24 - Immune Responses to Parasites & Fungi

Question 1

What is defense against helminthic infections mediated by

Answer 1

• Th2 cells which results in the production of IgE antibodies and activation of eosinophils
• Too big to be phagocytosed

Question 2

Eosinophils

Answer 2

• Granulocytes identified by bilobed nucleus and large specific granules that store cytokines, cationic proteins and enzymes
• IL-5 (produced by Th2) has central role in development
• Bind to worm larvae through antibody and complement receptors, and release intracellular granyles

Question 3

Mast cells

Answer 3

Long-lived, tissue-resident cells found in mucosal and epithelial tissues throughout the body

Question 4

Basophils

Answer 4

Found in blood, representing less than 1% of circulating WBCs

Question 5

Mast cells and basophils

Answer 5

• Roles in parasitic diseases and allergic reactions, vasodilation, angiogenesis and regulation of many cell types
• Mast cells are different from basophils in several aspects including surface receptors, location, lifespan, composition of granules

Question 6

Vasoactive mediators released by mast cells

Answer 6

Histamine, serotonin, tryptase, inflammatory cytokines

Question 7

IgE and mast cells (and basophils)

Answer 7

• Monomeric antibody with two identical heavy chains of the epsilon (ε) class
• Typically found at very low concentration in serum (most bound to Fc receptors on mast cells)
• Cross-linkage of FcεRI by IgE molecules by antigen, induces degranulation and release of immunomodulatory and vasoactive mediators

Question 8

What do Th2 cells secrete

Answer 8

IL-4, IL-5 and IL-13

Question 9

Il-4

Answer 9

• Act on B cells to stimulate production mainly of IgE antibodies
• Activation of alternative macrophage (enhanced fibrosis/tissue repair)

Question 10

IL-5

Answer 10

Eosinophil development, activation and survival

Question 11

IL-13

Answer 11

• Stimulates mucus secretion and intestinal peristalsis
• Act on B cells to stimulate production mainly of IgE antibodies
• Activation of alternative macrophage (enhanced fibrosis/tissue repair)

Question 12

Th2 cell effector functions in helminth infections

Answer 12

• Increased cell turnover and mucus production prevents adherence
• Increased contractility of mucosal smooth muscle
• Activation of M2 macrophages
• Recruits and activates eosinophils
• Drive mast cell recruitment

Question 13

Acute schistosomiasis

Answer 13

Toxaemic and allergic reaction to the migrating and maturing larvae of Schistosoma

Question 14

Chronic schistosomiasis

Answer 14

• Eggs retained in the gut wall induce granuloma formation
• Th2 responses favor egge transit and granuloma formation
• Th1 and Th17 responses associated with tissue damage and mortality

Question 15

How are chronic schistosomiasis granulomas different to TB granulomas

Answer 15

TB granuloma does not have a strong Th2 bias

Question 16

How do helminths, or their secretions, modulate allergic responses

Answer 16

• Modulate immune system directly (some parasite antigens have been shown to inhibit the progression of some inflammatory disease)
• Alter gut microbiome

Question 17

Principle defense mechanism against protozoa that survive within macrophages

Answer 17

• Cell mediated immunity, particularly macrophage activation by Th1 cell derived cytokines
• IFN-γ and TNF-α act synergistically to promote optimal activation of macrophages

Question 18

Key mediators of T cell priming (Th1)

Answer 18

IL-12, produced by dendritic cells and macrophages

Question 19

Principal mechanism of protective immunity in malaria

Answer 19

CD8 T cells and antibodies

Question 20

Innate immune response to fungi

Answer 20

• C-type lectin receptors (CLR), another PRR family, play central roles in immunity to fungal pathogens.
• TLR-2 recognises zymosan and activates macrophages
• TLR-4 also involved

Question 20

How do phagocytes, particularly neutrophils kill fungi

Answer 20

• Degranulation and release of toxic materials onto hyphae
• Ingestion of yeast or conidia

Question 21

Principal mediators of innate immunity against fungi

Answer 21

Phagocytes and the complement system (opsonisation)

Question 22

Role of innate immunity and Th17 cells in defense against fungal infection

Answer 22

• Innate lymphoid cells (ILC3s) releases IL-17, which recruit neutrophils and induce the production of antimicrobial peptides
• Th1 and Th17 cells play a dominant protective role in most fungal infections

Question 23

Th17 effector functions in infections by extracellular bacteria

Answer 23

• IL-17 and IL-22 induce production of antimicrobial peptides by epithelial cells
• Increases epithelial cell turnover
• Activation of stromal cells and myeloid cells to produce G-CSF which stimulates neutrophil production
• Activation of stromal cells and epithelial cells to produce chemokines that recruit neutrophils
• Produce CCL20 which is a chemoattractant for other Th17 cells