Parasite Immune Evasion

Question 1

What are 4 mechanisms of parasite immune evasion?

Answer 1

• Intracellular hiding
• Antigen mimicry
• Immunosuppression
• Antigenic variation

Question 2

What is intracellular hiding?

Answer 2

Parasites reside within host cells to hide from immune detection, especially humoral immunity (antibodies & complement)

Question 3

What are parasites protected from due to intracellular hiding?

Answer 3

• Neutralising antibodies
• Complement-mediated lysis

Question 4

What is an example of a parasite that utilises intracellular hiding?

Answer 4

T. cruzi

Question 5

What cells do T. cruzi infect?

Answer 5

A wide range of host cells, including:
- Neurons
- Smooth and cardiac muscle cells

Question 6

What does invasion of neurons allow for?

Answer 6

Neurons are long-lived cells, so allows for chronic infection to be established

Question 7

What does T. cruzi chronic infection cause?

Answer 7

Triggers low-grade, persistent inflammation (especially in heart and GI tract).

Question 8

What long term conditions can arise from T. cruzi induced persistent inflammation in the heart and GI tract?

Answer 8

• Cardiomyopathy
• Megacolon

Question 9

What does intracellular hiding make the immune defence dependent on?

Answer 9

Shields from antibodies.
Dependent on T cells, which can be manipulated/evaded by the parasite

Question 10

What is antigenic mimicry?

Answer 10

Parasites coat themselves with host-like molecules (immunological camoflage), making it difficult for the host to distinguish them as non-self

Question 11

What does antigenic mimicry prevent?

Answer 11

• Activation of immune cells
• Formation of effective, high-affinity antibody response

Question 12

What is an example of a parasite that uses molecular mimicry?

Answer 12

Schistosoma species

Question 13

What host proteins do Schistisoma use for molecular mimicry?

Answer 13

MHC molecules
Blood group antigens

Question 14

What can antigenic mimicry lead to within the host?

Answer 14

Induction of autoimmunity, if the immune system begins attacking similar host antigens

Question 15

What is immunosuppression?

Answer 15

Parasites actively suppress or modulate the host’s immune response, making it less responsive or misdirected

Question 16

What can immunosuppression involve?

Answer 16

• Interference with cytokine signalling
• Inhibition of antigen presentation
• Expansion of Tregs
• Secretion of immunosuppressive molecules

Question 17

What are two examples of pathogens that use immunosuppression?

Answer 17

T. brucei/cruzi
Filarial worms

Question 18

How does T. brucei modulate immune response?

Answer 18

• Suppresses pro-inflammatory cytokines
• Induce regulatory immune responses

Question 19

How does T. cruzi modulate immune response?

Answer 19

Interferes with macrophage signalling pathways and inhibits MHC expression

Question 20

How do filarial worms modulate immune response?

Answer 20

• Suppresses pro-inflammatory cytokines
• Induce regulatory immune responses

Question 21

What are regulatory immune responses?

Answer 21

Mechanisms that suppress/resolve inflammation to prevent tissue damage

Question 22

What are the key players in regulatory immune responses?

Answer 22

• Tregs
• Anti-inflammatory cytokines

Question 23

How do parasites (like T. brucei and filarial worms) induce regulatory immune responses?

Answer 23

They can:
- Directly induce Treg expansion/conversion from conventional T cells
- Stimulate anti-inflammatory cytokines
- Drive alternative M2 macrophage activation

Question 24

What does M2 macrophage phenotype do?

Answer 24

Promotes wound healing rather than microbicidal activity

Question 25

What is the overall impact of parasites inducing regulatory immune response?

Answer 25

- Prevents sterilising immunity, allowing chronic infection - Makes host more vulnerable to secondary infections - Reduces vaccine efficacy

Question 26

What are the two most prevalent pro-inflammatory cytokines?

Answer 26

- TNF-a - IL-1B

Question 27

What are the two most prevalent anti-inflammatory cytokines?

Answer 27

- IL-10 - TGF-B

Question 28

What is antigenic variation, and why is it beneficial for parasites?

Answer 28

Antigenic variation is the process by which parasites frequently change surface antigens to avoid detection by the host’s adaptive immune system. It prevents lasting immunity and enables chronic or relapsing infection.

Question 29

Which parasite is the classic example of antigenic variation?

Answer 29

Trypanosoma brucei, the causative agent of African trypanosomiasis (sleeping sickness), which uses Variant Surface Glycoprotein (VSG) switching.

Question 30

What is Variant Surface Glycoprotein (VSG), and what role does it play in T. brucei immune evasion?

Answer 30

VSG forms a dense surface coat on T. brucei. Only one VSG is expressed at a time, creating a uniform antigenic surface. When the host produces antibodies, T. brucei switches VSGs to escape immune detection.

Question 31

What is monoallelic expression, and how is it achieved in T. brucei?

Answer 31

Monoallelic expression means only one VSG gene is active at a time. It occurs in a specialised structure called the Expression Site Body (ESB), where only one VSG expression site is transcriptionally active.

Question 32

How does T. brucei generate new VSG variants?

Answer 32

Transcriptional switching – activating a different VSG expression site. Gene conversion – copying a silent VSG gene into the active site.

Question 33

What is the clinical effect of antigenic variation in T. brucei infections?

Answer 33

It leads to successive waves of parasitaemia, each corresponding to a new VSG variant, enabling chronic infection despite an active immune response.

Question 34

Why is it important that only one VSG is expressed at a time?

Answer 34

A single VSG coat ensures: Shielding of invariant surface proteins (e.g. nutrient transporters). Prevention of complement deposition. Avoidance of immune recognition — co-expression would expose vulnerable areas.

Question 35

What is the hygiene hypothesis in the context of parasitic worm infections?

Answer 35

It suggests that reduced exposure to helminths in industrialised societies has led to increased incidence of allergic and autoimmune diseases due to loss of natural immune regulation.

Question 36

How have humans and helminths co-evolved?

Answer 36

Over millions of years, helminths developed mechanisms to modulate host immunity (e.g. inducing regulatory responses), and the human immune system adapted to their persistent presence.

Question 37

How do parasitic worms modulate the immune system?

Answer 37

-Induce regulatory T cell responses - Promote secretion of anti-inflammatory cytokines like IL-10 and TGF-β - Suppress excessive inflammation

Question 38

What immune disorders are linked to lack of helminth exposure?

Answer 38

Increased prevalence of: - Asthma - Eczema - Inflammatory Bowel Disease (IBD)

Question 39

What is one therapeutic approach inspired by the hygiene hypothesis?

Answer 39

Controlled helminth infection is being investigated to treat autoimmune and allergic conditions by restoring immune balance.

Question 40

Why might loss of helminth exposure promote hypersensitivity?

Answer 40

It may result in unregulated Th2 responses and a lack of immune tolerance, making individuals more prone to allergies and autoimmune reactions.