broad range of microbes Chapter 43: The Immune System What is the difference between non-specific & specific immunity….aka innate & acquired immunity? INNATE IMMUNITY Rapid responses to a broad range of microbes ACQUIRED IMMUNITY Slower responses to specific microbes External defenses Internal defenses Skin Mucous membranes Secretions Phagocytic cells Antimicrobial proteins Inflammatory response Natural killer cells Humoral response (antibodies) Cell-mediated response (cytotoxic lymphocytes) Invading microbes (pathogens) Phagocytic cells include: Neutrophils Monocytes/macrophages Eosinophils Dendritic cells

Figure 43.4 Phagocytosis Microbes MACROPHAGE Vacuole Lysosome containing enzymes 1 2 3 4 5 6 Pseudopodia surround microbes. are engulfed into cell. microbes forms. and lysosome fuse. Toxic compounds and lysosomal destroy microbes. Microbial debris is released by exocytosis. Microbial debris can either be released or presented for immune system to “see.”

broad range of microbes Chapter 43: The Immune System What is the difference between non-specific & specific immunity….aka innate & acquired immunity? INNATE IMMUNITY Rapid responses to a broad range of microbes ACQUIRED IMMUNITY Slower responses to specific microbes External defenses Internal defenses Skin Mucous membranes Secretions Phagocytic cells Antimicrobial proteins Inflammatory response Natural killer cells Humoral response (antibodies) Cell-mediated response (cytotoxic lymphocytes) Invading microbes (pathogens) Phagocytic cells include: Neutrophils Monocytes/macrophages Eosinophils Dendritic cells Antimicrobial proteins include: Lysozyme Complement system Interferons

Figure 43.6 Major events in the local inflammatory response Pathogen Pin Macrophage Chemical signals Capillary Phagocytic cells Red blood cell Blood clotting elements Blood clot Phagocytosis Fluid, antimicrobial proteins, and clotting elements move from the blood to the site. Clotting begins. 2 Chemical signals released by activated macrophages and mast cells at the injury site cause nearby capillaries to widen and become more permeable. 1 Chemokines released by various kinds of cells attract more phagocytic cells from the blood to the injury site. 3 Neutrophils and macrophages phagocytose pathogens and cell debris at the site, and the tissue heals. 4 Chemicals released: Histamine – causes dilation & increased permeability of capillaries Prostaglandins – increase blood flow to deliver clotting elements thrombin, fibrin, etc.

broad range of microbes Chapter 43: The Immune System What is the difference between non-specific & specific immunity….aka innate & acquired immunity? INNATE IMMUNITY Rapid responses to a broad range of microbes ACQUIRED IMMUNITY Slower responses to specific microbes External defenses Internal defenses Skin Mucous membranes Secretions Phagocytic cells Antimicrobial proteins Inflammatory response Natural killer cells Humoral response (antibodies) Cell-mediated response (cytotoxic lymphocytes) Invading microbes (pathogens) Phagocytic cells include: Neutrophils Monocytes/macrophages Eosinophils Dendritic cells Antimicrobial proteins include: Lysozme Complement system Interferons Natural killer cells

Chapter 43: The Immune System What is the difference between non-specific & specific immunity….aka innate & acquired immunity? Where do these phagocytic cells reside? Lymphatic system – most Tissues & organs – macrophages

Figure 43.5 The human lymphatic system 1 2 3 4 Interstitial fluid bathing the tissues, along with the white blood cells in it, continually enters lymphatic capillaries. Fluid inside the lymphatic capillaries, called lymph, flows through lymphatic vessels throughout the body. Within lymph nodes, microbes and foreign particles present in the circulating lymph encounter macro- phages, dendritic cells, and lymphocytes, which carry out various defensive actions. Lymphatic vessels return lymph to the blood via two large ducts that drain into veins near the shoulders. Adenoid Tonsil Lymph nodes Spleen Peyer’s patches (small intestine) Appendix Lymphatic vessels node Masses of lymphocytes and macrophages Tissue cells vessel Blood capillary Interstitial fluid

broad range of microbes Chapter 43: The Immune System What is the difference between non-specific & specific immunity….aka innate & acquired immunity? Where do these phagocytic cells reside? Lymphatic system – most Tissues & organs – macrophages 3. How does the body mount a specific/acquired immune response? B cells – humoral response T cells – cell-mediated response For both, the cells recognize specific shapes INNATE IMMUNITY Rapid responses to a broad range of microbes ACQUIRED IMMUNITY Slower responses to specific microbes External defenses Internal defenses Skin Mucous membranes Secretions Phagocytic cells Antimicrobial proteins Inflammatory response Natural killer cells Humoral response (antibodies) Cell-mediated response (cytotoxic lymphocytes) Invading microbes (pathogens)

Figure 43.7 Epitopes (antigenic determinants) binding sites Antibody A Antigen Antibody B Antibody C Epitopes (antigenic determinants) Antigen – any foreign molecule recognized by the body – antibody generator Epitope – specific shape recognized by an immune cells Both B cells & T cells have receptors that must be complementary to the epitope

Chapter 43: The Immune System What is the difference between non-specific & specific immunity….aka innate & acquired immunity? Where do these phagocytic cells reside? How does the body mount a specific/acquired immune response? How are the B cell & T cell receptors similar?

Figure 43.8 Antigen receptors on lymphocytes binding site binding site Disulfide bridge Light chain Heavy chains Cytoplasm of B cell b chain Disulfide bridge a chain V C T cell A T cell receptor consists of one chain and one b chain linked by a disulfide bridge. (b) A B cell receptor consists of two identical heavy chains and two identical light chains linked by several disulfide bridges. (a) Variable regions Constant Transmembrane region Plasma membrane B cell Cytoplasm of T cell Constant regions embedded in membrane Variable regions that bind to epitopes (vary) Quarternary proteins B cells – 2 heavy & 2 light chains “Y” T cells – α and β chains - “I”

Chapter 43: The Immune System What is the difference between non-specific & specific immunity….aka innate & acquired immunity? Where do these phagocytic cells reside? How does the body mount a specific/acquired immune response? How are the B cell & T cell receptors similar? How do T cell receptors recognize antigens?

Figure 43.9 The interaction of T cells with MHC molecules Infected cell Antigen fragment Class I MHC molecule T cell receptor Cytotoxic T cell (a) Microbe Antigen- presenting cell Class II MHC Helper T cell (b) 1 2 The combination of MHC molecule and antigen is recognized by a T cell, alerting it to the infection. A fragment of foreign protein (antigen) inside the cell associates with an MHC molecule and is transported to the cell surface. Class I MHC molecule of an infected cell MHC usually empty but now filled TC recognizes filled MHC & tries to form complementary receptor Class II MHC of a phagocytic cell Antigen-presenting cell (APC)

Chapter 43: The Immune System What is the difference between non-specific & specific immunity….aka innate & acquired immunity? Where do these phagocytic cells reside? How does the body mount a specific/acquired immune response? How are the B cell & T cell receptors similar? How do T cell receptors recognize antigens? How does our body recognize “self” from “non-self?” MHC – Major Histocompatibility Complex Cell markers that must be compatible for organ & tissue donations How do B cells & T cells get their name? Where they mature B cells – bone T cells – thymus

Figure 43.10 Overview of lymphocyte development Bone marrow Lymphoid stem cell B cell Thymus T cell Blood, lymph, and lymphoid tissues (lymph nodes, spleen, and others)

Chapter 43: The Immune System What is the difference between non-specific & specific immunity….aka innate & acquired immunity? Where do these phagocytic cells reside? How does the body mount a specific/acquired immune response? How are the B cell & T cell receptors similar? How do T cell receptors recognize antigens? How does our body recognize “self” from “non-self?” How do B cells & T cells get their name? How is the variable region of a receptor formed? Gene rearrangement aka activation NOT ALL CELLS IN OUR BODY HAVE THE SAME DNA

Figure 43.11 Immunoglobulin gene rearrangement DNA of undifferentiated B cell DNA of differentiated pre-mRNA mRNA Cap Transcription of resulting permanently rearranged, functional gene RNA processing (removal of intron; addition of cap and poly (A) tail) B cell receptor Light-chain polypeptide Intron Variable region Constant V1 V2 V3 V4–V39 V40 J1 J2 J3 J4 J5 V C 2 3 4 Translation Poly (A) Deletion of DNA between a V segment and J segment and joining of the segments 1 All variable regions do gene rearrangement – heavy & light (B), α and β (T) Analogous to alternative mRNA splicing but DNA is completely deleted Self-reactive receptors are eliminated

Chapter 43: The Immune System What is the difference between non-specific & specific immunity….aka innate & acquired immunity? Where do these phagocytic cells reside? How does the body mount a specific/acquired immune response? How are the B cell & T cell receptors similar? How do T cell receptors recognize antigens? How does our body recognize “self” from “non-self?” How do B cells & T cells get their name? How is the variable region of a receptor formed? What happens after a receptor binds to an antigen? - Clonal selection

Figure 43.12 Clonal selection of B cells Antigen molecules Antigen receptor B cells that differ in antigen specificity Antibody molecules Clone of memory cells Clone of plasma cells Some proliferating cells develop into long-lived memory cells that can respond rapidly upon subsequent exposure to the same antigen. bind to the antigen receptors of only one of the three B cells shown. The selected B cell proliferates, forming a clone of identical cells bearing receptors for the selecting antigen. Some proliferating cells develop into short-lived plasma cells that secrete antibodies specific for the antigen. Future infections Current infection T cells also go through clonal selection T receptors not released like Ab from B cells Note the ER in plasma/effector cells – secreting cell

Chapter 43: The Immune System What is the difference between non-specific & specific immunity….aka innate & acquired immunity? Where do these phagocytic cells reside? How does the body mount a specific/acquired immune response? How are the B cell & T cell receptors similar? How do T cell receptors recognize antigens? How does our body recognize “self” from “non-self?” How do B cells & T cells get their name? How is the variable region of a receptor formed? What happens after a receptor binds to an antigen? What is the difference between a primary & secondary immune response?

Figure 43.13 The specificity of immunological memory Antibodies to A to B Antibody concentration (arbitrary units) 104 103 102 101 100 7 14 21 28 35 42 49 56 Time (days) Day 1: First exposure to antigen A 1 Primary response to produces anti- bodies to A 2 Day 28: Second exposure to antigen A; first antigen B 3 Secondary response to anti- gen A produces antibodies to A; primary response to anti- gen B produces antibodies to B 4

Chapter 43: The Immune System What is the difference between non-specific & specific immunity….aka innate & acquired immunity? Where do these phagocytic cells reside? How does the body mount a specific/acquired immune response? How are the B cell & T cell receptors similar? How do T cell receptors recognize antigens? How does our body recognize “self” from “non-self?” How do B cells & T cells get their name? How is the variable region of a receptor formed? What happens after a receptor binds to an antigen? What is the difference between a primary & secondary immune response? Let’s consider the immune response….

Figure 43.14 An overview of the acquired immune response - TH Humoral immune response Cell-mediated immune response First exposure to antigen Antigens engulfed and displayed by dendritic cells Activate Gives rise to Helper T cell Active and memory helper T cells (Gene rearrangement) (Clonal selection)

Figure 43.15 The central role of helper T cells in humoral and cell-mediated immune responses After a dendritic cell engulfs and degrades a bacterium, it displays bacterial antigen fragments (peptides) complexed with a class II MHC molecule on the cell surface. A specific helper T cell binds to the displayed complex via its TCR with the aid of CD4. This interaction promotes secretion of cytokines by the dendritic cell. Proliferation of the T cell, stimulated by cytokines from both the dendritic cell and the T cell itself, gives rise to a clone of activated helper T cells (not shown), all with receptors for the same MHC–antigen complex. The cells in this clone secrete other cytokines that help activate B cells and cytotoxic T cells. Cell-mediated immunity (attack on infected cells) Humoral (secretion of antibodies by plasma cells) Dendritic cell Bacterium Peptide antigen Class II MHC molecule TCR CD4 Helper T cell Cytokines Cytotoxic T cell B cell 1 2 3 CD4 on T cell keeps APC bound to T cell during gene rearrangement Cytokines from APC stimulate TH to secrete its own cytokines TH cytokines exert (+) feedback on TH & stimulate TC & B cells

Figure 43.14 An overview of the acquired immune response - TC Humoral immune response Cell-mediated immune response First exposure to antigen Antigens engulfed and displayed by dendritic cells Antigens displayed by infected cells Activate Gives rise to Helper T cell Cytotoxic T cell Active and memory helper T cells Memory cytotoxic T cells Active cytotoxic T cells Defend against infected cells, cancer cells, and transplanted tissues Secreted cytokines activate (Gene rearrangement) (Clonal selection)

Figure 43.16 The killing action of cytotoxic T cells Perforin Granzymes CD8 TCR Class I MHC molecule Target cell Peptide antigen Pore Released cytotoxic T cell Apoptotic target cell Cancer Cytotoxic A specific cytotoxic T cell binds to a class I MHC–antigen complex on a target cell via its TCR with the aid of CD8. This interaction, along with cytokines from helper T cells, leads to the activation of the cytotoxic cell. 1 The activated T cell releases perforin molecules, which form pores in the target cell membrane, and proteolytic enzymes (granzymes), which enter the target cell by endocytosis. 2 The granzymes initiate apoptosis within the target cells, leading to fragmentation of the nucleus, release of small apoptotic bodies, and eventual cell death. The released cytotoxic T cell can attack other target cells. 3 CD8 on T cell keeps infected cell bound to T cell during gene rearrangement Granzymes released from TC digest a hole and allow perforins to create a pore Infected cell commits suicide (apoptosis)

Fig. 43.14 An overview of the acquired immune response – B cells Humoral immune response Cell-mediated immune response First exposure to antigen Intact antigens Antigens engulfed and displayed by dendritic cells Antigens displayed by infected cells Activate Gives rise to B cell Helper T cell Cytotoxic T cell Plasma cells Memory B cells Active and memory helper T cells Memory cytotoxic T cells Active cytotoxic T cells Secrete antibodies that defend against pathogens and toxins in extracellular fluid Defend against infected cells, cancer cells, and transplanted tissues Secreted cytokines activate (Gene rearrangement) (Clonal selection) Pathogens in fluid Infected cells

Figure 43.17 Humoral immune response 2 1 3 B cell Bacterium Peptide antigen Class II MHC molecule TCR Helper T cell CD4 Activated helper T cell Clone of memory B cells Cytokines Clone of plasma cells Secreted antibody molecules Endoplasmic reticulum of plasma cell Macrophage

Chapter 43: The Immune System What is the difference between non-specific & specific immunity….aka innate & acquired immunity? Where do these phagocytic cells reside? How does the body mount a specific/acquired immune response? How are the B cell & T cell receptors similar? How do T cell receptors recognize antigens? How does our body recognize “self” from “non-self?” How do B cells & T cells get their name? How is the variable region of a receptor formed? What happens after a receptor binds to an antigen? What is the difference between a primary & secondary immune response? Let’s consider the immune response…. What are the 5 classes of antibodies? - GAMED

Figure 43.18 The five classes of immunoglobulins First Ig class produced after initial exposure to antigen; then its concentration in the blood declines Promotes neutralization and agglutination of antigens; very effective in complement activation (see Figure 43.19) Most abundant Ig class in blood; also present in tissue fluids Only Ig class that crosses placenta, thus conferring passive immunity on fetus Promotes opsonization, neutralization, and agglutination of antigens; less effective in complement activation than IgM (see Figure 43.19) Present in secretions such as tears, saliva, mucus, and breast milk Provides localized defense of mucous membranes by agglutination and neutralization of antigens (see Figure 43.19) Presence in breast milk confers passive immunity on nursing infant Triggers release from mast cells and basophils of histamine and other chemicals that cause allergic reactions (see Figure 43.20) Present primarily on surface of naive B cells that have not been exposed to antigens Acts as antigen receptor in antigen-stimulated proliferation and differentiation of B cells (clonal selection) IgM (pentamer) IgG (monomer) IgA (dimer) IgE J chain Secretory component Transmembrane region IgD

Chapter 43: The Immune System What is the difference between non-specific & specific immunity….aka innate & acquired immunity? Where do these phagocytic cells reside? How does the body mount a specific/acquired immune response? How are the B cell & T cell receptors similar? How do T cell receptors recognize antigens? How does our body recognize “self” from “non-self?” How do B cells & T cells get their name? How is the variable region of a receptor formed? What happens after a receptor binds to an antigen? What is the difference between a primary & secondary immune response? Let’s consider the immune response…. What are the 5 classes of antibodies? 13. How are antigens removed?

Figure 43.19 Antibody-mediated mechanisms of antigen disposal Binding of antibodies to antigens inactivates antigens by Viral neutralization (blocks binding to host) and opsonization (increases phagocytosis) Agglutination of antigen-bearing particles, such as microbes Precipitation of soluble antigens Activation of complement system and pore formation Bacterium Virus Bacteria Soluble antigens Foreign cell Complement proteins MAC Pore Enhances Phagocytosis Leads to Cell lysis Macrophage MAC – membrane attack complex

Chapter 43: The Immune System What is the difference between non-specific & specific immunity….aka innate & acquired immunity? Where do these phagocytic cells reside? How does the body mount a specific/acquired immune response? How are the B cell & T cell receptors similar? How do T cell receptors recognize antigens? How does our body recognize “self” from “non-self?” How do B cells & T cells get their name? How is the variable region of a receptor formed? What happens after a receptor binds to an antigen? What is the difference between a primary & secondary immune response? Let’s consider the immune response…. What are the 5 classes of antibodies? How are antigens removed? What is the difference between passive & active immunity? Passive – transfer of antibodies – breastfeeding, injection (rabies) Active – body creates its own antibodies during an infection – vaccine What needs to match for blood transfusions? Type – A, B, AB or O Rh factor Pregnancy issues – Rh- mom with prior Rh+ fetus having another Rh+

Based on Glycoproteins on RBC surface

Table 43.1 Blood Groups That Can and Cannot Be Safely Combined in Transfusion Type O- : Universal donor Type AB+ : Universal recipient

Chapter 43: The Immune System What is the difference between non-specific & specific immunity….aka innate & acquired immunity? Where do these phagocytic cells reside? How does the body mount a specific/acquired immune response? How are the B cell & T cell receptors similar? How do T cell receptors recognize antigens? How does our body recognize “self” from “non-self?” How do B cells & T cells get their name? How is the variable region of a receptor formed? What happens after a receptor binds to an antigen? What is the difference between a primary & secondary immune response? Let’s consider the immune response…. What are the 5 classes of antibodies? How are antigens removed? What is the difference between passive & active immunity? What needs to match for blood transfusions? What needs to match for organ transplants? MHC 17. What happens with an allergic response?

Figure 43.20 Mast cells, IgE, and the allergic response IgE antibodies produced in response to initial exposure to an allergen bind to receptors or mast cells. 1 On subsequent exposure to the same allergen, IgE molecules attached to a mast cell recog- nize and bind the allergen. 2 Degranulation of the cell, triggered by cross-linking of adjacent IgE molecules, releases histamine and other chemicals, leading to allergy symptoms. 3 Allergen IgE Histamine Granule Mast cell Allergies are hypersensitivities to allergens Anaphylactic shock – widespread mast cell degranulation causes abrupt dilation of peripheral capillaries & quick drop in BP

Chapter 43: The Immune System What is the difference between non-specific & specific immunity….aka innate & acquired immunity? Where do these phagocytic cells reside? How does the body mount a specific/acquired immune response? How are the B cell & T cell receptors similar? How do T cell receptors recognize antigens? How does our body recognize “self” from “non-self?” How do B cells & T cells get their name? How is the variable region of a receptor formed? What happens after a receptor binds to an antigen? What is the difference between a primary & secondary immune response? Let’s consider the immune response…. What are the 5 classes of antibodies? How are antigens removed? What is the difference between passive & active immunity? What needs to match for blood transfusions? What needs to match for organ transplants? What happens with an allergic response? What are some autoimmune diseases? Lupus Rheumatoid arthritis - Insulin-dependent diabetes - MS – multiple sclerosis

Chapter 43: The Immune System What is the difference between non-specific & specific immunity….aka innate & acquired immunity? Where do these phagocytic cells reside? How does the body mount a specific/acquired immune response? How are the B cell & T cell receptors similar? How do T cell receptors recognize antigens? How does our body recognize “self” from “non-self?” How do B cells & T cells get their name? How is the variable region of a receptor formed? What happens after a receptor binds to an antigen? What is the difference between a primary & secondary immune response? Let’s consider the immune response…. What are the 5 classes of antibodies? How are antigens removed? What is the difference between passive & active immunity? What needs to match for blood transfusions? What needs to match for organ transplants? What happens with an allergic response? What are some autoimmune diseases? What happens with AIDS? - Acquired Immune Deficiency Syndrome