Presentation on theme: "Specific Defenses of the Host: The Immune Response"— Presentation transcript:
1 Specific Defenses of the Host: The Immune Response Chapter 17Specific Defenses of the Host:The Immune Response
2 Specific Defenses of the Host: The Immune Response Acquired immunity - Developed during an individual's lifetime
3 Distinct Cells in Adaptive Immune System Lymphocytes (B cells, T cells)Determining specificity of immunitySpecialized epithelial and stromal cellsProviding anatomic environmentAPC (antigen presenting cells) - antigen presentation –mediation of immunologic functionsMonocyte/macrophageDendritic cellsNatural killer cells and other members of myeloid cells (leukocyte that is not lymphocyte)
5 Dual Nature of the Adaptive Immune System Red bone marrow stem cells produce lymphocytes1. B cells -Humoral immunity–Some lymphocytes that mature in redbone marrow become B cells.Antibody productionAntibodies are found in serum and lymph.2. T cells - Cell-mediated immunitySome lymphocytes migrate through the thymus become T cells (T-lymphocytes)Activation of macrophages, natural killer cells (NK)Antigen-specific cytotoxic T-lymphocytesRelease of various cytokines in response to an antigen.
7 Immune system The most important nature of immune system is self/non-self recognition.Self/non-self recognition is achieved by having every cell of the body displays an individual specific marker.Any cell not displaying this marker is treated as non-self and attacked.The process is so effective that undigested proteins are treated as antigens.
8 Major Histocompatibility Complex (MHC) The major histocompatibility complex (MHC) is a set of cell surface molecules (proteins) encoded by a large gene family in all vertebrates.On the cell surface, each MHC molecule displays a molecular fraction, called epitope, of a protein.The presented antigen can be either self or nonself.MHC population on the cell membrane gives information about the balance of proteins within the cell.MHC molecules mediate interactions of leukocytes, with other leukocytes or body cells.In humans, MHC is also called human leukocyte antigen (HLA).
9 MHC proteins transfer information about proteins within a cell to the cell surface
10 Humoral ImmunityAn antigen (Ag), or immunogen, is a chemical substance that when introduced into the body stimulates the production of specific antibodies (antibody generation)Antibody (Ab) – A protein produced by B cells in response to recognition of an antigenProtein made in response to exposure to bacteria and other pathogens, toxins, plant pollen and red blood cells that the body recognized as alien, or non-self.Capable of combining specifically with that antigen.Highly specific recognition of foreign antigens (non-self)A vast universe of distinct antigenic specificitiesMechanisms for elimination of microbes bearing such antigensImmunologic memoryTolerance of self-antigens
11 The Nature of Antigens As a rule, antigens are proteins or large polysaccharides.Only large molecules, infectious agents, or insoluble foreign matter can elicit an immune response in the body.)A hapten is a small molecule that cannot cause the formation of antibodies unless combined with a carrier molecule;1. Can elicit an immune response only when attached to a large carrier such as a protein.The carrier may be one that also does not elicit an immune response by itself.2. Once the body has generated antibodies to a hapten-carrier, the small-molecule hapten may also be able to bind to the antibody independent of the carrier molecule.
12 The Nature of Antibodies Antibody is a large Y-shaped protein an immunoglobulin (Ig)They are secreted form of the B-cell receptorThe antibody recognizes a unique part of the antigen - epitope ( a portion of a molecule to which an antibody binds) or antigenic determinants.Figure 17.3
13 Antibody StructureThe Ig monomer consists of four paired polypeptide chains connected by disulfide bonds.Two identical heavy chainsTwo identical light chainsEach chain has two domains: one constant domain (C) and one variable domain (V)The constant domains or C domains of the heavy and light chains make up the C regionThe type of heavy chain present defines the class of antibody (IgA, IgD, IgE, IgG, and IgM)The variable or V domains of the heavy and light chains together make up the V region of the antibody and confer on it the ability to bind specific antigen epitope.Figure 17.5a-c
14 Ag-Ab Binding Antigen-antibody complex Affinity - the strength of the reaction between a single antigenic determinant and a single antibodySpecificity - Specificity refers to the ability of an individual antibody combining site (V) to react with only one antigenic determinant or the ability of a population of antibody molecules to react with only one antigen.
16 IgG antibodies Monomer 80% of serum antibodies Fix complement In blood, lymph, intestineCross placentaEnhance phagocytosis; neutralize toxins & viruses; protects fetus & newbornHalf-life = 23 days
17 IgM antibodies Pentamer 5-10% of serum antibodies Fix complement In blood, lymph, on B cellsAgglutinates microbes; first Ab produced in response to infectionInvolved in response to ABO blood groupHalf-life = 5 days
18 IgA antibodies Dimer 10-15% of serum antibodies In secretions, mucus, salvia, tears, and breast milkMucosal protectionHalf-life = 6 days
19 IgD antibodies Monomer 0.2% of serum antibodies In blood, lymph, on B cellsOn the surface of B cells, initiate immune responseHalf-life = 3 days
20 IgE antibodies Monomer 0.002% of serum antibodies On mast cells and basophils, in bloodAllergic reactions; lysis of parasitic wormsHalf-life = 2 days
21 Clonal SelectionHematopoietic stem cell differentiate to produce naive B lymphocytesEach lymphocyte bears a single type of receptor with a unique specificity - can recognizes only one type of antigen epitopeNaive cells mature into inactive B lymphocytes.1. Most of them will neverencounter a matching foreignantigen2. Those that get in contact witha matching antigen are activatedand produce many clonesof themselves – plasma cells thatproduce antibodies3. Some become memory cells
22 Clonal deletion Body doesn't make Ab against self, self-tolerance Clonal deletion -the process of destroying B and T cells after they have expressed receptors for self-antigens and before they develop into fully immunocompetent lymphocytes
23 Activation of B cells to produce antibodies The first exposure to a microbe or an antigen, either by infection or by vaccination, leads to the activation of B lymphocytesplasma cells antibody producing cells1. T-dependent antigensAntigens which requireparticipation of T cellsfor immune response2. T independent antigensAntigens that stimulate B cells without help of T cellsRepeating subunits – polysaccharides orlipopolysaccharidesCan bind multiple receptors of the B-cell
24 Cell-Mediated Immunity Red bone marrow stem cells give rise to T cellsmature in the thymus glandmigrate to lymphoid tissuesAn antigen must be processed by an antigen-presenting cell and positioned on the surface of the APC (antigen presenting cell).T cells recognize antigens in association with MHC on an APC
25 Antigen-Presenting Cells APCs - B cells, Dendritic cells and Macrophages.
26 Classes of T Cells T cells are classified according to their functions and cell-surface glycoproteins called CDs.Helper T CellsCytotoxic T CellsRegulatory T Cells
27 Helper T Cells Helper T cells, or CD4 cells, are activated by MHC class II on APCs.After binding an APC, CD4 cells secrete cytokines that activate other T cells and B cells.TH1 cells activate cells involved in cellular immunity.TH2 cells are associated with allergic reactions and parasitic infections.
29 Cytotoxic T Cells Cytotoxic T cells (TC), or CD8 cells, are activated by endogenous antigens and MHC class I on a target cell and are transformed into a CTL (cytotoxic T lymphocyte).CTLs lyse the target cell or induce apoptosis in the target cell.
31 Apoptosis Programmed cell death is also called apoptosis Cytotoxic T cells are able to directly induce apoptosis in cellsopening up pores in the target's membrane and releasing chemicals which bypass the normal apoptotic pathway.
32 Regulatory T Cells Regulatory T cells (TR) are vital for keeping the immune system in check, helping to avoid immune-mediated pathology and unrestricted expansion of effector T cellSuppress other T cells when Ag no longer presentInvolved in the checkpoints to prevent immune responses to self.Regulatory T cellsMature dendritic cellRegulatory T cellProliferationT cells compete forcytokine signalsT cells competefor same antigenCytotoxicT cell
33 Extracellular Killing by the Immune System Natural killer (NK) cells lyse virus-infected and tumor cells. They are not immunologically specific.
34 Antibody-Dependent Cell-Mediated Cytotoxicity In ADCC, NK cells and macrophages lyse antibody-coated cells.
35 Cytokines: Chemical Messengers of Immunity Cells Cells of the immune system communicate with each other by means of chemicals called cytokines.Interleukins (IL) are cytokines that serve as communicators between leukocytes.Chemokines cause leukocytes to move to the site of infection.Gamma Interferon activates macrophages
37 Immunological Memory The amount of antibody in serum is called the antibody titer.The response of the body to the first contact with an antigen is called the primary response. It is characterized by the appearance of IgM followed by IgG.Subsequent contact withthe same antigen results in avery high antibody titer andis called the secondary,anamnestic, or memory response.Memory B cellsThe antibodies are primarily IgG
38 Antiserum Serum containing antibodies is often called antiserum. When serum is separated by gel electrophoresis, antibodies are found in the gamma fraction of the serum and are termed immune serum globulin, or gamma globulin
39 Types of adaptive Immunity Acquired active immunity;resulting from infectionnaturally this type of immunity may be long-lasting.Acquired passive immunityAntibodies transferred from a mother to a fetus (trans placental transfer) or to a newborn in colostrum results in naturally in the newborn;can last up to a few months.Artificially acquired active immunityImmunity resulting from vaccinationcan be long-lasting.Artificially acquired passive immunityrefers to humoral antibodies acquired by injection;can last for a few weeks.
40 Learning objectives Differentiate between humoral and cellular immunity.Define antigen, epitope, and hapten.Explain the function of antibodies and describe their structural and chemical characteristics.Name one function for each of the five classes of antibodies.Compare and contrast T-dependent antigens and T-independent antigens.Differentiate between plasma cell and memory cell.Describe clonal selection.Describe four outcomes of an antigen-antibody reaction. Differentiate between helper T, cytotoxic T, and regulatory T cells.Differentiate between TH1 and TH2 cells.Define apoptosis.Define antigen-presenting cell.Describe the function of natural killer cells.Describe the role of antibodies and natural killer cells in antibody-dependent cell-mediated cytotoxicity.Identify at least one function of each of the following: cytokines, interleukins, interferons.Distinguish a primary from a secondary immune response.Contrast the four types of adaptive immunity.