Immunological Response To Fungi

IMMUNOLOGICAL RESPONSE
TO FUNGI
INTRODUCTION
 Fungi are saprophytic, heterotrophic organisms that are well adapted
to grow in nature supported by diverse nutritional substrates.
 Fungi reproduce both sexually and asexually and have various

economic importance.
 Some fungi are known to be responsible for some diseases in plants

and animals.
 The known pathogenic fungi are opportunistic organisms.

CLASSIFICATION OF FUNGI INFECTION
Fungi infection also known as mycoses, can be classified into three
groups:
 Superficial Infection such as ring worm infection caused by Tinea spp,

Microsporum canis.
 Systemic infection such as Coccidiomycosis and Histoplasmosis

infection caused by Coccidiode immitis and Histoplasma capsulatum.
 Intermediate infection such as Candidiasis and Aspergillosis infection

caused by Candida albicans and Aspergillus fumigatus.
FUNGAL IMMUNOLOGICAL RESPONSE: CELL
WALL STRUCTURE
 Fungi have a cell wall which initiates the innate immune systems of humans.
 Fungal cell wall compose of PAMP which are β-glucans, chitin and mannans and
other cell wall glycans.
 These PAMPs could Avoid innate receptors

depending on the fungal species, by shielding
and remodeling, thereby impairing recognition
of these ligands.
FUNGAL IMMUNOLOGICAL RESPONSE (Contd)
INNATE IMMUNE RESPONSE
The immune mechanisms of defense against fungal infection are
numerous.
Innate effector cells, mainly macrophages and neutrophils, are the first
line of defense against inhaled fungal spores.
Innate fungal recognition is accomplished through the sensation of cell

wall and intracellular PAMPs by soluble, membrane-bound, and
intracellular PRRs of myeloid and epithelial cells.
INNATE IMMUNE RESPONSE
(Contd)
Innate immune system PRRs consist of four major classes namely, CLRs,
TLRs, NOD, and RIG-I)-like receptors.
PRRs bind fungi, they signal using their intracellular tails or associated
molecules (FcRγ) resulting in phagocytosis.
And in turn drives the develop-
ment of adaptive immunity.
ADAPTIVE IMMUNE RESPONSE
Adaptive response is initiated by antigen presenting cells (APCs)of the
fungus.
Monocytes can rapidly differentiate into dendritic cells that transport

ingested fungi to draining lymph nodes
 T helper cells are primed resulting in the recruitment and activation of

memory T cells and naïve T cells.
The immune cells take up and process the antigen for display by MHCII
molecules to naïve T cells.
ADAPTIVE IMMUNE RESPONSE (Contd)
Cytokines and IL present in the micro-environment will polarize the T helper
lymphocytes response towards a predominant Th1, Th2 or Th17 response.
Production of IL-12 leads to protective Th1 cells activation which activate

pathogenic Th17 cells promoting inflammation and dampening Th1
responses.
The production of IL-4 leads to activation of Th2 responses
TH2 opposes antifungal function in effector cells and promoting allergic

manifestations. (Luigina et al 2008).
IMMUNOLOGICAL RESPONSE OF
Candida albicans.
Candida albicans is an oral indigenous fungus
C. albicans is recognized by many receptors including (TLRs) and (CLRs).
Histatin 5 is secreted by human salivary glands and has the most potent
fungicidal activity against C. albicans
The β-defensin 2 and 3 produced by epithelial cells demonstrate

antifungal activity against C. albicans (Vylkova et al 2007).
IMMUNOLOGICAL RESPONSE OF
Candida albicans (Contd)
Phagocytosis is one of the frontline processes of innate second line
defense.
The cell wall components of C. albicans which consist of mannans, β-

glucans, and chitins are virulence factors that activate phagocytosis.
Phagocytosis of β-glucans (PAMP) by macrophages can activate the

production of (ROS), which is critical for pathogen killing.
 TLR2 recognizes β-glucan of C. albicans while TLR4 senses mannans of the microorganism and
induces cytokine production (Netea et al 2006).
 Dectin-1, a C-type lectin recognizes

β-glucan and synergizes with
TLR2 and TLR4 for TNF-α
production by macrophages
 It plays a role in facilitating the signaling

for activation of phagocytosis
in dendritic cells
 Dectin-2 recognizes the α-mannans of C.albicans

and induces NF- κB activation which is required
for proinflammatory cytokine production
such as IL-6 and IL-8
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IMMUNOLOGICAL RESPONSE

 Fungi reproduce both sexually and asexually and have various

 Some fungi are known to be responsible for some diseases in plants

 The known pathogenic fungi are opportunistic organisms.

 Superficial Infection such as ring worm infection caused by Tinea spp,

 Systemic infection such as Coccidiomycosis and Histoplasmosis

 Intermediate infection such as Candidiasis and Aspergillosis infection

 These PAMPs could Avoid innate receptors

Innate fungal recognition is accomplished through the sensation of cell

Monocytes can rapidly differentiate into dendritic cells that transport

 T helper cells are primed resulting in the recruitment and activation of

Production of IL-12 leads to protective Th1 cells activation which activate

The production of IL-4 leads to activation of Th2 responses

TH2 opposes antifungal function in effector cells and promoting allergic

C. albicans is recognized by many receptors including (TLRs) and (CLRs).

The β-defensin 2 and 3 produced by epithelial cells demonstrate

The cell wall components of C. albicans which consist of mannans, β-

Phagocytosis of β-glucans (PAMP) by macrophages can activate the

 Dectin-1, a C-type lectin recognizes

 It plays a role in facilitating the signaling

 Dectin-2 recognizes the α-mannans of C.albicans

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