Parasitic infections affect millions globally and cause severe illness. Immunity to parasites is complex due to their large size and multiple antigens. Effective immune responses include antibodies, T cells, macrophages, and eosinophils working together. While immunity can develop, parasites also evade the immune system through mechanisms like antigenic variation, residing intracellularly, or encystment.

1. IMMUNITY TO PARASITIC
INFECTION
BY
Dr. Akase E I
Department of Medicine
ABUTH Zaria.

2. Introduction
• Caused by Protozoa, Helminth,Arthropods
• Affects millions of people in the tropics
• Responsible for severe and debilitating illness
• The effects are either due to the parasites or
consequence of host response to the invader.

4. • Nature and extent of pathological effects depend on:
▫ The site
▫ Mode of infection
▫ Level of parasite burden
• Development of protective immunity is more
complex in parasite compared to viruses and bacteria.

5. Parasitic Life Cycle

7. Pathogenic mechanisms
• Mechanical tissue damage
▫ Physical obstruction of anatomical site
 Ascaris lumbricoides
 Wuchereria bancrofti
 Brugia malayi
▫ Compression
 Taenia solium (cysticerci)
 Echinococcus granulosus ( hydatid cyst)

8. • Physiological effects
▫ Malabsorption
 Gardia spp ( Fat malabsorption)
▫ Competition for essential nutrient leads to host
deprivation: Vit B12 depletion- Diphylobothrium
latum( pernicious anaemia)
▫ Metabolite production:
 Trypanosma cruzi :Neurotoxin with CNS effects
 Plasmodium spp : substance with vasoconstrictor effects.

10. Unique features of parasitic infections
1. Parasites infect very large number of people
 Malaria, for example, kills 1-2 million people every year.
2. Protozoan parasites and worms are considerably
larger than bacteria and viruses and consequently
contain a greater variety and greater quantity of
antigens.
 Some species can also change their surface antigens, a
process known as antigenic variation.
 Parasites that have complicated life histories may express
certain antigens only at a particular stage of development,
giving rise to a stage-specific response.
 The protein coat of the sporozoite (the infective stage of the
malarial parasitic transmitted by the mosquito) induces the
production of antibodies that do not react with the
erythrocytic state;
 the different stages of the worm T. spiralis also display
different surface antigens.

11. 3. Most parasites are host specific-parasites have
become well adapted to their hosts and show marked
host specificity
▫ There are some exceptions to this general rule: E.g.
T. gondii is not only able to invade and multiply in all nucleated
mammalian cells, but can also infect immature mammalian
erythrocytes, insect cell cultures, and the nucleated erythrocytes
of birds and fish.
4. Host resistance to parasite infection may be genetic
 The possession of certain HLA antigens, widespread in native West
Africans but rare in Caucasians, appears to correlate with
protection against severe malaria.
 Certain African populations lack the Duffy antigen – presumably
from the pressures of natural selection – and are totally resistant to
infection by Plasmodium vivax which requires this antigen for
entry.

12. Immune defence mechanisms
• Due to the large size of parasite they display more
antigens to immune system
• Most parasitic infections are chronic and show degree
of host specificity
▫ Exception is Trichinella spiralis which is able to infect
many animal species.
• No single defense mechanism acts in isolation against
a particular parasite.

13. • Cell mediated immune mechanisms are more
effective against intracellular protozoa.
• Antibody with the aid of certain effector cells is
involved in the destruction of extracellular target.
• Depends on the stage of life cycle, CMI or humoral
immunity may be of utmost importance

14. Innate defenses
• Physical barrier
 Protective against many parasite except blood feeding
insect
 Schistosomes evolved active mechanism for penetrating
intact skin
• Individuals are genetically less susceptible to certain
parasites
 Sickle cell trait- malaria
 Duffy blood group antigen- Plasmodium vivax

15. • Other innate mechanisms
▫ Direct cellular responses by
 Monocytes
 Macrophages
 Granulocytes
 Natural killer cells
▫ Substance produce by acquired immune reaction
enhance antiparasitic properties of the cells above.
▫ Leishmania survives in non-stimulated resident
macrophages but are destroyed by activated
macrophages.

16. • Macrophages
▫ Helps in elimination and control of protozoa and
worms
▫ Secrete cyokines
 Interleukin (IL -1)
 Tumour necrosis factor(TNF)
 Colony stimulating factor
▫ They are also phagocytes
▫ They kill parasite by oxygen dependent and
independent mehanisms.

17. ▫ Specific antibody IgG and IgE can mediate the
attachment of the macrophage to the surface of parasites
that are too large to internalize but are vulnerable to
antibody dependent cell mediated cytotoxicity.
▫ Acting as antigen presenting cells, they can aid
elimination by helping in the initiation of an immune
response.
▫ Some products of parasite cause macrophage activation
eg Trypanosoma.brucei and malaria.

18. • Granulocyte
▫ Neutrophil and eosinophil are important
▫ Kill through oxygen dependent and independent mech
▫ Phagocytic capacity of neutrophil is superior to
eosinophils.
▫ Eosinophilia and high levels of IgE are characteristic of
many parasitic worm infection.
▫ Eosinophilia is T cell dependent

19. • Mast cells
▫ Stored mediators which help in elimination of worms
▫ Parasite antigens cause the release of mediator from
mast cells.
▫ The molecules stimulate local inflammatory reaction
▫ IgE dependent release of mast cell products helps in
expulsion of the worm.
▫ The number of mucosal mast cells rises during a
parasitic worm infestation due to a T cell dependent
process.

20. • Platelets
▫ Activation results in the release of toxic materials.
▫ May injure or destroy some parasites including:
 Toxoplasma gondii
 Schistosoma
 Trypanosoma cruzi
▫ Substance release does not require antibody

21. Acquired immunity
• Generate antibody and effector cells directed against
specific parasite antigens
• Memory B and T cells are also produced.
• Such acquired immunity is ineffective in protecting
the host against recurrent infection

22. • Antibody
▫ Specific immunity to parasite results in antibody
production
▫ Infection with protozoa – IgG,IgM production
▫ Helminths – IgE is produced additionally
▫ Intestinal protozoa(Entamoeba,Gardia)- IgA
• T cell
▫ The type of T cell that is effective depends on the
parasite
▫ CD4⁺ T cells transfer protection against L.major and L.
tropical

23. ▫ Necessary for elimination of other parasites
▫ Help in antibody production
▫ Secrete cytokines which interract with other effector
cells.
▫ IL-2 production has been shown to be deficient during
parasitic infection (Tryp, malaria).

24. The role of TH2 responses in defense against helminths
Eosinophils are better at killing helminths than are other
leukocytes; the TH2 response and IgE provide a mechanism
for bringing eosinophils to helminths and activating the cells.

25. • Humoral defence mechanism against parasite
▫ Neutralization
 Blocks attachment of host cell-protozoa
 Inhibit evasion of intracellular parasites-protozoa,worm
 Binding to toxins or enzymes
• Physical interference
▫ Obstruct orifices of parasites - worms
▫ Agglutination – protozoa
• Opsonization
• Increases clearance by phagocytes-Protozoa

26. • Cytotoxicity
▫ Complement mediated lysis –protozoa, worm
▫ Antibody –dependent cell mediated cytotoxicity

27. Antibodies in Parasitic infections
1. Antibody can act directly on protozoa to damage them,
either by itself or by activating the complement system
2. Antibody can neutralize a parasite directly by blocking its
attachment to a new host cell, as with Plasmodium spp.,
whose merozoites enter red blood cells through a special
receptor: their entry is inhibited by specific antibody.
3. Antibody may also act to prevent spread, for example in
the acute phase of infection by T. cruzi.
4. Antibody can enhance phagocytosis by macrophages.
Phagocytosis is increased even more by the addition of
complement. These effects are mediated by Fc and C3
receptors on the macrophages

28. 5. Antibody is also involved in ADCC, for example, in
infection caused by T. cruzi, T. spiralis, S. mansoni and
filarial worms.
Cytotoxic cell such as macrophages, neutrophils and eosinophil adhere to
antibody-coated worms by means of their Fc and C3 receptors and
exocytose in apposition to the parasite.
6. Different antibody isotypes may have different effects. In
individuals infected with schistosomes parasite-specific
IgE is associated with resistance to infection and there is
an inverse relationship between the amount of IgE in their
blood and reinfection. IgG4 appears to block the action of
IgE; reinfection is more likely in children who have high
levels of IgG4.
7. The development of immunity seems to depend upon a
switch from IgG to IgE that occurs with age; infection
rates are highest in 10- to 14-year-olds, when IgG4 levels
are also at their highest.

29. Adaptive immunity to parasites
Parasite Immune response Effector mechanism
Helminths
TH2 cells --> IL-4, IL-5
--> IgE, eosinophils
Eosinophils kill IgE-coated
parasites (form of ADCC)
Leishmania
T cells produce IFN-g -->
activation of phagocytes
Phagocytes kill parasites
living in endosomes
Malaria
CD8+ T cells -->
secretion of cytokines
Role of antibody?
IFN-g, TNF activate
macrophages, neutrophils
to kill parasites

30. Outcome of parasitic infections
• Sterilizing immunity-where after recovery from initial
infection, the organism is completely eradicated and the host
left with solid immunity to re-infection(Rare: Leishmaniasis
tropica)
• Non-sterilizing immunity-where prior infection does not
confer any immunity to future infection (intestinal amoebiasis)
• Concomitant immunity/Premunition- where by initial
infection is not eliminated but becomes established, and the
host then acquires resistance to invasion by new worms of the
same species (Schistosomiasis; malaria)
• Immunopathology Immune complex mediated nephrotic
syndrome
• Non specific Immunosuppression- Burkitt’s Lymphoma in
malaria endemic areas

31. Escape mechanisms
• Intracellular habitat
▫ Plasmodium
▫ Trypanosomes
▫ Leishmania spp
• Encystment
▫ Toxopasma gondii
▫ Trypanosoma cruzi

32. • Resistance to microbicidal products of phagocytes
▫ Leishmania donovani
• Masking of antigens
▫ Schistosomes
• Variation of antigen
▫ Trypanosomes
▫ Plasmodium

33. • Sharing of antigens between parasite and
host(molecular mimicry)
▫ Schistosomes
• Continuous turn over and release of surface antigens
of parasite
▫ Schistosomes
• Suppression of immune system
▫ Trichinella spiralis
▫ Schistosomes

34. Immuno-pathological consequences of
parasitic infections
1. In malaria African trypanosomiasis and visceral
leishmaniasis, the increased number and heightened activity
of macrophages and lymphocytes in the liver and spleen lead
to enlargement of those organs.
2. In schistosomiasis much of the pathology results from the T
cell-dependent granulomas forming around eggs in the liver.
3. The gross changes occurring in individuals with elephantiasis
are probably caused by immunopathological responses to
adult filariae in the lymphatics.
4. The formation of immune complexes is common; they may
be deposited in the kidney, as in the nephritic syndrome of
quartan malaria, and may give rise to many other
pathological changes.

35. 5. The IgE of worm infections can have severe effects on the host due
to release of mast-cell mediators.
6. Anaphylactic shock may occur when a hydatid cyst ruptures.
7. Asthma-like reactions occur in Toxocara canis infections, and in
tropical pulmonary eosinophilia when filarial worms migrate
through the lungs
8. Autoantibodies which probably arise as a result of poly-clonial
activation, have been detected against red blood cells, lymphocytes
and DNA (e.g. in trypanosomiasis and in malaria).
9. Antibodies against the parasite may cross-react with host tissues.
For example, the chronic cardiomyopathy, enlarged oesophagus
and megacolon that occur in Chagas' disease are thought to result
from the autoimmune effects on nerve ganglia of antibody and of
cytotoxic T cells that cross-react with T. cruzi.

36. VACCINES
• Some vaccines that are composed of attenuated living
parasites have proved successful in veterinary
practice.
• However, so far there are none in use against human
parasites, although much effort has been directed
towards the development of subunit vaccines against
malarial parasites and schistosomes in particular.
• Some clinical trials of vaccines against malaria, based
on combination of putatively protective peptides are
in progress

37. Points of attack of potential malaria
vaccines
Smith et al (2006)

38. Thank you for listening