Adaptive Immunity. PowerPoint Lecture Presentations prepared by Mindy Miller-Kittrell, North Carolina State University C H A P T E R

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1 CSLO7. Describe functions of host defenses and the immune system in combating infectious diseases and explain how immunizations protect against specific diseases. PowerPoint Lecture Presentations prepared by Mindy Miller-Kittrell, North Carolina State University C H A P T E R Adaptive Immunity 16

2 FACT 16.1 CONCEPT 16.1 The Body s Third Line of Defense Adaptive Immunity Adaptive immunity is the body's ability to recognize and defend itself against specific pathogens but slower also called Acquired immunity because exposure to pathogens needed for activation Five attributes of adaptive immunity Specificity Inducibility (acquired immunity) Clonality Unresponsiveness to Self Memory

3 CONCEPT 16.1 Adaptive Immunity Involves activity of lymphocytes WBC

4 Two main types of lymphocytes FACT ) B lymphocytes (B cells) Arise and Mature in the bone marrow 2) T lymphocytes (T cells) Lymphocyte Arise in bone marrow but Mature in the thymus

5 6 Elements of Adaptive Immunity The Tissues and Organs of the Lymphatic System Antigens B Lymphocytes (B Cells) and Antibodies T Lymphocytes (T Cells) Clonal Deletion Immune Response Cytokines

6 The Tissues and Organs of the Lymphatic System CONCEPT 16.2 Composed of lymphatic vessels, lymph, lymphatic cells, tissues, and organs Major Function: Return fluid back to blood, Screen the tissues of the body for foreign antigens Lymphatic vessels (One-way system that conducts lymph from tissues and returns it to the circulatory system) Lymph (colorless, watery Liquid with similar composition to blood plasma - arises from fluid leaked from blood vessels into surrounding tissues)

7 Figure 16.2 The lymphatic system. Blood capillary From heart Tissue cell Lymphocytes arise and mature in primary lymphoid organs Bone marrow B cells Thymus T cells To heart FACT 16.3 Intercellular fluid Valve Lymphatic capillary Lymph to heart via lymphatic vessels Gap in wall Tonsils Cervical lymph node Lymphatic ducts Thymus gland Axillary lymph node Heart Breast lymphatics Spleen Abdominal lymph node Intestines Peyer s patches in intestinal wall Appendix Part of mucosaassociated lymphoid tissue (MALT) Afferent Mature Lymphocytes lymphatic vessel Medulla go to Cortex secondary lymphoid organs Valve (prevents backflow) Lymphatic nodule Vein Artery lymph node, spleen, tonsils and MALT (mucosa associated lymphoid tissue) Efferent lymphatic vessel Red bone marrow Inguinal lymph node Lymphatic vessel Capsule Primary follicle

8 Figure 16.2 The lymphatic system. Blood capillary From heart Tissue cell All lymph returned back to blood via heart Intercellular fluid Tonsils CONCEPT 16.2 Cervical lymph node Lymphatic ducts Thymus gland Major Function of lymph: Lymph to heart via lymphatic vessels Gap in wall Valve Return fluid back to blood, To heart Screen the tissues Lymphatic of the capillary body for foreign antigens Axillary lymph node Heart Breast lymphatics Spleen Abdominal lymph node Intestines Peyer s patches in intestinal wall Appendix Part of mucosaassociated lymphoid tissue (MALT) Valve (prevents backflow) Cortex Afferent lymphatic vessel Medulla Vein Artery Red bone marrow Inguinal lymph node Lymphatic vessel Lymphatic nodule Efferent lymphatic vessel Capsule Primary follicle

9 Figure 16.2 The lymphatic system. Blood capillary From heart Tissue cell CONCEPT 16.2 Intercellular fluid Lymph to heart via lymphatic vessels Lymph carries toxins/pathogens Gap in wall Valve To heart lymph node Cortex Afferent lymphatic vessel Lymphatic capillary Medulla On the way flows through 1000 lymph nodes which contain lymphocytes Vein Valve (prevents backflow) Artery Lymphatic nodule Efferent lymphatic vessel Capsule Primary follicle

10 CONCEPT 16.3 To heart FACT 16.3 Many afferent (inbound) One/two efferent (outbound) Valve (prevents backflow) Cortex Afferent lymphatic vessel Medulla Vein Artery Facilitates interaction between pathogens and immune cells and material in lymph Lymphatic nodule Efferent lymphatic vessel Capsule contains primary follicles site of clones of B cells which proliferate Flows in one direction towards the heart Lymph Node

11 6 Elements of Adaptive Immunity The Tissues and Organs of the Lymphatic System Antigens B Lymphocytes (B Cells) and Antibodies T Lymphocytes (T Cells) Clonal Deletion Immune Response Cytokines

12 What are Antigens? CONCEPT 16.4 Antigens (biochemical shapes) Molecules the body recognizes as foreign and worthy of attack Antigens recognized by three-dimensional regions called epitopes on antigens e.g. bacterial or viral molecules lipid A or other toxins Egg, Nut, Penicillin Allergy?

13 Figure 16.3b-d Antigens are molecules that provoke a specific immune response. Extracellular microbes Endogenous antigens CONCEPT 16.5 Autoantigens (normal cell antigens) Intracellular virus Exogenous antigens Virally infected cell Autoantigens Normal (uninfected) cell Self tolerance Immune cells which treat autoantigens as foreign are eliminated Endogenous antigens

14 6 Elements of Adaptive Immunity The Tissues and Organs of the Lymphatic System Antigens B Lymphocytes (B Cells) and Antibodies T Lymphocytes (T Cells) Clonal Deletion Immune Response Cytokines

15 B Lymphocytes (B Cells) CONCEPT 16.6 Found primarily in the spleen, lymph nodes, and MALT Small percentage of B cells circulate in the blood Major function is the secretion of antibodies (humoral immunity) which especially works against extracellular pathogens and toxins Antigen Each of the antibody act against a specific antigen Antigen Binding Site Exact binding between ABS and epitope is responsible for specificity of an antibody immune response

16 Figure 16.5 Basic antibody structure. ABS FACT 16.4

17 activation Activated B-lymphocyte Called Plasma cells CONCEPT 16.7 produce B-lymphocyte B-cell Receptor (BCR) Similar in structure to antibodies but attached to membrane clones with same specificity

18 CONCEPT 16.8 Heavy chain Light chain Epitope Antigenbinding sites Variable region Variable region B cell receptor (BCR) Disulfide bond Each B lymphocyte has multiple copies of the BCR- All identical and able to bind a specific antigen Cytoplasmic membrane of B lymphocyte Cytoplasm

19 FACT 16.5

20 5 Classes of antibodies FACT 16.5 IgG highest numbers 80% in blood - and longest-lasting antibody only antibody to cross placenta and protect developing child IgM first antibody produced pentamer best for complement activation Class switching IgM to IgG IgA associated with body secretions mono/dimers tears/saliva/milk IgE involved in response to parasitic infections and allergies IgD exact function is not known not secreted but membrane bound

21 Pathogenic antigen IgM BCR Class switching Ist makes IgM then it makes IgG Activated B cell is called Plasma cell IgG CONCEPT 16.9

22 Figure T-independent antigen by a B cell. Polysaccharide with repeating subunits BCRs Plasma cells B cell T-independent response by B cells is Fast but there is no memory Antibodies CONCEPT 16.10

23 Antibody function CONCEPT ) Antigen-binding sites are complementary to epitopes 2) Antibodies function epitope mediated by stem Activation of complement and inflammation Neutralization Opsonization Killing by oxidation Agglutination Stem part Antibody-dependent cellular cytotoxicity (ADCC)

24 Figure 16.6 Functions of antibodies. Adhesin proteins Bacterium Soluble becomes insoluble Toxin Virus 1 Neutralization 3 Agglutination NK lymphocyte Opsonization F c receptor protein Pseudopod of phagocyte 4 F c receptor protein Perforin allows granzyme to enter, triggers apoptosis and lysis Antibody-dependent cellular cytotoxicity (ADCC) 2 Oxidation Bacteria die CONCEPT 16.11

25 Figure 16.6 functions of antibodies. Neutralization Adhesin Opsonins coat Pathogens proteins and stimulate phagocytosis IgA Toxin Opsonins e.g. IgG Bacterium Virus CONCEPT Agglutination Opsonization - changing the surface of an antigen to enhance phagocytosis NK lymphocyte IgG F c receptor protein Oxidation Pseudopod of phagocyte Neutrophils and macrophages F c receptor protein Perforin allows granzyme to enter, triggers apoptosis and lysis Antibody-dependent cellular cytotoxicity (ADCC) Bacteria die

26 Classical pathway Antigen Alternative pathway C3b Endotoxin and glycoproteins Lectin pathway Mannose Lectins Antibody C3b Factors B, D, and P Complement proteins 1, 2, 4 Complement proteins Complement cascade Activation (C3 C3a + C3b) Opsonization Inflammation C5 convertases C5 C5a + C5b Inflammation Membrane attack complex and cell lysis

27 all Activate complement Figure 15.9 The classical pathway and complement cascade. IgM 1 H 2 O H 2 O H 2 O C1 becomes an active enzyme when it binds to antibody-antigen complexes. Pathogen Enzymatic C1 Antigen Antibody Membrane attack complex Causes chemotaxis of phagocytes and triggers inflammation Causes inflammation C9 C9 C5a C9 C9 C9 C9 C9 C9 C9 C9 C8 C7 C5b C6 C5b 6 5 Cytoplasmic membrane H 2 O C5b combines with C6, C7, C8, and several molecules of C9 to form a membrane attack complex (MAC). A MAC drills a circular hole in the pathogen s cytoplasmic membrane, leading to lysis of the cell. This enzyme cleaves C5 into C5a and C5b. 2 Enzyme C1 splits molecules of C2 and of C4. Complement cascade 3 Fragments of C2 and C4 combine to form a second enzyme that splits C3 into C3a and C3b. 4 Causes chemotaxis of phagocytes and triggers inflammation C3b combines with the remaining fragments of C2 and C4 to form a third enzyme. Acts as opsonin

28 6 Elements of Adaptive Immunity The Tissues and Organs of the Lymphatic System Antigens B Lymphocytes (B Cells) and Antibodies T Lymphocytes (T Cells) Clonal Deletion Immune Response Cytokines

29 T Lymphocytes (T Cells) 70-85% of all lymphocytes in blood Cell-mediated immune responses (T cells) especially intracellular pathogens e.g. cells infected with viruses Have T cell receptors (TCRs) on their cytoplasmic membrane FACT 16.6 CONCEPT 16.13

30 X Dendritic cells (also tumor cells) MHC + antigen TCR Antigen presentation T cells perform cell-mediated immune response FACT 16.7 CONCEPT 16.14

31 Figure The two classes of major histocompatibility complex (MHC) proteins. Antigen-binding sites (grooves) TCR Class I MHC on every nucleated cell Cytoplasmic membrane FACT 16.8 CONCEPT Class II MHC on B cell or other antigen-presenting cell (APC) MHC B cells, macrophages, dendritic cells Cytoplasm

32 TCRs only bind epitopes associated with an MHC protein T cells act primarily against cells that harbor intracellular pathogens Some T cells act against body cells that produce abnormal cell-surface proteins e.g. cancer cells Do not secrete antibodies but act directly against cells therefore called cell-mediated immune response

33 What are MHC? FACT 16.8 The Roles of the Major Histocompatibility Complex and Antigen-Presenting Cells Group of antigens first identified in graft patients Important in determining compatibility of tissues for tissue grafting Major histocompatibility antigens are glycoproteins found in the membranes of most cells of vertebrate animals Hold and position antigenic determinants for presentation to T cells

34 Preparation for an Adaptive Immune Response Antigen Processing Antigens processed for MHC proteins to display epitopes Different processes for 1) endogenous antigens and 2) exogenous antigens FACT 16.9 CONCEPT 16.16

35 Figure The processing of T-dependent endogenous antigens. by all cells Class I MHC on every nucleated cell 1 Polypeptide is catabolized. MHC I protein in membrane of endoplasmic reticulum Epitopes MHC I protein epitope complex 2 Lumen of endoplasmic reticulum Epitopes are loaded onto complementary MHC I proteins in the ER. 3 Golgi bodies package MHC I protein epitope complexes into vesicles. endogenous antigens = Class I MHC 4 Vesicles fuse with cytoplasmic membrane. FACT 16.9 CONCEPT Cytoplasmic membrane 5 MHC I protein epitope complexes on cell surface MHC I protein epitope complexes are displayed on cytoplasmic membranes of all nucleated cells.

36 Figure The processing of T-dependent exogenous antigens by APCs mostly dendritic cells Phagocytosis by APC Exogenous pathogen with antigens MHC II protein epitope complex 1 MHC II protein in membrane of vesicle Epitopes in phagolysosome 2 Vesicles fuse and epitopes bind to complementary MHC II molecules. exogenous antigens = Class II MHC Class II MHC on B cell or other antigen-presenting cell (APC) FACT 16.9 CONCEPT Vesicle fuses with cytoplasmic membrane. MHC II protein epitope complexes on cell surface Cytoplasmic membrane MHC II protein epitope complexes are displayed on cytoplasmic membranes of antigenpresenting cell.

37 Types of T lymphocytes FACT Based on surface glycoproteins and characteristic functions, three types 1) Cytotoxic T lymphocyte (Tc or CD8) Directly kills other cells 2) Helper T lymphocyte (Th or CD4) produces cytokines AIDS binds CD4 Helps regulate B cells and cytotoxic T cells Includes type 1 and type 2 helper T cells 3) Regulatory T lymphocyte (Tr or CD4/CD25) produces cytokines -prevents autoimmune diseases

38 Figure 16.15a A cell-mediated immune response. FACT Active cytotoxic T (Tc) cell TCR Viral epitope MHC I protein CD8 KILL 2 different methods Virally infected cell Intracellular virus

39 Figure 16.15b-c A cell-mediated immune response. FACT modes in which Tc kills perforin granzyme or CD95 cytotoxic pathway. Tc cell Perforin Granzyme Tc cell Inactive apoptotic enzymes Perforin complex (pore) Granzymes activate apoptotic enzymes Active enzymes induce apoptosis Inactive apoptotic enzymes CD95L CD95 Enzymatic portion of CD95 becomes active Active enzymes induceapoptosis Virally infected cell Virally infected cell

40 Figure 16.15a A cell-mediated immune response. How do Tc cells get activated Active cytotoxic T (Tc) cell TCR Viral epitope MHC I protein CD8 KILL Virally infected cell Intracellular virus CONCEPT 16.17

41 Figure Activation of a clone of cytotoxic T (Tc) cells. 1 1 Antigen presentation Dendritic cell MHC I MHC II Epitope TCR DC MHC I CD8 Epitope TCR 2 2 Th cell Th differentiation Th1 cell activates Tc cell. Immune Response Cytokines Th1 cell 4 IL-2R IL-2R IL-2 IL-2 IL-12 Active Tc cells IL-2 Self-stimulation 4 Inactive Tc cell IL-2 receptor (IL-2R) 3 Tc cell Immunological synapse Clonal expansion Memory T cell An enhanced cell mediated immune response upon subsequent exposure to the same antigen is called a memory response Active Tc cells 3 IL-2 CONCEPT 16.17

42 Figure A T-dependent antibody immune response. Repertoire of Th cells (CD4 cells) Th cell CD4 TCR Epitope CD4 CD28 TCRs 1 APC presents antigen to Th cells for Th activation and cloning. APC MHC II APC CD80 (or CD86) 2 Th cell differentiates into Th2 cell. Th cell clones IL-4 CCR3 CCR4 Th2 cell MHC II proteins T-dependent response by B cells is slow but has memory Repertoire of B cells IL-4 3 Th2 cell TCR Epitope MHC II Th2 cell B cell CD4 Th2 cell activates B cell. CD40L CD40 Clone of plasma cells 4 CONCEPT Antibodies Memory B cells

43 6 Elements of Adaptive Immunity The Tissues and Organs of the Lymphatic System Antigens B Lymphocytes (B Cells) and Antibodies T Lymphocytes (T Cells) Clonal Deletion Immune Response Cytokines

44 CONCEPT Clonal Deletion elimination of a cell kills its offsprings (clones) Vital that immune responses not be directed against autoantigens Immune system must be tolerant of self impaired leads to autoimmune disease Body eliminates self-reactive lymphocytes Lymphocytes that react to autoantigens undergo apoptosis

45 Figure 16.9 Clonal deletion of B cells. Stem cell (in red bone marrow) CONCEPT Cell with autoantigens BCRs with 3 differently shaped binding sites B cells Cell with autoantigens End result is those which recognize autoantigens are eliminated 4 Apoptosis Blood vessel To spleen

46 Figure 16.8 Clonal deletion of T cells. Stem cell (in red bone marrow) CONCEPT Thymus Thymus cells 2 MHC TCRs with differently shaped binding sites Epitope Recognize MHC? No 3 Yes Receive survival signal T cells Thymus cells Thymus cells express all proteins in a body End result is those which recognize MHC but do not recognize autoantigens survive Others eliminated Apoptosis 4 Recognize MHC-autoantigen? No Yes Few Most Apoptosis Repertoire of immature Tc cells Regulatory T cell (Tr)

47 6 Elements of Adaptive Immunity The Tissues and Organs of the Lymphatic System Antigens B Lymphocytes (B Cells) and Antibodies T Lymphocytes (T Cells) Clonal Deletion Immune Response Cytokines

48 CONCEPT Immune Response Cytokines Soluble regulatory proteins that act as intercellular signals secreted by various leukocytes and form network Interleukins (ILs) Signal among leukocytes Interferons (IFNs) Antiviral proteins that may act as cytokines Growth factors Proteins that stimulate stem cells to divide Tumor necrosis factor (TNF) Secreted by macrophages and T cells to kill tumor cells and regulate immune responses and inflammation Chemokines Chemotactic cytokines that signal leukocytes to move

49 Figure The production of primary and secondary antibody immune responses. CONCEPT Secondary response = faster, greater and different antibody profile Because of memory B cells CLASS SWITCHING Same B cells make antibodies with same specificity but different Fc stem memory B cells Faster, stronger response

50 Types of Acquired Immunity (Specific immunity acquired during an individual's life) CONCEPT ) Naturally acquired (active or passive) Response against antigens encountered in daily life Active infections Passive (womb) IgG cross placenta (newborn) IgA in breast milk 2) Artificially acquired (active or passive) Response to antigens introduced via a vaccine Active antigens in vaccine Passive antibodies/antisera or antitoxins from others Active = slow but have memory Passive = fast but no memory

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