University of Mosul

College of Medicine
Lecture: (5, Immune response to parasitic
infections)
Subject/year: Medical Parasitology/3rd
Lecturer: Dr. Ahmed Abdullah Ahmed
Department: Microbiology
Date: 2024
 ‫ﻣﻼﺣﻈﺔ‪ :‬ﰎ ﺗﺮﺗﻴﺐ اﳌﻠﺰﻣﺔ ‪ ،‬ﻛﺎﻧﺖ ﻣﻜﺘﻮﺑﺔ ﺑﺸﻜﻞ ﻛﻼم ﺷﺮﺣﻲ …‬
‫وأﻧﺎ ﻋﻤﻠﺘﻬﺎ ﺑﺸﻜﻞ ﻧﻘﺎط ورؤوس ﻧﻘﺎط ﻟﺘﺴﻬﻴﻞ اﳊﻔﻆ واﻟﻔﻬﻢ 📝‬

‫‪① Immune‬‬ ‫‪response to helminthes‬‬

‫‪infections‬‬
 :‫اﻟﺪﻳﺪان اﻟﻄﻔﻴﻠﻴﺔ ﻫﻲ أﺳﻴﺎد اﻟﺘﻌﺪﻳﻞ اﳌﻨﺎﻋﻲ وذﻟﻚَ ﻷﻣﺮﻳﻦ‬
Helminthes are masters of immune modulation
in order to:
①• Overcome the efforts of the host to expel them

②• Create an environment that is permissive for

long-term parasitism.
.‫ اﻟﺘﻐﻠﺐ ﻋﻠﻰ ﺟﻬﻮد اﳌﻀﻴﻒ ﻟﻄﺮدﻫﻢ‬-١

.‫ ﺧﻠﻖ ﺑﻴﺌﺔ ﻣﺘﺴﺎﻫﻠﺔ ﻟﻠﺘﻄﻔﻞ ﻋﻠﻰ اﳌﺪى اﻟﻄﻮﻳﻞ‬-٢

 The immune response to helminths:
Following exposure to helminths, key changes are
observed
The immunein the innate
response immune system,
to helminths involvesinclude:
key changes in the innate
• Modification
immune system following
of DCsexposure.
. These changes include:
• 1.Most helminths stimulate the host to selectively
Modification of Dendritic Cells (DCs): Helminths modify DCs.
2.produce Th2Response:
Th2 Cytokine cytokines,Mostdecrease Th1 cytokine
helminths stimulate the host to
selectively produce
responses. ThisTh2 cytokines
usually and
leads todecrease Th1 mast
strong IgE, cytokine
cell,
responses. This usually
and eosinophil leads to strong IgE, mast cell, and eosinophil
responses.
responses.
• 3.Helminthic infections
Inhibition of Th17 Immunealso inhibit
Response: T17 immune
Helminthic infections also
inhibit the Th17 and
response immune response.
increases T-regulators cells subsets that
4.recognize
Increase in auto
T-Regulatory Cells:and
antigens Helminthic
releaseinfections increase T-
regulatory
regulator cell subsets that recognize autoantigens and release
cytokines
regulatory IL-10IL-10
cytokines and TGF- β
and TGF-β.
‫اختصارللكلام‬
‫ﻫﺎ وردة ﺷﺒﻴﻚ ﺧﻔﺖ ﻣﺠﺮد ﻣﺨﻄﻂ ﻟﻠﻜﻼم اﻟﻔﻮق 😁‬
• CLR= C-type-lectin receptor
• TLR= toll like receptor
• AAMs= altrenatively activated macrophages
• ARG1= arginase 1 ‫اﺧﺘﺼﺎرات ﺗﻮﺿﻴﺤﻴﺔ ﻻ ﲢﻔﻈﻬﺎ‬
• YM1= YM1 protein
• FCR= Fc receptor
• DC= dendretic cells
• NFKB = Nuclear factor kappa B inflammatory pathway
• Th= T helper
• Treg= T regulatory
• TGF-B = transforming growth factor B
 Importance of immune modulation by
helminthes
• The importance is clear under the explanation
ofHygiene
1. the hygieneTheory: theory( low rate of infection
•during
Low rates lifeofmayinfection increase during life may
the increase
level of auto the level of
autoimmune diseases.
immune diseases). …!‫هذي نظرية ترجّ ح أن عدم اإلصابة بالديدان قد يكون سبب لألمراض المناعية‬
👌‫يعني اإلصابة بهذي الديدان تقي من األمراض المناعية ألنّ ها تح ّور الجهاز المناعي فهذي تعتبر فائدة‬
• Higher quality of life and refined standards of
2. Developed World Impact:
•living
Higherinquality
the developed
of life and refined world led to
standards of a decrease
living in the
in theworld
developed infections
have led to burden.
a decrease in the infection burden.
! ‫يسولف عن بلدان العالم ال ُمتقدمة … هذي البلدان عندهم نظام تعقيم وحياة متقدمة أدت إلى انخفاض اإلصابات‬

‫لو سألنا عن األمراض المناعية… بأي دول تكونأكثر؟ أكيد يكون الجواب بلدان العالم المتقدمة‬
 ‫مفهوم وسهل هذا الكالم‬

• The limited exposure to microbial infections

especially during childhood may have led to
failure of the immune system to program itself
to face these infections. This eventually result
in an off-balanced, dys-regulated immune
responses.
• Children born ّ ‫طق الر‬
‫يفية‬ and ‫ المنا‬grow in a rural areas,
1. Childrento
exposed in Rural
a Areas:
diverse spectrum of parasitic
• Children born and grow in rural areas are exposed to a
agents,
diverse spectrum developof parasitic autoagents. immune diseases less
• They develop autoimmune ‫المناطق ا َلحض ّرية‬ diseases less frequently
frequently
than those from than those from urban districts.
urban districts.
• (‫ن‬ ‫عي أحسن من أوالد ا َلح َضر )المد‬
Additionally, children ‫ضة للعوامل الط‬to
‫فيلية فيكون جهازهم المنا‬born ‫نونأكثر عُ ر‬ ‫أبناء الريف يكو‬
mothers
… ‫يعني األمراض المناعية بأبناء ا ّلريف أقل‬
exposed to farm animals and consumed raw
milk,
2. Maternal during pregnancy,
Exposure have and
to Farm Animals lesser Raw chanceMilk: to
• Children born to mothers who were exposed to farm
get autoimmune
animals and consumed raw disorders.
milk during pregnancy have a
lesser chance of developing autoimmune disorders.
… ‫أطفال األمّ هات الالتي يتعاملن مع حيوانات الريف أو يتناولن الحليب الخام )غير المطبوخ( أثناء الحمل‬
…‫ناعية‬ّ ‫قل عرضة لألمراض الم‬ ّ ‫يكونون أ‬
‫‪② Examples‬‬ ‫‪for immune response in‬‬
‫‪protozoal infections‬‬
‫‪immunocompetent or Immunocompromised‬‬ ‫يتناول كل واحد منهم بحسب‪:‬‬
‫لذا أضفت باألخير ساليدينكمقارنة بينهم كلهم 📝‬
‫المؤشّ ر كلّه رؤوس نقاط هنا يعني كل الساليد مطلوب حفظه !‬
 T.gondii
1.• NK Cell
In an Proliferation:
immunocompetent host, NK cell proliferation is accelerated by
• In an immunocompetent
production host, NK cell proliferation is accelerated
of IL-12 and IFN-g.
by the production of IL-12 and IFN-g.
• IFN-g probably
2. Macrophage acts in concert with TNF-α to further stimulate the release
Activation:
of oxidants
• IFN-g by macrophages.
likely acts with TNF-α to stimulate macrophages to release oxidants.
3.• Parasite-Specific
After several daysTpost-infection,
Cell Response:parasite-specific T cell response occurs.
• After several days post-infection, a parasite-specific T cell response occurs.
4.• Long-term
Both CD4 THost cellsProtection:
and CD8 T cells act together for long-term host
• Both CD4 T cells and CD8 T cells act together for long-term host protection.
protection.
5. Toxoplasmosis in AIDS Patients:
• About 20% of AIDS patients display symptoms of toxoplasmosis.
• About 20% of AIDS patients display symptoms of toxoplasmosis.
6.• Symptomatic
During the lastT. gondii
stagesInfection in Late-stage Toxoplasma
of AIDS, symptomatic AIDS: gondii infection is
• During the last stages of AIDS, symptomatic Toxoplasma gondii infection
often observed.
is often observed.
• If nerve cells
7. Toxoplasma bearing CD4(TE)
Encephalitis receptors as glial cells
in HIV-infected harbor Toxoplasma
Individuals:
• Ifpseudocyst
nerve cellsbradyzoites
bearing CD4 and then infected
receptors with
as glial HIV,
cells theseToxoplasma
harbor bradyzoites will
pseudocyst
be freedbradyzoites
to infect new and thencells
nerve infected withToxoplasma
causing HIV, these bradyzoites will be
encyphalitis(TE).
freed to infect new nerve cells, causing Toxoplasma encephalitis (TE).
Cryptosporidium parvum and Microsporidia:
• Individuals with normal immune systems can
control
1. Controlparasitic
of Parasitic infection
Infection: by the production of
• Individuals
IFN-g by CD4with
T normal
cells. immune systems can control
parasitic infection by the production of IFN-g by CD4 T cells.
• Th-1 immune response is responsible to fight the
2. Th-1 Immune Response:
infection
• Th-1 immune andresponse
depletion of Th1forcells
is responsible reduces
fighting the
the infection.
ability of macrophages
• Depletion of Th1 cells reducestothe
control
ability ofthe organisms,
macrophages
to control the organisms, allowing the disease to flourish.
allowing the disease to flourish.
• AIDS
3. Clinicalpatients
Implications indevelop
AIDS Patients:cryptosporidial or
• AIDS patients develop cryptosporidial microsporidal
microsporidal
chronic diarrhea andchronic diahrea
intestinal infections. and extra
intestinal infections.
 Leishmania :
• It is an intracellular parasite infecting reticuloendothelial
cells
• 1. Macrophages infected by Leishmania parasites activates
Macrophage Activation:
• the Th1 T immune
Macrophages infectedresponse
by Leishmaniareleasing more
parasites IFN-gama.
activate the Th1 immune
response, releasing more IFN-gamma.
• 2. Visceral Leishmaniasis impair cellular immune response
Visceral Leishmaniasis and Cellular Immune Response:
• and increases
Visceral HIV replication.
Leishmaniasis impairs cellular immune response.
• • HIVIncreases HIV replication.
infection suppresses cell-mediated immunity ‫يعني يزيد‬
‫عليه المرض‬due to T
3. cell
HIV Coinfection
inhibition and
andImmune Suppression:
lessens the regulatory effects of the
• HIV infection suppresses cell-mediated immunity, inhibiting T cell function.
• macrophages, promoting
Lessens the regulatory effects of Leishmania multiplication.Thus
macrophages, promoting Leishmania
macrophages infected with both Leishmania and HIV
multiplication.
• display an intensification
Macrophages of Leishmania
infected with both both infections.
and HIV display
intensification of both infections.
• 4. InOpportunistic
late stage of human immunodeficiency virus (HIV)
Infection:
• infection VLHIV
In late-stage caninfection,
presentvisceral
as opportunistic infection.
leishmaniasis can present as an
opportunistic infection. rate is 5% in India and 20% in African
• HIV coinfection
5. HIV Coinfection Rate:
• countries
HIV coinfection rate is 5% in India and 20% in African countries.
Plasmodium spp..
Plasmodium
1. Suppression spp.:of CD4 T Helper Cell Functions:
• Suppressionof
• Suppression of CD4
CD4T Thelper cell functions
helper inhibits CD8
cell functions cytotoxic
inhibits CD8
cell differentiation and the release of IFN-gamma,
cytotoxic
therefore,cell differentiationhepatocytes
sporozoite-infected and inhibit release
will not of IFN-g,
be lysed.
therefore, sporozoite-infected hepatocytes will not be lysed,
2. Reduction of IFN-gamma:
• Reduction
• Reduction ofofIFN-g prevents
IFN-gamma activation
prevents of ofmacrophages
activation macrophages andand
results in the
results inrelease of uncontrolled
the release numbers numbers
of uncontrolled of merozoites during the
of merozoites
extra-erythrocytic phase.
during the extra erythrocytic phase.
• 3. Blood
Immunosuppression
stage parasitesby Blood Stage Parasites:
induce immunosuppression by
• Blood stage parasites induce immunosuppression by inducing
induction of anergy ,inhibition of reactivity of Dendritic cells
anergy, inhibiting reactivity of dendritic cells,
and andactivation
activatingof T-regulatory
T-regulatory T cells.
T cells.
• AIDS patients display an increased incidence of cerebral
4. Clinical Implications in AIDS Patients:
malaria.
• AIDS patients display an increased incidence of cerebral malaria.
Giardia lamblia

The flagellate Giardia lamblia is an extracellular parasite of the

Giardia lamblia:
small intestine.
1. Immune Control:
• The flagellate Giardia lamblia is an extracellular
• The infection is mainly controlled by______________
parasite IgA
of the
andsmall intestine.from the host.
IgM secretions
• The infection is mainly controlled by IgA and IgM
2. Impact of CD4 T Cell Depletion:
secretions
• There is from thethat
evidence host.
depletion of CD4 T cells results in a
•marked
Theredecrease in thethat
is evidence clearance of theof
depletion motile
CD4trophozoites.
T cells results
in3. aImmunocompromised
marked decrease Patients:
in the clearance of the motile
trophozoites.
• In an immunocompromised patient, prolongation and
•relapse
In anofimmunocompromised
giardiasis are evident, and levels ofprolongation
patient, IgG, IgM, and and
IgA antibodies are depressed.
relapse of giardiasis are evident and levels of IgG, IgM,
and IgA antibodies are depressed.
 ً ‫مهم‬
‫جدا‬

Antigenic Variation in Trypanosoma brucei

• Trypanosomes exhibit unique antigenic variation of their
glycoproteins.
• • There is a cyclical fluctuation in the trypanosomes in the blood of
infected vertebrates after every 7- 10 days.
• • Each successive wave represents a variant antigenic type (VAT) of
trypomastigote possessing variant-specific surface antigens (VSSAs)
or variant surface glycoprotein (VSG) coat antigen.
• It is estimated that a single trypanosome may have as many as
1,000 or more VSG genes that help to evade immune response.
Besides this, trypanosomes have other mechanisms also that help
them to evade host immune response.
‫ أيام تظهر وجبة جديدة بالدم وكل وجبة لها مستضدات وبروتينات مختلفة عن السابقة باإلضافة إلى‬10- 7 ‫كل‬
‫ جين في كل تريبانوسوم‬1000 ‫جينات تسمح لها بتغيير بروتينات السطح … قد يصل عدد هذي الجينات إلى‬
!‫وبهذي الطريقة باإلضافة إلى ُطرق ُأخرى تخدع الجهاز المناعي فما يتمكن من تدميرها أو تكوين أجسام مضادة لها‬
 Vaccination against parasitic
infections ‫م‬ ‫مه‬
• The most effective vaccine against P. falciparum is a
pre-erythrocytic vaccine, such as RTS, S, which directly
arrests the circumsporozoite proteins present on the
surface of sporozoites.
• The RTS, S vaccine arrests the P. falciparum parasites
and induce their destruction before they enter the
liver, where they could develop.
• The RTS, S/AS01 vaccine was acknowledged by the
WHO, and received a grant for further assessment and
appraisal to ensure its effectiveness before including it
in mass immunization
 ‫ساليدات من إضافتي مقارنة لما سبق ذكره‬
Immunocompetent Host Response:

• T.gondii: NK cell proliferation accelerated by IL-12 and IFN-g,

followed by parasite-specific T cell response involving both CD4 and
CD8 T cells.

• Cryptosporidium/Microsporidia: Control of parasitic infection

by production of IFN-g by CD4 T cells, Th-1 immune response
responsible for fighting infection.

• Leishmania: Macrophage activation by Leishmania parasites

induces Th1 immune response releasing IFN-g.

• Plasmodium spp.: Suppression of CD4 T helper cell functions

inhibits CD8 cytotoxic cell differentiation and IFN-g release.

• Giardia lamblia: Infection controlled mainly by IgA and IgM

secretions from the host.
Clinical Implications in Immunocompromised Individuals:

• T.gondii: Increased susceptibility in AIDS patients, leading to

toxoplasmosis symptoms.

• Cryptosporidium/Microsporidia: Development of chronic diarrhea

and intestinal infections in AIDS patients.

• Leishmania: Intensification of both Leishmania and HIV infections,

with visceral leishmaniasis presenting as an opportunistic infection.

• Plasmodium spp.: Increased incidence of cerebral malaria in AIDS

patients.

• Giardia lamblia: Prolongation and relapse of giardiasis in

immunocompromised patients.