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Flashcards in Rob's Fungal Immunity Deck (50)
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1

Which fungi classes cause disease in humans

3 phyla causing disease in humans Zygomycota Basidiomycota `Ascomycota (bottom 2 more closely related)

2

Give an example of ascomycota

 Candida and  Aspergillus

3

Give examples of basidiomycota

Mushrooms(cryptococci)

4

List Fungi causing infections

Aspergillus (ascomycota) Cryptococcus (basidiomycota) Candida albicans (ascomycota)

5

How can aspergillus cause problems

Have spores called conidium.Normally fine, most people inhale every day Only a problem if you have no neutrophils Can germinate (leading to fungal ball) and cause bleeding in LUNGS

6

How can Cryptococcus neoformans cause disease

Mushroom group (microscopic) .Fimbrae that allow it to adhere to surfaces .Commonest cause of death in HIV patients (subsaharan Africa) .Inhaled through lungs but can disseminate to brain if lack of CD4+ T cells. Leads to cryptococcal meningitis. Can then develop cryptococcomas (fungal ball) , and stroke like symptoms.

7

What is cryptococcoma

Ball of fungus which has germinated. CNS (cryptococcus neoformans)

8

How can candida albicans cause disease

Candida is commensal on skin and gut But in immunocompromised/catheterised, can develop invasive infeection. Can get into the back of the eye creates mass =candida endophthalmitis, for example

9

Outline cellular immunity to fungal infection

Innate immune system very important. Loss of neutrophils is a key risk factors .Most fungi encountered at mucosal surface (in gut, yeast or on lungs as moulds). Opsonisation, phagocytes and complemet all important. Dendritic cells present antigen to T cells Can lead to Th1, Th2 and Th17 responses(these then determine innate response-circle).

10

Why are NK cells important in cellular immunity to fungal infection

They produce IFN-g which primes macrophage to deal with fungus

11

Outline how fungi change shape Candida, cryptococcus and aspergillus

Can start as unicellular organisms then become mutlicellular ▪Candidal dimorphism (starts of as budding yeast but when it is involved in invasioive infections changes into  hyphal forms, which are muticellular filamentoius structurees) allows tissue invasion ▪Crytpococcus divides in the host as a yeast. Forms a capsule to evade phagocytosis ▪Aspergillus species inhaled as conidia, invade tissues as hyphae

12

How can fungi be sensed

Toll like receptors (innate receptor). Losing the toll systems put you at high risk of fungal disease

13

What are c-type lectins

Part of immunoglobulin super family.Detect carbohydrate on fungal cell wall. Important for phagocytosis of fungi (TLR cannot do it alone, need c -type lectins).

14

What receptors are important in fungal infection

TLR, c-type lectins and scavenger receptors

15

T/F scavenger receptors normally phagocytose non-inflammatory materials

T

16

What deficiencies could result in chronic mucocutaneous candidasis

 c-type lectin is really importnat in fungal immunity. Mutations and thus deficiency of Dectin 1[Dectin 1 (a c-type lectin). It binds candida. Without dectin 1 ,cannot produce IL-6 or bind ],  and CARD9, a protein in the downstream signalling pathays for many c-type lectins, can result in chronic mucocutaneous candidiasis.

17

What is worse, dectin 1 or CARD9 deficiency

CARD9, because this is the signalling molecule for the actiation of many receptors

18

Why is CARD9 required in fungal immunity

Functional Card9 is Required for TNFα Production in Response to βGlucan ,and is also Required for T cell Th17 Differentiation in Humans. (SHOWS THAT DEFECTIVE INNATE RECEPTORS MEANS THAT ADAPTIVE IMMUNE SYSTEM CAN THEN NOT BE TRAINED TO DEAL WITH THE FUNGI

19

Why is Th17 response importnat in fungal disease

Mucosal protection .But in CARD9 deficiency, Th17 does not differentiate properly (showing that innate immune reponse interacts with adaptive one) and you get chornic mucocutaneous candidasis

20

Explain why fungal infections  are  important in stem cell transplantation, give an example of one that is important.

Apergillosis (stem cell transplantation occurs in leukaemia. All your own bone marrow wiped out with txic drugs. Give someone else's bone marrow. That bone marrow will act as your bone marrow, creating your red and white cells. But it will also attack your own immune system to destroy all of the bone marrow cancer) But during that period of the transplanted bone marrow killing your bone marrow and then producing new cells, there are less neutrophils and less innate immunity, and these patents very susceptible to fungal infection including aspergillosus .TLR4 polymophoisms can alter risk of pulmonary aspergillosis in transpantation

21

What proteins are  important in risk of invasive aspergillosis in stem cell transpantation

Dectin 1 and TLR4

22

Mutations in which haemostasis related protein increases susceptibility to fungal disease

Plasminogen (as well as dectin1, TLR4)

23

Why will fungal immunogenics be important

E.g in transplant patients you can look at their TLR4 phenotype and see if this is going to place them at a risk of a certain infection and then give prophylactic medication (ABs)

24

What are important innate immunity cells in fungus infection

Both macrophages and neutrophils contribute to fungal immunity However for Aspergillus neutrophils are of primary importance

25

What happens if you took neutrophil away from lung and put aspergillus there

It would grow as it would in a test tube Basically, without neutrophils aspergillus will grow so easily and body doesn't really do anything with it

26

Outline one way in which neutrophils deal with fungi

Neutrophl extracellular nets DNA released by dead neutrophils and this binds the aspergillus (in this cause aspergillus fumigatus) and is very sticky This is the reason for very sticky mucus in these sorts of infections

27

Other function of neutrophil DNA other than coding for proteins

Neutrophil extracellular trap And, when released from cells, acts as a DAMP (along with histones, actin etc.)

28

When do Th1 responses occur and when do Th2 responses occur generally

Th2 is development of allergic response i.e. eosinophil and mast cell degranulation Th2 is promoted by worms and parisitic infections because they are too big to phagocytose, so Th1 response isn't approrpiate Th1 response occur against intracellular parasites such as bacteria and viruses which can be phagocytosed

29

What are the important cytokines for Th1 and Th2

Th1: TNF-a, IFN-g and IL-6 and IL-12 stimulates macropahges Th2: IL4/IL-10 for eosinophil and mast cells

30

Outline the T helper response to fungi

DEPENDS on fungal morphogenesis. At first, the fungi might be in the yeast form but then can take different forms (hyphae form/capsule) Dendritic cells take up antigen. For the yeast form of candida, leads to Th1 (as it's smaller and can be phagocytosed) In the hyphae form of candidam there is Th2 response as now the yeast is filamentous and big so requires allergic response not phagocytic Same for aspergillus conida (Th1) vs aspergillus hyphae (Th2)