Block 2 Lecture 4 -- Parasites Flashcards
What are types of parasites?
1) protozoa
2) helminths
3) ectoparasites
Why are parasites problematic?
- evoke weak innate immune response
- - mechanisms of evasion
How do parasites resist the innate response?
1) some too large for phagocytosis
2) replicate and resist degradation within phagocytes
3) penetrate through skin
How many species of leishmaniasis?
20
What are the types of leishmaniasis?
1) cutaneous
2) mucocutaneous
3) visceral
Characterize cutaneous leishmaniasis
bad - scars
Characterize mucocutaneous leishmaniasis?
2nd worst form - ulcers
Characterize visceral leishmaniasis
worst form - death
What is the tx for leishmaniasis?
amboB/amBisome
Th1 overactivation =
pro-inflammatory diseases
– T2DM, GVHD, arteriosclerosis
Th2 overactivation =
anti-inflammatory Ab-mediated diseases
– infection, allergy, autoimmunity
What is the signature cytokine of the Th1 response?
IFN-gamma
What is the signature cytokines of the Th2 response?
IL-4
What is classical macrophage activation?
enhanced killing induced by IFN-gamma
What is alternative macrophage activation?
tissue repair stimulated by IL-4 and IL-13
What are the results of Th1 immune response?
1) classical macrphage activation
2) complement binding
3) IgG
What are the results of Th2 immune response?
1) Ab production
2) mast cell degranulation
3) intestinal mucous secretion and peristalsis
4) eosinophil activation
5) alternative macrophage activation
What causes opsonization in Th1?
IFN-gamma – IgG
What causes complement activation in Th1?
IFN-gamma – IgG
What causes classical macrophage activation in Th1?
IFN-gamma (from Th1 CD4, Treg and NK)
What causes Th1 differentiation/proliferation?
IL-12 (from macrophages, DCs) stimulates T cell to make IFN-gamma to cause feedback
What causes Th2 differentiation/proliferation?
IL-4 (from mast, eosinophils) stimulates T cell to make IL-4 to cause feedback
What causes alternative macrophage activation?
IL-4 and IL-13
What causes intestinal mucous secretion and peristalsis?
IL-4 and IL-13
What causes activation of eosinophils?
IL-5
What causes production of IgE?
IL-4 targeting B cells
What causes mast cell degranulation?
recognition of epsilon receptor of IgE
What cytokines do Th2 CD4’s produce?
IL-4, IL-5, IL-13
What cytokines do Th1 CD4’s produce?
IFN-gamma
What do Tfh cells in Th1 produce?
IFN-gamma
What do Tfh cells in Th2 produce?
IL-4
How are helminths that are too large to be phagocytosed eliminated?
1) IgE binds
2) mast cell degranulates
What component (Th1/Th2) has best ADCC?
Th2
What other Abs are involved in Th2?
IgA and IgG
– both bind helminth to activate eosinophil degranulation
How is IgA production stimulated?
TGF-beta
How is IgG production stimulated?
IFN-gamma
What immune response is required to fight trypanosomiasis and why?
Th2…trypomastigotes injected in bloodstream are never phagocytosed
What are the hosts in trypanosomiasis?
tsetse fly + human
Common name for trypanosomiasis?
african sleeping sickness
What are the hosts in leishmaniasis?
female sandfly + mammals
What are the stages of infection in malaria?
1) sporogonic
2) exo-erythrocytic
3) erythrocytic
What is the sporogonic cycle in malaria?
mosquito stages, plus when mosquito injects sporozoites into human
What is the exo-erythrocytic cycle in malaria?
1) injected sporozoites infect hepatocyte
2) form intracellular schizont
3) schizont ruptures and invades blood
What is the erythrocytic cycle in malaria?
1) schizont infects RBC
2) trophozoite matures and ruptures
2) trophozoite forms gametocytes to be ingested by mosquito
What organism is involved in hookworm?
Filariform larvae
What are the stages of infection of hookworm?
1) infective: enters through unbroken skin, migrates to intestine
2) diagnostic: eggs spread in feces
Describe the infection stages in leishmaniasis.
1) promastigotes invade macrophages, granulocytes, or are phagocytosed
2) multiply into amastigoes
3) leave and infect other cells
How does leishmaniasis evade the immune system?
1) alters complement system
2) avoid innate mechanisms
3) modulate cytokines
4) inhibit Ag-presentation and T activation
5) alter T-cell differentiation
How does leishmaniasis alter the host complement system?
phosphorylates complement proteins
sheds MAC
How does leishmaniasis avoid innate mechanisms?
- inhibits formation of phagolysosome
- scavenges ROS
- inhibits enzymes
How does leishmaniasis modulate cytokines?
- suppresses activating cytokines
- induces inhibitory cytokines
How does leishmaniasis inhibit antigen presentation/T activation?
- suppresses MHC class II expression
- inhibits p-MHC formation
- downregulates B7
How does leishmaniasis alter T-cell differentiation?
induces Th2 response
