Week 6: Parasitic and Fungal Infections Flashcards
How are parasites distributed world wide?
- Poor saniation
- Poor living conditions
- Tropical regions
What are the types of parasites?
- Protozoan (unicellular)
- Metazoan (multicellular)
What are the major mucosal routes of parasites?
- Swimming in contaminated water
- Eating undercooked meat
- Eating fresh food that has washed with contaminated water
- Living in unsanitary conditions
- Unprotected sex
- Bites of spiders
- Poor handwashing
- Going barefoot
What are the barriers of pathogen colonization?
- Unbroken skin
- Acidic pH (stomach and vagina)
- Urine flow
- Antimicrobial peptides (skin and mucosal surfaces)
- Commensal microbes
What parasites reside in extracellular space?
- Protozoan parasites tend to inhabit intracellular spaces
- Metazoan parasites typically don’t replicate within the hosts
- Metazoan parasites (worms) are quite large and usually inhabit body cavities like the gut
Why are parasites a great challenge?
Threatens the immune system due to their diversity and lifestyle
What does the effectiveness of parasitic response depend on?
- Type of organism
- Location of the infection (intra and extra)
- Life cycle stage of the parasite
How does the immune system respond to parasites?
- Less immunogenic
- Surface antigens mimic human proteins
- Eject the parasite out by force
What stimulates expulsion responses?
Type 2 immune response that involves the activation of effector T cell subsets that coordinate IgR and eosinophilic responses
What are the functions of type 2 immune response?
- Generate TH2 cells
- Induce IgE mediated immune responses
- Leads to degranulation of mast cells, eosinophils, and basophils
Describe the extracellular response to worms?
- Tuft cells can sense parasitic products and alert the immune system
- Worms stimulate epithelial cells and tuft cells in the gut to produce alarmins
What are alarmins?
A specific set of cytokines released during cellular damage that tells other immune cells that damage occurred
What are the alarmins?
IL25 (act on innate cells cause IL13 secretion), IL33, TSLP
What is the intestinal response to worms?
- Alarmins, activate basophils, mast cells, and eosinophils
- Granulocytes secrete the polarizing cytokine IL4 to generate TH2 effector cells
What is the function of IL4 and 13?
To induce B cell isotope switching to produce IgE plasma cells
What is the function of IL5?
Increases eosinophil numbers (eosinophilia)
What are the products of toxic mediator?
Histamine, heparin
What is the biological effect of histamine and haparin?
- Poison parasites
- Cause smooth muscle contraction
What amplifies TH2 cell response?
IL4 and 13
What are the lipid mediators?
Leukotrienes C4, D4, and E4
What are the biological effects of Leukotrienes C4, D4, and E4?
- Smooth muscle contraction
- Mucus secretion
What do leukotriene and IL13 act on?
Goblet and panted cells to enhance production and secretion of mucs
What is the function of IL13?
Increases turnover of epithelial cells
How does mucus eliminate parasites?
Binds and flush them from the extracellular space
Describe the function of IgE with worms?
Crosslinking of IgE to worm antigen triggers the degranulation of eosinophils, basophils, and mast cells
What do IgE bind on?
cell surface receptor
FcεRI receptors on:
1. Mast cell (connective tissue)
2. Basophils (blood)
3. Activated eosinophils (mucosal surfaces)
What happens when 2 or more IgE bind to the FcεRI binds to antigen of worm?
Leads to degranulation
What is ADCC?
enzyme released by degranulated eosinophils that kills parasite
What is the function of primary and secondary mediators?
- Cause mucus production and smooth muscle contraction and influx of other immune cells
- Lead to physical removal of the parasite
- Causes spasms of the gut and airways to expel the parasite
- Sneezing, vomiting, and diarrhea lead to ejection of the pathogen
What is the TH2 response to parasites?
Generates cytokines that cause activated of immune cells to expel the parasite
What is the TH1 response to parasite?
Generates an inflammatory response which can lead to tissue damage but do not kill the parasite
What are the morphologic forms of fungi?
- yeasts
- mold
- dimorphic
What are the fungi characteristics?
- Eukaryotic
- 5 million species
- Heterotrophic
- Ubiquitous in th evironment
- Obligate aerobes or facultative anaerobes
What is heterotrophic?
- Gain nutrients from external sources
- Saprobes (decomposers)
- Secrete degradative enzymes (proteases, nucleases, celluloses)
Describe the fungal cell structure?
- Membrane bound organelles
- Eukaryotic nucleus
- Uses DNA as its nucleic acid
- Ribosomes are 80s (40s and 60s)
- Vacuole
- Enclosed by a cell wall surrounding a cell membrane
What is a vacuole?
Enclosed compartment containing water, nutrients, and enzymes
1. Helps maintain pH
2. Contains waste products
How does fungal cell wall differ from bacterial?
Protect cells from osmotic shock, determine cell shape and have components that are antigenic (more than bacteria)
What are the components of a fungal cell wall?
- Mannoproteins
- Glucans
- Chitins
- Cell membrane
- Ergosterol
What is mannoprotein?
Highly glycosylated mannose that plays a role in adherence to host cells
What is gluons?
- Major component of cell wall
- Branched b-(1,3)-glucan and b-(1,6)-glycan (not found in humans)
- Synthesized in the cell membrane and exported to cell wall
What is chitin?
Long chain polymer of N-acetyl glucosamine that is produced by chitin synthase in cell membrane
What are the components of the cell membrane of a fungal cell wall?
- Lipid bilayer that is selectively permeable
- Contains integral proteins
- Facilitiates cell wall synthesis
What is ergosterol?
DOminant fungal sterol component of fungal cell membrane
What are the site of infection of fungal diseases?
- superficial
- Cutaneous
- Subcutaneous
- Deep or systemic
What are the routes of acqutiion of fungus?
Exo and engodenous
What is the difference between primary and opportunistic virulence?
Pri: inherently virulent, infects healthy host
Opp: Low virulence, infects immunocompromised host
What is superficial fungal disease?
Epidermis and no inflammation
What is cutaneous fungal disease?
Skin, hair, nails
What is subcutaneous fungal disease?
Wounds, inflammatory
What is deep or systemic fungal disease?
Lungs, abdominal viscera, bones, CNS
What is exogenous fungal disease?
Environmental, airborne, cutaneous, percutaneous
What is endogenous fungal disease?
Latent reactivation, commensal organism
Describe the microbiome involvement of fungal infections?
- Commensal fungal organisms also help “crowd out” pathogenic fungi
- This is why antibacterial medications may result in oral thrush or vulvovaginal candidiasis (yeast infections)
- Commensal microbes suddenly have no competition for resources
Describe the innate immunity of fungal infections?
- PRRs on innate on DC’s and macrophages bind to PAMPs (fungal cell wall components)
- TLR2/6 recognize glucans and zymosan
- Increases the phagocytic ability of macrophages
- Macrophages produce inflammatory cytokines and chemokines that attract neutrophils
- Neutrophils phagocytosize fungal cells
- Neutropenic individuals are especially susceptible to fungal infections
How do macrophages and DCs response to fungal infections?
Carry anti fungal PRRs recognize fungal cell wall PAMPs to initiate tsignaling and antigen presentation
1. Dectin (Receptor like lectin on innate immune cells)
2. TLR2/6
These innate cells then secrete cytokines that polarize Helper T cells to become effector T cells
Describe the function of TH17 with fungal infections?
- secrete IFN-g that activates macrophages to clear the pathogen.
- IFN-g enhances the phagocytic functions of macrophages
- secrete IL-17 and IL-22 to clear pathogen and cause production of anti-microbial peptides.
- IL-17 enhances the phagocytic functions of neutrophils
