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

SunmbalAwais 2,417 views 61 slides Jan 10, 2024
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About This Presentation

This presentation answers the following questions!!
How Immune Cells communicate with each other?
Receptors of Immune System?
Receptors of Innate Immune System?
What are PRRS?
What are PAMPS?
What are DAMPS?
What is the structure of PRRS?
What is the mechanism of PRRS?
What are the types of PRRS?
Wh...


Slide Content

PRESENTED BY SUNMAL AWAIS 23016160-003 1 ST 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 : B CR (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 . I nnate 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

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

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 1 st in the family of PRR in Drosophila . It is a pattern recognition molecule of innate immune system . STRUCTURE : NATURE : T ype 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

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

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

REFERENCES https ://en.wikipedia.org/wiki/Pathogen-associated_molecular_pattern https://en.wikipedia.org/wiki/Pattern_recognition_receptor https://www.annualreviews.org/doi/10.1146/annurev.immunol.24.021605.090552 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4272446/

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