Intestinal Protozoa Flashcards
Mucosal immune system main components
- Epithelium
- Lamina propria
- Organised lymphoid tissue
- Luminal mucus and secretions
Soluble IgA (sIgA) in mucosal immunity
- Most common antibody in mucosal secretions
- Specific transport into mucosal secretions
- Resistant to luminal proteases (but not completely)
- Inhibits bacterial adhesion/neutralises viruses
- Inhibits binding of allergens to immune cells
- Inhibits inflammatory effects of other Igs
Peyer’s patches
Aggregated lymphoid follicles found in the small intestine
Involved in the induction of the immune response
Alpha-4-beta-7 (a4b7)
Integrin that binds to epithelial cells via MadCAM-1
All trans retionic acid (ATRA)
An isoform of retionic acid
Shown to upregulate a4b7
Cells treated with ATRA migrate to the gut
Oral tolerance
When antigens are introduced orally, no immune response is generated against them
Human immune correlations of protozoan infection
- Crypto: AIDS, MBL deficiency, CD40 deficiency
- Giardia: IgA deficiency, CVID, NOT AIDS
- Entamoeba histolytica: HLA class II, leptin receptor, microbiota, NOT AIDS
Effector mechanisms of immunity to Cryptosporidium spp.
Important: IFN-gamma, IL-12, NK cells, CD4 T cells
Not important: CD8 T cells, B cells
Interferon gamma Effects
- induces iNOS and NADPH oxidases
- induces expression of class 1 and 2 MHC on APCs as well as processing enzymes (TAP, etc.)
- activates lysosomal activity in macrophages
- increases synthesis of IgG2a and IgG3
- promotes leucocyte binding and adhesion
- induces IDO which depletes Trp
- induces NRAMP (DMT) which depletes Fe
- induces cellular antiviral proteins
Mechanisms of immunity against Isospora/Cyclospora
- Mechanisms are unknown, but involve CD4+ T cells
- Immune responses against Eimeria, closely related to Isospora, in mice and chickens also involves CD4+ T cells and IFN-g.
- Chronic infections often observed in AIDS patients, suggesting importance of CD4+ T cells
- Chemotherapy is possible for HIV+ patients but often has to be continued prophylactically
Dendritic cells in immunity to Crypto
- Role of DCs implicit in T cell dependence of the crypto response
- Th1 responses critical for defence against crypto; DCs a major source of IL-12
- Role of DCs established in a mouse model
- Transgenic mouse with CD11c promoter linked to diphtheria toxin receptor (CD11cDTR-Tg)
- On administration of DT, DCs die
Giardia immunology mechanisms
- IL-6 is important in control
- Giardia killed by a-defensins
- CD4+ T cells required
- Giardia not more persistent in AIDS but it is prolonged in IgA deficiency and CVID
- Anti-Giardia IgA associated with recovery in humans and in mice (Th2)
Variant-specific surface proteins (VSPs)
Proteins found in Giardia for immune evasion
Only one is expressed at a time
Three factors in pathogenesis of E. histolytica infection
- The gal/GalNAc lectin recognises galactose and Nacetyl-galactosamine on human mucin glycoproteins, allowing establishment of asymptomatic infection
- Secreted cysteine proteinases are major virulence factors
- Secreted pore-forming proteins can be cytolytic to both host cells and bacteria
Host response to E. histolytica
- No increased virulence/duration in AIDS
- Trophozoites induce host cells in colon explants to release proinflammatory cytokines/chemokines (IFN-g, IL-1, IL-6, IL-8).
- Influx of neutrophils to site of ulceration
- IFN-g, TNF-a are involved in immunity: activation of macrophages and neutrophils to kill parasites
- Gal/GalNAc lectin induces IL-12 production by macrophages
