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Immune System Types of Immunity: Innate: non-specific, all plants and animals have it Adaptive: pathogen-specific, only in vertebrates, involves B and T cells Plant Defenses:• Nonspecific responses• Receptors recognize pathogen molecules and trigger defense responses– Thicken cell wall, produce antimicrobial compounds, cell death• Localize effects Animal Defenses: INNATE (all animals)Recognition of traits shared by broad ranges of pathogens, using a small set of receptorsRapid response Barrier defenses include: Skin mucous membranes secretions – lysozyme in tears, saliva, mucusInternal Defenses include: phagocytic white blood cells (WBCs): Neutrophils (engulf) Macrophage (“big eaters”) Eosinophils (parasites) Dendritic cells (adaptive response) natural killer cells – go after virus-infected and cancer cells antimicrobial proteins: Interferons (inhibit viral reproduction) Complement system (~30 proteins, membrane attack complex) inflammatory response: Mast cells release histamine Blood vessels dilate, increase permeability (redness, swelling) Deliver clotting agents, phagocytic cells Fever ADAPTIVE (vertebrates only)Recognition of traits specific to particular pathogens, using a vast array of receptorsSlower responseLymphatic System: involved in adaptive immunity Humoral response: antibodies defend against infection in body fluidsCell-mediated response: cytotoxic cells defend against infection in body cells Lymphocytes (WBCs): produced by stem cells in bone marrow• T cells: mature in thymus– helper T, cytotoxic T• B cells: stay and mature in bone marrow– plasma cells à antibodies • Antigen: substance that elicits lymphocyte response• Antibody (immunoglobulin – Ig): protein made by B cell that binds to antigens Major Histocompatibility Complex (MHC)Proteins displayed on cell surfaceResponsible for tissue/organ rejection (“self” vs. “non-self”)B and T cells bind to MHC molecule in adaptive responseClass I: all body cells (except RBCs)Class II: displayed by immune cells; “non-self” Origin of Self-Tolerance• Antigen receptors are generated by random rearrangement of DNA• As lymphocytes mature in bone marrow or the thymus, they are tested for self-reactivity• Some B and T cells with receptors specific for the body’s own molecules are destroyed by apoptosis, or programmed cell death• The remainder are rendered nonfunctional Proliferation of B cells and T cells• In the body there are few lymphocytes with antigen receptors for any particular epitope• In the lymph nodes, an antigen is exposed to a steady stream of lymphocytes until a match is made• This binding of a mature lymphocyte to an antigen initiates events that activate the lymphocyte• Once activated, a B or T cell undergoes multiple cell divisions• This proliferation of lymphocytes is called clonal selection• Two types of clones are produced: short-lived activated effector cells that act immediately against the antigen and long-lived memory cells that can give rise to effector cells if the same antigen is encountered again Immunological Memory• Primary immune response: 1st exposure to antigen• Memory cells:– Secondary immune response: repeat exposure à faster, greater response Adaptive immunity defends against infection of body fluids and body cells• Acquired immunity has two branches: the humoral immune response and the cell-mediated immune response• In the humoral immune response antibodies help neutralize or eliminate toxins and pathogens in the blood and lymph• In the cell-mediated immune response specialized T cells destroy affected host cells Helper T Cells: A response to nearly all antigens• A type of T cell called a helper t cell triggers both the humoral and cell-mediated immune responses• Signals from helper T cells initiate production of antibodies that neutralize pathogens and activate T cells that kill infected cells• Antigen-presenting cells have class I and class II MHC molecules on their surfaces• Class II MHC molecules are the basis upon which antigen-presenting cells are recognized• Antigen receptors on the surface of helper T cells bind to the antigen and the class II MHC molecule; then signals are exchanged between the two cells• The helper T cell is activated, proliferates, and forms a clone of helper T cells, which then activate the appropriate B cells Cytotoxic T cells: A response to infected cells• Cytotoxic T cells are the effector cells in the cell-mediated immune response• Cytotoxic T cells recognize fragments of foreign proteins produced by infected cells and possess an accessory protein that binds to class I MHC molecules• The activated cytotoxic T cell secretes proteins that disrupt the membranes of target cells and trigger apoptosis B Cells and Antibodies: a response to extracellular pathogens• The humoral response is characterized by secretion of antibodies by B cells• Activation of the humoral immune response involves B cells and helper T cells as well as proteins on the surface of pathogens• In response to cytokines from helper T cells and an antigen, a B cell proliferates and differentiates into memory B cells and antibody secreting effector cells called plasma cells Antibody function• Antibodies do not kill pathogens; instead they mark pathogens for destruction• In neutralization, antibodies bind to viral surface proteins preventing infection of a host cell• Antibodies may also bind to toxins in body fluids and prevent them from entering body cells• In opsonization, antibodies bind to antigens on bacteria creating a target for macrophages or neutrophils, triggering phagocytosis• Antigen-antibody complexes may bind to a complement protein—which triggers a cascade of complement protein activation• Ultimately a membrane attack complex forms a pore in the membrane of the foreign cell, leading to its lysis• B cells can express five different forms (or classes) of immunoglobulin (Ig) with similar antigen-binding specificity but different heavy chain C regions• IgD: Membrane bound• IgM: First soluble class produced• IgG: Second soluble class; most abundant• IgA and IgE: Remaining soluble classes Immunizations/vaccines: induce immune memory to nonpathogenic microbe or toxinPassive immunity: via antibodies in breast milkAllergies: hypersensitive responses to harmless antigensAutoimmune Diseases:– Lupus, rheumatoid arthritis, Type I diabetes, multiple sclerosisHIV: infect Helper T cells– AIDS = severely weakened immune system Immune rejection• Cells transferred from one person to another can be attacked by immune defenses• This complicates blood transfusions or the transplant of tissues or organs Blood Groups• Antigens on red blood cells determine whether a person has blood type A (A antigen), B (B antigen), AB (both A and B antigens), or O (neither antigen)• 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 Tissue and Organ Transplants• MHC molecules are different among genetically nonidentical individuals• Differences in 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 the donor tissue to reject the recipient Allergic reactions• When 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, within seconds of allergen exposure Autoimmune Diseases• In individuals with autoimmune diseases, the immune system loses tolerance for self and turns against certain molecules of the body• Autoimmune diseases include systemic lupus erythematosus, rheumatoid arthritis, insulin-dependent diabetes mellitus, and multiple sclerosis Exertion, stress and the immune system• Moderate exercise improves immune system function• Psychological stress has been shown to disrupt immune system regulation by altering the interactions of the hormonal, nervous, and immune systems• Sufficient rest is also important for immunity Immunodeficiency Diseases• Inborn immunodeficiency results from hereditary or developmental defects that prevent proper functioning of innate, humoral, and/or cell-mediated defenses• Acquired immunodeficiency develops later in life and results from exposure to chemical and biological agents• Acquired immunodeficiency syndrome (AIDS) is caused by a virus Latency• Some viruses may remain in a host in an inactive state called latency• Herpes simplex viruses can be present in a human host without causing symptoms Attack on the immune system• Human immunodeficiency virus (HIV) infects helper T cells• The loss of helper T cells impairs both the humoral and cell-mediated immune responses and leads to AIDS• HIV eludes the immune system because of antigenic variation and an ability to remain latent while integrated into host DNA• People with AIDS are highly susceptible to opportunistic infections and cancers that take advantage of an immune system in collapse• The spread of HIV is a worldwide problem• The best approach for slowing this spread is education about practices that transmit the virus Cancer and immunity• The frequency of certain cancers increases when adaptive immunity is impaired• 20% of all human cancers involve viruses• The immune system can act as a defense against viruses that cause cancer and cancer cells that harbor viruses• In 2006, a vaccine was released that acts against human papillomavirus (HPV), a virus associated with cervical cancer
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