14. IMMUNITY SYSTEM.pptx

IMMUNITY SYSTEM LECTURE NO. CONTENTS  Definitions  Differentiate between the concepts of “Innate” and “Adaptive” immunity  Cells and tissues of the immune system  WHAT IS THE IMMUNE SYSTEM?  The body’s defence against disease causing organisms, malfunctioning cells, a...

IMMUNITY SYSTEM LECTURE NO. CONTENTS  Definitions  Differentiate between the concepts of “Innate” and “Adaptive” immunity  Cells and tissues of the immune system  WHAT IS THE IMMUNE SYSTEM?  The body’s defence against disease causing organisms, malfunctioning cells, and foreign particles  IMMUNITY  Immunity refers to protection against infection.  The Immune System is the collection of cells, tissues and molecules that functions to defend us against infectious microbes.  The coordinated reaction of the immune system against infections (and other foreign substances) is known as the Immune Response. CONTINUED:  Abnormalities of the immune system that result in defective immune responses make individuals susceptible to infections by viruses, bacteria, fungi and parasites.  Many common diseases are caused by uncontrolled or excessive immune responses.  E.g. rheumatic fever, asthma, glomerulonephritis, inflammatory bowel disease and autoimmune thyroiditis and multiple sclerosis.  INNATE AND ADAPTIVE IMMUNITY  INNATE (present before birth, “NATURAL, NATIVE”).  ADAPTIVE (developed by exposure to pathogens, “ACQUIRED, SPECIFIC”).  INNATE IMMUNITY  Innate immunity is mediated by cells and proteins that are always present and ready to fight against microbes (hence, “innate”), and are called into action immediately in response to infection.  immediate response  Non specific  COMPONENTS OF INNATE IMMUNITY  Four major components of innate immunity are: 1. Epithelial barriers of the skin, GI tract and respiratory tract, which prevent microbe entry (and have to be breached for a microbe to establish infection, e.g. by cuts and burns); 2. Phagocytic leukocytes (neutrophils and macrophages); 3. A specialized cell type called the natural killer (NK) cell; and 4. Several circulating plasma proteins, the most important of which are the proteins of the complement system (about which we will hear more later).  ADAPTIVE IMMUNITY  Adaptive immunity is normally silent, and responds (or “adapts”) to the presence of infectious microbes by becoming active, expanding, and generating potent mechanisms for neutralizing and eliminating the microbes.  Slow response  Highly specific  COMPONENTS OF ADAPTIVE IMMUNITY  The components of the adaptive immune system are lymphocytes and their products.  There are two types of Adaptive immunity 1. Humoral immunity: antibodies produced my B lymphocytes. 2. Cell-mediated (or cellular) immunity: direct cellular reactions to antigens mediated by T lymphocytes CONTINUED:  Antibodies provide protection against EXTRACELLULAR microbes in blood, mucosal secretions and tissues. T lymphocytes provide defence against intracellular microbes.  Their action is direct killing or by activating CONTINUED:  Inflammation is an example of Innate and Adaptive immunity.  The cells of innate and adaptive immunity are recruited to sites of infection and injury, and activated to get rid of the infectious agents and dead tissues. SECOND LINE OF DEFENSE  CELLS AND TISSUES OF THE IMMUNE SYSTEM  All the cells of the immune system develop from precursors in the bone marrow,  after which they circulate in the blood and live in lymphoid organs (lymph nodes, spleen, tonsils)  in almost all the tissues of the body.  They can rapidly migrate to any site of infection, where they are needed.  WHITE BLOOD CELLS (LEUKOCYTES) If invaders actually get within the body, then your white blood cells (WBCs) begin their attack Among circulating WBCs, the major phagocytes are neutrophils and monocytes.  PHAGOCYTES  They ingest and destroy microbes, other injurious agents, and one’s own dead and damaged cells.  Neutrophils respond rapidly to foreign stimuli and to injury; their reaction is part of acute inflammation.  When blood monocytes enter tissues, they mature, and are called macrophages.  These cells are present under epithelia, in connective tissues, and in all organs.  Macrophages respond more slowly than do neutrophils but for longer times; this reaction is typical of chronic inflammation.  Macrophages also help to repair damaged tissue.  LYMPHOCYTES  The most important cells of adaptive immunity are lymphocytes.  Present in the circulation and various lymphoid organs.  About 10¹² lymphocytes are present in human  Each T or B lymphocyte expresses receptor for a single antigen  Each lymphocyte has a unique DNA rearrangement. CONTINUED:  B lymphocytes (so called because they mature in the bone marrow) secrete proteins called antibodies, which bind to and eliminate extracellular microbes.  T lymphocytes (which mature in the thymus) function mainly to fight with microbes that are living inside cells (where they are inaccessible to antibodies)  TYPES OF T-LYMPHOCYTES  There are two main types of T lymphocytes: 1. HELPER T CELLS: CD4+ T cells “help” B lymphocytes by secreting soluble molecule CYTOKINES to make the most effective antibodies and “help” macrophages to kill ingested microbes, 2. CYTOTOXIC (CYTOLYTIC) T LYMPHOCYTES (CTLS): CD8+ T cells directly kill infected host cells and thus serve to eliminate reservoirs of infection.  CONTINUED:  A third, small population of lymphocytes is called “regulatory T cells” because they control immune responses and prevent inappropriate reactions. There are several other small populations of lymphocytes.  These various types of lymphocytes can be distinguished by their expression of surface proteins.  The surface proteins are named according to the standardized “CD” nomenclature.  For example, helper T cells are CD4+ and cytotoxic T lymphocytes are CD8+.  In order to get immune responses started, foreign substances have to be captured and displayed to lymphocytes.  MAJOR HISTOCOMPATIBILITY COMPLEX MOLECULES  The Peptide Display System of Adaptive Immunity  MHC = Human Leukocyte Antigen (HLA) complex  Highly polymorphic: diversity whereby a vast range of peptides can be displayed by MHC molecules for recognition by T cells.  CLASS-I MHC  coded by three linked loci HLA-A, HLA-B, and HLA-C recognition by CD8 T cells  display peptides synthesized in the cytoplasm of the cell (e.g. viral antigens)  present on all nucleated cells  CLASS-II MHC  coded by HLA-D region with at least three subregions (DP, DQ, DR) recognition by CD4+ T cells  Display peptides synthesized outside of the cell (e.g. bacterial antigens)  Present only on a few cell types, mainly antigen presenting cells (e.g. dendritic cells), macrophages, and B cells  CLASS-III MHC  Proteins include some complement components C2, C3 and Bf  Encoded tumor necrosis factor (TNF) and lymphotoxins (LT, TNF-ß)  Do not form a part of peptide display system CONTINUED:  Each person has a unique MHC antigenic profile (the HLA haplotype)  Inherits one HLA from each parent thus 2 different molecules of every locus  Different MHC alleles bind to different peptide fragments depending on the particular amino acid sequence of a given peptide.  The best defined APCs are specialized type of cells called  SUPPRESSOR & DENDRITIC CELLS  SUPPRESSOR T CELLS:  They act to suppress the functions of both helper T cells and Cytotoxic T cells to regulate the activities of other cells.  DENDRITIC CELLS:  A Dendritic cell is a type of macrophage (i.e., APC) with many spiny cytoplasmic processes, found in many places especially skin (Langhans cells) and brain (microglia), and many other less known places like liver.  NK CELLS  NK cells are types of lymphocytes which specialize in direct killing of cells which the come in contact with pathogen  Natural killer cells are a type of cytotoxic lymphocyte that constitute a major component of the innate immune system. NK cells play a major role in the rejection of tumors and cells infected by viruses COMPLEMENT SYSTEM FOR ANTIBODY ACTION  Complement is a collective term to describe a system of about 20 different proteins. The principal factor in this system are 11 proteins designated C1-C9, B and D.  These enzyme precursors are normally inactive form and are activated before CELL TYPE PRINCIPLE FUNCTION Help for B cells and macrophages (CD4+ helper T lymphocyte cells), killing of infected and tumor cells (CD8+ cytotoxic T lymphocytes) Antibody production (B cells develop into plasma B lymphocyte cells, which make antibodies) Capture and display of foreign (e.g. microbial) Dendritic cells antigens Phagocytosis and killing of microbes; antigen Macrophages capture and display; tissue repair Phagocytosis and killing of microbes Neutrophils SUMMARY REFERENCES