IMMUNOPARASITOLOGY

With parasites some inherent characteristics have an obvious

effect on the immune response
1. Size: diversity of size is considerable
2. Elaborate life cycles and location in the host
Blood parasites
Tissue parasites
Intestinal parasites
3. Multiplication potential
4. Parasite specificity
5. Antigenic complexity
Shared antigenic relationship amongst various species of nematodes and cestodes
but marked disparity amongst trematodes
In protozoa cross-reacting inter-generic and inter-species reactivity is common
At a functional level SOMATIC & METABOLIC antigens are identified. As a rule most
immunogenic antigens are METABOLIC.

6. Evasion mechanisms
 Immuno-parasitology-general principles
1. All parasites elicit immune responses
2. The absence of an immune response results in greater
susceptibility and more severe disease manifestations
drug-induced immuno-suppression
immuno-deficienc
3. Persistence of parasites in the host is due to their ability to
evade host defence mechanisms
4. Specific (acquired) immune response during a primary
infection develop slowly, and although they bring the
infection under control, usually fail to eliminate the parasite
completely
Occult infection
Tissue sequestration
5. Response to secondary infection are efficient and often
(protozoa) or rarely (helminths) result in resistance to
infection
 Immuno-parasitology-general principles
Types of protection
complete-protection (sterile immunity) : associated with
clinical recovery including elimination of the parasite and
subsequent long lasting resistance to re-infection e.g.
Human cutaneous leishmaniasis, rodent trypanosomiasis
and cattle pulmonary dictyocaulosis.
partial protection (non-sterilizing immunity): immune
response which induces acquired resistance to re-infection,
persistence of parasites at controlled levels. Referred as
concomitant immunity in Schistosomiasis and
premunition in malaria
no protection-apparent absence of acquired immunity:
parasites can persist for very long periods even for life span
of the host causing symptoms e.g. African and American
trypanosomiasis, Amoebic meningoencephalitis, visceral
leishmaniasis, hookworm.
 H ost suscept i b il it y t o par a sit i c i n f e ct i o n

G enet i c f a ct o r s N ut r it io nal st a t u s Age and sex Pr e gnancy l o cal dis ease I m m unodef ic i e ncy

bl o od gr o up A: m aln ut r i t i o n ALA m ala r ia cer v ic al cancer O ppor t u ni s t i c in f e ct i o ns

D uf f y gr o up negat iv e i n vasi v e am oebia sis hypochlo r h ydia
t r ic hom onas bow el st a sis
 I m m u n it y in p a r a s it ic d is e a s e s

I n n a t e im m u n i t y A c q u ire d im m u n ity

h e a m o g lo b in o p a th ie s S p e c i f ic N o n s p e c i f ic
d u ffy
g a s t r ic a c id ity
i n t a c t s k in

A n t ib o d y m e d ia t e d C e ll m e d ia t e d I n je c tio n o f B C G

Ig M , Ig G , Ig E A c t iv a t e d m a c r o p h a g e s
N a t u r a l k i l l e r c e l ls
C y t o t o x ic T -ly m p h o c y t e s
A DC C
 Effector mechanisms
Antibodies
binding of AB to parasites surface may prevent their movement,
attachment, penetration of cells, release of excretory/secretory
products, reproduction
most protective effects are due to secondary mechanisms: e.g.
antibody-dependent complement and cell-mediated lysis (ADCC)
complement-fixing antibodies (protozoa), ADCC (helminths)
Cell-mediated immunity (CMI)
cytotoxic T-lymphocytes (CTL): MHC-restrictes lysis of parasites
or cells containing parasites
natural killer cells (NK cells): play a role in early host defence
against protozoa
cytokines: in vivo activation of macrophages-killing of intracellular
protozoa via reactive oxygen and nitrogen intermediates,
tryptophan degradation
 Effector mechanisms
Antibody-dependent cellular cytotoxicity (ADCC)
involves antibody (mainly IgG) and cells that have Fc
receptor: macrophages, eosinophils, neutrophils. Parasites
susceptible to ADCC include Plasmodium, Trypanosomes,
Leishamania, Schistosomes and trichinella
complement lysis: both classical and alternative pathways
are operational. Classical pathway is triggered by immune
complexes while alternative pathways is triggered by
parasite molecules. Complement can lyse parasites either
alone or in the presence of antibody
 IMMUNE-PATHWAYS ACTIVATED BY PARASITE ANTIGEN

Membrane
bound antigen
antigen

APC
Antigenic peptides +MHC

Suppressor cells
T-cell
B cells
Lymphokines
Helper cells

Plasma cells
Eosinophil Activation
Cytotoxicity proliferation & proliferation

Specific Non-specific
antibody antibody
 PARASITE SURVIVAL-EVASION
MECHANISMS

Parasite survival is a basic challenge-if parasites totally elude the

immune response and were sufficiently virulent, they would kill their

hosts upon their survival depends and preclude their own survival.

Conversely, if they were too easily destroyed by the immune response,

their survival would be similarly jeopardised. Consequently, immunity

and escape from surveillance are relative phenomena which are

ordinarily in a constant balance and tension.

 Antigenic variation
Antigenic mimicry-concomitant immunity and
camouflage
Intracellular parasitism
failure to fuse the lysosomes
resistance to killing
escape from the lysosomes
Suppression of the immune system
polyclonal activation: Jamming the immune system
immune complex formation
destroy the CMI:humoral ratio
burkitts lymphoma
Immunopathology-hypersensitivity reactions
Type I reaction:
TPE
Lofflers pneumonia
Leaking of hydatid cyst
CLM, larva currens, swimmers itch
Type II reaction:
Anaemia in malaria
mega disease in American trypanosomiasis
Type III reaction:
immune complex mediated nephritis in malaria, leishmania,
trichinosis, schisto & African trypanosomiasis
Type IV reaction:
local inflammation in filariasis, trichinosis, schiosto, toxo in the retina,
 EXAMPLE 1: MALARIA
Factors favouring parasite survival:
Intracellular location
Antigenic variation
Polymorphism
Immunosuppression
Polyclonal activation
Circulating antigens
Host resistance to Plasmodium:
Host genetics
Host physiology
Immune mechanisms-non-specific macrophages, complement,
acute phase reactants, specific antibodies and memory cells
 Malaria antigens
Sporozoite antigen-most prominent
Circumsporozoite antigen-glycoprotein that accounts for more than
95% of molecules expressed on the surface
Gene encoding this molecule has been cloned and both
recombinant and synthetic versions have been used for the
development of a malaria vaccine
Erythrocytic cycle antigens
Merozoite surface-glycophorin-binding proteins 195KD protein
Antigen on RBC: RESA or Pf 155 (ring infected erythrocyte surface
antigen,
Histidine rich protein (Pf92) cytoadherence molecule
Rhoptry proteins-Py235, Pf140, Pf41
 Immune mechanisms of host resistance
to Plasmodium
Sporozoite:
Primary infection: NONE
Secondary infection: antibody response to circumsporozoite antigen,
antibody-mediated complement lysis and antibody-dependent cellular
cytotoxicity.
Exoerythrocytic cycle:
Primary & secondary infections-interferon- reduces the number of infected
hepatocytes in vivo & in vitro and specific antibodies to parasite surface
molecules (30 and 60kD) prevent entry into hepatocytes
Erythrocytic cycle: I0 & 20 infections

Antibody response to Antibody-dependent complement

Merozoite surface antigens
Antigens on infected RBC
Glycophorin-binding proteins
Rhoptry proteins
Cytoadherence molecules
lysis & cellular cytotoxicity
Merozoites
Infected RBC
Antibody-dependent cellular cytotoxicity
Cytotoxic T-cells