Innate Immunity & Antigen-Antibodies PDF

Introduction to the immune system Amal Eissa Saafan [email protected] 0111-657-7840 Amal Eissa second year second semester 5/12/2021 1...

Introduction to the immune system Amal Eissa Saafan [email protected] 0111-657-7840 Amal Eissa second year second semester 5/12/2021 1 2020  Immunity The study of our protection from foreign macromolecules or invading organisms and our responses to them. The immune system A functional system – NOT an organ system ❖ 1.First line Barrier tissues such as the skin Cells that respond rapidly to the presence of the invader. ❖ 2.A second line the specific or adaptive immune system the production of antibodies and cell-mediated responses. Amal Eissa second year second semester 5/12/2021 2 2020  Innate immunity vs Adaptive Immunity Non-specific Immunity Specific Immunity Response is antigen-independent Response is antigen-dependent There is immediate maximal There is a lag time between response exposure and maximal response Not antigen-specific Antigen-specific Exposure results in no immunologic Exposure results in immunologic memory memory System in place prior to exposure to Induced by antigen antigen Lacks discrimination among Shows fine discrimination antigens Amal Eissa second year second semester 5/12/2021 3 2020  Cells of the immune system Amal Eissa second year second semester 5/12/2021 4 2020  1.Cells of the innate immune Monocytes (~5% of WBCs) Big eaters system Migrate into the tissues and become Macrophages a. Phagocytic cells (monocyte/macrophages and PMNs), b. NK cells, c. basophils, mast cells eosinophiles. 2.Cells that link the innate and adaptive immune systems (APC) -Dendritic cells -Macrophages. 3.Cells of the adaptive immune system B and T lymphocytes. Amal Eissa second year second semester 5/12/2021 5 2020  T-lymphocytes B-lymphocytes 1. Name: thymus gland. 1.Name: Bursa fabricus 2. Constitute 70% of total lymphocytes. 2. Constitute 30% of total lymphocytes. 3. Long life span (months or years). 3.short life span (days or weeks). 4.Up on stimulation, they proliferate and 4. Up on stimulation, they proliferate and differentiate into plasma cells producing differentiate into effector T-cells. specific antibody. 5. Have receptors for antigens called T-cell 5.Have receptors for antigens(IgM or IgD) receptor (TCR). called B-cell receptor (BCR). 6. Produce memory cells. 6.Produce memory cells. 7. Form rosettes with RBCs. 7. Have receptors for Epstein-Bar virus. 8. Have cluster of differentiation (CD1-8). 8. No CD. Amal Eissa second year second semester 5/12/2021 6 2020  Organs of the immune system A. Central(primary)lymphoid: bone marrow and thymus. B. Peripheral (secondary) lymphoid: lymph nodes, spleen, mucosa associated lymphoid tissue (MALT), tonsils and Peyer’s patches of the gut. Amal Eissa second year second semester 5/12/2021 7 2020  INNATE (NON-SPECIFIC) IMMUNITY I-Anatomical Barriers : A- Mechanical Factors 5.Coughing 1.Skin Sneezing, blinking 4.The trapping effect of 2. Cilia and peristaltic mucus movement 3.Flushing action of saliva, tears, urine Amal Eissa second year second semester 5/12/2021 8 2020  I-Anatomical Barriers: B- Chemical factors 1-Fatty acids in sweat and 3.Low pH in stomach, 2.Lysozyme and sebacious glands saliva and vagina phospholipase in tears /saliva/nasal secretions 4.Defensin (low Mol Wt 5. Pulmonary surfactants: act as proteins) in lung and intestine ospsonin Amal Eissa second year second semester 5/12/2021 9 2020  I-Anatomical Barriers: C- Biological factors Normal flora – microbes in many parts of the body Normal flora : 1. Secrete toxins as colicin 2.Competes with pathogens for nutrients and space. 3- Make conditions unsuitable for m.o Amal Eissa second year second semester 5/12/2021 10 2020  II- Humoral barriers (secretory molecules) components of Blood Complement proteins Coagulation proteins Cytokines WBCs Amal Eissa second year second semester 5/12/2021 11 2020  1-Complement System Complement proteins: role in innate immune system Complex group of 9 serum proteins (C1 thro’ C9) acting in sequanes. 4.Chemotaxis: C5a 2- Direct lysis of pathogens : C5b-9 3. Facilitates 1- Vasodilatation and phagocytosis increase permeability Amal Eissa second year second semester 5/12/2021 (anaphlatoxins: C3a and C5a12 (Opsonization):C3b 2020  2. Coagulation System Some products of the coagulation system ❑1. increase vascular permeability, ❑2. chemotactic agents for phagocytic cells ❑3.Direct antimicrobial effect. Example: beta-lysin, a protein produced by platelets during coagulation can lyse many Gram positive bacteria. Amal Eissa second year second semester 5/12/2021 13 2020  3. Lactoferrin and transferrin By binding iron ( an essential nutrient for bacteria), limit bacterial growth. Amal Eissa second year second semester 5/12/2021 14 2020  4.Interferons (IFN) Glycoproteins produced by virus infected cells “Interfere” with virus replication Warn the neighbouring cells that a virus is around... It is one of the cytokines family Mechanism: They stimulate the synthesis of translation inhibition proteins, so inhibit viral spread. Inhibition of They are non-specific with respect to what virus host protein they can inhibit. synthesis They are species-specific There are 3 types of interferon, 1. Alpha interferon produced by leukocytes; 2.Beta produced by fibroblast-epithelial cells 3.Gamma interferon produced by T-cells and is the only one that is specifically 5/12/2021 Amal Eissaproduced second year second semester 15 2020  5. Interleukin-1 (IL-1) Small proteins – secreted by cells of the immune system Affect the behaviour of other cells Key players in innate and acquired immunity 1. Induces fever (endogenous pyrogen) 2.Production of acute phase proteins, 3.Antimicrobial because they can opsonize bacteria. Amal Eissa second year second semester 5/12/2021 16 2020  6. Acute phase proteins C-reactive protein (CRP) : β-globulins produced by liver : enhancing the opsonization Enhance cidal action of complement. Amal Eissa second year second semester 5/12/2021 17 2020  7. Basic polypeptides Derived from cells during infection. Include spermine and spermidine that kill tuberculosis. Destroy bacteria through the ability of the NH2 group which reacts non-specifically with acidic substances found in bacteria. Amal Eissa second year second semester 5/12/2021 18 2020  C. Cellular Barriers to Infection 1. Neutiophils (Microphages, PMN) Phagocytic cells Produce inflammatory and immune mediators. 2. Monocytes ( Macrophages) Monocytes in blood and macrophages in tissues. Phagocytic, APC Amal Eissa second year second semester 5/12/2021 19 2020 3. Natural killer cells(LGL) Not B-lymphocytes / T-lymphocytes Kill virus /bacteria infected cells (Intracellular pathogens) Kills cancer cells lymphokine activated killer (LAK) cells: NK cells on exposure to IL-2 and IFN-gamma become LAK cells. Amal Eissa second year second semester 5/12/2021 20 2019  4. Eosinophils Produce inflammatory and immune mediators participate in hypersensitivity reaction. 5. Basophils (in connective tissue mast cells): produce inflammatory mediators participate in hypersensitivity reaction. 6. Killer (K) cells: ❖not a morphologically distinct type of cell. ❖any cell that mediates antibody-dependent cellular cytotoxicity 5/12/2021 (ADCC). Amal Eissa second year second semester 2020 21  Phagocytosis Amal Eissa second year second semester 5/12/2021 22 2020  Inflammation Macrophages release cytokines (IL-1) and tumor necrosis factor-α (TNF- α), prostaglandins and leukotrienes. Increased blood supply to the infected area. Increased capillary permeability. Infiltration of leukocytes especially microphages and macrophages outside the blood vessels. Chemotaxis. Amal Eissa second year second semester 5/12/2021 23 2020  Immunogens / Antigens Amal Eissa second year second semester 5/12/2021 24 2020  Immunogens and antigens Immunogen : a substance that induces an immune response [i.e. a humoral (antibody response) or cell-mediated immune response] Immune response generator Antigen: any substance that binds to an antibody (or a T-cell receptor) Though the two terms are used interchangeably – there are differences between the two Amal Eissa second year second semester 5/12/2021 25 2020  Haptens Haptens are small molecules which are non-immunogenic, never induce an immune response by themselves. But when coupled to a carrier molecule. Haptens have the property of antigenicity but not immunogenicity Amal Eissa second year second semester 5/12/2021 26 2020  Epitopes Epitope: the portion of an antigen that is recognized and bound by an Ab or a T Cell receptor One protein may have multiple antigenic determinant. Antibody: It is a specific protein which is produced in Amal Eissa second year second semester 5/12/2021 27 response to an immunogen and 2020 which reacts with an antigen.  FACTORS INFLUENCING IMMUNOGENICITY A. Contribution of the Immunogen ❖ 1.Foreignness: The immune system normally discriminates between self and non-self. Normally, the body is tolerant to its own components and does not initiate an immune response against them. ❖ 2.Size: Bigger>Smaller Amal Eissa second year second semester 5/12/2021 28 2020 ❖ 3.Chemical composition: More complex- more immunogenic Proteins > polysaccharides ❖ 4.Physical form: Particulate> Soluble ❖ 5.Degradability: Antigens that are easily phagocytosed are more immunogenic Amal Eissa second year second semester 5/12/2021 29 2020  FACTORS INFLUENCING IMMUNOGENICITY B. Contribution of the biological system ❖ Genetics Difference across species (interspecies) Differences within a species (intraspecies) Genetics ❖ 2.Age. Extreme of age Amal Eissa second year second semester 5/12/2021 30 2020 FACTORS INFLUENCING IMMUNOGENICITY C. Method of Administration 1. Dose: Amount of dose of antigen (Too high, too low) The number of doses administered. 2. Route: S.C route is more than the I.V or intragastric routes. Why???? IV carried to the spleen S.C carried to lymph nodes 3. Adjuvant: Substances that can enhance the immune response to an immunogen. The mechanisms of action: 1- Prolongation of antigen persistence. 2-Facilitate uptake into APC. Amal Eissa second year second semester 5/12/2021 31 2020  CLASSIFICATION I OF ANTIGENS A. Thymus-independent Antigens: directly stimulate the B cells to produce antibody without the requirement for T cell help. B. Thymus-dependent Antigens: Do not directly stimulate the production of antibody without the help of T cells. Amal Eissa second year second semester 5/12/2021 32 2020  CLASSIFICATION II OF ANTIGENS A. Bacterial Antigens: a-Soluble antigens e.g. exotoxins, enzymes. b-Cellular antigens e.g. capsular, flagellar. B.Viral antigens: a-Protein coat viral antigens. b-Soluble antigens e.g. soluble nucleoproteins. C.Human tissue antigens (isoantigens): a-Blood group antigens. b-Histocompatibility antigens. D. Superantigens: Antigens which activate a large fraction of the T cells. Examples: Staphylococcal enterotoxins (food Amal Eissa second year second semester poisoning). 5/12/2021 2020 33  CLASSIFICATION III OF ANTIGENS a.Isoantigens (alloantigen) is an antigen in an individual of one species which is capable of produce an immune response in different individual of the same species.Rhesus. b. Heterophile antigens: Antigens which share the antigenic determinants (identical or similar), and antibody formed to any of them could react with the other(cross reaction). Rheumatic fever. c. Hetero-antigen is an antigen derived from one species which capable of stimulating an immune response in another species. d. Auto-antigen: is self-antigen (normal constituent of the body tissue). Amal Eissa second year second semester 5/12/2021 34 2020