Lecture 2: Basics of Immunity PDF

MIHS (65102) MBBS Batch 30 Lecture 2 Basics of Immunity I Prepared by: Dr. B. Shandra Devi By: Dr. Shandra Devi Balasubramaniam 1  L2: Basics of Immunity The objectives of this lecture are to discuss types of immunity, various cells and organs...

MIHS (65102) MBBS Batch 30 Lecture 2 Basics of Immunity I Prepared by: Dr. B. Shandra Devi By: Dr. Shandra Devi Balasubramaniam 1  L2: Basics of Immunity The objectives of this lecture are to discuss types of immunity, various cells and organs of the immune system and the factors that determine the antigenicity. Topic outcomes At the end of the lecture, students should be able to: classify immunity. describe the lines of defense of immunity. differentiate between innate and acquired immunity, active and passive immunity, natural and artificial immunity. list the primary and secondary lymphoid organs and the different cells involved in immunity. explain the terms antigen, immunogens, hapten, epitope, adjuvant, superantigen and heterophile antigen. discuss the factors that determine antigenicity. Prepared by: Dr. B. Shandra Devi 2 Immune system has a vital role Function of Immune System? protects your body from harmful substances, germs and cell changes that could make you ill. 3 Prepared by: Dr. B. Shandra Devi Prepared by: Dr. B. Shandra Devi 4 Immunity Immunity refers to the body’s ability to fight pathogens. The immune system works by identifying a foreign antigen and developing antibodies against it. White blood cells are important components of the immune response. The antibodies are IgA (Immunoglobulin A), IgE, IgG, IgM, and IgD. They comprise globular proteins. Immunoglobulins detect the antigen and initiate a suitable response. Either they kill the pathogen themselves or activate killer T cells to act on it. All the antibodies and immune cells together form the immune system. Prepared by: Dr. B. Shandra Devi 5 Classify immunity Prepared by: Dr. B. Shandra Devi 6 Prepared by: Dr. B. Shandra Devi 7 Component of Innate Immunity Innate immunity is the one present in your body since birth. It is the body’s first line of defense when it comes in contact with a pathogen. It indicates to the body about an invasion, and the systems use physical and chemical barriers to kill the invader before it causes damage. These barriers collectively protect you from bacteria, viruses, parasites, and other pathogens. Prepared by: Dr. B. Shandra Devi 8 Innate immunity depending on their action on the pathogen. Specific immunity is the action of immune cells or organs on a specific stimulus only. They do not react to any other indication. For example, the stomach’s low pH only acts on specific bacteria and yeast present in food. On the other hand, skin helps kill bacteria on the skin and stops them from entering the body. Non-specific immunity is based on immunoglobulins (IgA, IgD, IgE, IgG, IgM). They bear the responsibility of attacking various pathogens and throwing them out of the body. They also include dendritic cells, mast cells, neutrophils, eosinophils, macrophages, and natural killers. Prepared by: Dr. B. Shandra Devi 9  10 Prepared by: Dr. B. Shandra Devi Prepared by: Dr. B. Shandra Devi 11 Adaptive or Acquired Immunity Adaptive immunity is the opposite of innate immunity. An organism acquires it through the course of its life. When an antigen comes in contact with the body’s immune system, it produces antibodies. The body takes around 14 days to create antibodies. These antibodies do not fight the pathogen one time only. They remember the antigen and act on it on repeated interaction. Adaptive immunity is categorized as active Immunity and passive immunity. Prepared by: Dr. B. Shandra Devi 12 Prepared by: Dr. B. Shandra Devi 13 Components of Adaptive Immunity Immunoglobulins Macrophages Immunoglobulins are produced in The other cells involved in adaptive antibody-mediated immunity immunity are macrophages and or humoral immunity. They form in CTLs (cytotoxic T lymphocytes). response to an antigen. B- They make up cell-mediated lymphocytes medicate immunity. It destroys the harboring immunoglobulin to protect against of antigens, multicellular parasites, toxins and pathogens. They are cancer cells, and transplanted typically present in body fluids or tissues. It is crucial as the body may humor. reject a transplanted organ taking it as a foreign body. Prepared by: Dr. B. Shandra Devi 14 Prepared by: Dr. B. Shandra Devi 15 Describe the lines of defense of immunity. Prepared by: Dr. B. Shandra Devi 16 Function of Immune cells Recognize React – kill pathogen, stimulate wound healing, clearance of cellular debris, coordination of immune response (cytokines & chemokines). Regulate – can destroy own cells, so need to regulate to control immune cells from destroying Remember – T & B lymphocytes (previous infection) Prepared by: Dr. B. Shandra Devi 17  Immune cells develop from HSC. Hematopoietic stem cells (HSCs) are multipotent primitive cells that can develop into all types of blood cells, including myeloid-lineage and lymphoid-lineage cells Innate immune cells Granulocytes 18 Prepared by: Dr. B. Shandra Devi Prepared by: Dr. B. Shandra Devi 19  Cytokines are signaling proteins that help control inflammation in your body. They allow your immune system to mount a defense if germs or other substances that can make you sick enter your body. Too many cytokines can lead to excess inflammation and conditions like autoimmune diseases. Prepared by: Dr. B. Shandra Devi 20  Do not help much in pathogen clearance but initiate activation of T- cells Prepared by: Dr. B. Shandra Devi 21 Prepared by: Dr. B. Shandra Devi 22  Extracellular pathogen intracellular pathogen The extracellular spaces are protected by the humoral T cells can detect the presence of an intracellular immune response, in which antibodies produced by B pathogen because infected cells display on their cells cause the destruction of extracellular surface peptide fragments derived from the microorganisms and prevent the spread of intracellular pathogen's proteins. infections. Prepared by: Dr. B. Shandra Devi 24 How does the immune system protect from foreign invaders (bacteria, viruses, toxins)? The human body has three primary lines of defense to fight against foreign invaders Three lines of defense: 1st line defense: physical and chemical barriers 2nd line defense: non-specific innate responses 3rd line defense: specific adaptive responses Prepared by: Dr. B. Shandra Devi 26  1st line defense (Innate immunity) Physical and chemical barriers form the first line of defense when the body is invaded. Prepared by: Dr. B. Shandra Devi 27  2nd line defense (Innate immunity) The second line of defense is nonspecific resistance that destroys invaders in a generalized way without targeting specific individuals: Phagocytic cells ingest and destroy all microbes that pass into body tissues. Macrophages are cells derived from monocytes (a type of white blood cell). Macrophages leave the bloodstream and enter body tissues to patrol for pathogens. Inflammation is a localized tissue response that occurs when your tissues are damaged and in response to other stimuli. Inflammation brings more white blood cells to the site where the microbes have invaded. The inflammatory response produces swelling, redness, heat, pain Fever inhibits bacterial growth and increases the rate of Prepared by: Dr. B. Shandra Devi 28 tissue repair during an infection.  1.The microbe attaches to the phagocyte. 2.The phagocyte's plasma membrane extends and surrounds the microbe and takes the microbe into the cell in a vesicle. 3.The vesicle merges with a lysosome, which contains digestive enzymes. 4.The digestive enzymes begin to break down the microbe. The phagocyte uses any nutrients it can and leaves the rest as indigestible material and antigenic fragments within the vesicle. 5.The phagocyte makes protein markers, and they enter the vesicle. 6.The indigestible material is removed by exocytosis. 7.The antigenic fragments bind to the protein marker and are displayed on the plasma membrane surface. The macrophage then secretes interleukin-1 which activates the T cells to secrete interleukin 2 IL-1: cytokines that plays a central role in the regulation of immune and inflammatory responses to. IL-2: increases the growth and activity of other T lymphocytes and B lymphocytes, and affects the development of the immune system. Prepared by: Dr. B. Shandra Devi 29 Prepared by: Dr. B. Shandra Devi 30  3rd line defense (part of Adaptive immunity) This system relies on antigens, which are specific substances found in foreign microbes. 1.When an antigen is detected by a macrophage, this causes the T-cells to become activated. The activation of T-cells by a specific antigen is called cell-mediated immunity. The body contains millions of different T-cells, each able to respond to one specific antigen. 2.The T-cells secrete interleukin 2. Interleukin 2 causes the proliferation of certain cytotoxic T cells and B cells. 3.From here, the immune response follows 2 paths: one path 31 uses cytotoxic T cells and the other uses B cells. Prepared by: Dr. B. Shandra Devi Differentiate between innate and acquired immunity, active and passive immunity, natural and artificial immunity. Prepared by: Dr. B. Shandra Devi 32 Prepared by: Dr. B. Shandra Devi 33 Prepared by: Dr. B. Shandra Devi 34  35 Prepared by: Dr. B. Shandra Devi  36 Prepared by: Dr. B. Shandra Devi Vaccine Prepared by: Dr. B. Shandra Devi 37 Some of the B-cells become plasma cells capable of producing Memory T cells are antigen-specific T cells that antibodies. Other B-cells become memory cells that get stored in remain long-term after an infection has been your body. Plasma cells make millions of antibodies over the next eliminated. The memory T cells are quickly several days. All antibodies are customized to destroy only the converted into large numbers of effector T cells specific pathogen that produced the antigen. upon reexposure to the specific invading antigen, thus providing a rapid response to past infection.  Part of adaptive immunity Humoral immunity produces antigen-specific antibodies and is primarily driven by B cells. Cell-mediated immunity on the other hand does not depend on antibodies for its adaptive immune functions and is primarily driven by mature T cells, macrophages and the release of cytokines in response to an antigen. Humoral / B-cell B cells 25% of the total lymphocyte population –can be up to 50% depending to the immune response. important B cell surface markers (CD19, CD20 and CD21, MHC II) Essential for humoral immunity, known as the antibody- mediated immune response plasma cells are mature B cells that secrete antibodies, which recognise specific foreign antigens and bind to them or destroy them memory B cells “remember” the offending foreign antigens to allow the immune system to mount a quicker antibody response to any subsequent infections Cell-Mediated/T cell Immunity T cells -70% of the total lymphocyte population can be up to 90% depending the immune response. all T cells express CD3 on their surfaces, along with T cell receptors (TCRs) which recognise specific antigens presented in an MHC I or MHC II molecule Various T cell subtypes with different roles. Example: helper T cells (CD4) facilitate the activation of the immune response and stimulate division and differentiation of various effector cells cytotoxic T cells (CD8) –known as killer or effector T cells – provide cell- mediated immunity by targeting and killing infected cells regulatory T cells (CD25 + FOXP3) –known as suppressor T cells – play a vital role in limiting the immune response to prevent excessive damage to tissues and organs memory T cells (CD62 + CCR7) “remember” what has happened to allow the immune system to mount a faster, more effective response should the offending organism be foolish enough to return  Adaptive immunity is initiated when an innate immune response fails to eliminate a new infection, and antigen and activated antigen-presenting cells are delivered to the draining lymphoid tissues. Prepared by: Dr. B. Shandra Devi 42 Prepared by: Dr. B. Shandra Devi 44 Prepared by: Dr. B. Shandra Devi 45