Soluble-Molecule-BS.pdf

Soluble Molecules involved in Immune Responses Dr. Sa’dia Tasnim MBBS, MPH(RCH), MS(Immunology) Lecturer, Dept. of Immunology, BUHS Biologically active Molecules / Biologically active Molecules / soluble soluble involved in innat...

Soluble Molecules involved in Immune Responses Dr. Sa’dia Tasnim MBBS, MPH(RCH), MS(Immunology) Lecturer, Dept. of Immunology, BUHS Biologically active Molecules / Biologically active Molecules / soluble soluble involved in innate involved in Adaptive immune responses immune responses Antibodies Cytokines-IL, IFN Complements Antimicrobial Peptides Cytokines Complements Various membrane bound receptors; e.g. PAMPs, PRR – TLR, CLR  Antimicrobial Peptides  Antimicrobial peptides and proteins function in innate defense by attacking microbes directly or impeding their reproduction  Kill pathogenic bacteria in various ways. Defensins α-Defensins β-Defensins Cationic (+) peptides Antibacterial Disrupt microbial membranes and synthesis of RNA, DNA, and proteins Produced among others by neutrophils, epithelial cells Pattern-Recognition Receptors Receptors of the innate immune system Recognize unique antigens (motifs) in microorganisms (Danger Signals!!!) These antigens are absent in the host (nonself) PRRs are germline-encoded host sensors, which detect molecules typical for the pathogens. They are proteins expressed, mainly, by cells of the innate immune system, such as dendritic cells, macrophages, monocytes, neutrophils and epithelial cells. To identify two classes of molecules: 1. Pathogen-associated molecular patterns (PAMPs), which are associated with microbial pathogens, and 2. Damage-associated molecular patterns (DAMPs), which are associated with components of host's cells that are released during cell damage or death. Interaction between PAMPs & PRRs PRRs – Pattern Recognition Receptors on HOST CELLS PAMPs – Pathogen- Associated Molecular Patterns on MICROBES *Also called primitive pattern recognition receptors because they evolved before other parts of the immune system, particularly before adaptive immunity. *PRRs also mediate the initiation of antigen-specific adaptive immune response and release of inflammatory cytokines. Types: Based on their localization 1. Membrane-bound PRRs (a)Toll like receptor (TLRs) (b)C type lectine receptor (CLRs) 2. Cytoplasmic PRRs (a) NOD like receptor (NLRs) (b)RIG-I like receptor (RLRs) Principle functions of PRRs 1.Opsonization 2.Activation of complement 3.Phagocytosis 4.Activation of pro inflammatory signaling pathways 5.Induction of apoptosis TLR(Toll like receptor): They are single, membrane-spanning, non-catalytic receptor usually Expressed on the membranes of leukocytes including dendritic cells, macrophages, natural killer cells, cells of the adaptive immunity (T and B lymphocytes) and non immune cells (epithelial and endothelial cells, and fibroblasts) Recognize structurally conserved molecules derived from microbes. Once these microbes have breached physical barriers such as the skin or intestinal tract mucosa, they are recognized by TLRs, which activate immune cell responses. The TLRs include TLR1, TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR8, TLR9, TLR10, TLR11, TLR12, and TLR13, though the last three are not found in humans. TLR's received their name from their similarity to the protein coded by the toll gene identified in Drosophila in 1985 by Christiane Nüsslein-Volhard and Eric Wieschaus. Structure: Exterior – Leucine-rich repeats; Interior – TIR (Toll-IL-1 Receptor) domain Can form heterodimer Differential signaling through dendritic cell PRRs influences helper T cell functions. Nucleotide-binding oligomerization domain-like receptors (NLRs)/NOD- Like Receptors (NLRs) Cytosolic PRRs Recognized –  PAMPs & DAMPs  Stress/ Damage signal Similar to the TLRs :linked to signal transduction NLR family : 23 Members Structure  3 Domains  C-terminal Leucine-rich repeat domain (LRR)  Central nucleotide binding & Oligomerization >> NACHT, NOD, NBD  N-terminal Effector binding domain (EBD) >> CARD, PYD, BIR C-Type Lectin Receptors (CLRs) Plasma membrane receptors on monocytes, macrophages, dendritic cells, neutrophils, B cells, and T-cell subsets Recognize carbohydrate components of fungi, mycobacteria, viruses, parasites, and some allergens (peanut and dust mite proteins) Human : 15 CLRs that function as PRRs Most recognize sugar moieties  mannose --> mannose receptor, DC-SIGN  fucose --> Dectin-2, DC-SIGN -  glucans --> Dectin-1 Functions : 1. Signaling 2.Phagocytosis