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Games Parasites Play

Every organism has to cope with an assortment of predators and parasites.

Many biologists feel that one of the most potent forces of evolutionary adaptation is that created by the interactions between a host and its parasites.

As the host evolves measures that give it greater protection from a parasite, the parasite evolves countermeasures.

This page examines some of the mechanisms by which parasites evade host defense measures. The emphasis will be on human parasites.

Gaining Superficial Entry

Most parasites enter their human host through
  1. food and water
  2. air
  3. the bites of arthropod vectors like mosquitoes, fleas, and ticks.

However, for categories 1 and 2, entry begins in only a superficial sense. The gastrointestinal tract, lungs, and genitourinary tract are simply part of the outside folded in. Parasites that arrive there are still outside the internal environment of the body.

Some organisms are content with this. Some of our epithelial surfaces (e.g., nasopharynx, colon) are colonized by a vast array of microorganisms. Most are commensals, usually living harmlessly in these sites. Some, however, may gain the upper hand and cause disease in individuals with weakened immune systems (e.g., in AIDS patients).

A few are pathogenic.

Two examples:

Gaining Entry Into the Internal Environment

To get into the true interior of the body, invading parasites must pass through an epithelial barrier. For those injected by biting vectors, this is no problem.

But the others must find a trick. One of these: Helicobacter pylori secretes a protein that disrupts the tight junctions and adherens junctions that seal epithelial cells.

Once within the body, intracellular pathogens, e.g., viruses and some bacteria and protists, must have a mechanism to invade their host cells.

Some tricks:

Using phagocytic cells, like macrophages and neutrophils, to gain entry into the internal environment is a risky strategy because phagocytes are poised to destroy engulfed bacteria. However, some bacteria have evolved mechanisms to avoid destruction even after they have been engulfed by phagocytes.

Three examples:

Evading Antibody-Mediated Immunity

Parasites that live in the blood or the interstitial fluid that bathes cells are at risk of being destroyed by antibodies directed against them.

A common countermeasure is to periodically alter the epitopes on the parasite surface so that antibodies can no longer recognize them.


Trypanosoma brucei

Trypanosomes are flagellated protozoans that swim in the blood. (This photomicrograph is courtesy of Turtox.) In humans they cause trypanosomiasis or African sleeping sickness.

Once introduced into the blood (from the bite of an infected tsetse fly), they multiply rapidly and may soon reach a population density of >106 organisms per milliliter.

Soon, however, this number drops rapidly (remission) only to be followed a week or two later by another wave of population growth (relapse). This pattern continues indefinitely.

Recurring waves of parasitemia in a patient with sleeping sickness. Each peak represents the development of a clone of trypanosomes expressing a new variant surface glycoprotein (VSG). [From K. Vickerman, Ciba Foundation Symp. 25:53, 1974.]

The periods of remission are caused by the appearance of antibodies directed against the glycoprotein molecules that coat the organisms.

The relapses are caused by the appearance of a small number of parasites that express a new version of the glycoprotein coat (designated VSG for variant surface glycoprotein).

The switch to a new active VSG gene is probably a chance event. However, if its owner is bathed in antibodies against the earlier dominant VSG, it now has a competitive advantage that allows it to propagate until it, too, has to face an immune response from the host.

This autoradiogram (Courtesy of P. Borst; from P.A.M. Michels, et al., Nucleic Acids Research 10:2353, 1982.) shows Southern blots of nuclear DNA from clones of Trypanosoma brucei expressing different variant surface glycoproteins (VSGs). The DNA was digested with the same restriction enzyme (PstI) in every case. The probe was a fragment of cDNA from a clone designated 118.

Plasmodium falciparum

This sporozoan is the most dangerous of the several that cause malaria. Like the others, it spends most of its life in the human within red blood cells (RBCs).

Link to its life cycle.

One might think that tucked within an RBC, it would be safe from antibodies in the plasma. But, in fact, the parasite synthesizes a protein that appears at the surface of the RBC. These molecules anchor the RBCs to the walls of the blood vessels so they won't be swept into and destroyed by the host spleen.

The surface protein also elicits an immune response. To evade this problem, the parasite periodically alters the composition of the protein so that it is no longer recognized by the current crop of antibodies. It does this by switching to expressing another one of the 60 genes that encode variants of this protein.

Plasmodium falciparum plays another game. During the period when its gametocytes — the stage that infects the mosquito vector — are present, infected children exude some airborne attractant that lures Anopheles mosquitoes to them.

Human Immunodeficiency Virus (HIV)

Although an intracellular parasite, new HIV virions are exposed to blood and lymph as they are escape from dying cells and must find a new cell to infect.

Although the immune system mounts an antibody response to them (the basis of the most common test for HIV infection), this response does not lead to a cure.

Blood Flukes (Schistosomes)

As their name suggests, these flatworms live in the blood, taking up final residence in the veins draining the Their presence induces antibodies that — with the aid of macrophages and eosinophils It appears that the resident worms coat themselves with host antigens and thus disguise themselves as normal components of the body ("self").

Neisseria meningitidis

The bacterium Neisseria meningitidis is one of the major causes of bacterial meningitis, a life-threatening infection of the meninges. This organism has at least two tricks by which it evades antibody-mediated immunity.

Evading Cell-Mediated Immunity

Many viruses (all of which are intracellular parasites) exploit receptor-mediated endocytosis to sneak their way into their host cell.

They have evolved surface molecules that serve as decoy ligands for receptors on the target cell surface. Binding to these receptors tricks the cell into engulfing the virus.

Some examples: The process can be remarkably fast. A team in Munich (Seisenberger et al., Science, 30 November 2001) succeeded in attaching single fluorescent molecules to single virions of adeno-associated virus (AAV) and watched them infect a HeLa cell: Once within a cell, a virus is safe from attack by antibodies. But it is still subject to being destroyed by an attack by CD8+ cytotoxic T lymphocytes (CTL). Fragments of proteins synthesized by the virus will be deposited in the groove of class I histocompatibility molecules and displayed at the cell surface. These will be recognized as "foreign" and elicit an attack which will destroy the host cell along with its content of viruses.
Link to discussion of antigen presentation to T cells.

Some countermeasures:

Leaving the Host

One basic rule is that a parasite must not kill its host before the parasite has succeeded in reproducing and moving on to a new host.

Many parasites leave their host by the same route by which they entered:

For some, completing their life cycle requires that they sequentially parasitize one or more alternate hosts. While this may seem to complicate their lives, in every case it actually increases their chances for survival. (Humans are more likely to eat an infected fish than their own feces.)

Some parasite life cycles involving multiple hosts:

Altering Host Behavior

Some parasites alter the behavior of their host in ways that increase their chances of moving on to a new host. These are parasites that need an alternate host in order to complete their life cycle.

Some examples:

Acute vs. Chronic Infections

The relative success of the measures and countermeasures taken by parasites and their host affects the dynamics of their association. For humans, it results in illnesses ranging from acute to chronic.

Acute Infections

In these, the parasite must move on to a new host before it either kills — or is killed by — its present host. Some examples of these "hit-and-run" diseases: influenza, smallpox, polio, measles.


Chronic Infections

In these, the parasite survives for long periods without either killing or being killed by its host. Some examples: malaria, trypanosomiasis, tuberculosis, leprosy, schistosomiasis.


Commensals play games, too!

Microorganisms that live harmlessly within our body (commensalism), or even benefit us (mutualism) are nonetheless seen as foreign by the immune system and are at risk of attack by it. How they avoid attack is a mystery for most, but is understood for one common inhabitant of the human colon, Bacteroides fragilis.

This bacterium coats itself in a polysaccharide capsule (much the way that the pneumococcus does — Link). Unlike the pneumococcus, however, B. fragilis periodically switches the chemical composition of its capsule by switching on a different gene needed for its synthesis. By periodically changing the surface exposed to antibodies, the bacterium avoids being damaged by them (the same strategy used by trypanosomes).

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5 November 2018