Chapter 15 - Adaptive Immunity PDF

Chapter 15 -- Adaptive, Specific Immunity, & Vaccinations Defense - 2 categories: - - - Phagocytic cells - Dendritic cells: - located throughout the body, ambush predators of microbial invaders, phagocytize them, then inform cells of adaptive immunity of an...

Chapter 15 -- Adaptive, Specific Immunity, & Vaccinations Defense - 2 categories: - - - Phagocytic cells - Dendritic cells: - located throughout the body, ambush predators of microbial invaders, phagocytize them, then inform cells of adaptive immunity of an invasion - Eosinophils and Neutrophils (Granulocytes): phagocytize pathogens and both have the ability to exit the blood to attack invading microbes in the tissues (diapedesis) - Macrophages (Agranulocytes) Attributes of Adaptive Immunity - Specificity - Inducibility - Clonality - Unresponsiveness to self - Memory The two sides of the 3^rd^ line B cells - Mature in bone marrow - Become plasma cells - Produce antibodies - Provide *Humoral Immunity* *T Cells* - *T cells* - *Mature in thymus* - *Become killer T cells* - *Whole cell kills pathogen* - *Provide Cell-Mediated Immunity* Natural Markers - All of our cells also have molecules present in the cell membrane that tell the immune system that they belong to the body - the composition of these natural markers is genetically determined - one important set called: **Major histocompatibility complex** or **MHC** MHC: The Major Histocompatibility Complex Three Classes of MHC molecules: I, II, III: - Class I molecules occur on all cells except erythrocytes (RBC). They serve to identify \"SELF\" and will stimulate Ab production when introduced into someone else causing tissue rejection. In this sense they are like antigens and are sometimes referred to as such. - Class II molecules are [found only on macrophages, B-cells and some others]. Non-antigenic (do not stimulate Ab in tissue transplants). Necessary for communication between macrophages and T-cells. - Class III molecules (minor class) affect complement activation Lymphocyte Development and Differentiation & CST - Lymphocytes produced in bone marrow - B lymphocytes and T lymphocytes undergo maturation before being ready to fight for the body (occurs before birth) - This maturation involves the development of millions of individual B and T cells that can react to any possible antigen that enters the body in a lifetime = clonal selection theory CST - Both B and T cells undergo genetic changes to be able to respond to antigens - When becoming immunocompotent cells will have unique genes that will produce and place unique receptors on their cell surface - The unique receptor found on each of these cells is what recognizes unique antigens Foreign Marker - Also called *antigens*, are molecules that are part of the microbe that the immune system recognizes and responds to - can be part of cell wall, cell membrane, capsule, flagella, toxin, virus envelope - can be composed of protein, lipoprotein, glycoprotein, nucleoprotein, polysaccharide Antigens - "Villains" - Anything that can stimulates antibody (Ab) production - ALWAYS large molecules - complex molecules are better antigens because higher abundance of epitopes **Two** important characteristics: - ***immunogenicity*** = stimulate production of antibodies or proliferation of specific T cells, or both. - ***reactivity*** = ability of antigen to react specifically with the produced antibodies or T-cells. Types of Antigens exogenous antigens: - toxins and other secretions and components of microbial cell walls, membranes, flagella, and pili endogenous antigens: - protozoan, fungi, bacteria, and viruses that reproduce inside a body's cells autoantigens: normal cell antigens - autoimmune: when your own body doesn't recognize its own cells, treat as pathogens, and attack Antigen Present Cells APC: capture, ingest, and degrade antigens into epitopes - Present it to B-cells and T-cells - Examples: - B cells, macrophages, and dendritic cells. - Microbes once entering the body are recognized by immune system cells - The macrophage is the [antigen presenting cell] (APC) of the body - Function: phagocytize the microbe, digest it and place parts of microbe on its cell surface with the MHC - **Now** goes to lymphoid tissue to show educated lymphocytes T Lymphocytes - Mature in the Thymus - Receptor on the T cell is two parallel proteins - once the T cells are mature they are released into the body to fight microbes - circulate and the find residence in lymph tissue Types - Cytotoxic T cells - Helper T cells -- I & II - Suppressor T - Amplifier - Memory Helper cells (T~H,~ CD4 cells) - assist in initiating nearly all immune cells reactions. They are "corner-stone" cells that if absent will result in a person having a severely compromised immune system. - T~H~1: helping the attack cells known as cytotoxic T-cells. - How? by secretions of lymphokine interleukin (IL-2) - T~H~2: helps B-cells. Secretes cytokines (protein messengers that regulate the immune system). - also called CD4 cells because these T cells contain a surface antigen called CD4 - person with a normal immune system usually has a CD4 count of about 1000 or higher per ml. - In early stages of HIV infection, a patients - CD4 count can remain at a normal level for several years. CD4 count will decline over the yrs. When it falls to count of 200 or less the patient is said to have AIDS Helper T cell activation - Helper T cell is activated by Antigen presenting cell in two steps: - Physical contact between helper T and APC (must include contact with antigen) - Macrophage secretes interleukin 1 - **Now** activated helper T cell can assist in activating B cell and other T cells Cytotoxic T cell Activation - Helper T cell and APC activate Cytotoxic T cell in two steps: - APC contacts cytotoxic T cell with antigen - helper T cell secretes interleukin 2 - **Now** activated T cell will undergo change to produce two types of cells: Killer T cells and memory T cells - Activated Killer T (cytotoxic T cell) - seeks out and destroys antigen containing cells with [lymphotoxins] = granzymes & perforins - "attackers" destroy specific target cells. - secrete perforins (proteins that punch holes in the infected cell\'s cell membrane). This kills the infected cell, but prevents the virus from replicating & spreading to other cells. - Cytotoxic T cells are also very important in removing cancer cells. B Lymphocyte - Matures in the [bone marrow] - receptor placed on B cells is an antibody molecule = IgD - once B cells are mature they will be released into the body to fight microbes - they will circulate and then find residence in lymph tissue B Cell activation - B cell phagocytizes and processes microbe (no APC) - Helper T activates B cell in two steps: - Physical contact between B cell and helper T cell (must include contact with antigen) - Helper T cell secretes cytokine: interleukin 2 - Now B cell is activated - Activated B cell undergoes change and produces two types of cells: plasma cells and memory B cells Plasma Cells - Produces antibodies - function of antibodies: - opsonization = augments phagocytosis - activates complement = MAC - antigen-antibody aggregates = causes large clumps, ties up microbe - neutralization = microbe cannot bind target cell Memory B Cell - Lives long term in the lymph tissue and is activated when a subsequent exposure occurs Classes of Antibodies *IgM* -- 10% - exists as pentamer - circulates in blood -- can't get out! - first antibody produced (1st exposure) by plasma cell *IgG* -- 70-75% - Monomer - most prevalent antibody in fluids - Second antibody produced (1^st^ exposure) by plasma cell; produced by memory B cells (2^nd^ exposure) = **[provides long term immunity]** - only antibody that crosses the placenta *IgA --* 5% - monomer or dimer - found at surface of membranes = saliva, mucous, tears, colostrum - called **secretory IgA** *IgD* - monomer, still a mystery - small amounts in blood - Serves as receptor on educated B cells *IgE* - monomer - uncommon in blood unless one has allergy or parasitic worm infection - stimulates histamine release *First exposure* - plasma cell produces - first IgM in smaller quantities - second IgG in larger quantities *Second exposure* -- memory B cell produces - IgG in large quantities = [long term immunity] Specific Immunity Classification - Natural Active Immunity - Natural Passive Immunity - Artificial Active Immunity - Artificial Passive Immunity Vaccines - Include: - live, attenuated cells or viruses - killed whole cells or inactivated viruses - antigenic components of cells or viruses - genetically engineered microbes or microbial antigens - Toxoid = inactivated toxin molecule Live attenuated - Weakened strain of a pathogen intending to cause a subclinical infection that will induce adaptive immunity - Activate humoral and cellular immunity & memory - Disadvantages - Long-term storage challenges - Clinical infections - Reverting back to full virulence Ex: - chickenpox, german measles, red measles, mumps, TB, typhoid fever, yellow fever Inactivated vaccines - Contain whole pathogens that have been killed or inactivated with heat, chemicals, or radiation. - Structure of key antigens must remain intact - Stabile in storage - cannot cause severe infection - Disadvantages - Weaker and less comprehensive bc doesn't induce an active infection. - Only humoral immunity - Cannot pass to new host - Usually require higher doses & multiple boosters -- inflammation at site - Ex: - Cholera, HepA, influenza, plague, rabies Subunit: - Expose patient to key antigens of the pathogen - Produced by chemical degrading or producing the antigens via genetic engineering - Low risk of side effects - Ex: - Anthrax, hepB, influenza, meningitis, papillomavirus, pneumococcal pneumonia, whooping cough Toxoid - Inactivated bacterial toxins (toxoids) - Activate humoral immunity that neutralize the toxins - Ex: - Botulism, diphtheria, pertussis, tetanus Conjugate - Subunit vaccine with a protein conjugated to a capsule polysaccharide. - Developed to enhance the efficacy of subunit vaccine against pathogens with protective polysaccharide capsules. - Children under 2yrs responds better than the subunit vaccines - Ex: meningitis DNA Vaccines - Most promising of all of the newer approaches to immunization - DNA inserted into a plasmid and inoculated into a recipient (human) - Some of recipient cells take in plasmid and produce foreign proteins - Foreign proteins cause B and T cell response with memory cells - At the present time vaccines that are in animal trials: - Lyme disease, hepatitis C, herpes simplex, Influenza, tuberculosis, papillomavirus, malaria, and SARS