Chapter 43 The Immune System

Overview: Reconnaissance, Recognition, and Response An animal must defend itself from the many dangerous pathogens it may encounter Two major kinds of defense have evolved: innate immunity and acquired immunity

Innate immunity is present before any exposure to pathogens and is effective from the time of birth It involves nonspecific responses to pathogens Innate immunity consists of external barriers plus internal cellular and chemical defenses Key internal defenses are macrophages and other phagocytic cells

LE 43-1 3 µm

Acquired immunity, or adaptive immunity, develops after exposure to agents such as microbes, toxins, or other foreign substances It involves a very specific response to pathogens Recognition is by white blood cells called lymphocytes Some lymphocytes produce antibodies; others destroy infected cells, cancer cells, or foreign tissue

broad range of microbes LE 43-2 INNATE IMMUNITY Rapid responses to a broad range of microbes ACQUIRED IMMUNITY Slower responses to specific microbes External defenses Internal defenses Skin Phagocytic cells Humoral response (antibodies) Mucous membranes Antimicrobial proteins Secretions Inflammatory response Invading microbes (pathogens) Cell-mediated response (cytotoxic lymphocytes) Natural killer cells

Concept 43.1: Innate immunity provides broad defenses against infection A pathogen that breaks through external defenses encounters innate cellular and chemical mechanisms that impede its attack

External Defenses Skin and mucous membranes are physical barriers to entry of microorganisms and viruses Mucous membrane cells produce mucus, a viscous fluid that traps microbes and other particles In the trachea, ciliated epithelial cells sweep mucus and any entrapped microbes upward, preventing microbes from entering the lungs

LE 43-3 10 µm

Secretions of the skin and mucous membranes provide an environment hostile to microbes Secretions give the skin a pH between 3 and 5, acidic enough to prevent colonization of many microbes Skin secretions include proteins such as lysozyme (present in saliva, tears, and mucous secretions), which digests bacterial cell walls

Internal Cellular and Chemical Defenses Internal cellular defenses depend mainly on phagocytosis White blood cells called phagocytes ingest microorganisms and initiate inflammation

Phagocytic Cells Phagocytes attach to prey via surface receptors (such as certain polysaccharides on the surface of bacteria) and engulf them, forming a vacuole that fuses with a lysosome.

LE 43-4 Microbes Pseudopodia MACROPHAGE Vacuole Lysosome containing enzymes

Macrophages, a type of phagocyte, migrate through the body and are found in organs of the lymphatic system The lymphatic system defends against pathogens

LE 43-5 Interstitial fluid Lymphatic capillary Adenoid Tonsil Blood capillary Lymph nodes Spleen Lymphatic vessel Tissue cells Peyer’s patches (small intestine) Appendix Lymphatic vessels Lymph node Masses of lymphocytes and macrophages

Inflammatory Response In local inflammation, histamine and other chemicals released from injured cells promote changes in blood vessels These changes allow more fluid, phagocytes, and antimicrobial proteins to enter tissues

LE 43-6 Pathogen Pin Blood clot Macrophage Blood clotting elements Chemical signals Phagocytic cells Capillary Phagocytosis Red blood cell

Natural Killer Cells Natural killer (NK) cells attack virus-infected body cells and cancer cells They trigger apoptosis in the cells they attack

Concept 43.2: In acquired immunity, lymphocytes provide specific defenses against infection Acquired immunity is the body’s second major kind of defense An antigen is a foreign molecule that is recognized by lymphocytes and elicits a response from them A lymphocyte recognizes and binds to a small portion of the antigen called an epitope

Antigen- binding Epitopes sites (antigenic determinants) Antibody A LE 43-7 Antigen- binding sites Epitopes (antigenic determinants) Antibody A Antigen Antibody B Antibody C

Antigen Recognition by Lymphocytes Two main types of lymphocytes circulate in the blood of vertebrates: B lymphocytes (B cells) and T lymphocytes (T cells) A single B cell or T cell has about 100,000 identical antigen receptors All antigen receptors on a single cell recognize the same epitope

B Cell Receptors for Antigens B cell receptors bind to specific, intact antigens Secreted antibodies, or immunoglobulins, are structurally similar to B cell receptors but lack transmembrane regions that anchor receptors in the plasma membrane Video: T Cell Receptors

LE 43-8 Antigen- binding site Antigen- binding site Antigen- binding Disulfide bridge V V Light chain V V Variable regions C V V C C C Constant regions C C Transmembrane region Plasma membrane  chain b chain Heavy chains Disulfide bridge B cell Cytoplasm of B cell Cytoplasm of T cell T cell A B cell receptor consists of two identical heavy chains and two identical light chains linked by several disulfide bridges. A T cell receptor consists of one a chain and one b chain linked by a disulfide bridge.

T Cell Receptors for Antigens and the Role of the MHC Each T cell receptor consists of two different polypeptide chains V V C C

T cells bind to antigen fragments that are bound to cell-surface proteins called MHC molecules MHC molecules are so named because they are encoded by a family of genes called the major histocompatibility complex

Infected cells produce MHC molecules, which bind to antigen fragments and are transported to the cell surface, a process called antigen presentation A nearby T cell can then detect the antigen fragment displayed on the cell’s surface Depending on their source, peptide antigens are handled by different classes of MHC molecules

Class I MHC molecules are found on almost all nucleated cells of the body They display peptide antigens to cytotoxic T cells

Infected cell Microbe Antigen- presenting cell Antigen fragment LE 43-9 Infected cell Microbe Antigen- presenting cell Antigen fragment Antigen fragment Class I MHC molecule Class II MHC molecule T cell receptor T cell receptor Cytotoxic T cell Helper T cell

Class II MHC molecules are located mainly on dendritic cells, macrophages, and B cells They display antigens to helper T cells

Lymphocyte Development Lymphocytes arise from stem cells in bone marrow Newly formed lymphocytes are alike but later develop into B cells or T cells, depending on where they mature

Blood, lymph, and lymphoid tissues (lymph nodes, spleen, and others) Bone marrow Thymus Lymphoid stem cell B cell T cell Blood, lymph, and lymphoid tissues (lymph nodes, spleen, and others)

Generation of Lymphocyte Diversity by Gene Rearrangement Random, permanent gene rearrangement forms functional genes encoding the B or T cell antigen receptor chains

LE 43-11 V4–V39 DNA of undifferentiated B cell V1 V2 V3 V40 J1 J2 J3 Intron C Deletion of DNA between a V segment and J segment and joining of the segments DNA of differentiated B cell V1 V2 V3 J5 Intron C Functional gene Transcription of resulting permanently rearranged, functional gene pre-mRNA V3 J5 Intron C RNA processing (removal of intron; addition of cap and poly (A) tail) mRNA Cap V3 J5 C Poly (A) Translation Light-chain polypeptide V C B cell receptor Variable region Constant region B cell

Testing and Removal of Self-Reactive Lymphocytes As B and T cells mature in the bone and thymus, their antigen receptors are tested for self-reactivity Lymphocytes with receptors for antigens that are already in the body are destroyed by apoptosis or rendered nonfunctional

Clonal Selection of Lymphocytes In a primary immune response, binding of antigen to a mature lymphocyte induces the lymphocyte’s proliferation and differentiation This process is called clonal selection Clonal selection of B cells generates a clone of short-lived activated effector cells and a clone of long-lived memory cells Animation: Role of B Cells

LE 43-12 Antigen molecules B cells that differ in antigen specificity receptor Antibody molecules Clone of memory cells Clone of plasma cells

In the secondary immune response, memory cells facilitate a faster, more efficient response

Concept 43.3: Humoral and cell-mediated immunity defend against different types of threats Humoral immune response involves activation and clonal selection of B cells, resulting in production of secreted antibodies Cell-mediated immune response involves activation and clonal selection of cytotoxic T cells

LE 43-14_3 Humoral immune response Cell-mediated immune response First exposure to antigen Antigens engulfed and displayed by dendritic cells Antigens displayed by infected cells Intact antigens Activate Activate Activate Secreted cytokines activate B cells Helper T cell Cytotoxic T cell Gives rise to Gives rise to Gives rise to Active and memory helper T cells Memory cytotoxic T cells Active cytotoxic T cells Plasma cells Memory B cells Secrete antibodies that defend against pathogens and toxins in extracellular fluid Defend against infected cells, cancer cells, and transplanted tissues

Helper T Cells: A Response to Nearly All Antigens A surface protein called CD4 binds the class II MHC molecule This binding keeps the helper T cell joined to the antigen-presenting cell while activation occurs Activated helper T cells secrete cytokines that stimulate other lymphocytes Animation: Helper T Cells

LE 43-15 Peptide antigen Dendritic cell Cytotoxic T cell Class II MHC molecule Helper T cell Cell-mediated immunity (attack on infected cells) Bacterium TCR Humoral immunity (secretion of antibodies by plasma cells) CD4 Dendritic cell Cytokines B cell

Cytotoxic T Cells: A Response to Infected Cells and Cancer Cells Cytotoxic T cells make CD8, a surface protein that greatly enhances interaction between a target cell and a cytotoxic T cell Binding to a class I MHC complex on an infected cell activates a cytotoxic T cell and makes it an active killer The activated cytotoxic T cell secretes proteins that destroy the infected target cell

LE 43-16 Released cytotoxic T cell Cytotoxic T cell Perforin Cancer Granzymes TCR CD8 Apoptotic target cell Class I MHC molecule Pore Target cell Peptide antigen Cytotoxic T cell

Animation: Cytotoxic T Cells

Antibody Classes The five major classes of antibodies, or immunoglobulins, differ in distribution and function

B Cells: A Response to Extracellular Pathogens Activation of B cells is aided by cytokines and antigen binding to helper T cells Clonal selection of B cells generates antibody-secreting plasma cells, the effector cells of humoral immunity

LE 43-17 Macrophage Bacterium Peptide antigen B cell Class II MHC molecule Secreted antibody molecules Clone of plasma cells TCR CD4 + Endoplasmic reticulum of plasma cell Cytokines Helper T cell Activated helper T cell Clone of memory B cells

Antibody-Mediated Disposal of Antigens The binding of antibodies to antigens is also the basis of antigen-disposal mechanisms Microbes are eliminated by phagocytosis and complement-mediated lysis Animation: Antibodies

LE 43-19 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 Complement proteins Virus Bacteria MAC Pore Bacterium Soluble antigens Foreign cell Enhances Leads to Phagocytosis Cell lysis Macrophage

Active and Passive Immunization Active immunity develops naturally in response to an infection It can also develop following immunization, also called vaccination In immunization, a nonpathogenic form of a microbe or part of a microbe elicits an immune response to an immunological memory

Passive immunity provides immediate, short-term protection It is conferred naturally when IgG crosses the placenta from mother to fetus or when IgA passes from mother to infant in breast milk It can be conferred artificially by injecting antibodies into a nonimmune person

The immune system can wage war against cells from other individuals Concept 43.4: The immune system’s ability to distinguish self from nonself limits tissue transplantation The immune system can wage war against cells from other individuals Transplanted tissues are usually destroyed by the recipient’s immune system

Blood Groups and Transfusions Antigens on red blood cells determine whether a person has type A, B, AB, or O blood Antibodies to nonself blood types exist in the body Transfusion with incompatible blood leads to destruction of the transfused cells Recipient-donor combinations can be fatal or safe

A red blood cell antigen called the Rh factor creates difficulties when an Rh-negative mother carries successive Rh-positive fetuses

Tissue and Organ Transplants MHC molecules stimulate rejection of tissue grafts and organ transplants

Chances of successful transplantation increase if donor and recipient MHC tissue types are well matched Immunosuppressive drugs facilitate transplantation Lymphocytes in bone marrow transplants may cause a graft versus host reaction in recipients

Concept 43.5: Exaggerated, self-directed, or diminished immune responses can cause disease If the delicate balance of the immune system is disrupted, effects range from minor to often fatal

Allergies Allergies are exaggerated (hypersensitive) responses to antigens called allergens In localized allergies such as hay fever, IgE antibodies produced after first exposure to an allergen attach to receptors on mast cells

The next time the allergen enters the body, it binds to mast cell–associated IgE molecules Mast cells release histamine and other mediators that cause vascular changes leading to typical allergy symptoms An acute allergic response can lead to anaphylactic shock, a life-threatening reaction that can occur within seconds of allergen exposure

LE 43-20 IgE Histamine Allergen Granule Mast cell

Autoimmune Diseases In individuals with autoimmune diseases, the immune system loses tolerance for self and turns against certain molecules of the body Rheumatoid arthritis is an autoimmune disease leading to damage and inflammation of joints

Other examples of autoimmune diseases: Systemic lupus erythematosus Multiple sclerosis Insulin-dependent diabetes

Immunodeficiency Diseases Inborn or primary immunodeficiency results from hereditary or congenital defects that prevent proper functioning of innate, humoral, and/or cell-mediated defenses Acquired or secondary immunodeficiency results from exposure to chemical and biological agents

Inborn (Primary) Immunodeficiencies In severe combined immunodeficiency (SCID), both the humoral and cell-mediated branches of acquired immunity fail to function

Acquired (Secondary) Immunodeficiencies Acquired immunodeficiencies range from temporary states to chronic diseases

Stress and the Immune System Growing evidence shows that physical and emotional stress can harm immunity

Acquired Immunodeficiency Syndrome (AIDS) People with AIDS are highly susceptible to opportunistic infections and cancers that take advantage of an immune system in collapse Because AIDS arises from loss of helper T cells, it impairs both the humoral and cell-mediated immune responses The loss of helper T cells results from infection by the human immunodeficiency virus (HIV) Animation: HIV Reproductive Cycle

The spread of HIV is a worldwide problem The best approach for slowing this spread is education about practices that transmit the virus