Adaptive Immune System Chapter 16

Overview of Adaptive Immunity Adaptive immunity is the body’s ability to recognize and defend itself against distinct invaders and their products Five attributes of adaptive immunity 1. _______________ Any adaptive response acts against only one particular molecule shape and not others. Specific pathogens 2. _______________ Activation of adaptive cells only in response to specific pathogens 2

Five attributes of adaptive immunity continued.. 3. _____________ Once induced cells of the adaptive system proliferate (expand) to form many generations of nearly identical cells (clones). 4. _____________________________ The adaptive system does not act against normal body cells. 5. __________________________ An adaptive immune response has memory which allows a quick response if you encounter the pathogen again

Innate vs. adaptive Innate Adaptive Nonspecific response A fever is a fever whether triggered by a cold virus or Ebola Always ready and fast acting Born with these systems Adaptive Specific immune response to a pathogen If you have a cold virus antibodies are produced specifically for that virus Slower Not born with an adaptive system Antibodies can be transferred through breast milk

Types of Acquired Immunity Specific immunity acquired during an individual’s life _________________ Distinguished as either active or passive Active- normal exposure and response to pathogen Passive immunity Receive antibodies from another individual Newborns respond slowly to antigen IgG crosses the placenta providing protection IgA in breast milk- ____________________ 5

Dual Nature of Adaptive Immunity T and B cells develop from stem cells in red bone marrow Stem cells develop in bone marrow Red bone marrow of adults Differentiate to B cells in adult red bone marrow Thymus Differentiate to T cells in thymus Migrate to lymphoid tissue such as spleen, but especially lymph nodes

Dual Nature of Adaptive Immunity Two types of adaptive immune responses

Where does the Adaptive Immune response take place? The Tissues and Organs of the Lymphatic System Act as a surveillance system that screens the tissues of the body for foreign antigens Composed of lymphatic vessels and lymphatic cells, tissues, and organs 8

The Nature of Antigens Include various bacterial components as well as proteins of viruses, fungi, and protozoa Food and dust can also contain antigenic particles

Types of antigens Derived from normal cell processes Extracellular microbes Exogenous antigens Toxins and other secretions Components of cell walls, membranes, flagella Endogenous antigens are not accessible to immune cells Immune cells will respond if the endogenous antigen is incorporated into the bodies cells cytoplasmic membranes (external display) Derived from normal cell processes Endogenous antigens Intracellular virus Virally infected cell Autoantigens (normal cell antigens) Normal (uninfected) cell

The Nature of Antibodies Globular proteins called immunoglobulin's Secreted by _____________________ Antibodies (Ab) interact with________________ _______________

antigenic determinants on antigen Epitopes (antigenic determinants). Antibody A antigenic determinants on antigen Antigens: components of cell wall Binding sites Bacterial cell Antibody B

Antibodies Classes of antibodies ____–first antibody produced ____–most common (80% of serum antibodies) and longest-lasting antibody ____– associated with body secretions, provides nursing newborns some protection against foreign antigens, newborn receives antibodies against antigens that have infected their mothers _____–involved in response to parasitic infections and allergies _____–exact function is not known 13

Humoral Response The introducing the players: Extra cellular antigen B cells BCRs T helper cells (T-dependent humoral immunity only) CD4 MHC class II proteins Exogenous antigen processing Cytokines (chemical signalling)

B Cells and Antibodies Arise and mature in the red bone marrow Found primarily in the spleen and lymph nodes Small percentage of B cells circulates in the blood 15

B Cells and Antibodies The process leads to the secretion of antibodies starts when B cells are exposed to extracellular antigens. B cells carry immunoglobulin's on surface of cell Called B cell receptors (BCRs) Each B lymphocyte has multiple copies of the same B cell receptor Each B cell generates a single BCR ~500,000 identical copies per cell Billions of different BCR’s in a human

Figure 16.4 B cell receptor (BCR) Epitope Antigen- binding sites Heavy chain Variable region Light chain Cytoplasmic membrane of B lymphocyte Transmembrane portion of BCR B cell receptor (BCR) Cytoplasm

T Cells T Helper lymphocyte T cells mature in the thymus Have T cell receptors (TCRs) on their cytoplasmic membrane TCRs do not recognize epitopes directly TCRs only bind epitopes associated with a MHC protein Have either CD 4 or CD 8 protein (to recognize MHC) T Helper lymphocyte T helper cells require ______________________ _____________________

The Roles of the Major Histocompatibility Complex (MHC) Major histocompatibility antigens are proteins found in the membranes of most cells of vertebrate animals

The Roles of the Major Histocompatibility Complex (MHC) Antigens bind to MHC molecules Two classes of MHC proteins _______________Found on every nucleated cell _______________Found only on B cells and antigen presenting cells (APC) Antigen-binding grooves Cytoplasmic membrane Class I MHC on every nucleated cell Class II MHC on B cell or other antigen-presenting cell (APC) 20

Antigen Presenting Cells (APC) and Antigen Processing Digest antigen Display antigen fragments on APC surface with MHC Exogenous Antigen processing Antigen presenting cells internalize the antigen and digest the in the phagolysosome A vesicle containing MHC II fuses with the phagolysosome and the antigens can bind to its complementary MHC II molecule

Role of CD4 T helper cells recognize antigens presented with their ______and _____protein on T helper recognizes _____________ T helpers become activated when antigen is presented on a MHC II and matches its ______

Complex of MHC class II molecule and antigen fragment Exogenous Processing An APC encounters, in this case a B cell, and ingests a microorganism. The antigen is enzymatically processed into short peptides, which combine with MHC class II molecules and are displayed on the surface of the APC. A receptor (TCR) on the surface of the T helper cell (TH cell) binds to the MHC–antigen complex. The APC is stimulated to secrete a costimulatory molecule. These two signals activate the TH cell, which produces cytokines. TH cell receptor (TCR) The cytokines cause the TH cell to become activated. B cell T helper cell Antigen Complex of MHC class II molecule and antigen fragment Cytokines Antigen fragment (short peptides) Microorganism carrying antigens Costimulatory molecule, (required to activate T cells that have not previously encountered antigen)

Humoral Immune Responses Two types ________________humoral immunity 24

T-dependent humoral immunity The process T-dependent Antigen is presented with __________to TH cell TH cell produces _________that activate the B cell Once B cell is activated the B cell undergoes _____ _____________________ B cells differentiate into:

Clonal selection and differentiation of B cells. Stem cell Stem cells differentiate into mature B cells, each bearing surface immunoglobulins against a specific antigen. Antigen B cells B cell III complexes with its specific antigen and proliferates. I II III IV Memory cells Some B cells proliferate into long-lived memory cells, which at a later date can be stimulated to become antibody-producing plasma cells. See Figure 17.17. Other B cells proliferate into antibody-producing plasma cells. Plasma cells Plasma cells secrete antibodies into circulation. Antigens in circulation now attached to circulating antibodies Cardiovascular system

T-dependent humoral response worksheet

T-independent humoral immunity When a molecule with ________________ ____________________________the BCRs on a B cell 1. The B cell is activated 2. undergoes clonal expansion 3. the clones become plasma cells which secrete antibodies

(T-independent antigen) T-independent humoral immunity Polysaccharide (T-independent antigen) Epitopes B cell receptors

T-independent humoral response worksheet

Humoral Immune Responses Memory B Cells and the Establishment of Immunological Memory Produced by B cell proliferation but do not secrete antibodies Have BCRs complementary to the antigenic determinant that triggered their production Long-lived cells that persist in the lymphoid tissue Initiate antibody production if antigen is encountered again 31

Outcomes of Antigen–Antibody Binding

The results of antigen–antibody binding. PROCTECTIVE MECHANISM OF BINDING ANTIBODIES TO ANTIGENS Agglutination Activation of complement Reduces number of infectious units to be dealt with Causes inflammation and cell lysis Complement Bacteria Bacterium Lysis Opsonization Antibody-dependent cell-mediated cytotoxicity Coating antigen with antibody enhances phagocytosis Antibodies attached to target cell cause destruction by macrophages, eosinophils, and NK cells Phagocyte Eosinophil Epitopes Large target cell (parasite) Neutralization Perforin and lytic enzymes Blocks adhesion of bacteria and viruses to mucosa Blocks attachment of toxin Virus Toxin Bacterium

Cell mediated response The Players Intracellular antigen (virally infected cells) T cytotoxic cells (Tc) Cytotoxic T lymphocytes (CTLs) CD8 T helper cells APCs Macrophages Dendritic cells MHC class I

T Cells and Cell Mediated Immunity T cytotoxic cells (Tc) Have ______________which recognize Endogenous antigen packaged with ___________protein on _____ ________________________________ Produce perforins and granzyme Directly kills infected cells Tc and CTLs require antigen-presenting cells with MHC class I

Antigen presenting cells (APC) Macrophages Dendritic cells- “scouts” most important! Found under surface of skin and mucous membranes After acquiring antigen they will migrate to lymph nodes to interact with B and T cells

A dendritic cell.

Antigen Processing Endogenous – from pathogens living within a cell the antigen is broken down and packaged inside the cell with MHC I and displayed on the cell surface Processed antigen MHC class I Virus-infected cell (example of endogenous antigen) Virus-infected cell Processed antigen presented with Virus Virus-infected cell 39

Cell-Mediated Immune Responses See worksheet or next 3 slides explain process 40

Cell-Mediated Immune Responses Steps involved in activation of CTL’s (see worksheet) Antigen presentation- an APC (usually dendritic cell) presents antigen on a MHC class I protein to Tc cells (T cytotoxic cells) The one with matching TCR binds to dendritic cell CD8 on Tc cell recognizes MHC I Helper T cell stimulates Tc cell -A T helper cell will provide a signal to the Tc to undergo differentiation into a CTL and clonal expansion 41

Steps involved in activation of CTL’s Differentiation- the signal from the Th cell causes the Tc cell to differentiate into a CTL Clonal expansion- CTLs reproduce to form memory T cells and CTL clones Self-stimulation- the clonal CTLs cells no longer need an APC or helper T cell, they will signal themselves and leave the lymph node ready to attack virally infected cells

Steps involved in activation of CTL’s Activated CTLs with their TCRs and CD8 will recognize virally infected cells with endogenous antigen packaged with MHC class I, since viral antigens are presented on the cytoplasmic membrane CTLs will bind to the infected cell with its TCR and complementary MHC I/antigen complex Once bound the CTL kills their target By activating apoptotic factors Perforin and granzymes

Figure 16.15b A cell-mediated immune response: perforin-granzyme cytotoxic pathway Tc cell Perforin Granzyme Perforin complex (pore) Inactive apoptotic enzymes Granzymes activate apoptotic enzymes Active apoptotic enzymes induce apoptosis Virally infected cell

Apoptosis.

Natural Killer (NK) Cells Granular leukocytes destroy cells that don’t express MHC I Kill virus-infected and tumor cells Attack parasites

Immunological Memory Primary response occurs after initial contact with Ag Secondary (memory) response occurs after second exposure

Figure 16.19 The production of primary and secondary humoral immune responses--overview