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PRESENTED BY
SUNMAL AWAIS
23016160-003
1ST SEMESTER
PhD BIOCHEMISTRY & MOLECULAR BIOLOGY
UNIVERSITY OF GUJRAT
PATTERN RECOGNITION
RECEPTORS (PRRS)
&
PATHOGEN-ASSOCIATED
MOLECULAR PATTERNS (PAMPS
INTRODUCTION
 How immune system communicates?
 How immune cells sense and respond to changes?
 BY RECEPTOR-LIGAND TNTERACTION
RECEPTORS
Ligand
Receptor
 Receptors are specialized proteins located on
the surface or within cells that are capable of
recognizing and binding to specific molecules,
such as hormones, neurotransmitters, antigens,
or other signaling molecules.
 They play critical roles in various biological
processes by initiating cellular responses upon
ligand binding.
Bonding between Ligand and Receptor
RECEPTORS OF
IMMUNE SYSTEM
IMMUNE
RECOGITION
& RESPONSE
 The immune system is our body's defense network
against a wide array of pathogens, including
bacteria, viruses, fungi, parasites etc, that seek to
invade and harm the body.
Immune recognition (detection of threats)
Immune response (activation of defense
mechanisms)
 Challenges of immune system includes
elimination of antigen and communication with
other immune cells
INNATE
IMMUNITY
RESPONSE
ADAPTIVE
IMMUNITY
RESPOSE
RECEPTORS OF
ADAPTIVE IMMUNE
RECOGNITION SYSTEM
Adaptive immunity is the third line of defense and provides a slow, specific response to any
foreign invader.
 It is known as Specific Recognition as the recognition is against specific antigens unique to
individual pathogens or foreign substances.
 It includes two type of responses
Humoral Response or Antibody-mediated Response on B-cells
Cell mediated Response on T-cells
T-CELL RECEPTORS
Cells: T-Cells
Receptors: TCR (T-Cell Receptors)
Nature of Receptors: Always membrane bounded
Human T- cell (From SEM) Binding of T-cell receptor with Antigen
Structure of T- cell Receptor
B-CELL RECEPTORS
Cells: B-Cells
Receptors: BCR (B-Cell Receptors)
Nature of Receptors: Membrane-bounded & Soluble
Human B- cell (From SEM) Structure of B-cell Receptor
B-cell Differentiation
RECEPTORS OF
INNATE IMMUNE
RECOGNITION SYSTEM
Innate immunity is the first line of defense and provides a rapid, non-specific response to any
foreign invader.
Innate immune system includes all aspects of the host’s immune defense mechanisms that are
encoded in their mature functional forms by the germ-line genes of the host.
These include Barrier Defense (First Line of Defense)
Internal Defense (Second Line of Defense)
PATTERN RECOGNITION
RECEPTORS
(PRRS)
 Pattern Recognition Receptors (PRRs) are a class of
proteins that play a crucial role in the innate immune
system's ability to detect and respond to pathogens.
 PRRs are specialized in recognizing conserved
molecular patterns, known as Pathogen-Associated
Molecular Patterns (PAMPs), which are commonly
found on the surface of various microorganisms.
OCCURANCE OF
PRRS
LYMPHOID
CELLS
MYELOID
CELLS
OTHER AREAS
CELLULAR
LOCALIZATION
OF PRR
MEMBRANE-
BOUND PRRS
Toll like receptors
(TLRs)
C-type lectin receptors
(CLRs)
CYTOPLASMIC
PRRS
NOD-like receptors
(NLRs)
RIG-I-like receptors
(RLRs)
ENDOSOME-
ASSOCIATED
PRRS
Toll like receptors
(TLRs)
TLR3, TLR7, TLR8, TLR9
STRUCTURE OF
PRRS
 Extracellular Domain:
Many PRRs have an extracellular domain that is
responsible for ligand recognition.
 Transmembrane Domain:
PRRs that are located on the cell surface or within
endosomes typically have a transmembrane
domain that anchors them to the cell membrane.
 Cytoplasmic Domain:
The cytoplasmic domain of PRRs is involved in
signal transduction following ligand binding.
FUNCTION OF
PRRS
RECOGNIZE
Pathogen-Associated Molecular Patterns
(PAMPS)
Microbial-Associated Molecular Patterns
(MAMPS)
Damage-Associated Molecular Patterns
(DAMPS)
response
PATHOGEN-ASSOCIATED
MOLECULAR PATTERNS
(PAMPS)
Pathogen-Associated Molecular Patterns (PAMPs) are conserved molecular structures
commonly found on pathogens but not on host cells.
These patterns are recognized by Pattern Recognition Receptors (PRRs) of the innate
immune system, triggering immune responses aimed at eliminating the invading
pathogens.
PAMPs are essential components of the host-pathogen interaction and play a crucial
role in the initiation of the innate immune response.
Bacterial Cell Wall Components
 Peptidoglycan
 Lipopolysaccharide (LPS)
Viral Components
 Double-stranded RNA (dsRNA)
 Viral glycoproteins
Fungal Components
 β-Glucans
Parasite-Derived Molecules
 Glycans
EXAMPLES
DAMAGED-ASSOCIATED
MOLECULAR PATTERNS
(DAMPS)
Damaged-Associated Molecular Patterns (DAMPs)
are endogenous molecules that are released by
stressed, injured, necrotic or dying cells.
These patterns are also recognized by Pattern
Recognition Receptors (PRRs) of the innate immune
system, triggering immune responses ad alerting the
presence of cellular damage or stress.
For example intracellular DNA, RNA can act as
DAMP when released into extracellular space.
MECHANISM OF
PAMPS RECOGNTION
BY PRRS
 Recognition and Binding of Pathogen-Associated Molecular Patterns (PAMPs)
• PRRs recognize specific molecular patterns known as PAMPs, which are commonly found on pathogens
but are absent or rare in host cells.
 Activation and Signaling
• Upon binding to their specific ligands (PAMPs), PRRs undergo conformational changes that lead to the
activation of downstream signaling pathways.
• This activation triggers a series of intracellular events, including the recruitment of adaptor proteins and
the activation of transcription factors like NF-κB and IRFs (interferon regulatory factors).
 Cytokine and Chemokine Production
• Activated PRRs induce the production of pro-inflammatory cytokines (e.g., interleukins, tumor
necrosis factor) and chemokines that orchestrate the recruitment and activation of immune cells to
the site of infection.
• These mediators amplify the immune response and coordinate the elimination of pathogens.
 Antimicrobial Responses
• PRR activation leads to the induction of antimicrobial mechanisms, such as the production of
antimicrobial peptides, reactive oxygen species (ROS), and nitric oxide (NO), which directly target
and kill pathogens.
 Inflammatory Responses
• PRR activation also contributes to the initiation of inflammation, which is a crucial component of
the immune response against pathogens.
• Inflammation helps to contain and eliminate the infection but must be carefully regulated to avoid
excessive tissue damage.
 Linking Innate and Adaptive Immunity
• PRR activation bridges the innate and adaptive immune responses by influencing antigen
presentation, co-stimulatory molecule expression, and cytokine production, which are essential for
the activation and regulation of adaptive immune cells (e.g., T and B lymphocytes).
TYPES OF PRR
TOLL LIKE
RECEPTORS (TLR)
 Discovered 1st in the family of PRR in Drosophila.
 It is a pattern recognition molecule of innate immune system.
 STRUCTURE:
NATURE: Type I transmembrane proteins
DOMAINS:
N-terminal domain (NTD):
Located outside the membrane
Middle single helix transmembrane domain:
Traverses the membrane
C-terminal domain (CTD):
Located towards the cytoplasm
CELL
MEMBRANE
TLRS
TLR1
TLR2
TLR4
TLR5
TLR6 ENDOSOMAL
TLRS
TLR3
TLR7
TLR8
TLR9
 PRESENCE: Expressed on various immune cells such as macrophages, dendritic cells, and B cells,
as well as non-immune cells like epithelial cells.
 LIGAND: It recognizes Peptidoglycan, Flagellin, viral nucleic acids (RNA and DNA), lipoproteins, and
other microbial components.
 RESPONSE: Upon ligand binding, TLRs initiate signaling cascades leading to the activation of
transcription factors like NF-κB and IRF3/7 that results in the production of pro-inflammatory cytokines,
type I interferons, and other molecules that mediate the immune response.
C-TYPE LECTIN
RECEPTORS (CLR)
 It is a pattern recognition molecule of innate
immune system.
 STRUCTURE: CLRs are a diverse group of
proteins characterized by the presence of one or
more C-type lectin-like domains (CTLDs),
which are involved in carbohydrate recognition.
.
 PRESENCE: Expressed on plasma
membrane of various immune cells.
 TYPES: CLRs can be further classified
based on their structure and function into
several subgroups, including simple CLRs,
transmembrane CLRs, and soluble CLRs
 LIGAND: CLRs recognize a wide
range of carbohydrate structures,
including mannose, fructose, and
galactose residues present on
pathogens (PAMPs) and self-antigens.
 Some CLRs can also recognize
glycosylated proteins and lipids.
 RESPONSE: Upon ligand binding,
CLRs can trigger various immune
responses, including phagocytosis,
cytokine production, antigen
presentation, and modulation of
immune cell activation and
differentiation.
NUCLEOTIDE
OLIGOMERIZATION DOMAIN
(NOD) LIKE
RECEPTORS (NLR)
 It is a pattern recognition molecule of innate immune system.
 STRUCTURE: NLRs are characterized by the presence of a central nucleotide-
binding and oligomerization domain (NACHT), which is involved in oligomerization
and signaling.
 They also contain leucine-rich repeats (LRRs) at the C-terminus, which are
responsible for ligand recognition, and a variable N-terminal effector domain that
determines their downstream signaling functions.
.
 PRESENCE: Cytoplasmic receptors
 LIGAND & RESPONSE: NLRs play a
crucial role in the recognition of
intracellular pathogens, as well as in the
sensing of endogenous danger signals.
Upon activation by microbial
components or cellular stress signals,
NLRs can oligomerize and initiate
signaling cascades that lead to the
production of inflammatory cytokines
and the induction of antimicrobial
responses.
DIAGNOSIS
OF PRRS
DIAGNOSIS
Protein
Expression and
Localization
Clinical
Correlation
Studies
Functional
Genomics
and
Proteomics
Genetic
Analysis
Gene
Expression
Analysis
APLICATIONS
OF PRR IN
IMMUNOLOGY
Detection of Pathogens
Initiation of Immune Responses
Linking Innate and Adaptive Immunity
Tolerance and Autoimmunity
Tissue Repair and Resolution of Inflammation
APLICATIONS OF PRR IN
MEDICINE AND
BIOTECHNOLOGY
Development of Novel Therapeutics
Vaccine Development
Diagnostic Tools
Microbiome Engineering
Immune Modulation
Biotechnology Applications
ROLE OF PRRS
IN DISEASES
Infectious
Diseases
Inflammatory
Conditions
Cancer
Autoimmune
Disorders
1. https://en.wikipedia.org/wiki/Pathogen-associated_molecular_pattern
2. https://en.wikipedia.org/wiki/Pattern_recognition_receptor
3. https://www.annualreviews.org/doi/10.1146/annurev.immunol.24.021605.090552
4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4272446/
THANK YOU

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Pathogen Recognition Receptors (PRRS) & Pathogen Associated Molecular Patterns (PAMPS).pptx

  • 1. PRESENTED BY SUNMAL AWAIS 23016160-003 1ST SEMESTER PhD BIOCHEMISTRY & MOLECULAR BIOLOGY UNIVERSITY OF GUJRAT
  • 4.  How immune system communicates?  How immune cells sense and respond to changes?  BY RECEPTOR-LIGAND TNTERACTION
  • 6. Ligand Receptor  Receptors are specialized proteins located on the surface or within cells that are capable of recognizing and binding to specific molecules, such as hormones, neurotransmitters, antigens, or other signaling molecules.  They play critical roles in various biological processes by initiating cellular responses upon ligand binding.
  • 7. Bonding between Ligand and Receptor
  • 9. IMMUNE RECOGITION & RESPONSE  The immune system is our body's defense network against a wide array of pathogens, including bacteria, viruses, fungi, parasites etc, that seek to invade and harm the body. Immune recognition (detection of threats) Immune response (activation of defense mechanisms)  Challenges of immune system includes elimination of antigen and communication with other immune cells
  • 12. Adaptive immunity is the third line of defense and provides a slow, specific response to any foreign invader.  It is known as Specific Recognition as the recognition is against specific antigens unique to individual pathogens or foreign substances.  It includes two type of responses Humoral Response or Antibody-mediated Response on B-cells Cell mediated Response on T-cells
  • 13. T-CELL RECEPTORS Cells: T-Cells Receptors: TCR (T-Cell Receptors) Nature of Receptors: Always membrane bounded Human T- cell (From SEM) Binding of T-cell receptor with Antigen Structure of T- cell Receptor
  • 14.
  • 15. B-CELL RECEPTORS Cells: B-Cells Receptors: BCR (B-Cell Receptors) Nature of Receptors: Membrane-bounded & Soluble Human B- cell (From SEM) Structure of B-cell Receptor
  • 18. Innate immunity is the first line of defense and provides a rapid, non-specific response to any foreign invader. Innate immune system includes all aspects of the host’s immune defense mechanisms that are encoded in their mature functional forms by the germ-line genes of the host. These include Barrier Defense (First Line of Defense) Internal Defense (Second Line of Defense)
  • 20.  Pattern Recognition Receptors (PRRs) are a class of proteins that play a crucial role in the innate immune system's ability to detect and respond to pathogens.  PRRs are specialized in recognizing conserved molecular patterns, known as Pathogen-Associated Molecular Patterns (PAMPs), which are commonly found on the surface of various microorganisms.
  • 24. MEMBRANE- BOUND PRRS Toll like receptors (TLRs) C-type lectin receptors (CLRs) CYTOPLASMIC PRRS NOD-like receptors (NLRs) RIG-I-like receptors (RLRs) ENDOSOME- ASSOCIATED PRRS Toll like receptors (TLRs) TLR3, TLR7, TLR8, TLR9
  • 26.  Extracellular Domain: Many PRRs have an extracellular domain that is responsible for ligand recognition.  Transmembrane Domain: PRRs that are located on the cell surface or within endosomes typically have a transmembrane domain that anchors them to the cell membrane.  Cytoplasmic Domain: The cytoplasmic domain of PRRs is involved in signal transduction following ligand binding.
  • 28. RECOGNIZE Pathogen-Associated Molecular Patterns (PAMPS) Microbial-Associated Molecular Patterns (MAMPS) Damage-Associated Molecular Patterns (DAMPS) response
  • 30. Pathogen-Associated Molecular Patterns (PAMPs) are conserved molecular structures commonly found on pathogens but not on host cells. These patterns are recognized by Pattern Recognition Receptors (PRRs) of the innate immune system, triggering immune responses aimed at eliminating the invading pathogens. PAMPs are essential components of the host-pathogen interaction and play a crucial role in the initiation of the innate immune response.
  • 31. Bacterial Cell Wall Components  Peptidoglycan  Lipopolysaccharide (LPS) Viral Components  Double-stranded RNA (dsRNA)  Viral glycoproteins Fungal Components  β-Glucans Parasite-Derived Molecules  Glycans EXAMPLES
  • 33. Damaged-Associated Molecular Patterns (DAMPs) are endogenous molecules that are released by stressed, injured, necrotic or dying cells. These patterns are also recognized by Pattern Recognition Receptors (PRRs) of the innate immune system, triggering immune responses ad alerting the presence of cellular damage or stress. For example intracellular DNA, RNA can act as DAMP when released into extracellular space.
  • 35.  Recognition and Binding of Pathogen-Associated Molecular Patterns (PAMPs) • PRRs recognize specific molecular patterns known as PAMPs, which are commonly found on pathogens but are absent or rare in host cells.  Activation and Signaling • Upon binding to their specific ligands (PAMPs), PRRs undergo conformational changes that lead to the activation of downstream signaling pathways. • This activation triggers a series of intracellular events, including the recruitment of adaptor proteins and the activation of transcription factors like NF-κB and IRFs (interferon regulatory factors).
  • 36.  Cytokine and Chemokine Production • Activated PRRs induce the production of pro-inflammatory cytokines (e.g., interleukins, tumor necrosis factor) and chemokines that orchestrate the recruitment and activation of immune cells to the site of infection. • These mediators amplify the immune response and coordinate the elimination of pathogens.  Antimicrobial Responses • PRR activation leads to the induction of antimicrobial mechanisms, such as the production of antimicrobial peptides, reactive oxygen species (ROS), and nitric oxide (NO), which directly target and kill pathogens.  Inflammatory Responses • PRR activation also contributes to the initiation of inflammation, which is a crucial component of the immune response against pathogens. • Inflammation helps to contain and eliminate the infection but must be carefully regulated to avoid excessive tissue damage.  Linking Innate and Adaptive Immunity • PRR activation bridges the innate and adaptive immune responses by influencing antigen presentation, co-stimulatory molecule expression, and cytokine production, which are essential for the activation and regulation of adaptive immune cells (e.g., T and B lymphocytes).
  • 37.
  • 39.
  • 41.  Discovered 1st in the family of PRR in Drosophila.  It is a pattern recognition molecule of innate immune system.  STRUCTURE: NATURE: Type I transmembrane proteins DOMAINS: N-terminal domain (NTD): Located outside the membrane Middle single helix transmembrane domain: Traverses the membrane C-terminal domain (CTD): Located towards the cytoplasm
  • 42. CELL MEMBRANE TLRS TLR1 TLR2 TLR4 TLR5 TLR6 ENDOSOMAL TLRS TLR3 TLR7 TLR8 TLR9  PRESENCE: Expressed on various immune cells such as macrophages, dendritic cells, and B cells, as well as non-immune cells like epithelial cells.
  • 43.  LIGAND: It recognizes Peptidoglycan, Flagellin, viral nucleic acids (RNA and DNA), lipoproteins, and other microbial components.  RESPONSE: Upon ligand binding, TLRs initiate signaling cascades leading to the activation of transcription factors like NF-κB and IRF3/7 that results in the production of pro-inflammatory cytokines, type I interferons, and other molecules that mediate the immune response.
  • 45.  It is a pattern recognition molecule of innate immune system.  STRUCTURE: CLRs are a diverse group of proteins characterized by the presence of one or more C-type lectin-like domains (CTLDs), which are involved in carbohydrate recognition. .
  • 46.  PRESENCE: Expressed on plasma membrane of various immune cells.  TYPES: CLRs can be further classified based on their structure and function into several subgroups, including simple CLRs, transmembrane CLRs, and soluble CLRs
  • 47.  LIGAND: CLRs recognize a wide range of carbohydrate structures, including mannose, fructose, and galactose residues present on pathogens (PAMPs) and self-antigens.  Some CLRs can also recognize glycosylated proteins and lipids.  RESPONSE: Upon ligand binding, CLRs can trigger various immune responses, including phagocytosis, cytokine production, antigen presentation, and modulation of immune cell activation and differentiation.
  • 49.  It is a pattern recognition molecule of innate immune system.  STRUCTURE: NLRs are characterized by the presence of a central nucleotide- binding and oligomerization domain (NACHT), which is involved in oligomerization and signaling.  They also contain leucine-rich repeats (LRRs) at the C-terminus, which are responsible for ligand recognition, and a variable N-terminal effector domain that determines their downstream signaling functions. .
  • 50.  PRESENCE: Cytoplasmic receptors  LIGAND & RESPONSE: NLRs play a crucial role in the recognition of intracellular pathogens, as well as in the sensing of endogenous danger signals. Upon activation by microbial components or cellular stress signals, NLRs can oligomerize and initiate signaling cascades that lead to the production of inflammatory cytokines and the induction of antimicrobial responses.
  • 51.
  • 55. Detection of Pathogens Initiation of Immune Responses Linking Innate and Adaptive Immunity Tolerance and Autoimmunity Tissue Repair and Resolution of Inflammation
  • 56. APLICATIONS OF PRR IN MEDICINE AND BIOTECHNOLOGY
  • 57. Development of Novel Therapeutics Vaccine Development Diagnostic Tools Microbiome Engineering Immune Modulation Biotechnology Applications
  • 58. ROLE OF PRRS IN DISEASES
  • 60. 1. https://en.wikipedia.org/wiki/Pathogen-associated_molecular_pattern 2. https://en.wikipedia.org/wiki/Pattern_recognition_receptor 3. https://www.annualreviews.org/doi/10.1146/annurev.immunol.24.021605.090552 4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4272446/