Lecture 13: Adaptive Immunity PDF

Lecture 13: Adaptive Immunity (specific host defense)  Characteristics of the Adaptive Immune Response Specificity Distinguishes between ‘self’ & ‘non-self’ Memory What are the differences between innate and adaptive immunity?  Adaptive Immunity – 2 Branches 1. Hu...

Lecture 13: Adaptive Immunity (specific host defense)  Characteristics of the Adaptive Immune Response Specificity Distinguishes between ‘self’ & ‘non-self’ Memory What are the differences between innate and adaptive immunity?  Adaptive Immunity – 2 Branches 1. Humoral Immunity B cells BCR Antibodies 2. Cellular Immunity T cells TCR Helper T cells (TH) Cytotoxic T cells (CTL)  Antigen & Epitopes Antigen (Ag) – protein or polysaccharide recognized by the immune system Epitopes – a subset of a particular Ag, where an Ab or TCR actually bind on the Ag  Ab Structure Are proteins, immunoglobulins (Ig) Bind to Ag! Made by B cells & plasma cell Major effector molecule of humoral Epitope immunity Antigen- binding Heavy chain sites Antigen-binding sites Variable Light chain Light chain region Variable region of heavy chain Variable region Fab (arm) of light chain Hinge Constant region of light chain Constant region of heavy chain CytoplasmicF (stem) c membrane of B lymphocyte Transmembrane portion of BCR Heavy chains B cell receptor (BCR) Cytoplasm Antibody specificity – # binding sites -  Effects of Ab Binding 1. Neutralization Adhesin Bacterium proteins Toxin Virus Neutralization  Effects of Ab Binding 2. Opsonization Pseudopod of phagocyte Fc receptor protein Opsonization  Effects of Ab Binding 3. Oxidation Bacteria die Oxidation  Effects of Ab Binding 4. Agglutination Agglutination  Effects of Ab Binding 5. Antibody-dependent cellular cytotoxicity (ADCC) NK lymphocyte Fc receptor protein Perforin allows granzyme to tnter, triggers apoptosis and lysis Antibody-dependent cellular cytotoxicity (ADCC) Major Histocompatibility Complex (MHC) Receptors found on all cells except RBCs Also known as human leukocyte antigen (HLA) Plays a role in recognition of self by the immune system and in rejection of foreign tissue Class I – markers that display Class II – receptors that recognize unique characteristics of self and react with foreign antigens; molecules and regulation of located primarily on macrophages immune reactions. Required for and B cells. Involved in T lymphocytes presenting antigen to T-cells  Lymphocyte Receptors Lymphocyte’s role in surveillance and recognition is a function of their receptors. B-cell receptors – bind free antigens T-cell receptors – bind processed antigens  * Activation of B Cells  T-dependent antigen – most proteins – B cells need Ag to also be recognized by T cells (confirmation that the Ag is indeed foreign) – B cells cannot become fully activated until a T cell recognizes the Ag presented in MHC class II molecules & secretes cytokines  T-independent antigen – large polysaccharides – Have repeating structures / subunits – Bind multiple BCR’s – B cells do not need T cell help to become fully activated B cell activation  B Cell Clonal Selection Each B cell will recognize only 1 Ag, and will make Abs that only bind this 1 Ag The BCR on the surface of B cells is what binds to this 1 Ag (made up of Abs on the surface of the B cell) In response to infection only B cells who can recognize the Ag (BCR-Ag binding) will become activated – A small % of the total # of B cells – All B cells are NOT activated during infection Through activation clonal ‘armies’ are made as only B cells that recognize Ag proliferate B cell Clonal Selection  Antibody Production 1st Ab produced is class IgM, IgG is made later The levels of Abs and specific Abs can be measured in the serum (liquid portion of blood) Ab levels can be used to monitor the immune response – Antibody titer A secondary/ memory response will produce Abs more quickly and in greater quantity Ab Titer Showing a Primary Response & Memory Response Primary (1o) Response 2o / Memory Response  Humoral & Cellular Immunity Humoral Immunity is effective against pathogens in circulation, or outside the cell – Bacteria, viruses, parasites, etc. Cellular Immunity provides a means of destroying intracellular pathogens, inside the cell – Intracellular Ag are not exposed to Abs – Infected cells must be detected and killed to clear some infections  Cellular Immunity – T cells 1. Helper T cells (TH) coordinate / direct immune responses Identified by CD4 glycoproteins on surface of cells 1. TH1 – Respond to most bacterial & viral pathogens; activate macrophages, activate CTL’s 2. TH2 – Respond to parasites and involved in allergies; activate B cells 3. T-regs – Regulate T cell responses, can put the ‘brakes’ on the immune response 2. Cytotoxic T cells (CTL) Kill host cells infected with intracellular pathogens Identified by CD8 glycoproteins on the surface of cells  Cellular Immunity – T cells Must be educated and learn the antigens present on a pathogen before they can attack! T cells are educated by Antigen Presenting Cells (APC) – 2 main APC’s: dendritic cells & macrophages APC’s display Ags to T cells on MHC molecules on the outside surface of the APC – MHC Class I molecules recognized by CTL (CD8+ T cells) – MHC Class II molecules recognized by TH cells (CD4+)  T cell Education Requires direct interaction with APC Takes place in secondary lymphoid organs APC patrol the body and phagocytose microbes, debris, & dead cells Once APC’s ‘eat’ something and are activated they go to the nearest 2o lymphoid tissue to display Ags to T cells – APC’s are activated through binding of Toll-like receptors; or by cytokines (produced by WBC’s & other cells)  TH cell (CD4+) Education Extracellular Antigen MHC Class II molecules Activation of CTL’s (CD8+)  CTL Killing Distinguish between antigens from intracellular pathogens and the host cell presented on MHC class I molecules CTL’s then are activated to release molecules that induces apoptosis in the target cell – Perforin: enzyme that makes pores in the cell membrane – Granzyme: proteases that induce apoptosis Apoptosis – programmed cell death, changes occur in the cell membrane to signal phagocytes to ingest them. Different from necrosis where cells lyse and their contents are released into extracellular space.  ADCC Antibody-dependent cell-mediated cytotoxicity NK Cells recognize when Abs have bound to a microbe by recognizing the Fc-region of the antibody via Fc receptors – Upon binding Abs via their Fc receptors, NK cells release perforin & granzymes which kill the target cell – NK cells do not learn each pathogen specifically! NK cells recognize when Abs are bound to microbes (here the Ab is specific & the NK cell recognition is nonspecific) CTL’s recognize specific Ags on MHC class I of infected cells  Cytokines Soluble molecules released mainly by leukocytes to communicate and coordinate / direct the immune response Include: – Interleukins (IL-1, IL-2, etc.) – Chemokines: signals for leukocyte extravasation and migration within tissues (chemotaxis) – Interferons (IFN-) – Tumor necrosis factors (TNF-) Generalized immune response of leukocytes accumulating at the site of infection (1) (2) 1) Expansion of immune cells Cells become activated & proliferate Clonal activation of only those T cells & B cells that recognize the particular Ags of the pathogen 2) Retraction of immune cells Cells undergo apoptosis A small portion of T cells & B cells will remain as memory cells so that the next time the pathogen is encountered the immune response will be faster & stronger!