Immunity 2022.pdf

Immunity Mahinda Kommalage MBBS, PhD Department of Physiology  ILOs Student should be able to 1. explain the term immunity. 2. classify the immune mechanisms. 3. state the components of immune system. 4. name the structures / mechanisms of innate immunity 5....

Immunity Mahinda Kommalage MBBS, PhD Department of Physiology  ILOs Student should be able to 1. explain the term immunity. 2. classify the immune mechanisms. 3. state the components of immune system. 4. name the structures / mechanisms of innate immunity 5. define the terms – antigen, antibody 6. list antigen presenting cells. 7.describe the role of macrophage in immune response. 8.describe the role of lymphocytes in immune response. 9. list the different subtypes of lymphocytes and describe their functions. 10. describe briefly the role of complement system in immune response. 11. explain following different types of immune responses - primary and secondary immune responses AND humoral and cellular immune response. Immune System Defenses against bacteria, viruses, fungi, parasites and foreign (non-self) macromolecules. Nonspecific (innate) immune – no activation by antigen specific manner. Specific (acquired) immune - activation of antigen - specific T and B lymphocytes.  Immune response Non-specific (innate) Phagocytes (neutrophils, Macrophages/monocytes) and eosinophils, Macrophages Lysozyme, Interferons and complement. Specific (adaptive) lymphocytes - T cells & B cells Immunoglobulin (Ab) Cytokines  Non-specific Immunity Anatomical barriers. Secretary molecules. Cellular component.  Anatomical barriers Mechanical factors The epithelial surfaces The skin Movement of cilia or peristalsis  Anatomical barriers Chemical factors Fatty acids in sweat inhibit the growth of bacteria Lysozyme and phospholipase in tears, saliva & nasal secretions. Biological factors The normal flora of the skin & GIT  Physico-chemical barriers to infections System/Organ Active Effector Mechanism component Skin Squamous Desquamation; flushing, organic acids cells; Sweat GI tract Columnar cells Peristalsis, low pH, bile acid, flushing, thiocyanate Lung Tracheal cilia Mucocialiary elevator, surfactant Nasopharynx and eye Mucus, saliva, Flushing, lysozyme tears Circulation and lymphoid Phagocytic cells Phagocytosis and intracellular killing organs NK cells and K- Direct and antibody dependent cytolysis cell IL2-activated cytolysis LAK Serum Lactoferrin and Iron binding Transferrin Interferons Antiviral proteins TNF-alpha antiviral, phagocyte activation Lysozyme Peptidoglycan hydrolysis Fibronectin Opsonization and phagocytosis Complement Opsonization, enhanced phagocytosis, inflammation  Cells in non-specific Immunity Phagocytes (neutrophils, Macrophages/monocytes) and eosinophils Natural killer cells (NK cells) Cell can migrate into the tissues and act on pathogen.  Cells in non-specific Immunity Neutrophils – phagocytose invading organisms and kill them intracellularly. Macrophages – Tissue macrophages and newly recruited monocytes. Natural killer (NK) and lymphokine activated killer (LAK) cells –non-specifically kill virus infected and tumour cells. Eosinophils –have proteins in granules that are effective in killing certain parasites. Phagocytose  Qualities of these cells Chemotaxis - are attracted by various cytokines (eg. IL-8). Margination – Adhesion onto the endothelium.  Qualities of these cells Diapedesis – penetrate the endothelium. Engulf & damage the organism. Digestion/lysis of the microorganism with the aid of lysosomal enzymes.  Macrophage Macrophage phagocytes most invading organism – partly digest. Antigenic products are inside cytosol. Antigen pass to lymphocyte by cell to cell contact. In additionally, secrete Interleukin-I - promote growth of specific lymphocyte.  Substance important for nonspecific immune Cytokines- Interferons, Interlukin Complement Pathogen-associated molecular patterns (PAMPs) in bacteria/virus are recognized by pattern-recognition receptors (PRRs) in innate immune cells and that play a key role in innate immunity. Specific immunity Immunity target the antigen Two types Humoral (B cells) Cell mediated (T cells)  What is antigen? Each toxin or organism contain chemical compound its makeup. Can initiate acquired immunity. Most of them are large polysaccharides. With higher molecular weight - >8000  Lymphocytes For adaptive (specific) immunity. Types B cells T cells  Lymphoid tissues Primary lymphoid tissue - Bone marrow and thymus are primary lymphoid tissues. Development and maturation occur Secondary/Peripheral lymphoid organs Mature lymphocytes act against pathogens Lymph nodes, spleen, tonsils, mucosal lymphoid tissues such as Peyer's patches etc Humoral immunity Soluble mediators Antibodies Cytokines Complements (important in both innate and adoptive immune response)  Lymphocyte clones Antigen is recognized by immunoglobulin on B cells surface and the antigen-specific receptors (TCR) of T cells surface. When antigen contact with lymphocyte only certain lymphocyte activate. Activated B and T lymphocytes are highly specific for targeted antigen. Lymphocyte that can produce one B and T specific cells – clone of lymphocytes Millions of different lymphocytes store in bone marrow capable of producing highly specific B lymphocyte and T lymphocytes.  Activation of a clone Each B cell has about 100,000 antibody molecules in the surface. Each react only When high specific antigen contact with them. Then activate long process of producing highly specific antibody. In T cell, same happen – has surface receptor proteins.  Antigen presenting to T cells T cells recognize only antigens that are displayed on cell surfaces. But most viruses or intracellular bacteria or their products are inside the cells. T cells can detect the presence of intracellular pathogens because infected cells display on their surface peptide fragments derived from the pathogens' proteins. These foreign peptides are delivered to the cell surface by specialized host-cell glycoproteins, the MHC molecules  Antigen presenting to T cells n presenting Peptides from the cytosol are bound to MHC class I molecules and are recognized by CD8 T cells Peptides generated in vesicles are bound to MHC class II molecules and are recognized by CD4 T cells Finally produced cytotoxic T cells Antigen presenting Antigen presenting cells include dendritic cells, macrophages, Langerhans cells and B cells.  Memory cells Few lymphoblast form by activating B- lymphocyte clone make different B- lymphocyte – memory cells. Dormant like original clone. When there is next expose they activate very quickly and overcome antigen. Primary & secondary immune responses.  Primary immune response  Responding cell is new B-cell and T-cell  Lag phase is often longer  First antibody produced is mainly IgM  Amount of antibody produced depends on nature of antigen  Usually produced in low amount.  Antibody level declines rapidly.  Affinity of antibody is lower for its antigen.  Secondary immune response  Responding cell is memory cell  Lag phase is shorter  Mainly IgG antibody is produced  More antibodies are produced  Antibody level remain high for longer period (two doses of immunization!)  Antibodies have greater affinity for antigen Antibodies (Ab)/(Immunoglobulins – Ig) - by B cells  T lymphocytes T lymphocytes of a specific lymphocyte clone proliferate with exposure of antigen. Release large numbers of activated, specifically reacting T cells. Circulate in the body. T-lymphocyte memory cells are formed.  Cytokine Proteins/peptids, glycoproteins Released by cells such as Macrophage, dendritic cells, lymphocyte etc. Affect behaviour of other cells Responsible for inflammation/cell division/cell growth/cell death etc. Red ‘cytokine storm’ of COVID19, IL-6, IL-8 and TNF (IL-6 blocking drugs – tocilizumab use to treat in COVID) COVID 19 disease progress  Cytokine 1. interferon (IFN) Produced by virally infected cells and T cells Help to prevent spread of viral infection 2. Interleukins (IL) 3. Colony stimulating factors (CSF) 4. Tumor necrosis factors (TNFs)  Complements  A group of over 30 serum proteins  Control inflammation and many other functions  Most of the proteins are normally inactive.  In response microorganisms they become activated in an enzyme cascade.  Classic pathway, and alternative pathway to activate.  Important for both innate and acquired immune response – (bridge between two systems). Thanks