Parasite immunology

Question 1

Why do trypanosomes have a high DALY score?

Answer 1

Despite causing little mortality, they have very high morbidity. Also, they can occur in large epidemics.

Question 2

When and where was there an epidemic of VL and how many mortalities did it cause?

Answer 2

Sudan in the 80s. 100,000 lives were lost.

Question 3

How (/why) are immune reactions to trypanosomes complex?

Answer 3

• Lots of different species and strains
• Different lifecycle stages to interact with the immune system
• Mitigate the immune system to propagate themselves

Question 4

How does the antigenic load change as the infection progresses?

Answer 4

Antigenic load is HIGH as the infection progresses as there is lots of parasite replication

Question 5

What are the three trypanosomes?

Answer 5

Chagas
African trypanosomiasis
Leishmania

Question 6

Describe the progression of the cellular adaptive immune response.

Answer 6

Neutrophils and NK cells –> macrophages –> lymphocytes –> lymphocytes (post antigenic presentation).

Question 7

Describe the progression of the humoral adaptive immune response.

Answer 7

Acute phase response proteins –> complement and cytokines –> antibodies

Question 8

What is a granuloma? What is its purpose?

Answer 8

An orchestrated immune response around a parasite or an infected cell which lasts over a long time. Acts as a unit of containment.

Question 9

Which host factor determines if the parasite will be able to replicate or if the immune system will be able to control it? How is this factor controlled?

Answer 9

NO produced by NO synthase.

Control: switched on by TH1 cytokines to activate the NO production so it can kill the parasite.

Question 10

Describe how the TH response determines the outcome of disease. How is this regulated?

Answer 10

TH1 cytokines activate NO synthase so the parasite can be killed. TH2 cytokines BLOCK NO synthase so parasites are NOT killed. This is regulated by Treg cells producing IL10

Question 11

How does the immune response produce pathology in leishmania (i.e. how does immunopathology present)?

Answer 11

CL: granulomas and ulceration necrosis
ML: destructive hypersensitivity
VL: granuloma, destruction of lymphoid microenvironments

Question 12

Describe the presentation of acute and chronic infection with T cruzi.

Answer 12

Acute: kanker in skin or conjunctiva from infection of macrophages in these areas.

Chronic: dissemination of the parasites throughout the body (e.g. muscle). Nests of parasites form and disrupt organ function.

Autoimmune reaction is also responsible for pathology.

Question 13

Where is T cruzi usually located in the host?

Answer 13

Is labile throughout the host but prefers the mesentery of the colon over other tissues.

Question 14

Describe the presentation of pathology of acute and chronic infection with T brucei.

Answer 14

Acute: kanker at site of infection (due to an inflammatory response).
This infection can then get into the blood.
Chronic: later in infection, the parasites are found in the cerebrospinal fluid.

Question 15

Describe the immune response to leishmania.

Answer 15

T helper cells (TH1) produce IFN gamma and TNF and induce the production of NO from macrophages.

OR a TH2 response is produced (e.g. IL4, a TH2 cytokine which promotes survival of the parasite, and IL10 which suppresses an early TH1 response and prevents parasite clearance).

Question 16

Describe the immune response to T cruzi.

Answer 16

Antibodies can clear acute stage parasites. Macrophages then take over and clear parasites. There is a mixed TH1/TH2 response.

IL4 thought not to be so important in parasite clearance as seen with leishmania.

Polyclonal B cell activation.

Activation of toll-like receptors –> NKFB is produced LESS –> macrophages cannot release early pro-inflammatory cytokines (such as IL12) –> less activation of T helper cells.

Promote release of immature T cells which flood the host–> no localised and directed T cell response means immune evasion by parasite.

T cell apoptosis.

Question 17

Describe the immune response to T brucei.

Answer 17

Anti VSG antibodies coat blood parasites.

Short lived IgM response, IgG not required.

Simple immune response!

Question 18

Why does the simple immune response to T brucei fail?

Answer 18

• T brucei avoid phagocytosis
• Disabling of cell killing macrophages.
• Skewing/ eradication of T cell response
• Antigenic variation of parasites means they can avoid the very effective antibody response.

Question 19

How does the innate immune system respond to parasites? HOw is it regulated?

Answer 19

Complement cascade: C3 convertase generates IC3b. This is regulated by host surface proteins such as decay acceleration factor (controls the rate of production).