LECOM Pharmacy School BMS/PDA II-Immun 1 PDF

LECOM-Pharmacy School BMS/PDA II-Immun 1 Overview of the Immune System Dr. Saber Hussein  Why immunology for pharmacists? Pharmacists as healthcare providers must understand the human body and what keeps it healthy and what causes its disease Pharmacists might provide vaccines. T...

LECOM-Pharmacy School BMS/PDA II-Immun 1 Overview of the Immune System Dr. Saber Hussein  Why immunology for pharmacists? Pharmacists as healthcare providers must understand the human body and what keeps it healthy and what causes its disease Pharmacists might provide vaccines. Therefore you must know how immunization works Immunology helps understand mechanisms of action of some drugs such as: – monoclonal antibodies – cytokine analogs or antagonists – immunosuppressants – immune modulating drugs  Overview of the Immune System 1. Innate immunity 2. Adaptive immunity: 1. Humoral and 2. Cell-mediated immunity 3. Properties of adaptive immunity: 1. Specificity and 2. memory 4. Phases of the immune response 5. Cells of the immune system: Lymphocytes, antigen- presenting cells, effector cells 6. Tissues and organs of the immune system: Peripheral lymphoid organs, lymphocyte circulation  Learning Objectives 1. Know the protective role of the immune system 2. Differentiate between the adaptive (acquired) and the innate immunity 3. Know the fundamental role of the discrimination between self and nonself in the work of the immune system 4. Know the major branches of the immune system: the humoral and the cell-mediated immune response 5. Have an idea about the benefits and the harmful effects of the immune system 6. Recognize genetic recombination as a basis of the diversity of the immune response 7. Know that the immune system is usually regulated up and down  Protective role of the immune system Immune system evolved to protect us against: – Intra- and extracellular bacterial infections – Viral infections: Always intracellular – Fungal infections: Extracellular – Parasitic infestation: Some unicellular protozoa such as malarial parasites, Plasmodium species, are intracellular but most are large, extracellular and even lumen dweller – Malignant cells Intracellular pathogens live inside host’s (patient’s) cells Extracellular pathogens live outside host’s cells  Innate Immunity Synonyms: – Natural – None-adaptive – Nonspecific Cells involved: – All white blood cells except B and T lymphocytes – Phagocytes Monocytes (mono[nuclear leuko]cytes)/macrophages PMN (polymorphonuclear leukocytes)- Granulocytes esp. neutrophils, but include basophils and eosinophils – Natural killer (NK) cells Humoral or soluble components – Complement system Exterior defenses – Skin, Stomach acidity, Mucus, Cilia, Microflora, Lysozyme in tears, Flushing of urinary tract by urination Exterior Innate Defenses  Lysozyme Mechanism of Action More defining names: Muramidase N- acetylmuramide glycanohydrolase Glycoside hydrolase Lysozyme cleaves – peptidoglycan GlcNAc (β 1→4) MurNAc repeat linkages (NAG-NAM) in the cell walls of bacteria and the – GlcNAc (β 1→4) GlcNAc (poly-NAG) in chitin, found in the cells walls of certain fungi  Adaptive (Acquired) Immunity Develops in response to microorganisms and other foreign antigens (Ags) Anamnesis (recall to memory) – Improves after each encounter with the Ag ➔ has a memory Antibodies (Abs) = Immunoglobulins (Ig): – IgA, IgG, IgM, IgE, IgD Lymphocytes: – B cells – T cells  Antibody: A flexible adaptor Abs specific binding sites of the Fab region bind Ags – As with microbe 1 No specific Ag → No Ag binding – As with microbe 2 V C L chain The Fc region of the Ab Papain binds Fc receptors on H chain some cells such as phagocytes The Ag-Ab complex can activate the complement system via the Fc of the Ab  Phases of the Immune Response Recognition of Ag: – Naïve B lymphocytes recognize certain types of Ags – Naïve T lymphocytes recognize peptides presented by Ag presenting cells (APC) – Clonal expansion Activation phase – Differentiation: B cell → Ab producing cell T cell → Effector T cell Effector phase – Elimination of Ags by: Humoral immunity Cell-mediated immunity Decline (homeostasis) ➔ Apoptosis Memory ➔ Surviving memory cells  Active & Passive Immunization Active immunization – is acquired in response to Ag administration All vaccinations Passive immunization – acquired through administration of Ab from immunized individual Hepatitis A Anti-rabies treatment Anti-tetanus Adoptive transfer: – Transfer of immunity by transplantation of immunocompetent cells E.g. bone marrow transplant  Self and Nonself Discrimination between self and nonself Ags is fundamental for the function and evolution of the immune system This is the basis of immune response against pathogens and transplant rejection Self fanaticism – Reacting against foreign Ag because it is foreign – Not based on beneficial or harmful Ag  Humoral and Cell-mediated Immunity Acquired humoral (soluble) immunity is based on Abs made by B cells Complement and cytokines may be considered part of the humoral immunity Acquired cell-mediated immunity depends on T helper cells (TH) and cytotoxic T cells (Tc; CTL = cytolytic T lymphocytes) Other leukocytes participate in cellular immunity: – Phagocytes, – Macrophages, – Natural killer cells (NK)  Complement is a system of serum Complement proteins that interact with one Functions another and with other molecules to generate important effects 1. Lysis The complement system has an intrinsic ability to lyse the cell membranes of many bacterial species 2. Chemotaxis Complement products released in this reaction attract phagocytes to the site of the reaction 3. Opsonization Complement components coat the bacterial surface allowing the phagocytes to recognize the bacteria and engulf them  Cells of the Immune System Lymphocytes – T helper cells (TH) – Cytotoxic T cells (Tc) – B cells – NK PMNs – Neutrophil – Basophil & Mast cells – Eosinophil Monocytes – Dendritic cells – Macrophages Cells involved in the immune response Hematopoiesis Functions of Lymphocytes  Major histocompatibility complex (MHC) MHC is called HLA or human lymphocytes Ag Two classes: I & II Important in presenting Ags to the TH and TC cells – MHC I presents Ag peptides to TC – MHC II presents Ag peptides to TH  Cytokines Small peptides, synthesized by different cells involved in the immune system They are regulators: activate cells or inhibit cell functions Major means of communication among cells of the immune system and between them and others Examples: – Interleukins IL-2 IL-4 – Interferons IFNα IFNγ  Clonal Selection Theory 1. T and B cells exist with almost unlimited specificities before any contact with foreign Ags 2. Ag-specific receptors that recognize foreign Ags: 1. Abs are the B cell receptors on the surface of B cell & 2. T-cell receptor (TCR) on T cell 3. Each lymphocyte has a single specificity 4. The antigenic determinant (epitope) on the Ag binds with lymphocyte (B or T) and triggers their differentiation and proliferation 5. Negative selection by self Ags ➔ shut off cells that recognize them during maturation Clonal Selection  Benefits of the Immune System Immunization and defense against infectious disease Cancer detection and management A benefit of immunology (application): – Organ transplantation and blood transfusion  Harmful Effects of the Immune System Hypersensitivity or allergic reactions: – Type I: immediate hypersensitivity – Type II: Ab-mediated reactions – Type III: immune complex Ab-mediated – Type IV: delayed-type cell-mediated Autoimmune diseases – The immune system attacks body’s own Ags causing diseases like rheumatoid arthritis, diabetes mellitus and systemic lupus erythematosus Immunodeficiencies – Occur when one or more components of the immune system fail to function properly – This can be result of genetic defect (SCID) or acquired (AIDS) Graft rejection – Occurs because of immune response against transplant’s Ags  Genetic Recombination & Immune Response Diversity Antigenic specificities might exceed 106-107 One gene, one polypeptide theory – Do we need 107 genes to generate diversity of immune specificity? – Of course Not Instead, Genetic recombination occurs within a gene that encodes the Ig proteins Basic Ab composed of 2 types of polypeptides, each chain has a variable domain: – H-chain – L-chain Recombination in the variable domains of Ig and TCR generates Ab & T cell receptor (TCR) specificity Regulation of the immune system Why regulation? Immune response ➔ proliferation and increased synthesis of specific molecules that will not be useful after their job is finished (infection ➔ response ➔ cure) Homeostasis or equilibrium must be established by shutting down the system Deregulation of the immune system has severe consequences – Immune response to self Ags ➔ Autoimmunity