Parasitology and Immunology: Parasites, Their Life Cycles and the Immune Response
2. Host–parasite relations: adaptation, evasion and coevolution
Parasites show morphological adaptations: attachment organs (suckers, the hooked scolex of tapeworms, the toothed buccal capsule of hookworms), loss of organs (tapeworms have no gut and absorb food across a tegument enlarged by microtriches) and resistant coverings (cuticle, tegument, cyst walls that survive drying and stomach acid). Physiological ones include anaerobic metabolism in the oxygen-poor gut and inhibitors of host enzymes. Reproductive ones offset the low odds of reaching a new host: enormous egg output, hermaphroditism in most flatworms, and asexual multiplication inside intermediate hosts (sporocysts and rediae of flukes, schizogony of Plasmodium).
Parasites also evade immunity. African trypanosomes switch their variant surface glycoprotein (VSG), so each wave of parasitaemia is antigenically new; P. falciparum varies its red-cell surface protein PfEMP1. Others hide inside cells: Plasmodium in red cells, which carry no MHC, Leishmania inside macrophages, Toxoplasma in a vacuole that does not fuse with lysosomes. Schistosomes coat their tegument with host molecules. Hosts evolve in return: the sickle-cell trait (HbAS) protects against severe falciparum malaria, a balanced polymorphism, and red cells lacking the Duffy antigen resist P. vivax. Some parasites alter host behaviour to aid transmission: rodents infected with Toxoplasma lose their aversion to cat odour. That a well-adapted parasite spares its host is a tendency, not a law; virulence is favoured when transmission depends on the damage itself.
3. Protozoan parasites
| Parasite | Disease; hosts or vector | Infective stage and route | Key feature |
|---|---|---|---|
| Entamoeba histolytica | Amoebic dysentery, liver abscess; humans only | Mature four-nucleate cyst, faecal–oral | Trophozoites invade the colon wall (flask-shaped ulcers) |
| Giardia lamblia | Giardiasis: malabsorption, fatty diarrhoea | Four-nucleate cyst, faecal–oral, often in water | Binucleate trophozoite clings by a ventral adhesive disc; does not invade |
| Trypanosoma brucei | African sleeping sickness; tsetse fly (Glossina) | Trypomastigote injected in the fly's saliva | Extracellular in blood, later the CNS; VSG switching |
| Trypanosoma cruzi | Chagas disease; triatomine (reduviid) bug | Trypomastigotes in bug faeces rubbed into the bite or mucosa | Amastigotes multiply inside cells, notably heart muscle |
| Leishmania donovani | Visceral leishmaniasis (kala-azar); sandfly (Phlebotomus) | Promastigote injected by the sandfly | Amastigotes multiply inside macrophages of spleen, liver and marrow |
| Toxoplasma gondii | Toxoplasmosis; cat definitive, many mammals intermediate | Oocysts from cat faeces, tissue cysts in undercooked meat, across the placenta | Congenital infection |
The malaria parasite Plasmodium alternates between hosts. A female Anopheles injects sporozoites, which enter liver cells and multiply by exo-erythrocytic schizogony; the released merozoites invade red cells, pass through ring, trophozoite and schizont stages and burst out as new merozoites (erythrocytic schizogony). The synchronous bursting causes the fever paroxysm, every 48 h in P. vivax, P. ovale and P. falciparum (tertian) and every 72 h in P. malariae (quartan). Some merozoites become male and female gametocytes. In the mosquito gut these form gametes that fuse to a zygote; it becomes a motile ookinete, then an oocyst on the gut wall, where sporogony produces sporozoites that migrate to the salivary glands. Dormant liver hypnozoites of P. vivax and P. ovale cause relapses, and red cells infected with P. falciparum stick to vessel walls, which underlies cerebral malaria. Ronald Ross worked out transmission by mosquitoes while serving in India and received the 1902 Nobel Prize for it.
4. Helminth parasites
Parasitic helminths belong to two phyla. Trematodes (flukes) are flat and unsegmented, with oral and ventral suckers, mostly hermaphrodite, and use a snail as first intermediate host, in which larvae multiply asexually. Cestodes (tapeworms) are ribbon-like: a scolex for attachment, a neck that buds off proglottids, and a strobila of hermaphrodite proglottids, with no gut. Nematodes (roundworms) are cylindrical and unsegmented, with a complete gut, a pseudocoelom, separate sexes (the male smaller, often with a curved tail) and a cuticle moulted four times.
| Parasite | Definitive host | Intermediate host | How humans are infected; key point |
|---|---|---|---|
| Fasciola hepatica (liver fluke) | Sheep and cattle; humans occasionally | Snail (Lymnaea) | Metacercariae encysted on water plants; egg → miracidium → sporocyst → redia → cercaria → metacercaria |
| Schistosoma (blood fluke) | Human | Snail | Cercariae penetrate the skin in water; sexes separate |
| Taenia solium (pork tapeworm) | Human | Pig | Cysticerci in undercooked pork; scolex armed with hooks and four suckers |
| Taenia saginata (beef tapeworm) | Human | Cattle | Cysticerci in undercooked beef; scolex without hooks |
| Echinococcus granulosus | Dog | Sheep, cattle; humans accidentally | Eggs from dog faeces; hydatid cysts in liver and lungs |
| Ascaris lumbricoides | Human | None | Embryonated eggs swallowed; larvae migrate through liver, heart and lungs, are coughed up and swallowed |
| Ancylostoma duodenale (hookworm) | Human | None | Filariform larvae penetrate the skin; blood-feeding causes iron-deficiency anaemia |
| Wuchereria bancrofti (filarial worm) | Human | Mosquito (Culex; also Anopheles, Aedes) | Infective larvae deposited at the bite; microfilariae circulate at night; lymphatic filariasis |
| Enterobius vermicularis (pinworm) | Human | None | Eggs, often by self-reinfection; females lay eggs on perianal skin at night |
5. The immune system: innate defence and lymphoid organs
Innate immunity is present from birth, acts within minutes to hours, uses germline-encoded receptors and has no memory. It includes barriers (skin, mucus, lysozyme, stomach acid), phagocytes (neutrophils first, then macrophages), natural killer (NK) cells, complement, inflammation and antiviral type I interferons. Its pattern-recognition receptors, such as the Toll-like receptors, detect molecules common to microbes: TLR4 recognises bacterial lipopolysaccharide, TLR3 double-stranded RNA, TLR5 flagellin. Adaptive immunity, carried by lymphocytes, is specific and clonal, slower on first exposure, and leaves memory.
Primary lymphoid organs produce and select lymphocytes: the bone marrow (all blood cells; B-cell maturation) and the thymus (T-cell maturation). In birds B cells mature in the bursa of Fabricius, which gave B cells their letter. Secondary lymphoid organs, the lymph nodes, the spleen (for blood-borne antigen) and mucosa-associated tissue such as tonsils and Peyer's patches, are where naive lymphocytes meet antigen brought by dendritic cells.
Complement is activated by three routes: classical (C1q binding antibody on an antigen), lectin (mannose-binding lectin on microbial sugars) and alternative (spontaneous C3 hydrolysis on unprotected surfaces). All converge on a C3 convertase, giving opsonisation by C3b, inflammation and chemotaxis by C3a and C5a, and lysis by the membrane attack complex, C5b–C9. Innate defence is universal in animals (the Toll pathway was first found in Drosophila), but immunoglobulins, T-cell receptors and MHC, built by RAG-mediated V(D)J recombination, occur only in jawed vertebrates; lampreys and hagfish have a separately evolved lymphocyte receptor system.
6. Humoral immunity: antibodies and clonal selection
An antibody has two identical heavy chains and two identical light chains (κ or λ) joined by disulphide bonds. The variable domains of one heavy and one light chain form an antigen-binding site, shaped by three hypervariable loops (CDRs) on each chain; the heavy-chain constant region fixes the class and the effector function. Papain cuts at the hinge into two Fab fragments, each with one binding site, and one Fc; pepsin leaves one bivalent F(ab')2.
| Class | Form | Binding sites | Distinctive role |
|---|---|---|---|
| IgG | Monomer | 2 | Most abundant in serum; crosses the placenta; opsonises; dominant in secondary responses |
| IgM | Pentamer with J chain in serum | 10 | First antibody of a primary response; strongest complement activator; the monomer is a B-cell receptor |
| IgA | Dimer with J chain and secretory component in secretions | 4 | Mucosal surfaces, milk and colostrum |
| IgE | Monomer | 2 | Binds mast cells and basophils; allergy; defence against worms |
| IgD | Monomer | 2 | B-cell receptor, with IgM, on naive B cells |
Clonal selection (Burnet): each lymphocyte carries receptors of a single specificity, generated before any antigen is met by V(D)J recombination (RAG1 and RAG2) and junctional diversity. Antigen selects the matching clones, which divide (clonal expansion) and differentiate into antibody-secreting plasma cells and long-lived memory cells; self-reactive clones are deleted or silenced. For a protein antigen the B cell presents peptide on MHC class II to a helper T cell, which supplies CD40 ligand and cytokines; in the germinal centre the enzyme AID drives somatic hypermutation, which with selection gives affinity maturation, and class switching. A secondary response is faster, larger, mostly IgG and of higher affinity. Expansion is exponential, N = N0 × 2t/td: one cell dividing every 8 h for 4 days (12 divisions) gives 4,096 cells.
A titre is the reciprocal of the highest dilution of serum that still gives a detectable reaction. In a twofold series starting at 1:10, tube n holds a 1:(10 × 2n−1) dilution, so agglutination up to tube 6 means a titre of 320. A fourfold or greater rise between acute and convalescent sera points to a current infection. Active immunity is made by the host (infection, vaccine); passive immunity is borrowed antibody (maternal IgG across the placenta, antiserum).
7. Cell-mediated immunity and immunity to parasites
T cells see peptide bound to MHC. Class I molecules (an α chain with β2-microglobulin) sit on nearly all nucleated cells and present peptides of 8 to 10 amino acids from cytosolic proteins, cut by the proteasome and pumped into the ER by TAP, to CD8 T cells. Class II molecules (α and β chains) sit on dendritic cells, macrophages and B cells and present peptides from engulfed proteins to CD4 T cells. Activation needs signal 1 (T-cell receptor with peptide–MHC) and signal 2 (CD28 on the T cell binding B7 on the antigen-presenting cell); signal 1 alone causes anergy. In the thymus, positive selection keeps cells that recognise self MHC and negative selection removes strongly self-reactive ones.
- Th1 (IFN-γ): activates macrophages; intracellular microbes and protozoa
- Th2 (IL-4, IL-5, IL-13): switching to IgE, eosinophils, mast cells; worms
- Th17 (IL-17): recruits neutrophils; extracellular bacteria and fungi
- Treg (FoxP3; IL-10, TGF-β): suppresses responses and maintains tolerance; Tfh: helps B cells in germinal centres
Cytotoxic T cells kill infected cells with perforin and granzymes, which trigger apoptosis, and through Fas ligand. NK cells kill cells that have lost MHC class I (“missing self”) and antibody-coated cells by antibody-dependent cell-mediated cytotoxicity (ADCC) through their Fc receptor CD16. Against parasites the response depends on size and site. Worms are too big to engulf, so a Th2 response arms mast cells with IgE, recruits eosinophils that attack antibody-coated larvae, and increases mucus and gut contraction to expel the worms; eosinophilia and high IgE mark helminth infection. Intracellular protozoa such as Leishmania and Toxoplasma need Th1 help: IFN-γ activates macrophages to kill them. Mice infected with Leishmania major show this sharply: C57BL/6 mice mount a Th1 response and heal, BALB/c mice a Th2 response and develop progressive disease. In malaria, antibodies block sporozoites and merozoites, and CD8 T cells kill infected liver cells but not infected red cells, which lack MHC class I.
Key takeaways
- A parasite lives on or in a host and depends on it metabolically. The definitive host carries the adult or sexual stage, the intermediate host larval or asexual stages; for Plasmodium the mosquito is definitive and the human intermediate.
- Parasites adapt by attachment organs, loss of organs, resistant coverings, anaerobic metabolism and huge reproductive output, and evade immunity by antigenic variation, hiding in cells and host disguise; hosts answer with traits such as HbAS and Duffy negativity.
- Know each standard parasite by host, vector and infective stage: Entamoeba cyst, Giardia cyst, tsetse for T. brucei, triatomine bug for T. cruzi, sandfly for Leishmania, sporozoite for humans and gametocyte for mosquitoes in malaria.
- Flukes use snails and multiply as larvae; tapeworms need two hosts (T. solium eggs make humans intermediate hosts, causing cysticercosis); Ascaris, hookworm and pinworm need none, while Wuchereria needs a mosquito.
- Innate immunity uses germline receptors such as TLRs, phagocytes, NK cells and three complement pathways converging on C3. Antibodies have two heavy and two light chains; IgM is a pentamer with 10 sites, secretory IgA a dimer with 4, IgG crosses the placenta. Titre = reciprocal of the highest positive dilution.
- Clonal selection expands antigen-specific clones exponentially (N = N0 × 2n). MHC I presents cytosolic peptides to CD8 cells and MHC II engulfed ones to CD4 cells; Th1 and IFN-γ control intracellular protozoa, Th2, IgE and eosinophils control worms, and NK cells kill cells lacking MHC I.
Practice questions (18)
Attempt each one before opening the answer. Every explanation names the tempting wrong option as well as the right one, because that is where marks are lost.
Which statement correctly identifies the definitive host of Plasmodium vivax together with the reason?
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Answer: B — The female *Anopheles* mosquito, because the fusion of gametes and sporogony take place in it
The definitive host is the one in which sexual reproduction occurs. Gametocytes taken up by a female Anopheles form gametes that fuse in the mosquito gut, and sporogony follows on the gut wall, so the mosquito is definitive; the human, where only schizogony occurs, is intermediate. Large numbers of parasites in human blood are the tempting reason, but numbers do not define the host type. Male mosquitoes do not feed on blood and cannot transmit malaria.Which of the following are genuine adaptations of an adult tapeworm to life in the host's intestine?
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Answer: A — It has no digestive tract and absorbs nutrients across its tegument; D — Its proglottids are hermaphrodite and release very large numbers of eggs
A tapeworm has lost its gut and absorbs food through a tegument covered with microtriches, and its hermaphrodite proglottids produce huge numbers of eggs to offset the low chance of reaching a new host. The gut lumen is poor in oxygen and adult tapeworms rely largely on anaerobic metabolism. Tapeworms have a living tegument, not a chitinous exoskeleton, and do not moult.Blood samples taken every few days from a person infected with Trypanosoma brucei show successive waves of parasitaemia, and the parasites of each wave are not recognised by antibodies raised against the previous wave. What best explains this?
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Answer: D — Some parasites switch to a different variant surface glycoprotein, escaping the existing antibody
T. brucei is covered by one variant surface glycoprotein (VSG) at a time but carries a large repertoire of VSG genes. Antibody clears the dominant variant, while the few parasites that have switched to a new VSG grow out as the next wave. African trypanosomes live free in the blood, so hiding in red cells (a Plasmodium strategy) does not apply; coating with host molecules is the schistosome strategy and would not produce antigenically distinct waves; liver schizogony belongs to malaria.Which stage of Entamoeba histolytica is infective to humans, and why?
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Answer: C — The mature four-nucleate cyst, because its wall survives outside the host and in stomach acid
The mature four-nucleate cyst survives in water and food and passes through the stomach, then excysts in the intestine; it is the infective stage. Trophozoites are the invasive stage but die quickly outside the body and in gastric acid, which makes them the tempting but wrong choice. A binucleate trophozoite with a ventral disc describes Giardia, and oocysts from cat faeces belong to Toxoplasma.Which of the following statements about the life cycle of Plasmodium are correct?
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Answer: A — Synchronous rupture of schizonts in red cells coincides with the fever paroxysm; C — Hypnozoites of *P. vivax* in the liver can cause relapses months after the first attack
The paroxysm follows the synchronous release of merozoites, toxins and debris when schizonts burst, and P. vivax (like P. ovale) leaves dormant hypnozoites in the liver that reactivate as relapses. Humans are infected by sporozoites; gametocytes infect the mosquito. The multiplication in liver cells is exo-erythrocytic schizogony; sporogony occurs only in the mosquito.In a simple model of an untreated malaria infection, each infected red cell releases 16 merozoites at the end of a 48-hour erythrocytic cycle, every merozoite invades a fresh red cell, and no parasites are cleared. Starting from 1,000 freshly infected red cells at time zero, how many red cells are infected after 6 days?
Numerical answer — type the value.
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Answer: 4096000
6 days = 144 h = 144 ÷ 48 = 3 complete cycles. Each cycle multiplies the infected cells by 16, so the number is 1,000 × 16³ = 1,000 × 4,096 = 4,096,000. Counting six cycles (one per day) is the usual slip.A person accidentally swallows eggs of Taenia solium passed by a tapeworm carrier. What is the most likely consequence?
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Answer: B — Cysticerci develop in tissues such as muscle and brain, the human acting as an intermediate host
Eggs of T. solium hatch in the human intestine, and the larvae cross the gut wall and lodge in muscle, eye and brain as cysticerci: cysticercosis, with the human in the role normally taken by the pig. An intestinal tapeworm arises only from eating cysticerci in undercooked pork, which is the tempting confusion. Snails are intermediate hosts of flukes, not tapeworms, and hydatid cysts are larvae of Echinococcus.Which helminth typically infects humans when a larva living in moist soil penetrates the skin of bare feet?
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Answer: D — *Ancylostoma duodenale*
The filariform larva of the hookworm Ancylostoma duodenale develops in moist soil and penetrates the skin. Ascaris and Enterobius infect by swallowed eggs; Ascaris is tempting because its larvae also migrate through the lungs, but they hatch from swallowed eggs. Taenia saginata is acquired by eating cysticerci in beef.Deworming dogs regularly reduces human hydatid disease in a sheep-rearing district, whereas surgically treating infected people has no effect on transmission. Why?
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Answer: A — Humans are accidental intermediate hosts whose cysts dogs do not eat, so the cycle runs between dogs and livestock
Echinococcus granulosus lives as an adult in the dog's intestine and as hydatid cysts in sheep and cattle; dogs are infected by eating offal containing cysts. A human with a cyst is a dead end, because no dog eats it, so treating people removes no source of eggs, while deworming dogs cuts egg output at its only source. The adult worm does not live in humans, dogs are not intermediate hosts, and sheep do not harbour the adult.What is the bursa of Fabricius?
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Answer: B — The primary lymphoid organ of birds in which B lymphocytes mature
The bursa of Fabricius is a cloacal outgrowth in birds where B cells mature, and the B of B cell comes from it. The secondary lymphoid organ that filters blood in mammals is the spleen, positive selection of T cells takes place in the thymus, and fish have no bursa.Which of the following statements about innate immunity are correct?
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Answer: A — The alternative pathway of complement can be activated without any antibody; C — C3b deposited on a microbe acts as an opsonin that promotes phagocytosis; D — Toll-like receptor 4 recognises the lipopolysaccharide of Gram-negative bacteria
The alternative pathway starts from spontaneous C3 hydrolysis on unprotected surfaces, C3b is the main complement opsonin, and TLR4 is the lipopolysaccharide receptor. NK cells are innate lymphocytes whose activating and inhibitory receptors are germline-encoded; V(D)J recombination builds only B- and T-cell receptors.Count theoretical antigen-binding sites. A sample contains 3 molecules of pentameric serum IgM, 2 molecules of dimeric secretory IgA and 5 molecules of monomeric IgG. What is the total number of antigen-binding sites?
Numerical answer — type the value.
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Answer: 48
Each antibody monomer has two binding sites. Pentameric IgM: 5 × 2 = 10 sites, so 3 × 10 = 30. Dimeric secretory IgA: 2 × 2 = 4 sites, so 2 × 4 = 8. IgG: 2 sites, so 5 × 2 = 10. Total = 30 + 8 + 10 = 48. (Large antigens may engage only about half the IgM sites, but the stem asks for theoretical valency.)Paired sera from a patient are tested by tube agglutination in a twofold serial dilution series that starts at 1:20 in tube 1. The acute-phase serum agglutinates up to tube 3 and the convalescent serum up to tube 6, with no agglutination in later tubes. Taking the titre as the reciprocal of the highest dilution that agglutinates, by what factor has the titre risen?
Numerical answer — type the value.
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Answer: 8
Tube n holds 1:(20 × 2n−1). Tube 3 is 1:80 and tube 6 is 1:640, so the titres are 80 and 640, and the rise is 640 ÷ 80 = 8-fold (three doubling steps, 2³). A rise of fourfold or more supports a current infection.Samples of a rabbit IgG antibody against sheep red cells are digested separately with papain and with pepsin, and the fragments are purified. Which fragment can still agglutinate sheep red cells?
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Answer: C — The F(ab')2 fragment from pepsin, because it keeps two linked antigen-binding sites
Agglutination requires cross-linking, so a fragment must carry at least two antigen-binding sites. Pepsin cuts below the hinge disulphides and leaves a bivalent F(ab')2 that can bridge two cells. Papain cuts above them, giving univalent Fab fragments that bind but cannot cross-link, which is why the Fab option is the tempting wrong answer; Fc has no antigen-binding site, and agglutination does not need complement.After a viral infection, 50 naive CD8 T cells specific for one viral peptide are activated. Each divides every 8 hours for 4 days with no cell death. In the contraction phase that follows, 95% of the expanded cells die and the rest persist as memory cells. How many memory cells remain?
Numerical answer — type the value.
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Answer: 10240
4 days = 96 h = 96 ÷ 8 = 12 divisions, so each cell gives 2¹² = 4,096 cells and the clone reaches 50 × 4,096 = 204,800 cells. 5% survive contraction: 0.05 × 204,800 = 10,240 memory cells.A virus-infected cell line lacks a functional TAP transporter. Compared with infected cells that have TAP, how will these cells fare against cytotoxic lymphocytes?
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Answer: A — They show little peptide-loaded MHC class I, so CD8 T cells recognise them poorly but NK cells kill them readily
TAP pumps cytosolic peptides into the ER, where they stabilise newly made MHC class I. Without it few peptide–class I complexes reach the surface, so CD8 T cells, which need them, recognise the cells poorly, while NK cells, which kill cells lacking class I (missing self), kill them more readily. TAP serves the class I pathway, not class II, which ends the tempting class II option; empty class I is unstable rather than abundant; and TAP is a peptide transporter present in nearly all nucleated cells.Chronic infection with intestinal helminths typically raises which pair of laboratory values, and through which response?
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Answer: C — Serum IgE and blood eosinophil count, through a Th2 response
Worms drive a Th2 response: IL-4 and IL-13 switch B cells to IgE, and IL-5 expands and activates eosinophils, so high IgE and eosinophilia are the classic laboratory signs. A Th1 response with IFN-γ is the tempting alternative but is directed at intracellular microbes, and type I interferons and NK cells are antiviral; the lectin pathway is not a hallmark of worm infection.BALB/c mice infected with Leishmania major develop progressive lesions with a Th2-dominated response, whereas C57BL/6 mice heal. If BALB/c mice are given a neutralising antibody against IL-4 at the time of infection, what is the most likely outcome?
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Answer: D — The response shifts to Th1 and IFN-γ-activated macrophages, so the mice control the infection
Leishmania amastigotes live inside macrophages and are killed only when IFN-γ from Th1 cells activates those macrophages. IL-4 drives and maintains the Th2 bias of BALB/c mice; neutralising it early lets a Th1 response develop, and the mice behave like resistant strains. IFN-γ, not IL-4, activates macrophages, and antibody and IgE cannot reach parasites hidden inside macrophages.