Lecture 19 - Microbial Evasion of the Immune System

Question 1

Give examples of how pathogens obstruct T cell activation

Answer 1

Bacteria:
Heliobacter pylori
Causes gastric ulcers.
Can block transcription of T-cell growth factor IL-2.

Viruses:
Human Immunodeficiency Virus (HIV)
Prevents phosphorylation of Tcell Receptor cascade.
Prevents formation of Immunological synapse.

Question 2

Describe how HIV infects cells

Answer 2

1) Infects cells of the immune system
(T-lymphocytes and macrophages)

2) Progressively destroys immune cells, impairs their function and reduces numbers
3) Weakening of the immune system results in increased susceptibility to opportunistic infections
4) Inability to battle secondary infections leads to disease and death

Infection of macrophages:
Interaction between viral gp120 with CD4 and CCR5 (co-receptor)
Infection of T-cells:
Interaction between viral gp120 with CD4 and CXCR4 (co-receptor)

Question 3

Describe how helminths manipulate our immune response

Answer 3

Large extracellular helminths interact with hosts through their:
Surface molecules
Secreted molecules
“IMMUNE MODULATION” = better parasite survival (links to hygiene hypothesis)
Can manipulate our host response, they secrete factors and have surface factors that basically subdue a lot of our immune system cells
They interact with the host through these immune modulators and this promotes parasitic survival. In order to not be targeted they have to give off complex system of immune modulation

Question 4

Describe the hygiene hypothesis with helminth parasites

Answer 4

Helminth infection ubiquitous throughout human evolution
i.e. our immune system has evolved in the presence of worms
Helminth infection now rare in Western world…
… correlates with massive increase in inflammatory diseases
e.g. allergy, autoimmunity (T1D, MS), intestinal inflammation, metabolic syndrome and obesity
Hygiene hypothesis states rise in “Western inflammatory diseases” is the direct result of reduced pathogen exposure (including helminths)
i.e. helminths essential for correct education of our immune system
Large extracellular helminths can modify host with their secreted molecules = “Excretory / Secretory” (ES) molecules
- Worms produce “parasite immunomodulatory molecules”
- These molecules bias host immune cells / limit inflammation
- This allow worms to prevent/limit immune attack i.e. chronic infection