Lec#19 .pptx

Immunology: Chaps 26 & 27 Before this class it is advisable that you look at the following three videos on youtube: http://www.youtube.com/watch?v=FXSuEIMrPQk &NR=1 http://www.youtube.com/watch?v=O1N2rEN Xq_Y&feature=channel http://www.youtube.com/watch?v=uwMYpTYsNZM&feature=c hannel Lecture O...

Immunology: Chaps 26 & 27 Before this class it is advisable that you look at the following three videos on youtube: http://www.youtube.com/watch?v=FXSuEIMrPQk &NR=1 http://www.youtube.com/watch?v=O1N2rEN Xq_Y&feature=channel http://www.youtube.com/watch?v=uwMYpTYsNZM&feature=c hannel Lecture Objectives After this lecture and readings you should be able to: -nonspecific (innate) and specific immunity mechanisms. • describe the physical and chemical barriers a pathogen must breach if a parasitic relationship is to be established • discuss antibody diversity generated through the clonal selection theory • discuss the role of T-cell receptors and MHC molecules in the functioning of T cells and B-cell activation • describe the roles of cytotoxic T cells and cytokines • discuss immunization Natural Defenses against Disease  1. Nonspecific Defenses  2. Specific Defenses: The Immune System B Cells: The Humoral Immune Response  T Cells: The Cellular Immune Response  Animal defense systems are based on the distinction between self and nonself.  There are two general types of defense mechanisms:  1. Nonspecific defenses, or innate defenses, are inherited mechanisms that protect the body from many different pathogens.  2. Specific defenses are adaptive mechanisms that protect against specific targets. 1. Nonpecific defenses or innate mmunity How are phagocytes involved in defence against bacterial invasion? Splinter Skin Bacteria introduced by splinter Damaged mast cells release histamine. Histamine diffuses into the capillaries. Blood capillary Bacteria Phagocytes move into infected tissue. Activated complement proteins attract phagocytes. Histamine causes the capillaries to dilate and become leaky. Phagocytes engulf bacteria and dead cells. Dead cells Histamine and complement signaling cease, phagocytes are no longer attracted, and the tissue returns to normal. Acute Inflammatory Response   the release of inflammatory mediators from injured tissue cells initiates a cascade of events which result in the signs of inflammation involves chemical mediators  selectins  cell adhesion molecules on activated capillary endothelial cells  integrins  adhesion receptors on neutrophils  chemotaxins  chemotactic factors released by injured cells  phagocytes accumulate in inflamed area and destroy pathogens 12 13 Ingestion and killing of microbes by a neutrophil Phagocytosis  Phagocytes must avoid attacking host cells  Host cell CD47 prevents attack  Phagocyte toll-like receptors bind bacteria  Phagocyte receptors bind opsonized bacteria   Cells coated with antibodies Phagocytes kill, digest engulfed bacteria  Produce peptides to kill bacteria  Kill with reactive oxidative burst  O2ˉ, HOOH, ˙OH, NO, NO2ˉ, NO3ˉ in phagosome http://www.youtube.com/watch?v=JnlULOjUhSQ&feature=related 2. Specific Defenses  Four characteristics of the immune system:  1. Specificity: Antigens are organisms or molecules that are specifically recognized by T cell receptors and antibodies. The sites on antigens that the immune system recognizes are the antigenic determinants (or epitopes).  Each antigen typically has several different antigenic determinants.  The host creates T cells and/or antibodies that are specific to the antigenic determinants.  Figure 18.6 Each Antibody Matches an Antigenic Determinant Antibody Structure and Diversity     IgG – Primary circulating antibody in blood  Coats antigen, eases engulfment by phagocytes IgD – On surface of B cells IgE – Bound by mast cells and basophils  Mediator of inflammatory response IgA – Secreted across mucosa  Dimer held together by J chain Specific Defenses: The Immune System  2.   3.   4.  Diversity: It is estimated that the human immune system can distinguish and respond to 10 million different antigenic determinants. Distinguishing self from nonself: Each normal cell in the body bears a tremendous number of antigenic determinants. It is crucial that the immune system leave these alone. Immunological memory: Once exposed to a pathogen, the immune system remembers it and mounts future responses much more rapidly. Specific Defenses: The Immune System  The immune system has two responses against invaders: The humoral immune response (B cells) and the cellular immune (T cells) response.  The two responses operate in concert and share mechanisms.  Four groups of proteins play key roles in defending against disease:  Antibodies, secreted by B cells, bind specifically to certain substances.  T cell receptors are cell surface receptors that bind nonself substances on the surface of other cells.  Major histocompatibility complex (MHC) proteins are exposed outside cells of mammals. These proteins help to distinguish self from nonself.  Cytokines are soluble signal proteins released by T cells. They bind and alter the behavior of their target cells. Specific Defenses: The Immune System FIRST THE B CELLS  Each person has millions of different B cellseach of which can make a different antibody  When a pathogen invades the body, it may be detected by and bound by the B cell whose membrane antibody fits.  This binding activates the B cell, which makes multiple soluble copies of an antibody with the same specificity as its membrane antibody…but needs a T helper cell !!  When a naïve B cell encounters an antigen for the first time the cell rapidly divides and differentiates into memory B cells and effector B cells (plasma cells)  Effector B cells secrete antibodies (2000 molecules of antibody per second); major effector molecules of humoral immunity Clonal Selection in B Cells …but this must be done with T helper cells T CELLS OR T LYMPHOCYTES  Arise in the bone marrow and mature in the thymus gland  T cell expresses a membrane bound antigen binding molecule called T-Cell Receptor (TCR)  TCR recognize only antigens that are bound to cell-membrane proteins called Major Histocompatibility Complex (MHC) ..back to the phagocyte 30 Macrophage TH Cell The macrophage displays the processed antigen on MHC II. A specific T helper cell identifies the processed antigen. Cytokines message the T helper cell to multiply. There are more of them to interact with B cells. 33 B cell has previously encountered an antigen. This is bound to antibody on B cell. The antigen is processed and and presents the antigen on MHCII. Thus the B cell can act as an APC and Ab producer. B cell is activated when T helper cell binds antigen presented on MHCII of B cell. B Cell TH Cell Specific Defenses: The Immune System  The cellular immune response is able to detect antigens that reside within cells.  It destroys virus-infected or mutated cells.  Its main component consists of T cells.  T cells have T cell receptors that can recognize and bind specific antigenic determinants. Specific Defenses: The Immune System  When the body encounters an antigen for the first time, a primary immune response is activated.  When the antigen appears again, a secondary immune response occurs. This response is much more rapid, because of immunological memory. 40 Immunological Memory Specific Defenses: The Immune System     Artificial immunity is acquired by the introduction of antigenic determinants into the body. Vaccination is inoculation with whole pathogens that have been modified so they cannot cause disease. Immunization is inoculation with antigenic proteins, pathogen fragments, or other molecular antigens. Immunization and vaccination initiate a primary immune response that generates memory cells without making the person ill.