Introduction to Immune System and Innate Immunity PDF

Introduction to immune system and innate immunity Dr. Zahraa A Mohammed 2024undergraduate  Lecture outlines 1- General concepts of immune system 2- The types of immunity 3- Properties of innate immune system 4- mechanisms of innate immune system  Introduction to immune syste...

Introduction to immune system and innate immunity Dr. Zahraa A Mohammed 2024undergraduate  Lecture outlines 1- General concepts of immune system 2- The types of immunity 3- Properties of innate immune system 4- mechanisms of innate immune system  Introduction to immune system Function of system The daunting role of the immune system is to afford protection. It is designed to recognize and immun respond to non-self antigen in a coordinated manner. Additionally, cells that are diseased, damaged, distressed or dying are recognized and eliminated by the immune system. To accomplish this goal, the immune system is equipped with a rapid response mechanism, exquisite specificity, adaptability, an intricate ↑ regulatory network, and memory.  The Immune response 2Areaction generated against a potential pathogenI is called an ( immune response). The immune system is divided into 2 e - complementary arms: 1- Innate Immunity. 2- Acquired Immunity.  & Xrapid response * first response 1- Innate Immunity: ① It is non-specific defenses of the body against ② ③ infections present since birth. It is the first line defense and it is not specific to any particular pathogen rather common to any foreign molecule or antigens. Also, it is immediately functional to fight against the broad range of pathogens and does not require prior exposure ⑪ to the pathogens. Components of innate immunity↳ *Types of innate immunity Anatomical barriers ③ Q ② – Mechanical, chemical, biological Humoral components – Complement, coagulation system, cytokines Cellular components – Neutrophils, monocytes & macrophages, NK cells, eosinophils - Mechanical/physical barriers  Physiological Barriers: 1/skin 2/chemical barriers 1) Skin: Few microorganisms are capable of penetrating intact skin, but many can enter sweat or sebaceous glands and hair follicles and establish themselves there. S Sweat and sebaceous secretions have antimicrobial properties (acid pH and certain chemical substances like fatty acid) Lysozyme : 0 a hydrolytic enzyme present in all mucous secretions including tears, saliva, skin, in respiratory and cervical secretions that can lyse gram positive by E cleaving peptidoglycan layer found in↳ bacterial cell wall - · ② Psoriasin : protein with antibacterial & - properties against E coli produced by -- skin. -  2) Mucous Membrane: In the respiratory tract: ① Bacteria tend to stick to a film of mucous - covers the surface and is constantly being driven upward by ciliated cells toward the natural orifices. ② Types of innat immunity in Lysozymes the respiratory tract ⑤ (chemical barriers). IgA ⑪ The phagocytes. 6 ⑤ Hair at the nares and cough reflex ( special => - protective mechanism) The gastrointestinal tract: ① Saliva contains numerous hydrolytic enzymes. ② Acidity of the stomach. ⑤ Proteolytic enzymes and active MQs in small intestine. Types of chemical barriers in git tract. The most mucous membrane of the body Carry a constant normal microbiota that itself opposes establishment of pathogenic ⑭ microorganisms(“Bacterial ‫يرايلهيتعمل‬mucous mambrane ‫معظم ال‬ ‫بالجسم تحتوي على بيئه بكت‬ interference”)and has important ‫على مهاجمه البكتريا الخارجيه‬ -) physiologic functions. o - - e.g. in the vagina the acid pH is maintained by normal Lactobacilli, inhibiting establishment of yeasts, anaerobes, and Gram-negative bacteria.  components of Innate Immunity The Innate system has both cellular and humoral factors. Cells: Phagocytic leukocytes, such as PMN. Macrophages. NK cells. Innate cellular components Cell Mechanism ② Neutrophils ① Phagocytosis and intracellular killing = - Neutrophils ③ Inflammation and tissue damage ② - Macrophages ① Phagocytosis - and intracellular killing - ③ Extracellular killing of infected or altered self Macrophages targets ⑪ ③Tissue repair - Antigen presentation for specific immune response - NK and LAK cells Killing of virus-infected and altered self targets - Eosinophils Killing of certain parasites * Eosinophils ↑ Alargic reaction The interaction of the invading microbs with -m these cells and other cells throughout the body triggers the release of: Complement. Cytokines. Chemokines. Armed with these tools, the host initiates its defense against the invading pathogens  Humoral components Component Mechanism Complement Lysis of bateria and some viruses Q - ② Opsonin ③ Increase in vascular permeability - - Recruitment and activation of phagocytic cells a Coagulation system Increase vascular permeability ·Recruitment of phagocytic cells - ③ B-lysin from platelets – a cationic detergent - Lactoferrin and Compete with bacteria for iron transferrin - Lysozyme Breaks down bacterial cells walls - Cytokines Various effects S & 1 Six · infaction sois  S ↑ - - 1j ile Pattern recognition reseptor Microbial Sensors: (PRR) When a pathogen enters the skin, it is - confronted with macrophages and other - phagocytic cells possessing “Microbial - sensors”. There are three major groups of microbial sensors: 1) Tool like receptors (TLRs). 2) NOD-like receptors (NLRs). 3) RIG-1 like helicases and MDA-5.  PRR & ess & > % - Pathogen associated molecular patterns(PAMPs): The microbial molecules that stimulate innate immunity ① and present in infectious agents ② Pattern recognition receptors(PRR):The receptors of innate immunity that recognize the structures shared by microbes Damage-associated molecular patterns(DAMPs):The innate immune system recognizes molecules that are released from damaged or necrotic host cells. Example include high mobility group box protein 1(HMGB1)  > first response - TLRs Precognize of immunity (PAMPs) initiating innot immunity. The TLRs are a family of evolutionary conserved pattern recognition receptors (PRRs) that recognize pathogen- associated molecular patterns (PAMPs). They constitute a first line of defense against a variety of pathogens and play a critical role in initiating the innate immune response.  TLRs To date, 10 human TLRs have been identified, and each receptor appears to be involved in the recognition of a unique set of microbial patterns e.g.:  TLR2 recognizes several glycolipids and peptidoglycan that are made by Gram- positive bacteria.  TLR3 engages dsRNA in viral replication.  TLR1 and TLR6 recognize multiple diacyle peptides (e.g. Mycoplasma). TLR4 is specific for Gram-negative lipopolysaccharide (LPS). TLR5 recognizes bacterial protein called flagellin. TLR7 and TLR8 interact with ssRNA in viral replication. TLR9 binds bacterial DNA. TLR10 remains an orphan receptor. ge TLR may found in blasma membrane or in cytoplasm , why? Because of their function if itextracullar or intracullar NOD-like receptors A large family of innate receptors sense DAMPs and PAMPs that are located in the n cytosol of cells and serve as intracellular - sensors for microbial products. They activate the nuclear factor kappa-light chain-enhancer of activated B cells (NF- ҡB) pathway and drive inflammatory responses similar to the TLRs. RIG-1-like helicases (Retinoic acid-inducible gene-1(and MDA-5( melanoma- differentiation- associated gene 5) These are cytoplasmic sensors of viral ssRNA. The engagement of ssRNA with these sensors triggers type 1 IFN production. These IFNs are highly - - effective inhibitors of viral replication. ↓ Function of #Ns  Phagocytosis : During infections, the number of circulating phagocytic cells often increases. The main - functions of phagocytic cells include: ④ ① ② ③ Chemotaxis, migration, ingestion and microbial killing. Microorganisms)y M.Os and other exogenous Ags that enter the lymphatic, lung, or blood stream are engulfed by a variety of phagocytic cells  Phagocytosis involves: 1- Extension of pseudopodia to engulf attach materia. 2- Fusion of the pseudopodia to trap the material in a phagosome. 3- Fusion of the phagosome with a lysosome to create a phagolysosome. 4- Digestion. 5- Exocytosis of digested contents. Mechanism of phagocytosis Phagocytosis A. A. Attachment via receptors B. – FcR, complement R, scavenger R, Toll-like Cytoplasm R (TLR) B. Pseudopod C. extension C. Phagosome formation D. D. Granule fusion and Phagolysosome formation Phagocytosis is the process whereby a phagocytic cells especially the PMN, recognizes the pathogen, ingests it ,and then destroy the engulfed organisms. This is multistep process: Steps of extravasation: Step 1: Rolling. Step 2: Activation by chemoattractants. Step 3: Arrest and adhesion. Step 4: Transendothelial migration.  Antimicrobial mechanisms used by phagocytes ‫امليكانيزم الي تستخدمها ال‬ phagocytes antimicrobial ‫حتى تسوي‬ 1) Acidification occurs within the & - phagosome. The phagosome pH is 3.5-4, - > - and this level of acidity is bacteriostatic or - - bactericidal. 2) Toxic oxygen-derived products are & = generated and include superoxide Oˉ2, hydrogen peroxide H2O2, and singlet oxygen Oˉ2 8 3) Toxic nitrogen oxides. 4) Antimicrobail peptides participate in killing.