immunity to protozoal infections

1. IMMUNITY
To
PROTOZOAL INFECTIONS

2. Introduction
• Protozoan parasites cause several diseases, such
as Malaria, Leishmaniasis, and Trypanosomiasis,
hampering human development worldwide
• Many protozoa cause infections that often follow
chronic courses, owing to coevolution between
parasites and host immune system
• The survival and transmission of pathogenic
protozoa depends on their ability to evade or
subvert host’s innate and adaptive immune
responses

3. • Both innate and adaptive immunity are crucial for anti-
microbial defense
• Although Th1-mediated cellular immunity has been
shown to be of importance for the anti-protozoan
defense, roles of innate immune systems acting on anti-
protozoan defense are unclear
• CARD9 is an essential adaptor protein regulating NF-kB
activation and inflammatory cytokine production
through ITAM-coupled receptors on myeloid cells
involved in innate immunity
• Production of inflammatory cytokines upon Leishmania
major infection in-vitro was impaired in CARD92/2
macrophages, indicating contribution of CARD9-
mediated signaling in innate immune response to L.
major

4. Immunity
Natural barrier
- Skin
- Mucus
- Cilia
- Gastric acid
- Bile
Innate
- IFN’s
- Complement
- Neutrophils
- Macrophages
- NK Cells
Acquired
Antibody
T- Cells

5. Generalized Immune Response to Parasitic
Infection
Macrophage
TH Cells
Cytokines Cytokines
Cytokines
Other effector
responses
T-cells & Cytokines: critical role
-CD8+ T cells .
-Antibody production & ADCC.
-Activate TH1 & TH2 subset from the naive TH cell.
-TH1 on intracellular invasion,TH2 on extracellular invasion.

7. -source-TH2,Mast cells
-B-cell proliferation,
IgE expression.
-eosinophil and mast cell
growth n function
Cytokines :The Cell signaling molecules
APC
T-precursor cells
TH1 TH 2
IL-2 IFN-γ IL-4 IL-2
Cytotoxic T Cell Macrophages
B-cells Eosinophils
Cytotoxicity TNF ROI NO
Antibody ADCC
Cellular Immunity Humoral Immunity
IL-12 IL-4

8. - Increased Density of Antigenic ligand presented to THo,
binds strongly to TCR on THo,
- Activation of TH1 to produce IL-2, IFN-γ, TNF-β.
- In mice, blocking Abs to IFN-γ -- increased susceptibility to disease.
- Phagocytosis, ADCC, increased Intracellular killing.
IFN-γ
-Induction of MHC 1 and MHC 2 on somatic cells, and on APC by latter.
-Act. of macrophages, neutrophills, NK cells.
-Promotion of CMI
Intracellular parasites -Elicit Cell mediated immune
response

9. - Increased IgE, Eosinophila,
- mast cell hyperplasia – induced by TH-2.
IL-5 ----- Differentiation and production of eosinophils.
IL-6 ----- stimulate growth and differentiation of B cells
IL-9 ----- T-cell growth factor, synergy with IL4.
IL-13 ----- Promotion of TH2 , inhibition of TH 1 activity
Extracellular parasites :
Humoral immune response.
-Critical factor responsible for TH-2 subset IL-4
Tho TH2 IL-4,5,6,9,13.
-Source of initial IL-4??
-ADCC
IL-4
Negative Regulation by IL-12 ,
TGF-β

10. How???
IL-10
- inhibits TH1 response.
- diminishes activation of
macrophage & allows
parasitic survival thus chronic
infection.
- maintains critical balance b/w
disease & protection.
- imp in preventing tissue
damage
- e.g. granuloma formation in
Schistosoma infection.
TGF-β
-produced by activated
monocytes, inflammatory
cells.
-reduce TH1& TH2 responses,
-acts synergistically with IL-10.
-parasite induce production of
TGF-β to promote its own
survival.
-IL-10 & TGF-β are also
produced by TH3 or
Regulatory T cells.

11. Effector In Parasitic Infection
-Activated Macrophages
-Eosinophils
-Mast cells & Goblet cells
-Platelets cells
-Humoral response
-Type 1& DTH
EOSINOPHILS
-strongly associated with allergic
& helminthic infection.
-IL-5 being growth factor.
-Charcot-leyden crystals
Major basic protien.eosinophil
peroxidase
-? Phagcytosis.
-larval killing.
PLATELETS
-Targets-larval stage of
flukes(T.gondii,T.cruzi)
-Inc by activity IFN-γ & TNF-
α).
-mediate ADCC with IgE.
Humoral response
- Ig
-4 major s -IgE,IgA1,IgA2,IgM,IgG.
-Actions-neutarlization,
Agglutination, C- activation,
Facilitated opsonisation.
-Imp. Against EC parasites.
-Inc.of IgE suggest Helminthic infec.
w/o any allergy
-due to IgG4 which compete with IgE

12. -chronicity of infection indicates unable to eradicate due to evasion,
thus results in Immunopathology.
Parasitic evasion-
-Ability of parasite to evade or subvert immune response
Known Mechanisms of Evasion are :-
• Antigenic variation
• Intracellular refuge
• Blocking of complement & Abs
• Inhibition of Effector cell function
• Defense against Reactive Oxygen spp.
• Inhibition of lymphocyte proliferation
• Immunomodulation by Cytokine homolog's

13. Parasites Habitat Effector
Trypanosoma brucei Blood Stream Ab+complement (C)
Plasmodium spp Hepatocyte, blood cell Abs, cytokine(TH-1)
Toxoplasma gondii Macrophage Oxy-metabolites, NO,
Lysosomal enzymes
Leishmania spp. Macrophage Oxy-metabolites, NO,
Lysosomal enzymes
Schistosoma mansoni Skin, lungs, PV Myeloid cells, Ab+C
Wuchereria bancrofti Lymphatic system Myeloid cells, Ab+C
Trichinella spiralis Blood, muscle, gut Myeloid cells, Ab+C
Helminthes Gut IgE
Plasmodium spp,
Trypanosoma ,
Schistosoma
Blood
Avoidance
Antigenic variation
Intracellular, Ag-var
Esc in cytoplasm, avoid
digestion in cyto.
Impairment of O-burst &
scavenging of products,
Avoidance of digestion
Host Ag, blockade of Abs,
Antioxidants
Cuticle, Antioxidants
Muscle encystment
cuticle
Immuno suppression

14. Specialized mucosal immune system of GIT.
Mucosa associated lymphoid tissue(MALT).
Intraepithelial lymphocytes macrophages.
T&B lymphocytes in the lamina propria together with secreted
IgA .
Immunity To Intestinal Protozoa

15. Entamoeba histolytica :
Humoral & CMI :
Humoral immune r onse short , transient & secretory
- Repeated infections & intestinal lesions in presence of high
titer& circulating antibody.
CMI Detected by DTH to Antigen
Limiting invasive Amebasis
Recurrence of amoebic liver abscess
Intestinal Amoebae

16. Giardiasis:
- Acquired immunity
- Resistance to reinfection
- Immunosuppressed individuals chronic infections
- Acute Giardiasis Specific Abs
- Chronic Giardiasis Hypogamaglobulinemia
Intestinal Flagellates

17. Trichomonas vaginalis:
- Antibody diminish with time.
- No protection against frequent reinfectiion.
- Reason for no immunity not clear
Immunity To Protozoa Inhabiting Urogenital Tract

18. Macrophage Inhibiting Protozoans
Leishmania spp.
Toxoplasma gondii Long chronic infections
Trypanosoma cruzi

19. Infect macrophage of skin
&viscera
Protective immune response Classical Th1 type CMI
response
Counteracted by Th2 response
Leishmania species

20. - Adequate immune
response.
- Permanent
protection.
- Reinfection in
immunosuppressive
patients.
- DTH response
Cutaneous
Leishmaniasis:
Visceral Leishmaniasis
(Kala azar)

22. African Trypanosomiasis.
- Local inflammatory response of subdermal tissue
- Immune response is shortly after infection.
- Successive waves of parasitemia.
- Toxic molecules ,internal &external Ag
Complement mediated damage & immunopathology.
- No evidence of protective CMI.
- Severe immunosupression
Immunity To Blood Inhabiting Protozoa

23. - caused by T.cruzi.
- Acute infection partially effective strong immune
response.
Specific antibody of all subclasses of immunoglobulin's.
Protective immunity T cell dependent CMI.
IMMUNE EVASION:
Inhibition of antibody binding by non protective IgM
Inhibition of complements by surface glycoprotein
antigen mimic autoimmunity
Chagas disease(New World Trypanosomiasis)

24. Toxoplasma gondii.
Trypanosoma cruzi.
Sarcosystis species.
Microsporidiana
Immunity To Tissue Inhabiting Protozoa

25. MALARIA
Immunity is largely strain specific.
Gradual build up of immunity.
Each stage antigenically distinct.
Circulating sporozoites in blood &liberations of
merozoites from liver into blood are most susceptible.
Targets for immune attack are numerous &complex
High serum immunoglobulin levels in endemic area.
.

26. Multiple exposure involving humoral & cellular
specific & non specific, genetic & acquired
characteristic.
Toxic molecules immunopathology
Black water fever Auto anti bodies.
Counter adaptations of parasites.

27. “Infectious disease will last
till humanity itself.”
Although not at all inclusive, hopefully this presentation has provided u
with some insight to the complex interaction between parasites and
humans .