Innate Immunity Lecture Notes PDF

12/30/24 Immunology I 1  Course details Course name: Basic Immunology Course code: MLTBI-1005|1 Instructor name: Muhammad Imran Lecturer Innate Immunity  Le...

12/30/24 Immunology I 1  Course details Course name: Basic Immunology Course code: MLTBI-1005|1 Instructor name: Muhammad Imran Lecturer Innate Immunity  Learning objectives General features of innate immunity Components Barriers Inflammatory mediators Cells Mechanism Ag Recognition Activation Ag Elimination Sana Arshad [DMLS-UoL] Immunology & Serology-I  Innate Immunity Also known as Natural or Nonspecific Immunity 1.exists prior to exposure to the microbe (antigen)” 2.Respond immediately after exposure to microbes 3.does not improve after exposure to the organism 4.innate immune processes have no memory Sana Arshad [DMLS-UoL] Immunology & Serology-I  Components of Innate Immunity 1.Anatomical Barriers: limit entry of microorganisms – Physical – Chemical 2.Humoral(Inflammatory mediators) 3.Cellular Sana Arshad [DMLS-UoL] Immunology & Serology-I  The innate immune system includes anatomical barriers against infection,both physical and chemical as well as cellular responses. Sana Arshad [DMLS-UoL] Immunology & Serology-I  The main physical barriers—the body’s first line of defense—are the epithelial layers of the skin and of the mucosal and glandular tissue surfaces connected to the body’s openings; Sana Arshad [DMLS-UoL] Immunology & Serology-I  these epithelial barriers prevent infection by blocking pathogens from entering the body. Chemical barriers at these surfaces include specialized soluble substances that possess antimicrobial activity as well as acid pH Sana Arshad [DMLS-UoL] Immunology & Serology-I  Pathogens that breach the physical and chemical barriers due to damage to or direct infection of the epithelial cell layer can survive in the extracellular spaces or they can infect cells. Sana Arshad [DMLS-UoL] Immunology & Serology-I  The cellular innate immune responses are rapid, typically beginning within minutes of invasion. These responses are triggered by cell surface or intracellular receptors that recognize conserved molecular components of pathogens. Sana Arshad [DMLS-UoL] Immunology & Serology-I  Some white blood cell types (macrophages and neutrophils) are activated to rapidly engulf and destroy extracellular microbes through the process of phagocytosis Sana Arshad [DMLS-UoL] Immunology & Serology-I Components Effectors Functions Physical 1.Skin To limit microbial entry 2.Mucous Membranes into the body 3 Respiratory Cilia Chemical Temperature, To limit spread and Acidic pH, replication of pathogens Lysozymes in tears and Bacterial cell wall secretions destruction Defensins (cationic Create pores in Other barriers peptide) membrane Normal flora of Occupy receptors, Throat, colon prevents colonization by 2.Inflammatory and vagina pathogen Mediators Complement Direct lysis of pathogen or Sana Arshad [DMLS-UoL] infected cells. Immunology & Serology-I Components Effectors Functions Inflammatory Cytokines and Activation of other Mediators Interferons immune Components. Acute-phase Mediation of proteins and response lactoferrin Leukotrienes and Vasodilation and Prostaglandins increased vascular Permeability. Cellular Polymorphonuclear Phagocytosis and components cells intracellular Neutrophils, destruction of Eosinophils microorganisms Basophils, Mast cells Sana Arshad [DMLS-UoL] Immunology & Serology-I Components Effectors Functions Cellular Mononuclear 1.Phagocytosis components Phagocytic-cells 2.Presentation of 1.Monocytes and foreign antigen macrophages to lymphocytes 2.Dendritic cells 3.Cytokine production Sana Arshad [DMLS-UoL] Immunology & Serology-I  Mechanisms of Innate Immunity Ag Recognition Activation Ag Elimination Interaction with Acquired Immunity Sana Arshad [DMLS-UoL] Immunology & Serology-I  Ag Recognition Receptors Pattern Recognition receptors (PRR) recognize pathogen associated molecular pattern(PAMP) Exist in Two forms: Cellular extra cellular Sana Arshad [DMLS-UoL] Immunology & Serology-I 1.Cellular Cell-surface associated Intra- cellular 2.Extra-cellular Soluble in plasma/other body fluids Sana Arshad [DMLS-UoL] Immunology & Serology-I  Cellular receptor 1.Receptors on the surface of cell Toll-Like receptor Mannan Binding Lectin Receptors 2.Receptors in the cytoplasm nucleotide-binding oligomerization domain(NOD) receptors RIG-1 helicase receptor Sana Arshad [DMLS-UoL] Immunology & Serology-I  Toll-like receptors Found on the surface of three types of cell Macrophages Dendritic cells Mast cells Mechanism: 1.TLRs recognize various microbial components Sana Arshad [DMLS-UoL] Immunology & Serology-I 2.activate transcription factor 3.Synthesis of many pro-inflammatory cytokines, which determine the immune response 1.Cell mediated 2.Humoral Sana Arshad [DMLS-UoL] Immunology & Serology-I  Mannan Binding Lectin Receptors Many bacteria and yeast have polysaccharide called mannan on their surface. MBL bind to mannan which activates complements, resulting in the death of the microbe. MBL also act as opsonin, which enhance phagocytosis. Sana Arshad [DMLS-UoL] Immunology & Serology-I  Intracellular receptors The nucleotide-binding oligomerization domain receptors in short NOD receptors Located in the cytoplasm of Macrophages Dendritic cells Epithelial cells Recognize peptidoglycan. Sana Arshad [DMLS-UoL] Immunology & Serology-I  Intracelular receptors: RIG-1 helicase Recognize nucleic acids of viruses e.g. Orthomyxovirus, Paramyxovirus, Rhabdovirus synthesize duoble-stranded RNA during replication which are recognized by RIG-1 helicase receptors Sana Arshad [DMLS-UoL] Immunology & Serology-I  Soluble Receptors/Molecules Complement MBP C-reactive Protein Immunoglobulins (Adaptive Immunity) Sana Arshad [DMLS-UoL] Immunology & Serology-I  Receptors for Soluble Molecules Don’t recognize pathogen directly Recognize soluble molecules bind to whatever Types: 1. Receptors for C-components 2. Receptors for CRP, Fibronectin 3. Receptors for Fc part of IgG 4. Receptors for Self MHC-I Sana Arshad [DMLS-UoL] Immunology & Serology-I  Activation Exposure to antigen Ligation through TLRs and other receptors Ligation through opsonins Cytokines Sana Arshad [DMLS-UoL] Immunology & Serology-I  Ag Elimination Depend on component Phagocytes: Phagocytosis and Intracellular Killing Non-phagocytes: Extracellular Killing Sana Arshad [DMLS-UoL] Immunology & Serology-I  Humoral components: Different; opsonization, neutralization, direct killing etc. Sana Arshad [DMLS-UoL] Immunology & Serology-I Phagocytosis and Intracellular Killing Binding through receptors Internalization (Phagosome formation) Phagosome lysosome fusion Killing Sana Arshad [DMLS-UoL] Immunology & Serology-I macrophage Sana Arshad [DMLS-UoL] Immunology & Serology-I Phagocytosis phases Sana Arshad [DMLS-UoL] Immunology & Serology-I  Cellular Components of Innate Immunity Neutrophils/PMN: Characteristic nucleus cytoplasm Granules Phagocytosis Inflammation Intracellular killing Tissue damage CD66 Sana Arshad [DMLS-UoL] Immunology & Serology-I Mononuclear Mononuclear Phagocytes Phagocytes  activated by bacterial LPS,peptidoglycan bacterial DNA and cytokines (gamma ineterferon)  antigen presentation for specific immune response  CD14 membrane marker  adhere to plastic and glass surfaces Sana Arshad [DMLS-UoL] Immunology & Serology-I  Dendritic Cells Covered with long membranous extensions Descendants of the myeloid line Langerhans cells → skin and mucous membranes Interstitial cells → major organs e.g. heart Phagocytose antigen and present it to T cells (APCs.) After capturing antigen, migrate to the blood and to lymphoid organs Sana Arshad [DMLS-UoL] Immunology & Serology-I Natural Natural Killer Killer cells cells  large largegranular granularlymphocytes lymphocytes (LGL) (LGL)  kill killinfected infected&&malignant malignantcell cell  Killing Killingisisnon nonspecific specificand andnot not dependent dependenton onMHC MHCI,MHC I,MHCIIII  Produce ProduceGamma Gammainterferon interferon which whichactivate activatemacrophages macrophages  activated activatedby byIL2 IL2and andIFN-γ IFN-γ  identified identifiedby byCD56 CD56&&CD16 CD16and and absence absenceof ofCD3 CD3 Sana Arshad [DMLS-UoL] Immunology & Serology-I  Lymphokine Lymphokine Activated Activated Killer Killer (LAK) Cell (LAK) Cell IIFF NN kills kills transformed malignant and malignant IL22 IL cells cells Sana Arshad [DMLS-UoL] Immunology & Serology-I  Other Cells Basophils Eosinophil Mast Cells Platlets Sana Arshad [DMLS-UoL] Immunology & Serology-I Sana Arshad [DMLS-UoL] Immunology & Serology-I  Learning outcomes After this lecture the students will be able to understand General features of innate immunity Components Barriers Inflammatory mediators Cells Mechanism 1 4 1 2 / 3 0 / 2 4  References W.Lavinson.,E, Jawetz. 10th edition. 2008. Review of Medical Microbiology and Immunology  Thank you 12/30/24 Immunology I 43