites shed their antigenic coats, either
spontaneously or after the binding of specific
antibodies. Such as in Entamoeba histolytica,
schistosome larvae, and trypanosomes.

4- Varying their surface antigens during their life
cycle in vertebrate hosts. Two forms of antigenic
variation are well defined:
◦ A) Stage-specific change in antigen expression, such that the
mature tissue stages of parasites produce different antigens
from the infective stages.
◦ B) Continuous variation of major surface antigens (e.g.
African trypanosomes)
 Infected individuals show waves of blood parasitemia, and each wave
consists of one antigenically unique parasite.
 The major surface antigen of African trypanosomes is called the
variable surface glycoprotein (VSG). Trypanosomes contain more than
1000 different VSG genes.



PfEMP1(P. falciparum erythrocyte membrane
protein) is encoded by a large multigene family
(VAR genes) and parasites switch to new variants
(antigenic variation again).
The parasite genome encodes 60 VAR genes, only
one is expressed at a time (allelic exclusion).
It exhibit not only extensive polymorphism between
isolates from different patients, they also under go
clonal variation so that each new generation of
parasites exhibits different variant from the previous
one.

1- Parasites become resistant to immune effector
mechanisms during their residence in vertebrate
hosts.
◦ Lung stage schistosome larvae develop a tegument that is
resistant to damage by antibodies and complement or by
CTLs.
◦ Trypanosoma cruzi synthesize membrane glycoproteins,
similar to decay accelerating factor, that inhibit complement
activation.
◦ Leishmania major promastigotes induce rapid breakdown
or release of the membrane attack complex. thus reducing
complement-mediated lysis.


2- Parasites evade macrophage killing by various
mechanisms:
◦ Toxoplasma gondii inhibits phagolysosome fusion.
◦ Trypanosoma cruzi lyses the membranes of phagosomes
and enters the cytoplasm before fusion with lysosomes.
3- Some parasites express ectoenzymes that cleave bound
antibody molecules and thus become resistant to antibodydependent effector mechanisms.

Parasites also inhibit host immune responses by
multiple mechanisms:
◦ Induction of immunosuppressive cytokines production by
activated macrophages and T cells.
Thank you