PARASITE IMMUNOLOGY

Prof. Agustina Tri Endharti, SSi.PhD

FKUB
Immunological reactions to parasites
infection:
Depending on the habitat in the human
body
Blood / body fluids: humoral reactions
Tissue: cellular reaction
The main mechanism
Opsonization  phagocytosis  activation
complement  mediator inflammation
 Immune response to helminth / helminth infections

Helminth infections in general: Helminth adaptation

chronic

The host does not get sick / die :Avoiding host

immune reactions
Respon hospes thd helminth
Humoral & cellular immunity: Helminth which is in the blood
circulation Schistosoma
 Filaria (stadium mikrofilaria)
 Larva A. lumbricoides
 Larva hook-worms

Cellular immunity
Helminth yg berada dlm jaringan (Hipersensitifity IV tipe slow
reaction)
 Telur Schistosoma in tissue (granuloma)
 Larva T. spiralis (trichinosis) capsul / inflammatory cell
 Larva T. solium (sistiserkosis) capsul / inflammatory cell
IMMUNE RESPONSE TO HELMINTH

 Helminth is an extracellular parasite, large in

size difficult phagocytosis

 Intestinal nematodes cause inflammatory

reactions and hypersensitivity
Response in acute phase - IgE & eosinophil activity
→ inflammation = worm expulsion.

Response to chronic phase = chronic inflammation:

Th1 / activated macrophages – granulomas

Th2 / B cell responses ↑ IgE, mast cells & eosinophil

= inflammation
 Immune response to intestinal
helminth infections
Defense mechanism against
helminthes infections → played by Th2
activation
IL-4 Helps to produce IgE by B cells Intestinal
IL-13 contraction ↑
Mucus production ↑
IL-5 Activating eosinophil → eosinophilia
IL-9 Activating mast cells → histamine →
intestinal spasms → worm expulsion
from the intestinal lumen
Setelah IgE melapisi parasit , reseptor Fc (FcɛRI)
dari eosinophil akan mengenali IgE. Selanjutnya, interaksi antara
FcεRI dan bagian Fc dari IgE yang terikat pada cacing
In helminth infections → eosinophils are
more effective than other leukocyte cells
because: granules contain lysozyme which
is more toxic than proteolytic enzymes →
produced by neutrophils and macrophages
General description of immune response:
Eosinophilia

Increase in IgE and IgG antibodies

Inhibit helminth: Humoral & cellular ADCC
mechanism (antibody dependent cell
mediated cytotoxicity)
Helminth larvae in the blood
Microfilaria
cystosomula
Humoral and cellular reaction to helminth

 Menstimuli beberapa mekanisme sistem imun

 Umumnya gabungan humoral dan selular
Contoh terhadap nematoda usus:
 A. lumbricoides didorong keluar oleh peristaltik usus
Caranya:
 Antigen menstimuli limfosit B menghasilkan IgG:
kerusakan membran
 Antigen menstimuli limfosit T mensekresi sitokin
menyebabkan sel goblet mensekresi mucin
 A. lumbricoides dpt didorong keluar, dibantu sel mast
Humoral and cellular reaction to helminth
 Stimulates several mechanisms of the immune
system
 Generally a combination of humoral and cellular
 Examples of intestinal nematodes:
 A. lumbricoides are pushed out by intestinal
peristalsis by Antigen stimulates B lymphocytes
to produce IgG: membrane damage
 Antigens stimulate T lymphocytes secreting
cytokines causing goblet cells to secrete mucin
A. lumbricoides can be pushed out, assisted by
mast cells
Usaha tubuh mendorong A. lumbricoides keluar
The immune response to helminth is very complex

Helminth: Big size => Multicellular

Has several stages Antigen variations (many epitopes)
Each epitope gives rise to an immune response
That plays an antigenic role: produce Metabolic secretion
produce Enzyme secretion, moulting fluid, sheath /
cuticle
 .

 Trematode, cestoda, nematode: share common

antigen cross reactions
 Surface antigen
 Somatic antigen / crude antigen
 Internal antigen / excretory-secretory antigen
immune response: Hyper-eosinophilia Increase
in IgE, IgG
 T-cell dependent (antigens need T cell help)
Schistosomiasis
 Manifestation of immune response: Humoral
(IgE, IgM, IgG) & cellular (eosinophil, neutrophil
and macrophag)
 Acute: serum sickness (Katayama fever)
 Chronic: granulomatous reaction & fibrosis
around the egg =>Type IV hypersensitivity
Evade immune response:
 larvae & adult stage Mimicry
 Shading (skin changes / cuticles)
 Immuno-suppressive
Host immune response to egg stage
(granulomatous tissue)

 Inside the egg there is miracidum

 Miracidium secretes protease which can
penetrate the vein wall into the intestinal lumen /
vesica urinaria
 With intestinal peristalsis, the egg is removed
The eggs are in the sub-mucosa intestinal
Granulomatous tissue
 inflammation cells (eosinophil, lymphocytes,
macrophags)
 Fibrous tissue
 Some eggs are carried by the bloodstream to
the liver
 Eggs trapped in the liver stimulate
granulomatous tissue formation: Inflammatory
cells: eosinophil, neutrophil, macrophag
 Fibrous / collagen tissue
 The granulomatous jar inhibits blood flow from
the portal vein to the sinusoid: Portal
hypertension (complications of schistosomiasis)
 Life Cycle

Females release eggs. Egg characteristics

- Pores, which allow the release of
1) Antigens
2) Enzymes (aid in passage of eggs through host
tissues)
Eggs enter lumen of excretory organs 50%  trapped in
tissues, carried away by blood circulation, lymph.
 Acute Infection
Cercariae penetrate skin  rash
-called schistosome or swimmer’s itch.
Eggs laid in target organs release antigens
 cause Katayama fever
-fever
-urticaria
-malaise
-diarrhea
 Chronic Infection
Symptoms of chronic infection caused by eggs that travel
to various parts of body
Eggs remain trapped in host tissues  secrete Ags 
granulomatous inflammatory immune response
Granulomas:

macrophages surrounded by lymphocytes
(CD4, CD8 T cells), which aggregate at site of infection.
Fibroblast cells

During late stage of chronic infection, they replace the
granulomas. Their proliferation is stimulated by factors
produced by the schistosome egg, & by cytokines from
macrophages & CD4 T cells.
Fibroblasts mediate collagen deposition in the granuloma,
leading to fibrosis (=fibrous connective tissues
development
Granuloma
Infected DCs present bacterial peptides on MHC class II to
CD4+ T cells, which generate Th1 effectors in the presence
of IL-12. These Th1 cells supply cytokines for the CTL
response and macrophage hyperactivation.
Host immune response to cestoda
 There are 2 types of immune responses:
Against adult intestinal worms (D. latum, T. saginata)
 Scolex & proglotid are always in contact with the
intestinal wall
 Cellular immune response (hypersensitivity reactions)
 Expulsion / pushed out
Against larvae in tissue (cysticercosis)
 Humoral & cellular immune response (larval migration in
the blood) ADCC (Antibody-dependent cell-mediated
cytotoxicity)
 Cellular immune response
Respon imun hospes terhadap kista hidatid
Hydatid cysts can develop and are found in: Kidney, liver
Lung brain
Fluid in cysts is very immunogenic, if rupture causes
anaphylactic shock & death (type H1)
Increase in IgE titer Eosinophilia
With the ADCC mechanism against proto-scolex, they don't
mature
Hydatid cyst fluid is used for immunodiagnosis: ELISA
Casoni skin test
Immune response of T. spiralis
 Stadium cysts in the muscle form a capsule /
wall host defense: non-specific (inflammatory
cells)
 Give rise to immunity: Larvae in ADCC
circulation / migration
 Adult in intestinal sub-mucosa
 Adults are pushed out of the host by intestinal
peristalsis
 Description of immune reaction: Eosinophilia
Increased levels of IgE, IgG
PARASITES MECHANISM AVOID FROM THE
IMMUNE HOSPES SYSTEM

Parasites can avoid the host immune response in

various ways:
HELMINTH:
1 Effect of size The large size of the worm makes it
difficult to be eliminated ex: A.lumbricoides
2. The parasite envelops itself with the host protein
(antibody from the host) so it is not considered
a foreign object
ex: Schistosomes - host blood proteins
DCs presenting worm peptides induce CD4 Th2 cell
differentiation. Th2 effectors produce cytokines that induce
activated B cells to undergo isotype switching to IgE.
Mast cells (and basophils; not shown) pre-armed with antiparasite IgE
are activated by worm antigens and release +histamine and toxic
proteins.
Activated eosinophils bind to worm-bound antibodies via their
FcεRIs and degranulate, releasing molecules that directly damage
the worm surface.
3. Molecular mimicry.
Parasit mempunyai kemampuan meniru struktur dan
fungsi molekul hospes
ex: schistosome mempunyai E-selectin
- adhesion / invasion.

4. Anatomical seclusion
Parasit dapat mengasingkan diri (bersembunyi)
dalam organ tubuh hospes
ex: larva Trichinella spiralis di dalam jaringan otot

5. Shedding / replacement surface

Parasit mengganti permukaannya atau melepaskan
dindingnya
 ex:trematoda, hookworm
Cellular adhesion molecules (CAM) are distributed throughout regions of plasma
membranes in contact with other cells and extracellular matrix. The classes of CAM
include cadherins, selectins, integrins
6. Immunosupression - manipulation of the
immune response.
- Severe nematode infections often occur without
symptoms –
- Parasites secrete anti-inflammatory substances
→ inhibits the recruitment (withdrawal) and
activation of leukocytes inhibits chemokine-
receptor interactions ex: Protein owned by
hookworms binds to the CR3 integrin and
inhibits neutrophil extravasation (cell migration
from the blood circulation to the tissues)
inhibiting TLR responses
of dendritic cells, thereby
impairing inflammatory
TH1/TH17 development.
abrogating epithelial cell
production of IL-33,
thereby pre-empting the
type 2 response.

TGF β mimic
7. Anti-immune mechanisms ex: liver
trematode larvae secrete enzymes that
can damage the body. Inhibiting the
process of antigen recognition - inhibits
antigen presentation by APC

8. Migration ex. Hookworms can migrate

from the intestine to avoid local
inflammatory reactions in the intestine
9. Production of parasite enzymes
Parasites secrete certain enzymes
ex: Filaria worms secrete anti-oxidant
enzymes such as glutathione peroxidase
& superoxide dismutase - resistant to the
mechanism of ADCC & oxidative stress
10. Immunosuppressive helminth-derived factors
could be useful to develop new therapeutic
strategies for treatment of chronic inflammatory
conditions
Mengubah komposisi gen agar menghasilkan varian yang
lebih besar untuk bermacam-macam keperluan  1 gen
dapat mengekspresikan puluhan/ribuan protein berbeda.

Bakteri  menghasilkan protein baru yang tidak/

sukar dikenali sistem imun 
menghindar dari intervensi imunitas host.

Manusia/mamalia  gen Ig dan TCR menghasil kan

diversitas yg mampu mengenal bermacam-macam antigen
di lingkungan hidupnya.
 T cell co-receptor molecules
Lck PTK TcR Lck PTK TcR

CD8 3 CD4 2

 

MHC Class I MHC Class II

CD4 and CD8 can increase the sensitivity of T cells to peptide antigen MHC
complexes by ~100 fold