2. CONTENTS
FUNGAL INFECTION
What ?
Why ?
Where ?
How ?
HOW FUNGI GET CAUGHT
Immune Response against Fungal
Infection
HOW FUNGI ESCAPE
Evasion of Immune System by Fungi
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3. What is a fungal infection ?
A fungal infection is caused by
fungi that invades the tissue and
cause a disease that's confined to
the skin, spreads into tissue, bones
and organs or affects the whole
body. Which includes skin rash to
vaginal infection resulting in
abnormal discharge.
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4. • There are millions of fungal species, but only a few hundred of
them can make people sick. Most invasive fungal infections are
caused by species from three genera: Candida, Aspergillus,
and Cryptococcus.
• Fungi can cause many different types of illnesses, including :
Asthma or allergies
Rashes or infections on the skin and nails
Lung infections
Bloodstream infections
Meningitis
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5. Why so serious ?
• Invasive fungal infections are associated with high
mortality rates with an estimated 1.5 million deaths
globally each year.
• Mucosal infections are more prevalent than invasive
infections and are a major cause of morbidity.
• An effective vaccine against fungal infections has not been
developed, and currently available antifungal drugs are
only partly successful in treating patients with invasive
fungal infections.
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6. Why fungal infection is caused ?
• Most of the disease-causing fungi are opportunistic
pathogens and attacks when the immune system
becomes weakened or during over activation of the
inflammatory response.
• Altered immune or impaired immune system status is
caused due to chemotherapy, immunosuppressive
drugs and HIV infection.
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7. How Does Fungal Infection Occur ?
• Fungi reproduce by spreading microscopic spores.
These spores are often present in the air and soil,
where they can be inhaled or come into contact with
the surfaces of the body, primarily the skin.
Consequently, fungal infections usually begin in the
lungs or on the skin.
• These can range from common skin and mucosal
infections, to a serious life-threatening sepsis and
organ failure.
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8. Immune Response To Fungal Infection
RECOGNITION
Fungi are recognized by cells of the innate immune system
(e.g. dendritic cells and macrophages) which bind to
pathogen-associated molecular patterns (PAMPs) present
in fungal cell walls and nucleic acids using pattern
recognition receptors (PRRs) on their surface and activate
distinct downstream immune responses.
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• Toll-like receptors
(TLR1, TLR2, TLR3, TLR4, TLR5, TLR6, TLR9)
• C-type lectins
(Dectin-1, Dectin-2, Mincle, dendritic cell-
specific intercellular adhesion molecule-3-
grabbing non-integrin [DC-SIGN]
• Mannose binding lectin
[MBL2]), and long pentraxin 3 (PTX3).
9. Lectin pathway
• The lectin pathway is a type of cascade reaction
in the complement system. After activation, it
proceeds through the action of C4 and C2 to
produce activated complement proteins further
down the cascade. the lectin pathway does not
recognize an antibody bound to its target but
starts with mannose-binding lectin (MBL) or
ficolin binding to certain sugars.
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• Mannan-binding lectin, also called mannose-binding protein, is a protein
belonging to the collectin family that is produced by the liver and can initiate the
complement cascade by binding to pathogen surfaces.
• Fungal pathogens such as Candida albicans and Cryptococcus neoformans bound
by MBL.
10. Immune Response on Recognition
• When PRRs bind fungi, they release
signal using their intracellular tails or
associated molecules (FcRγ) resulting
in phagocytosis, initiation of killing
mechanisms (e.g. production of
reactive oxygen species) and also help
drive the development of adaptive
immunity.
• Adaptive immunity to fungi is only
partially understood, although it
seems that CD4+ T-cells that make
IFNγ (Th1) or IL-17 (Th17) provide the
best protection during fungal
infections.
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11. • Upon recognition of fungi through these receptors, signaling
results in generation of Th1/17 adaptive immune responses and
activation of innate effector cells.
• Many C-type lectin receptors use the same signaling molecule,
CARD9, to activate these antifungal immune responses. As a
result, mice or humans deficient in CARD9 are highly susceptible
to fungal infections, because although they have the PRRs to
bind fungi, the receptors can’t signal and therefore there is no
immunity. CARD9 is the most important molecule for activating
antifungal immune responses discovered to date.
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13. Evasion of Fungi
The innate recognition of fungi by phagocytes is achieved largely through
the sensing of cell wall constituents, although other internal components
(such as fungal DNA) can also be detected.
• Phagocytes utilize a number of oxidative and non-oxidative
mechanisms which work synergistically to kill extracellular and
internalized fungi.
• Monocytes and macrophages display a remarkable ability to internalize
fungi, to secrete several proinflammatory cytokines and chemokines
and to exert significant fungicidal activity.
• NK cells may exert direct antifungal activity by secretion of interferon-γ
(IFN-γ) and perforin, or contribute to fungal clearance by regulation of
other innate and adaptive immune cells via cytokine production. 13
14. Evasion of Host Immune
by Fungi
Pathogenic fungi have developed many strategies to evade the host immune system.
Multiple escape mechanisms appear to function together
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15. Molecules Involved in
Host Immune Evasion
Function Effect on the Human Immune System
Fungi Where They
Have Been Described
Mannans Proper cell wall architecture
Shielding of β-1,3-glucans from Dectin-1
receptor
Candida spp, H.
capsulatum yeast
Melanin
Mechanical strength of the cell
wall, enzymatic degradation
resistance and UV protection
Resistance to phagocytosis
C. neoformans,
Paracoccidioides
brasiliensis,
and Sporothrix schenckii
α-1,3-Glucan
Proper cell wall structure and
architecture
Shielding of β-1,3-glucans from Dectin-1
receptor
H. capsulatum yeast
Endo β-1,3-glucanase
Trimming of β-1,3-glucan
segments exposed on the fungal
cell surface
Reduced recognition of the yeast via
Dectin-1 and as a consequence, a reduction
in stimulation of proinflammatory
cytokines
H. capsulatum yeast
Transferrin Receptors
Utilizing host iron-binding
proteins as a source of iron
Overcoming the host nutritional immunity
of iron by the host
C. albicans
Pra 1 Scavenger of host zinc
Overcoming the nutritional immunity of
zinc by the host
C. albicans
Rod A Cell wall hydrophobin Diminished host NETs formation A. fumigatus
Molecules Involved In
Host Immune Evasion
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16. “A man who is depleted by worry is
he who natural immunity is reduced”
STAY HAPPY ! STAY HEALTHY !
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