Chapter 43: The Body’s Defenses How does your body protect you from invaders?

Immune System Review Microorganism/Microbe Pathogen Antibiotic Antibody Antigen

Key Concepts 3 Lines of Defense Innate vs. Acquired immunity Phagocytes, Lymphocytes, Antibodies, etc… Humoral vs. Cell-Mediated immunity Distinguishing self from non-self Tissue transplantation Immune Diseases/Disorders

Using HIV to treat Cancer?? http://abcnews.go.com/WNT/video/doctors-hiv-treat-cancer-17929437

What do you think? How does your body INITIALLY defend itself from invasion? (1st line – specific or non?) What happens if the invader gets past the 1st line? (2nd line – specific or nonspecific?) What about more serious infections? (3rd line)

1st line Defense!! Skin, mucus, cilia, saliva, acids, tears, oils, bacteria, coughing, sneezing, vomiting Antimicrobial proteins & Lysozymes

Innate vs. Acquired Immunity Innate Immunity: Present before exposure; since birth Includes natural bodily defenses, mother’s milk, or casual exposure Broad-range capabilities, non-specific External defenses: skin, mucus membranes, tears Internal Phagocytic cells A.K.A.: “macrophages”; engulf invaders

Innate vs. Acquired Immunity Develops only after exposure Highly microbe-specific… how? Employ lymphocytes & antibodies Involves both Humoral & Cell-Mediated responses

Innate Immunity: Your first line of defense

Phagocytic White Blood Cells Recognize & bind to carbohydrate markers on foreign cell membranes Triggers receptor-mediated endocytosis Engulf & digest pathogens via Phagocytosis

Types of White Blood Cells Neutrophils: 60-70% of WBCs; engulf and destroy microbes at infected tissue; short lived Monocytes: 5% of WBCs; develop into…. Macrophages: “big eaters” enzymatically destroy microbes; can be found in spleen, lymph nodes, and other organs Eosinophils: 1.5% of WBCs; destroy large parasites extracellularly Natural killer (NK) cells: trigger apoptosis in virus-infected cells & cancer cells

Leukocyte vs. Lymphocyte White blood cells (WBC’s) Lymphocyte = Specific type of WBC that mature and migrate through the lymphatic system and target specific antigens via antibodies, receptors and toxin release

The Inflammatory Response “Inflammation” = pain, swelling, fever, redness, itching, and pus

Causes of Inflammation Injuries Exposure to microbes/pathogens Exposure to foreign objects or chemicals (insect bites, stings, medications, etc) Exposure to allergens (pollen, pet dander, foods, etc) Rare: sunlight, temperature, self!

The Inflammatory Response 3 Steps: 1. Tissue damage = release of chemical signals~ Mast cells release chemicals known as Histamine & Prostaglandins that trigger inflammation 2. Dilation increases permeability of capillaries~ Increased blood flow; leukocytes leak out to infected area Delivery of clotting factors & antimicrobial proteins 3. Phagocytosis of pathogens~ WBC’s engulf microbes or damaged tissue Fever: leukocyte-released chemicals increase body temperature

Acquired Immunity: Lymphocytes are the Key Defenders

Specific Immunity Antigen: a foreign molecule that elicits a response from a lymphocyte Lymphocyctes: WBC’s that originate from stem cells in bone marrow B Cells (mature in bone marrow) T Cells (mature in thymus) Antibodies: antigen-binding immunoglobulin, produced by B cells Antigen receptors: membrane receptors on B and T cells

Ch. 43 Research: Humoral vs. Cell-mediated Responses B cells vs. T cells Memory cells Clonal selection Autoimmune disease

T cells vs. B cells B cells: T cells: Mature in Bone Marrow Target in-tact Antigens Part of Humoral Response T cells: Mature in Thymus Target antigen fragments bound to MHC molecules on Infected Cells Part of Cell Mediated Response

Humoral vs. Cell-Mediated Humoral immunity B cell activation Production of antibodies Defend against intact antigens free in the lymph and blood plasma (bacteria, toxins, and viruses)

Humoral response: B cells Stimulated by an antigen-presenting macrophage (WBC w/ a germ on it) Activates Helper T cells T cells secrete cytokine chemicals that activate B cells B cells differentiate into memory B cells and antibody-producing plasma cells

Cytokines Cytokine: Proteins secreted by phagocytic cells (macrophages, etc.) and T-helper cells Activate Lymphocytes (B & T cells)

Humoral Response: B cells activate. Plasma cells secrete antibodies. Antibodies attach to antigens. Antigens agglutinate (stick together) & get disposed. Macrophages phagocytose or lyse the cell.

Cell-Mediated Cell-mediated immunity T cells are activated. T cells bind to and/or lyse infected cells. Defend against cells infected with bacteria, viruses, fungi, protozoa, parasites, even cancer!

Cell-mediated Response 1) Cell surface molecules expose antigens (foreign proteins). 2) Cytotoxic T cell releases perforin, a protein that forms pores in the target cell membrane. causes cell lysis and exposes pathogens to circulating antibodies for disposal

Cell Mediated Response Humoral Response Antigens on Infected Cells In Tact Antigens B Cell Activation T Cell Activation Secrete antibodies that defend against pathogens & toxins in extracellular fluid Defend against infected cells, cancer and transplanted tissues

Clonal Selection Clonal selection: Effector cells: Memory cells: antigen-driven cloning of lymphocytes Effector cells: short-lived cells that combat the antigen initially Memory cells: long-lived cells that bear receptors for the antigen and activate upon subsequent exposure.

Active vs. Passive Immunity Active: natural exposure to antigens causes one’s own lymphocytes to activate and produce antibodies May also be acquired by Immunizations Passive: direct transfer of antibodies through placenta or mother’s milk

HIV Human Immunodeficiency Virus Causes AIDS (Acquired Immune Deficiency Virus) HIV (a retrovirus) attacks helper T cells by binding with their cell receptor (CD4) This impacts both the Humoral and Cell Mediated responses 

Clonal Selection Hypothesis Each lymphocyte bears one specific type of receptor. Receptor/antigen binding is required for cell activation. Activated lymphocytes divide and give rise to cells with identical receptors to the parent. This is how your immune system “remembers” a pathogen later!

Clonal Selection Hypothesis First, those lymphocytes bearing receptors compatible to “self” tissues are destroyed (3) Second, those bearing receptors that match foreign antigens are activated then cloned (5/6)

Self/Nonself Recognition Self-tolerance: Capacity to distinguish self from non-self molecules Autoimmune diseases: Failure of self-tolerance mechanisms Multiple sclerosis, lupus, rheumatoid arthritis, insulin-dependent diabetes mellitus, Crohn’s disease

Abnormal immune function Allergies: hypersensitive responses to environmental antigens (allergens) causes dilation and blood vessel permeability Histamines are released from Mast cells Autoimmune disease: multiple sclerosis Lupus rheumatoid arthritis insulin-dependent diabetes mellitus Immunodeficiency disease: SCIDS (bubble-boy) A.I.D.S. (HIV)

Cancer & the Immune System Tumor cells are targeted by both Cytotoxic T cells and Natural Killer (NK) cells How might some tumors escape detection??

Treg research: Article Review What are “Regulatory T Cells” (Tregs)? What is their role in immunity? How might they be linked with cancer? Article: “Regulatory T cells and tumour immunity – observations in mice and men” by Gallimore and Godkin, 2007

Major Histocompatibility Complex Aka: “MHC” Cell surface proteins that display fragments of antigens or processed proteins on the cell surface Epitope: region of antigen surface recognized by antibodies

Induction of Immune Responses Primary immune response: lymphocyte proliferation and differentiation the 1st time the body is exposed to an antigen Plasma cells: antibody-producing B-cells Secondary immune response: immune response if the individual is exposed to the same antigen at a later time~ Immunological memory

Types of Immunoglobins IgM: 1st to circulate; indicates infection; too large to cross placenta IgG: most abundant; crosses walls of blood vessels and placenta; protects against bacteria, viruses, & toxins; activates complement IgA: produced by cells in mucous membranes; prevent attachment of viruses/bacteria to epithelial surfaces; also found in saliva, tears, and perspiration IgE: very large; small quantity; releases histamines-allergic reaction

Antibody-Mediated Antigen Disposal Neutralization (opsonization): antibody binds to and blocks antigen activity Agglutination: antigen clumping Precipitation: cross-linking of soluble antigens Complement fixation: lyses viruses and pathogenic cells & activates cell surface proteins to break down the cell

Immunity in Health & Disease Active immunity: natural: conferred immunity by recovering from disease artificial: immunization and vaccination; produces a primary response Passive immunity: transfer of immunity from one individual to another natural: mother to fetus; breast milk artificial: rabies antibodies ABO & Rh blood groups (antigen presence)