Functional Anatomy of Prokaryotic and Eukaryotic Cells © 2013 Pearson Education, Inc. Lectures prepared by Christine L. Case Chapter 17

© 2013 Pearson Education, Inc.

Immunity  Innate immunity: generic defenses against any pathogen;  should be born with this; instant protection  Adaptive immunity: induced resistance to a specific pathogen;  occurs when you come into contact with a pathogen. Specific  Is achieved by Lymphocytes  T-Cells  B-Cells- Humoral immunity  Immunity brought about by antibody production

© 2013 Pearson Education, Inc. Extracellular antigens A B cell binds to the antigen for which it is specific. A T-dependent B cell requires cooperation with a T helper (T H ) cell. The B cell, often with stimulation by cytokines from a T H cell, differentiates into a plasma cell. Some B cells become memory cells. Plasma cells proliferate and produce antibodies against the antigen. Intracellular antigens are expressed on the surface of an APC, a cell infected by a virus, a bacterium, or a parasite. A T cell binds to MHC–antigen complexes on the surface of the infected cell, activating the T cell (with its cytokine receptors). Activation of macrophage (enhanced phagocytic activity). The CD8 + T cell becomes a cytotoxic T lymphocyte (CTL) able to induce apoptosis of the target cell. B cell Plasma cell T cell T H cell Cytotoxic T lymphocyte Cytokines Lysed target cell Cytokines activate macrophage. Cytokines from the T H cell transform B cells into antibody-producing plasma cells. Cytokines activate T helper (T H ) cell. Memory cell Some T and B cells differentiate into memory cells that respond rapidly to any secondary encounter with an antigen. Humoral (antibody-mediated) immune systemCellular (cell-mediated) immune system Control of freely circulating pathogensControl of intracellular pathogens Figure The dual nature of the adaptive immune system.

© 2013 Pearson Education, Inc. Dual Nature of Adaptive Immunity  Humoral immunity  Due to antibodies  B cells- are responsible for producing antibodies  B cells mature in the bone marrow  Plasma cells- activated B cells that actually produce the antibodies.  Memory Cells – activate on subsequent exposures.  Cellular immunity  Due to T cells  T cells- are responsible for producing cytokines which will send instructions to other cells (like B cells).  T cells mature in the thymus  Are activated by macrophages that have engulfed a bacteria and presented its antigen on its cell membrane

© 2013 Pearson Education, Inc. Stem cells develop in bone marrow or in fetal liver Stem cell (diverges into two cell lines) Red bone marrow of adults Differentiate to B cells in adult red bone marrow B cell Thymus Differentiate to T cells in thymus T cell Migrate to lymphoid tissue such as spleen, but especially lymph nodes Figure 17.8 Differentiation of T cells and B cells.

© 2013 Pearson Education, Inc. Dual Nature of Adaptive Immunity  Antigens (Ag)- Cell markers, non self antigens are considered to be foreign and stimulate an immune response.  Antibodies(Ab)- produced by our bodies in response to a foreign antigen  Globular proteins called immunoglobulins  When the antibody and antigen combine, clumping occurs.

© 2013 Pearson Education, Inc. Figure 17.3c The structure of a typical antibody molecule. Antibody molecules shown by atomic force microscopy (see page 64) Antibodies

© 2013 Pearson Education, Inc. IgG Antibodies  80% of serum antibodies  Triggers complement system  In blood, lymph, and intestine  Cross placenta (passive immunity)  Enhance phagocytosis; neutralize toxins and viruses; protect fetus and newborn  Half-life = 23 days indicates there has been a immune response

© 2013 Pearson Education, Inc. IgM Antibodies  5–10% of serum antibodies  Mainly stays In blood  Responds to blood group antigens  Agglutinate microbes; first Ab produced in response to infection  Half-life = 5 days (better det. Of current infection

© 2013 Pearson Education, Inc. IgA Antibodies  10–15% of serum antibodies  Most abundant in secretions  Mucosal protection  Half-life = 6 days

© 2013 Pearson Education, Inc. IgD Antibodies  0.2% of serum antibodies  In blood, in lymph, and on B cells  On B cells, initiate immune response  No well know function  Half-life = 3 days

© 2013 Pearson Education, Inc. IgE Antibodies  0.002% of serum antibodies  On mast cells, on basophils, and in blood  Respond to Allergic reactions and of parasitic worms  Half-life = 2 days

© 2013 Pearson Education, Inc. Activation of B Cells  B cells differentiate into:  Antibody-producing plasma cells  Memory cells

© 2013 Pearson Education, Inc. Antigen–Antibody Binding  Agglutination  Opsonization – coating with antibodies  Activation of complement –(IgG or IgM)  Antibody-dependent cell-mediated cytotoxicity  Destruction is achieved by other cells besides antibody secreting cells  Neutralization – prevents attachment to other host cells

© 2013 Pearson Education, Inc. Figure 17.7 The results of antigen–antibody binding. PROCTECTIVE MECHANISM OF BINDING ANTIBODIES TO ANTIGENS Activation of complement (see also Figure 16.9) Agglutination (see also Figure 18.5) Opsonization (see also Figure 16.9) Antibody-dependent cell-mediated cytotoxicity (see also Figure 17.16) Neutralization (see also Figure 18.9) Reduces number of infectious units to be dealt with Coating antigen with antibody enhances phagocytosis Phagocyte Bacteria Causes inflammation and cell lysis Bacterium Lysis Antibodies attached to target cell cause destruction by macrophages, eosinophils, and NK cells Epitopes Eosinophil Perforin and lytic enzymes Large target cell (parasite) Blocks adhesion of bacteria and viruses to mucosa Bacterium Virus Blocks attachment of toxin Toxin Complement

© 2013 Pearson Education, Inc. T Cells and Cellular Immunity  T cells mature in the thymus

© 2013 Pearson Education, Inc. Table 17.2 Principal Cells That Function in Cell-Mediated Immunity

© 2013 Pearson Education, Inc. T Cells and Cellular Immunity  T cells respond to Ag by T-cell receptors  T cells require antigen-presenting cells

© 2013 Pearson Education, Inc. Antigen-Presenting Cells  Digest antigen  Ag fragments on APC surface with MHC

© 2013 Pearson Education, Inc. T Helper Cells  T cells  recognize Ags on APC  T cells produce cytokines and differentiate into:  T-cells  Memory cells

© 2013 Pearson Education, Inc. Figure Lineage of effector T helper cell classes and pathogens targeted. Antibodies B cell Recruits neutrophils; provides protection against extracellular bacteria and fungi Extracellular bacteria Fungi T H 1 cells T H 2 cells T H 17 cells IL-17 IL-4 IFN-  Cell-mediated immunity; control of intracellular pathogens, delayed hypersensitivity reactions (page 535); stimulates macrophages. Important in allergic responses, especially by production of IgE Stimulates activity of eosinophils to control extracellular parasites such as helminths (see ADCC, page 495). Neutrophil Mast cell Basophil Eosinophil Macrophage T H 1 cells T H 2 cells T H 17 cells Intracellular bacteria and protozoa T H cell Helminth

© 2013 Pearson Education, Inc. Figure Activation of CD4 + T helper cells. APC (dendritic cell) Antigen Costimulatory molecule, (required to activate T cells that have not previously encountered antigen) Microorganism carrying antigens Antigen fragment (short peptides) T H cell receptor (TCR) Complex of MHC class II molecule and antigen fragment A receptor (TCR) on the surface of the CD4 + T helper cell (T H cell) binds to the MHC–antigen complex. If this includes a Toll-like receptor, the APC is stimulated to secrete a costimulatory molecule. These two signals activate the T H cell, which produces cytokines. The cytokines cause the T H cell (which recognizes a dendritic cell that is producing costimulatory molecules) to become activated. Cytokines T helper cell An APC encounters 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.

© 2013 Pearson Education, Inc. T Cytotoxic Cells  or T C cells  Activated into cytotoxic T lymphocytes (CTLs)  Induce apoptosis in target cell

© 2013 Pearson Education, Inc. Figure Killing of virus-infected target cell by cytotoxic T lymphocyte. Processed antigen MHC class I Virus-infected cell (example of endogenous antigen) Virus-infected cellCytotoxic T lymphocyte (CTL) T cell receptors Infected target cell is lysed A normal cell will not trigger a response by a cytotoxic T lymphocyte (CTL), but a virus- infected cell (shown here) or a cancer cell produces abnormal endogenous antigens. The abnormal antigen is presented on the cell surface in association with MHC class I molecules. CD8 + T cells with receptors for the antigen are transformed into CTLs. The CTL induces destruction of the virus-infected cell by apoptosis. Processed antigen presented with MHC class I CTL

© 2013 Pearson Education, Inc. Figure Apoptosis.

© 2013 Pearson Education, Inc. T Regulatory Cells  Suppress T cells against self  Suppress an immune response

© 2013 Pearson Education, Inc.  Kill virus-infected and tumor cells  Attack parasites Natural Killer (NK) Cells

© 2013 Pearson Education, Inc. Cytokines  Chemical messengers  Overproduction leads to cytokine storm

© 2013 Pearson Education, Inc. Immunological Memory  Antibody titer is the amount of Ab in serum  Primary response occurs after initial contact with Ag  Secondary (memory or anamnestic) response occurs after second exposure

© 2013 Pearson Education, Inc. Figure The primary and secondary immune responses to an antigen. IgG IgM Initial exposure to antigen Second exposure to antigen Time (days) Antibody titer in serum

© 2013 Pearson Education, Inc. Types of Adaptive Immunity  Naturally acquired active immunity  Resulting from infection  Naturally acquired passive immunity  Transplacental or via colostrum  Artificially acquired active immunity  Injection of Ag (vaccination)  Artificially acquired passive immunity  Injection of Ab

© 2013 Pearson Education, Inc. Terminology of Adaptive Immunity  Serology: the study of reactions between antibodies and antigens  Antiserum: the generic term for serum because it contains Ab  Globulins: serum proteins  Gamma (  ) globulin: serum fraction containing the most Ab  Immunoglobulins: antibodies

Functional Anatomy of Prokaryotic and Eukaryotic Cells © 2013 Pearson Education, Inc. Lectures prepared by Christine L. Case Chapter 17 Chapter 18 Practical Applications of Immunology

© 2013 Pearson Education, Inc. 500,000 Chapter 18, unnumbered figure B, page 510, Reported numbers of measles cases in the United States, 1960–2010. (CDC, 2010) 350, ,000 50, , , , , , , Year Reported number of cases Year Reported number of cases Vaccine licensed

© 2013 Pearson Education, Inc. Vaccines Used to Prevent Bacterial Diseases DiseaseVaccine DiphtheriaPurified diphtheria toxoid Meningococcal meningitis Purified polysaccharide from Neisseria meningitidis Pertussis (whooping cough) Inactivated toxin plus acellular fragments of Bordetella pertussis Pneumococcal pneumonia Purified polysaccharide from seven strains of Streptococcus pneumoniae TetanusPurified tetanus toxoid Haemophilus influenzae type b meningitis Polysaccharide from Haemophilus influenzae type b conjugated with protein to enhance effectiveness

© 2013 Pearson Education, Inc. DiseaseVaccine InfluenzaInjected vaccine, inactivated virus (nasally administered: attenuated virus) MeaslesAttenuated virus MumpsAttenuated virus RubellaAttenuated virus ChickenpoxAttenuated virus PoliomyelitisKilled virus Vaccines Used to Prevent Viral Diseases

© 2013 Pearson Education, Inc. DiseaseVaccine RabiesKilled virus Hepatitis BAntigenic fragments of virus Hepatitis AInactivated virus SmallpoxLive vaccinia virus Herpes zosterAttenuated virus Human papillomavirusAntigenic fragments of virus Vaccines Used to Prevent Viral Diseases

© 2013 Pearson Education, Inc. Vaccines for Persons Aged 0–6 Years  Hepatitis B  Rotavirus  DTaP  Haemophilus influenzae type b  Pneumococcal  Inactivated poliovirus  Influenza  MMR  Varicella  Hepatitis A  Meningococcal

© 2013 Pearson Education, Inc. Types of Vaccines  Attenuated whole-agent vaccines- living pathogens  MMR vaccine  Inactivated whole-agent vaccines- dead pathogens or inactive viruses  Salk polio vaccine  Toxoids- inactivated toxins; used against toxin the pathogen produces  Tetanus vaccine

© 2013 Pearson Education, Inc. Types of Vaccines  Subunit vaccines- antigenic fragments  Acellular pertussis  Recombinant hepatitis B  Nucleic acid (DNA) vaccines- plasmids  West Nile (for horses)

© 2013 Pearson Education, Inc. Figure 18.1 Influenza viruses are grown in embryonated eggs.

© 2013 Pearson Education, Inc. Safety of Vaccines  No PERFECT vaccine or effects  Therapeutic index  Risk-versus-benefit calculation