Signaling Comunication

of
Recognizing Antigen
Assoc.Prof.DR.dr. Agung Putra, MSi, Med
Director of SCCR (Stem Cell & Cancer Research) Indonesia
Chairman of PERSEPSI (Perkumpulan Peneliti Sel Punca Indonesia)

MAGISTER ILMU BIOMEDIK

 Homeostasis State

Membentuk
Homeostasis melalui sirkuit sinyal
sinyal yang memicu kompleks
aktivitas seluler
Molekul yang diikuti dengan sinyal
disekresikan dapat inhibisi.
berbeda, bahkan
dalam satu jenis sel
yang sama.
Bentuk komunikasi • Sel dengan fungsi
molekuler antar sel eksitasi, di waktu
• Melalui pelepasan lain sebagai inhibisi.
Setiap organisme moleku tertentu
salingberinteraks • Tergantung pada
• Menuju keadaan karakteristik sel dan
homeostasis. niche.
 Inflammatory Response

In reply to internal or
external danger stimuli, the
body orchestrates an
inflammatory response.

Inflammation is the body’s

The exogenous triggers of
defense to microbial invasion or
this process are the
a critical response to tissue
damage-associated
injury under aseptic or sterile
molecular patterns (DAMPs)
condi tions.

The endogenous triggers of

this process are the damage-
associated molecular patterns
(DAMPs)

Source:
Complexity of Danger: The Diverse Nature of Damage- associated Molecular Patterns*
Liliana Schaefer
JOURNAL OF BIOLOGICAL CHEMISTRY 35237
 Recognizing antigen
The innate system possesses pattern-recognition The adaptive system has different receptors on its
receptors (PRRs) to recognize structures common B and T lymphocytes, that each one is exquisitely
to groups of disease-causing antigen. MHC
sensitive to one individual molecular structure.
PRRs act as the ‘early PAMP
The responses
warning system of immunity, TLR triggered by these
triggering a rapid DAMP
receptors offer more
inflammatory response which effective protection
precedes against infection but
are usually much
Essential for a slower to develop.
subsequent
adaptive Antibodies
response

https://www.creative-diagnostics.com/immune-
recognition-and-receptors.htm
 Recognizing antigen

Recognize the antigen is critical for TLR are pattern recognition receptors (PRRs) that are
promoting the immune response expressed on immune cell (non-lymphoid and lymphoid)

TLRs

Initiates intracellular signal

transduction cascades

lead to NF-κB activation

Upregulation of

Costimulatory molecules

Adhesion molecules Cytokines profiling

Essential to immune activation

 How to conduct the effective immune response

More immediate defense To address microbial invasions

system is required
Intense expansion of antigen-
An effective immune response specific lymphocytes is required.

Only a limited pool of

lymphocytes will have specificity This expansion may take several days
towards that antigen.
 Epitopes TCR & Antibodies Vs TLR

Epitope TCR TLR

& Antibodies

Overcome by the
Lack of variability in
presence of multiple
antigen recognition
receptor types

Despite their limited antigen

recognition capability

Binding molecules that are

indispensible to microbes

The benefit of the TLR fixed

receptor structure is that a
large number of innate
immune cells can recognize
a pathogen and respond
immediately.

Source:
Dual Role of Toll-like Receptors in Human and
Experimental Asthma Models:
Amin Zakeri and Momtchilo Russo
Front. Immunol., 15 May 2018 |
https://doi.org/10.3389/fimmu.2018.01027
DAMP: damage-associated molecular pattern
PAMP: pathogenic-associated moleculer pattern

the innate pathways are critical to the development

of a robust adaptive immune response

PAMPs and DAMPs are highly conserved motifs derived from

the pathogens themselves (PAMPs) or from self-molecules
that are normally hidden from the PRRs by
compartmentalization (intracellular DAMPs) or
sequestration in the ECM (extracellular DAMPs).

Innate Pathways of Immune Activation in Transplantation

Todd V. Brennan, Keri E. Lunsford, and Paul C. Kuo
 TLR-PAMP Signaling

The complexity of
Increased by
DAMP-TLR

CD14
MD2
CD36 Source:
Adaptor-inducing interferon Is Toll-like receptor 4 involved in the severity of COVID-19
pathology in patients with cardiometabolic comorbidities?
(TRIF) Simone Cristina Soares et all.
Journal Cytokine & Growth Factor

TLR Dimerization TRIF-related adaptor

molecule (TRAM)

MyD88-adaptor like NF- kB

pathway (via
(Mal) MyD88)

Adaptor molecules TIR domain- Sterile and armadillo Recruited, resulting in

motif-containing Interferon
(MyD88) containing activation of
protein (SARM) (via TRIF)
 Damage Associated Molecular Pattern (DAMP)

Five classes of PRRs

have currently been
described:

Cell surface or Cytoplasmic NOD-like Intracellular RIG-I AIM2 (absent in

Transmembrane C-
endosomal Toll-like receptors (NLRs) and (retinoic acid-inducible melanoma 2)-like
type lectin receptors
receptors (TLRs), Inflammasome gene-I)-like receptors receptors

Dectin-1
 Damage Associated Molecular Pattern (DAMP)

The complexity of DAMP-TLR-

mediated immune signaling is
further increased by accessory
Sterile molecules
inflammation
DAMPs represent a
heterogeneous group Following interaction
of molecules from with pattern
recognition receptors
in cross-talk with
Cluster of The various non-immune
differentiation CD36 extracell receptors
CD14 (preference Inside the various
ular
for DAMPs ) compartments of the
space.
cell

Myeloid
induced by the release of endogenous differentiatio DAMPs determine
molecules called DAMPs following n 2 (MD2)) the downstream
tissue stress or injury signaling outcome

Myocardial infarction, Aseptic

atherosclerosis, several inflammatory
autoimmune diseases, responses.
and cancer
of septic
inflammatory
responses
 PAMP-TLR
There are
currently 13 TLRs
identified in mice
andhumans.

Source:
The Role of Toll-like Receptors in the Pathogenesis and Treatment of Dermatological Disease
Jamie E.McInturff, 1Robert L.Modlin, JennyKim
Journal of Investigative Dermatology
DAMP
DAMP
TLR-DAMP Signaling
MATUR SEMBAH NUWUN