Immunity to Fungal Infections Flashcards
What is arguably the most common fungus
Candida albicans
Where does the majority of our interactions with fungi occur
At mucosal barriers (e.g. lung and gut)
What is hyphal-transition
How fungi switch from single to multicellular organisms
the process in which fungi switch from single to multicellular organisms is known as….
hyphal transition
When do fungal cells recruit Th1 responses (2)
ungi switch from single to multicellular organisms
When do fungal cells recruit Th2 responses (2 examples)
o Th2 T cell responses occur towards the multicellular hyphal-transition fungal structures
This is case for candida and aspergillus
For Cryptococcus, the single cell form will always stay as a X form in the human
yeast
For X, the single cell form will always stay as a yeast form in the human
Cryptococcus
When is a cryptococcus found in the hyphal form
Lower temperatures
What does cryptococcus do In the brain to evade phagocytosis
it will create a large capsule (which is partly induced by CO2 sensing) and this evades phagocytosis.
Which receptors are important in sensing fungi (2)
C-type Lectin receptors
Toll receptors
Why are C-type leptin receptors especially important
because they don’t just sense fungi but they also can enable phagocytosis which is something the Toll receptors don’t really do.
Which receptor sense fungi but also can enable phagocytosis
C-type leptin
What are 2 important damage receptors
- Galectin and CD36 are both scavenger receptors as well as damage receptors (sense host damage when a fungal infection occurs).
What are 2 important scavenger receptors
- Galectin and CD36 are both scavenger receptors as well as damage receptors (sense host damage when a fungal infection occurs).
Galectin and CD36 are both what types of receptor? (2)
- Galectin and CD36 are both scavenger receptors as well as damage receptors (sense host damage when a fungal infection occurs).
Which receptors are important in innate fungal immunity
- Galectin and CD36
- The Toll receptors
are C-type Lectin receptors
Example of a major fungal pattern recognition receptor?
- Dectin 1
What is Dectin 1 deficiency associated with
Chronic Mucocutaneous Candidiasis
What is Chronic Mucocutaneous Candidiasis caused by and what does it cause
A deficiency of the Dectin 1 receptors
tend to have lots of nail infections and severe candida infections on mucosal surfaces which can be very disfiguring and could even kill the individual.
What does dectin 1 do?
binds -Glucans on the fungal surface, particularly for Candida.
What does a dectin 1 deficiency cause to happen to the immune response?
the homozygous mutation for Dectin 1 (where it has been knocked out) were not able to make any inflammatory cytokines like IL-6 in response to macrophage challenge with Candida.
patients who had the mutation could not bind the Candida with their macrophages.
What Is card9 required for
CARD9 is required for T cell Th17 Differentiation in Humans
purpose of th17 cells?
these are the cell that recruit neutrophils to the mucosal surface
What cells recruit neutrophils to the mucosal surface
Th17
What does a CARD9 mutation affect and how does that lead to fungal infections and where are do these fungal infections tend to occur?
CARD9 is required for T cell Th17 Differentiation
Th17 cells are important because these are the cell that recruit neutrophils to the mucosal surface
patients with this mutation will have mucosal infections (as the neutrophils cannot be recruited
Which fungi are dectin 1 and CARD9 important for defence against
Aspergillus and candida
Why are stem cell transplant patients particularly vulnerable to fungal infections
Stem cell transplants make you quite vulnerable to fungal infections as the new white blood cells attack the old white blood cells meaning they don’t really have any innate immunity temporarily as the neutrophils are not being developed properly.
Which fungus causes pulmonary disease?
Aspergillosis
Loss of function of which 2 genes increase susceptibility to fungal infections?
TLR4 and CARD9
Mutations in which 3 proteins increase susceptibility to fungal infection??
Dectin-1, TLR4 and plasminogen
Which immune cell/s are more important n defence against Aspergillus fumigatus and Candidiasis
Neutrophils
Which immune cell/s are more important n defence against cryptococcus
macrophages and T cells are most likely more important.
X are VERY IMPORTANT in terms of controlling infection (of aspergillum and candidiasis)
neutrophils
Explain neutrophil nets: what are they, what do they do (2 functions), what fungal infections are they useful against (2)
- Neutrophil nets are contents of the nucleus of the cell. When have bacterial or fungal infections, neutrophils can explode and as well as releasing all their proteosomal contents, they also release a lot of DNA
DNA will trap the fungal organisms and stop them from germinating. This is seen with Apergillus and Candida
secondary function is to act as danger signals. They will recruit other cells to the site of infection.
What is stem cell T cell therapy
- When someone has stem cell transplants, it is possible to skim off the T cells specific for fungi and then in the lab, the T cells can be grown and when the patient gets a fungal infection, it can be given back to the patient.
How does Chronic Granulomatous Disorder impair fungal defence
- This is where the individuals who have this primary immune deficiency cannot make reactive oxygen species in their neutrophils so they cannot kill MOs like bacteria or fungi very well.
What mutation causes chronic granulomatous disorder and what does this cause at the cellular level
- This is due to a mutation in the gene called NADPH oxidase which sits on the phagosomal membrane and drives the H+ transport into the phagolysosome.
Individuals with Chronic Granulomatous Disorder are at increased risk of what infection
Staphylococcus infections and Aspergillus infections.
What can you do for chronic granulomatous disorder patients to increase their fungal defence
given bone marrow gene therapy to correct the defect in NADPH oxidase. After the therapy, the reactive oxygen species were able to kill the fungus. The neutrophils before the gene therapy could not make the neutrophil nets. After the gene therapy, they could in response to fungal stimulation.
3 common fungi found in the air?
- Aspergillus niger/fumigatus
- Cladosporium herbarum
- Alternaria alternata
What does an allergy to fungi suggest
Excessive immune response
what predisposes to fungal allergies?
Asthma
3 fungal disease associated with T1 HS reaction
- Associated with fungal allergic rhinitis and fungal allergic asthma and Allergic Bronchopulmonary Aspergillosis.
2 fungal disease associated with T3 HS reaction
It is associated with hypersensitivity pneumonitis (very deadly lung disease) and aspergilloma.
2 fungal disease associated with T4 HS reaction
is associated with Allergic Bronchopulmonary Aspergillosis and Hypersensitivity pneumonitis.
Predisposing conditions for bronchopulmonary aspergillosis (2)
- Asthma/ CF
What criteria defines bronchopulmonary aspergillosis (2)
- Total baseline serum IgE > 1000 IU/ml
o IgE is important for allergic responses - Positive immediate hypersensitivity skin test or Aspergillus-specific IgE
What criteria supports bronchopulmonary aspergillosis (2)
- Eosinophilia > 500cells/l
- Serum precipitating or IgG antibodies to Aspergillus fumigatus
- Consistent radiographic abnormalities.
Radiological features of bronchopulmonary aspergillosis (6)
- Dilated bronchi with thick walls.
- Ring or linear opacities.
- Upper or central region predilection.
- Proximal bronchiectasis
- Lobar collapse due to mucus impaction
o They can produce a lot of thick mucus - Fibrotic scarring
what is used to manage acute bronchopulmonary aspergillosis
steroids and antifungal
- Corticosteroids
- Itraconazole
Which type HSs can cause bronchopulmonary aspergillosis
1 and 4
Loss of TLR means more prone to what infection
Aspergillosis
