2012-47330

Biochem 175

Parasite Infection: Should you be worried?

Abstract
Parasites are opportunistic pathogens of the human body that has affected
millions of people causing malaria and schistosomiasis among others. The innate and
adaptive immune responses work together against these pathogens. However, the
long-term coevolution of parasites together with its host resulted in escape
mechanisms which made it harder to get rid of them. Cytokines such as IL-12, INF
and TNF that stimulates and enhances macrophages and NK cells all operate
together to get rid of the parasites before chronic infection worsens.
The human immune system is one complex network of various cells, each having their
own ways of protecting the human body from foreign organisms that will want to harm it.
Pathogens, organisms that have the ability to cause disease, can be divided into four kinds:
bacteria, viruses, fungi parasites. The focus on this review would only be on the parasites
which is a group of unicellular protozoans and multicellular invertebrates mostly helminths.
How would the immune system respond when a parasite invades the body? Would the
complex human immune system be triumphant in protecting the body against these
opportunistic organisms? Or would these parasites prove to be small but terrible?
Parasites infect millions of people and are the cause of many different diseases such
as malaria, schistosomiasis and leishmaniasis for a few examples. In general, they are host
specific, which means they choose immunodeficient hosts and can cause chronic infections.
They can spread through many different invertebrate means and have complicated life cycles,
which is one of the factors the immune system have to consider when protecting the body
from such organisms. Since they have different stages in life in which they can enter the hosts
body, their antigens would be stage specific which makes it harder for the immune system
(Behnke, 1990; Capron & Trottein, 2006; Clarke, Alabama, Eisen, Angeles, & Wagner, 1985).

Figure 1. Common parasites [1].

The human immune system responds to foreign bodies in two different ways, these
would be through the innate immune response and then the adaptive immune response.
Innate Immune Response
The human bodys first defense would be the physical and chemical barriers, the skin
and mucosal surfaces. However, humans are always prone to physical damage such as open
wounds, cuts, bites and burns, thus the various pathogens waiting around can penetrate these
barriers. Also, simply being around sick people, eating contaminated food or breathing polluted
air will have the same effect and also induce an infection. Extracellular parasites such as those
found in the blood, body fluids or the gut can be eliminated through humoral responses. If the
parasite still persists or for the others that found their ways inside the cells, innate immune
response ensues. An antibody, either alone or with a complement, can damage some

extracellular parasites, but would still be better when acting with an effector cell. As said
before, parasites are stage specific which makes a single infection need different effector
mechanisms against the different developmental stages of a parasite (Lopes, Zamboni, Lujan,
& Rodrigues, 2012; Parham, 2015a; Rollinghof, Bogdan, Gessner, & Lohoff, 2001).
First line of defense: macrophages, neutrophils, eosinophils and platelets
In the presence of parasites, antibodies and cytokines specifically produced for
parasitic antigens enhances the anti-parasitic activities of these cells. The macrophages would
first inhibit the increase in number of these parasites and also destroy them at the same time
through phagocytosis or through the release of cytotoxic molecules. Macrophages would also
release other molecules that will regulate the inflammatory response and enhance immunity
by activating the other cells and stimulating their proliferations. Some examples of cytokines
released are IL-12 which will stimulate natural killer (NK) cells and secrete INF or the TNF
released in response to parasite products which will then activate the other macrophages
(Owen, Judith A. Punt & Stranford, 2013; Parham, 2015b).
Granulocytes: neutrophils and eosinophils
Neutrophils are phagocytic and can kill pathogens in a more intense respiratory burst
than the macrophages. These granulocytes have secretory granules which contain highly
cytotoxic proteins which will be secreted once activated by the cytokines. Eosinophils, on the
other hand, are thought to be evolved specifically for the defense against parasites that are
too large to be phagocytosed. Mainly, eosinophils are able to control a worm infection by
limiting the spread of the infection. Also, the activity of eosinophils can be enhanced by mast
cells products enabling them to effectively kill parasites in partner with the mast cells. These
granulocytes can kill the parasites by both O2-dependent and O2-independent mechanisms,
ie. through respiratory burst and using nitric acid oxides (Cole & Blanden, 1982; Mogensen,
2009; Paul, 2013).
Macrophages, granulocytes and platelets on ADCC
Macrophages, neutrophils, eosinophils and platelets when activated by cytokines such
as TNF and enhanced by INF can effectively kill many types and sizes of parasites. These
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effector cells all bear Fc receptors on their surface membranes and thus enabling them to
participate in antibody-dependent cellular cytoxicity (ADCC) reactions such as those
associated with IgE (Akira, Uematsu, & Takeuchi, 2006).

Figure 2. Immune defense involves recognition of pathogens followed by their destruction [2].

Adaptive Immune Response

In some infections, the parasites can survive the innate immune response, and thus
the second line of defense comes in. The innate immune response will focus on delaying the
spread of infection and limiting the movement of the parasites in one place. The adaptive
immune response will then be called to recruit lymphocytes to enhance the immune response.
The macrophages from earlier will now act as antigen-presenting cells to enable the
production of antibodies which helps the lymphocytes adapt on the parasitic antigens.
Generally, the effector mechanisms of the adaptive immune response is just the same with
that of the innate immune response, only difference would be that only lymphocytes bearing
receptors will recognize the infecting parasitic antigens and will be selected to participate in
the adaptive response (Jirillo & Brandonisio, 2010; Owen, Judith A. Punt & Stranford, 2013;
Parham, 2015a).

Figure 3. The principal characteristics of innate and adaptive immunity [2].

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CD4+ and CD8+ T cells

Various parasite antigens will be present and for each one there would be a specific
type of T cell. As mentioned earlier, the parasite is stage specific which means it will produce
different sets of antigens depending on the cytokine produced. The T-helper cells would then
be divided into TH1 and TH2 subsets, of contrasting and cross-regulating cytokines profiles,
based on the cytokines. The TH1 responses is for the killing of intracellular phatogens while
the TH2 responses is for the extracellular ones. Cytokines secreted by TH2 cells will be the
basis of IgE and eosinophils as the markers of the immune response to extracellular parasites.
Furthermore, TH2 controlled effector mechanisms are also specific to intestinal worm
infections (Rollinghof et al.,(Cole & Blanden, 1982; Paul, 2013) 2001).
Escape Mechanisms
Despite the fact that parasites are generally bigger, and thus a great quantity and
quality of antigen can be presented, there will be instances the immune system will not function
well. The parasites have developed escape mechanisms from their coevolution with the host
immune system through the years. Parasitic infections would want to evade the effects of the
hosts immune system. Some can even exploit the immune system to their own advantage
(Zambrano-Villa, Rosales-Borjas, Carrero, & Ortiz-Ortiz, 2002). Examples discussed below.
Passive evasion
Passively evading the immune system is possible through (a) hiding away from the
immune system by invading tissues in the body that are immune-privileged, ie. CNS, in the
eyes or laying eggs in the fat globules, intestinal parasites are also preserved simply because
they are in the gut, (b) shielding surface components (parasite-associated molecular patterns)
once opsonized by the hosts immune system, (c) changing their surface identity through
antigenic variation, (d) become temporarily inactive and escape the immune system or (e)
simply be able to withstand an immune attack, ie. nematodes having thick extracellular cuticle
which can protect them from the toxins (Barbour, Dai, Restrepo, Stoenner, & Frank, 2006;
Blaxter, Page, Rudin, & Maizels, 1992; Bloom, 1979; Sacks & Sher, 2002; Turner, 2002).

Table 1. Comparison of main evasion mechanisms for selected protozoan parasites [3].

Active modulation and interference

A parasite can incorporate changes in its membrane for it to penetrate a macrophage
through a non-phagocytic pathway avoiding respiratory burst. This can also be done by
binding to the complement receptors. Another way to avoid respiratory burst is the presence
of enzymes that can protect them against the action of the oxygen radicals. It is also possible
to downregulate the expression of cytokines in the macrophage they inhabit thus reducing the
stimulation of the TH cells. Some parasites can also capture a gene from their hosts and
produce molecules that can disarm the hosts immune system. It is also possible to secrete

decoy MHC molecules to confuse the immune system. Plasmodium, schistosomes and
nematodes have been reported to produce competing ligands that can hinder the recognition
of the host. They can also interfere with the signaling of the different cells by reducing certain
signals or cytokines or by producing proteins that will bind instead to the receptors of the host
cells. One example would be the down-regulation of TNF which in effect blocks inflammation.
Tapeworms can also secrete an elastase inhibitor which prevents them from attracting
neutrophils. Nematodes and trematodes can also secrete proteases which will cleave
immunoglobulins, removing the Fc portion. Phosphorylchlorine can also be secreted which
inhibits the proliferation of both the T and the B cells (Blaxter et al., 1992; Locksley, 1997;
Loukas & Maizels, 2000; Reiner & Locksley, 1995; Sacks & Sher, 2002).
Parasites still have more escape mechanisms not mentioned and they can also still
evolve. In addition to the fact that the identification of its target antigens is difficult due to the
different developmental stages, the human immune system is also not that efficient. In the
end, it all boils down to the hosts personal hygiene, clean environment, balanced diet and a
healthy lifestyle. After all, prevention is still better than getting medication. Besides, it is said
that its not in the parasites interest to kill its host, that is at least not until transmission to
another host has been ensured.
Word count: 1490 words
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