2023 HUB105 Lec 13 Adaptve Imm.pdf

Lecture 13 Adaptive (specific) Immunity BChD I HUB 105 2023 Dept. Medical Biosciences University of the Western Cape  Introduction Forms 3rd line of defense when innate mechanisms are not enough and infection widespread. immunity (specif...

Lecture 13 Adaptive (specific) Immunity BChD I HUB 105 2023 Dept. Medical Biosciences University of the Western Cape  Introduction Forms 3rd line of defense when innate mechanisms are not enough and infection widespread. immunity (specific defenses) responds to specific threats and is provided by the coordinated activities of T cells and B cells which respond to the presence of specific antigens Develops a memory of that antigen thus responds better to a 2nd attack Not present at birth and is acquired. Properties of Immunity 1. Specificity 2. Versatility 3. Memory 4. Tolerance - T cells provide cell-mediated immunity or cellular immunity against abnormal cells and pathogens inside living cells. - B cells provide antibody-mediated immunity or humoral immunity against antigens and pathogens in body fluid. Specific defences: The immune response – Properties of immunity 1. Specificity - each T or B cell responds only to a specific antigen and ignores all others through a process known as antigen recognition 2. Versatility - the body produces many types of lymphocytes: o each fights a different type of antigen o active lymphocyte clones itself to fight specific antigen 3. Memory - inactive memory cells that are produced during the first exposure to a foreign antigen o stay in circulation o provide immunity against second exposure because they “remember” the previously encountered antigen 4. Tolerance - immune system ignores “normal” (self) antigens Specific defences: Overview of immune response Specific defences: Overview of immune response Antibody / Development of T and B cells Origin  2 grps Lymphoid stem cells develop in the Bone marrow: - A group remains in the bone marrow mature into B cells and NK cells - Another group migrate to Thymus proliferate and differentiate into various T cells  Activated T cells divide & differentiate into one of two classes: cytotoxic T cells or regulatory T cells (helper T cells, memory T cells, and suppressor T cells) Development of T and B cells Cytotoxic T Cells (TC) - are the primary providers of cellular immunity; they directly attack foreign cells (after transplants) or after the virus-infected body cells have been exposure to an antigen bound to the body’s cell membrane. - once activated, cytotoxic T cells divide to produce memory T cells and more active cytotoxic T cells Memory T Cells (TM) - remain “in reserve” and will immediately differentiate into cytotoxic T cells and helper T cells if the antigen appears a 2nd time in order to enhance the speed and effectiveness of the immune response Helper T Cells (TH) - when a phagocyte cell ingest and displays the antigenic material in the cell membrane. - the helper T cells activate and divide to produce memory T cells and more helper T cells, which stimulate the activity of B cells Suppressor T Cells (TS) - Inhibit function of T cells and B cells after the immune response. Activation of Lymphocytes Lymphocytes are stimulated to take action after exposure to antigens. Antigens are mostly protein based substances , toxins or foreign particles to the body (nonself) that triggers a protective immune response. Hapten are partial antigen’s, that once bound to body protein it gains antigenic properties and induces an immune response. However, cell membranes of the body have many surface antigens that lymphocytes recognised as normal (self). Antigens bound to glycoproteins, exposed on the cell membrane they are recognised as foreign , then T cells become activated. These glycoproteins are called Major histocompatibility complex (MHC) proteins (self). MHC proteins assist lymphocyte activation, when they bind to the antigen found in the cytoplasm of the cell and carry the antigen to the cell membrane to signal it’s presence, this process is known as Antigen presentation. Activation of Lymphocytes Two classes of MHC proteins: MHC I and MHC II Class I MHC proteins located in membranes of all nucleated body cells  Abnormal peptides , bacterial or viral peptides inside an infected cells cytoplasm binds to Class I MHC proteins; its carried to the surface of cell membrane to signal immune system, it indicates an abnormal cell that needs to be killed. Class II MHC proteins located in membranes of specialised cells, called antigen-presenting cells (APC) and lymphocytes.  Phagocytic cells become APC when they engulf and lyse pathogens or foreign antigens, these fragments bind to Class II MHC proteins, to indicate a dangerous antigen that needs to be disposed.  Phagocytic cells eg free and fixed macrophages, Kupffer cells (liver), microglia (CNS)  Class II MHC proteins appear in cell membrane only when the cell is processing antigens. http://cnx.org/content  Antigens and Class I MHC proteins antigen presentation Plasma membrane Antigen presentation The abnormal by Class I MHC peptides are Viral or bacterial displayed by Class I proteins is triggered by pathogen viral or bacterial MHC proteins on the infection of a body cell. plasma membrane. The infection results Transport in the appearance of vesicle abnormal peptides in the cytoplasm. After export to the Golgi apparatus, the MHC proteins reach The abnormal peptides the plasma are incorporated into membrane within Class I MHC proteins transport vesicles. Endoplasmic as they are synthesized reticulum at the endoplasmic reticulum. Nucleus Infected cell Antigen presentation in Class II MHC Proteins Plasma Antigenic fragments are membrane displayed by Class II Phagocytic APCs MHC proteins on the engulf the extracellular plasma membrane. pathogens. Antigenic fragments are bound to Class II MHC proteins. Lysosomal action The endoplasmic produces antigenic reticulum produces fragments. Class II MHC proteins. Nucleus Endoplasmic Lysosome reticulum Phagocytic antigen-presenting cell Cell-mediated Immunity T cells attack pathogens directly in cell-mediated immunity. Inactive T cells are activated when it recognizes a specific antigen on a Class I OR Class II MHC protein, process called antigen recognition. Recognition occurs with a specific MHC protein as T cell membranes have cluster of differentiation (CD) markers (receptors). - CD8 Markers found on cytotoxic T cells (CD8 T cell) respond to antigens on Class I MHC proteins - CD4 Markers found on helper T cells (CD4 T cell) respond to antigens on Class II MHC proteins After antigen recognition and binding of CD8 T cells and CD4 T cells to a specific antigen an immune response is activated. Cytotoxic T cells are activated , they start dividing in number, to seek out and destroy abnormal and infected cells. Cell-mediated Immunity Cell- Activation by ClassI MHC proteins mediated Immunity Antigen bound to Class I MHC protein Indicates that the cell is infected or otherwise abnormal CD8 T Cells Quick response increase cell production of Cytotoxic T Cells Memory T Cells Suppressor T Cells Attack & Destroy - Release perforin, Await Control or moderate lyse membrane reappearance immune response by -Secret lymphotoxin of the antigen T cells and B cells destroys target -Stimulate apoptosis, cell programmed death Cell- Activation by Class II MHC proteins mediated Immunity Antigen bound to Class II MHC protein Cytokines Functions Indicates presence of pathogens, -Enhance Innate toxins, or foreign proteins defenses such as, Inflammation, Phagocytosis and attract NK cell which all provide additional support to destroy Pathogens. CD4 T Cells undergo cell division 2 produce Active Helper T Cells Memory T Cells -secrete Cytokines - activate B cell, antibody- Inactive and Await mediated immunity reappearance -inc. TC cell of the antigen activation (cell-mediated Immunity) Antibody-mediated Immunity Helper T cells activated during cell-mediated immune response, promotes B cell activation and division. Activated B cells differentiate into plasma cells and memory B cells. Plasma cell: synthesises and secrets antibodies into interstitial fluid, which target the antigens. Memory B cells: reserved for next attack. 3 steps in antibody-mediated immunity: Step 1 = B cell sensitization; Step 2 = B cell activation and Step 3 = B cell division and differentiation Antibody-mediated Immunity : Antibodies Are proteins produced in response to and counteracting a specific antigen. Also called immunoglobulin's (Igs) Structure: 2 parallel prs of polypeptide chains, 1 pr of heavy chains (larger subunit) and 1 pr light chains (small subunit). Each chain has a constant and variable segment. Variable segment: form antigen binding sites for the antibody molecule. Binding site changes and specific for each antigen.(100million diff. Ab) Constant segment: forms the base of the antibody molecule. Antigen binding site Light chain Heavy chain Antibody-mediated Immunity : Antibodies B cells produce 5 different constant segments that form the bases for the 5 classes of antibodies/immunoglobulins: IgG, IgE, IgD,IgM and IgA IgM IgG IgA IgE IgD -1st Ig secreted -80% of all Ig -mainly in tears, -role in allergic -surface of B after antigen - largest & diverse saliva, mucus response cells, bind -form 5-antibody grp Ig -attack -bind 2 basophil, antigens in Starburst -resist many pathogens b4 mast cells extracellular -attack bacteria viruses, bacteria, enter internal - exposure to fluid that IgG is bacterial toxins tissues antigen results -this sensitizes insensitive to -can cross In release of other B cells -Agglutinates placenta, provide histamine to incr. incompatible passive immunity inflammation in bld types to foetus immed. area Antibody-mediated Immunity : Actions of Antibodies 1. Neutralization of antigen binding sites - pathogens have specific sites that bind to target areas on somatic cells; antibodies bind to those areas b4 pathogens attach. 2. Precipitation and agglutination - formation of immune complex, when a antibody bind to several antigens, they become insoluble and start clumping together. 3. Activation of complement system 4. Attraction of phagocytes 5. Opsonization increasing phagocyte efficiency 6. Stimulation of inflammation 7. Prevention of bacterial and viral adhesion Antibody-mediated Immunity : Actions of Antibodies Adaptive defenses Humoral immunity Antigen-antibody Antigen complex Antibody Inactivates by Fixes and activates Neutralization Agglutination Precipitation Complement (masks dangerous (cell-bound antigens) (soluble antigens) parts of bacterial exotoxins; viruses) Enhances Enhances Leads to Phagocytosis Inflammation Cell lysis Chemotaxis Histamine release Antibody-mediated Immunity : Actions of Antibodies Primary and secondary responses to antigen exposure first exposure: -produces initial primary response that takes time to develop -antigens activate B cells and plasma cells differentiate -antibody level slowly rises -peak response: can take 2 weeks to develop and declines rapidly second exposure: - triggers secondary response - is more extensive and prolonged -Large numbers of memory cells are already primed and respond immediately - by dividing and differentiating into plasma cells at lower antigen concentrations than the original B cells. -memory cells may survive for 20yrs or more secondary response can occur years after the first exposure Revision Questions 1. Define the following: adaptive immunity, cell-mediated and anti-body mediated immunity, antigen, antibody, hapten, MHC protein 2. Name and explain the origin of the 2 types of lymphocytes involved in cell- mediated and antibody-mediated immunity. 3. Compare the two forms of specific immunity. 4. Briefly explain the various functions of and name the 4 types of T lymphocytes. 5. Lymphocytes are activated exposure to antigens, explain this process. 6. Describe where the 2 classes of MHC proteins are located. 7. Explain how class I and II MHC proteins assist in an immune response. 8. In detail, explain what happens during cell-mediated immunity after activation of CD8 T cell and CD4 T cell. 9. Explain the process of antibody-mediated immunity. 10. What is the importance of the variable and constant segments. 11. Name 5 types of Ig and give a function of each. 12. Explain in detail the response within body, after the release of antibodies during antibody-mediated immunity. 13. Indicate the difference between antigen-presentation and antigen-presenting cells.