Chapter 21: The Immune System Flashcards
The 3 Lines of Defense Against Pathogens:
o External Barriers (innate) o a) skin o b) mucous membranes o Non-specific (innate) Internal Body Defenses o a) antimicrobial proteins o b) antimicrobial CELLS o c) fever o d) inflammatory process o Specific Immune System = “immunity”
Characteristics of Innate Defenses:
o Present at birth.
o Act instantly or very quickly.
o No prior exposure necessary.
o Response is the same EACH TIME the body is exposed to any foreign thing.
o Responses are effective against a wide range of pathogens, even pathogens our body has never seen before!
o Reduces the workload for our SPECIFIC defense mechanisms.
First Line of Defense:
External Barriers
o Skin:
o Hostile surface (dry, low pH, keratin).
o Closely packed cells; shed periodically.
o Coated with antimicrobial chemicals.
• Defensins (peptide that pokes holes).
• Lactic acid & dermcidin (from sweat).
• Lysozyme (from sweat, tears, mucus, saliva).
o Mucous Membranes:
o Mucus (sticky trap).
o Lysozyme (enzyme that is disruptive to pathogen cell walls).
o Cilia in respiratory tract.
o Coughing and sneezing.
o Tears.
o Cerumen.
o Low pH of gastric juice.
o Emesis.
o Diarrhea.
o Acid secretions of vagina.
o Acid pH of urine + periodic flow of urine.
Second Line of Defense:
Non-Specific Internal Body Defenses (4 Categories)
o 1. Antimicrobial Proteins.
o 2. Antimicrobial cells.
o 3. Pyrexia (fever).
o 4. Inflammatory process.
Second Line of Defense:
Antimicrobial Proteins
o Interferons. o Complement proteins. o Epithelial cell-derived chemicals. o Bacterial-derived chemicals (normal flora). o Proteins secreted by epithelial cells: o Cathelicidins. o Defensins. o Collectins. o Proteins secreted by bacteria that normally populate our mucous membranes.
Antimicrobial Proteins:
Interferons
o Small proteins that provide protection against viruses.
o Secreted by your own body cells that have become infected by a virus.
o These infected body cells (especially lymphocytes) secrete interferons into the IF (interstitial fluid), they bind to surface receptors on neighboring cells.
o Neighboring cells receive the signal and make anti-viral substances.
o Interferons also activate macrophages and NK cells.
o Alpha-Interferons: Produced by cells infected with viruses. Attract and stimulate NK cells and enhance resistance to viral infection.
o Beta-Interferons: Secreted by fibroblasts, slow inflammation in a damaged area.
o Gamma-Interferons: Secreted by T cells and NK cells, stimulate macrophate activity.
Antimicrobial Proteins:
Complement Proteins
o The complement system = 30 or more antimicrobial proteins that circulate in the blood in an inactive state.
o Many ways to activate the complement system!!!!
o When activated, 3 important effects:
o Inflammation.
o Enhanced Phagocytosis via opsonization.
o Cytolysis via membrane attack complexes (MACs).
Second Line of Defense:
Antimicrobial Cells
o Natural Killer Cells (NK Cells): o Immune surveillance. o Secrete perforins and granzymes. o Phagocytes: o Microphages: • Neutrophils. • Eosinophils. • Basophils. o Macrophages, from monocytes. o (Most lymphocytes are involved in specific defense mechanisms).
Antimicrobial Cells:
Natural Killer Cells
o Destroy bacteria, viruses, cancer cells, and cells of transplanted organs and tissues.
o The cells within a primary tumor may grow rapidly, and if the tumor has a surrounding capsule, the cells within may not provoke a massive response by NK cells.
o As a malignant tumor cells begin migrating into surrounding tissues, they can be detected and destroyed by NK cells.
o Sometimes a daughter cell will be produced that either doesn’t display tumor-specific antigens, or that secretes chemicals that destroy NK cells. Such as a cell will survive and be free to grow and divide.
o Once immunological escape has occurred, cancer cells can multiply and spread without interference by NK cells. They can even move throughout the body, establishing potentially lethal secondary tumors.
Antimicrobial Cells:
Phagocytes
o Neutrophils: Abundant, mobile, and quick to phagocytize cellular debris or invading bacteria. They circulate in the bloodstream and roam through peripheral tissues, especially at sites of injury or infection.
o Eosinophils: Less abundant than neutrophils. Phagocytize foreign compounds or pathogens that have been coated with antibodies.
o The two major classes of macrophages derived from the monocytes of the circulating blood.
o Fixed macrophages: Permanent residents of specific tissues and organs and are scattered among connective tissues. Normally don’t move within these tissues.
o Free macrophages: Travel throughout the body, arriving at the site of an injury by migrating through adjacent tissues or by recruitment from the circulating blood.
Neutrophils:
o Most abundant of the microphages. o First to arrive; usually first to die. o Really good at killing bacteria. o Phagocytosis (eating one/few at a time). o Respiratory burst (via degranulation). • Superoxide anions. • Hydrogen peroxide. • Hypochlorite ion. o Unfortunately, they kill just about everything in the vicinity (including themselves, and our body cells).
Eosinophils:
o Weak but useful phagocytes (antigen- antibody complexes).
o Surround much bigger parasites.
o Round worms, tapeworms, etc.
o Produce superoxide, hydrogen peroxide, and even a neurotoxin.
o Do induce inflammation, but then seem to modulate the inflammatory response by secreting the enzyme histaminase to limit allergic and inflammatory responses.
Basophils:
o Help out other WBCs.
o Release histamine (vasodilator).
o Release heparin (inhibits formation of clots, making it easier for WBCs to move around the infection site).
o Involved in hypersensitivity reactions, such as anaphylactic shock.
Monocytes:
o Monocytes emigrate from the blood in the tissue spaces to become MACROPHAGES (5X normal size).
o Fixed macrophages:
o Kupffer cells of liver.
o Alveolar dust cells of lung alveoli.
o Many fixed in spleen, lymph nodes and red bone marrow.
o Wandering macrophages (lookin’ for trouble).
o Not the first to arrive (8-12 hr), but they are deadly to pathogens and also “clean up”.
Macrophages are APCs (tattle-tales):
o Macrophages: o 1. Eat the pathogen. o 2. Digest the pathogen. o 3. Recycle/spit out parts of pathogen. o 4. Insert fragments of the pathogen into their own membrane.
Second Line of Defense:
Pyrexia
o Fever = abnormal elevation of body temp from many different causes.
o Exogenous pyrogens (e.g., endotoxins).
o Endogenous pyrogens (e.g., our own neutrophils and macrophages secrete “pyrogens” when they eat bacteria).
o IL-1 and IL-6 (interleukins).
o TNF-alpha (tumor necrosis factor).
o Pyrogens stimulate the hypothalamus (via release of prostaglandins) to raise the set point for body temp.
o 1. Pyrogens stimulate the hypothalamus to release PGE (prostaglandin E).
o 2. PGE increases the Hypothalamic set point.
Benefits of Moderate Fever:
o Intensifies effects of interferons.
o Enhances phagocytosis.
o Increases lymphocytic activity.
o Elevates metabolic rate, which accelerates tissue repair.
o Causes liver and spleen to sequester iron, zinc & copper (needed for bacterial replication).
o Kills and/or inhibits the growth of some microbes (but many like heat).
Dangers of High Fever:
o Proteins denature at high temps, including ENZYMES.
o Proteins in cell membranes can coagulate.
o Nerve damage begins at 41Degrees C (105.8 degrees F).
o Greater than 103 Degrees F: danger of heat stroke.
o Greater than 105 Degrees F: delirious/convulsions/coma.
o Greater than 110 Degrees F: irreversible brain damage or death.
Second Line of Defense:
Inflammation
o Inflammation is a non-specific LOCAL defensive response to tissue damage.
o Common response to most dz states!!!
o Purpose of inflammation:
o Dispose of pathogens and dead cells/debris.
o Prevent spread of infection.
o Prepare the site for tissue repair.
o Inflammation is regulated by cytokines.
o Inflammatory Chemicals: Histamine, Kinins, Prostaglandins, Complement proteins, cytokines (Interferons, Interleukins).
Inflammatory Process:
o Mast cells, basophils and damaged cells secrete or activate vasoactive chemicals. o Histamine. o Kinins and prostaglandins. o Interleukins. o Local vasodilation of blood vessels. o Heat. o Erythema (redness). o Local increased capillary permeability. o Edema. o Pain.
Benefits of Inflammation:
o Heat:
o Increased metabolic rate leads to increased mitosis and tissue repair.
o Increased capillary permeability:
o Easier for WBCs, fluid and plasma proteins (complement, antibodies, clotting proteins) to get into injured area.
o Edema:
o Compresses local veins and sends more interstitial fluid into lymphatic vessels.
o Attracts WBCs into the area.
Specific (Adaptive/Acquired) Immunity:
o Different from innate (non-specific) immunity because it is:
o 1. Systemic —not restricted to the initial site of infection.
o 2. Specific —fights a very specific pathogen or part of a pathogen.
o 3. Has memory —when the body is exposed a second time to the same pathogen, the specific immune system responds more quickly and more forcefully.
o 4. Depends heavily on lymphocytes.
The 2 Main Forms of Specific Immunity:
o CELLULAR IMMUNITY = Cell-mediated immunity
o T-lymphocytes (T-cells) directly attack foreign cells or diseased host cells.
o Many different types of T-cells!
o HUMORAL IMMUNITY
o Antibody-mediated immunity.
o B-lymphocytes (B-cells) differentiate into Plasma cells then secrete antibodies (good at targeting pathogens in ECF).
Antigens:
o Specific immunity requires recognition of a foreign antigen.
o Antigen (Ag) is any molecule that can trigger an immune response.
o Foreign proteins and glycoproteins.
o Foreign complex polysaccharides.
o Foreign lipids, lipoproteins, glycolipid.
o Some antigens are free molecules.
o Bacterial toxins, snake venoms, etc.
o Some antigens are components of cell membranes of pathogens.
Epitopes:
o Antigens are large, and usu. only certain PARTS of this large molecule triggers the immune response = EPITOPE = antigenic determinant. o Each antigen may have MANY different epitopes, let’s say that this Antigen #32 (found in a toxin) has 3 different epitopes on its surface, can specifically react with 3 different lymphocyte receptors. o Epitopes (antigenic determinants) can also interact with o ANTIBODIES (Ab) that are specific to their specific and unique shapes, more on antibodies (Ab) later.
Antigen Receptors:
o There are more than 7 billion unique individuals on our planet.
o There are at least 1 billion unique lymphocytes in our body.
o Each lymphocyte displays only one type of antigen receptor (but the lymphocyte has hundreds of receptors that are all the same).
o Each lymphocyte spends its entire life waiting to combine with a specific epitope.
o Antigen receptors are inserted in lymphocyte membranes:
o Before B-cells leave the red bone marrow.
o Before T-cells leave the thymus.
o Antigen receptors even recognize “artificial” molecules that don’t exist naturally.
Major Histocompatibility Proteins:
o All human nucleated cells (i.e., except RBCs) have hundreds of MHC proteins displayed on the surface of their cell membranes
o MHCs are glycoproteins (thus, these MHC proteins would be an antigen to someone else, but because they are on our very OWN cells, we sometimes call them “self antigens.”).
o MHC proteins are unique to each person (except for identical twins), serve as “identification tags” that label every cell of your body as “SELF”
o MHC proteins are the basis of histocompatibility testing = tissue compatibility between a donor organ and the recipient.
2 Types of MHC Proteins:
o MHC Type I proteins on cell membranes of all body cells except RBCs.
o MHC-I displays stuff produced/processed INSIDE our human cells:
o “This is what I MADE today”.
o MHC Type II proteins on cell membranes of Antigen Presenting Cells (APCs):
o MHC-II proteins display antigens eaten/engulfed by APCs: “This is what I ATE today”.
o This is a SIGNAL that stimulates other immune cells (e.g., T-Helper cells) to respond to the foreign Ag in ways that ENHANCE specific immunity.
o Types:
o Dendritic cells.
o Macrophages.
o B lymphocytes.
Types of T-Cells:
o T-cells with CD-8 markers:
o Cytotoxic T cells.
o T-cells with CD-4 markers:
o T-Helper Cells– Critical to all types of immunity!!!!
o T-HELPER CELLS ENHANCE ALL ASPECTS OF THE IMMUNE SYSTEM!
Process of Cytotoxic T-Cells in Cellular Immunity:
o 1. T cell identifies foreign antigens on MHC I proteins and binds tightly to target cell.
o 2. T cell releases perforin and granzyme molecules from its granules by exocytosis.
o 3. Perforin molecules insert into the target cell membrane, polymerize, and form transmembrane pores similar to those produced by compliment activation.
o 4. Granzymes enter the target cell via the pores. Once inside, granzymes activate enzymes that trigger apoptosis.
o 5. The T cell detaches and searches for another prey.
Process Where Helper T Cells Help in Humoral Immunity:
o 1. T Helper Cell binds with the self-nonself complexes of a B cell that has encountered its antigen and is displaying it on MHC II on its surface.
o 2. T Helper Cell releases interleukins as co-stimulatory signals to complete B cell activation.
Process Where Helper T Cells Help in Cellular Immunity:
o 1. T Helper Cell binds to dendritic cell.
o 2. T Helper Cell stimulates dendritic cell to express co-stimulatory molecules.
o 3. Dendritic cell can now activate CD8 cell with the help of interleukin 2 secreted by T Helper Cell.
Antibodies:
o Antibodies are small PROTEINS that can help out in a lot of different ways.
o Tips of Ab have a variable region that has a very specific antigen-binding site!
o IgG, IgA, IgM, IgE, and IgD are the Classes of Antibodies.
o Gawk At Monkey Dancing Enthusiastically most to least IgG, IgA, IgM, IgD, IgE.
Antibodies:
IgG
o Most abundant (80 percent of Abs in blood).
o Only antibody that crosses the placenta—passive immunity.
o Can fix complement.
Antibodies:
IgA
o 10-15 percent of Abs in blood.
o Found in sweat, tears, saliva, mucus, breast milk, GI secretions.
o Prevents pathogens from adhering to mucous membranes.
o Provides passive natural immunity to newborn.
Antibodies:
IgM
o 5-10 percent of Abs in blood.
o FIRST Ab to be secreted by plasma cells during primary response.
o Can fix complement.
Antibodies:
IgE
o 0.1 percent of Abs in blood.
o Found mainly on surface of mast cells and basophils.
o Involved in allergies and anaphylactic shock reactions.
Timing Affects Antibody Response:
o First exposure: Slow
o IgM is first antibody to be released
o Second exposure: Very rapid.
o IgG response is rapid and enormous!
Classes of Specific Immunity:
o ACTIVE IMMUNITY: Your body makes its own antibodies or activates its own T-cells against the pathogen.
o Natural (natural exposure to an antigen).
o Artificial (exposure via vaccination).
o PASSIVE IMMUNITY: Your body acquires antibodies or T-cells from another person or an animal.
o Natural (fetus via placenta; newborn via breast milk).
o Artificial (injection of immune serum).
Immune Disorders:
o Hypersensitivity reactions: o Immune system overacts. o Autoimmune diseases: o Immune system attacks your OWN body cells for no good reason. o Immunodeficiency diseases: o SCID. o AIDs.
Hypersensitivity Reactions:
o Type I (acute hypersensitivity):
o Includes most allergic reactions (involves IgE).
o Type II (antibody-dependent cytotoxic):
o Involves Abs bound to cell surfaces and complement rxns (e.g., blood transfusions).
o Type III (immune complex):
o Ag-Ab complex precipitates out beneath blood vessels/in tissues with intense inflammation (e.g.,Systemic Lupus Erythematosus).
o Type IV (delayed hypersensitivity):
o Cell-mediated (T-cell) mediated responses.
Autoimmune Disorders:
o Your own immune system attacks your OWN body cells.
o RA.
o Myasthenia gravis.
o MS.
o Graves’ disease.
o Type I Diabetes mellitus.
o SLE (systemic lupus).
o 5 percent of adults have autoimmune d/o (2/3 of them are women).
o Make AUTOANTIBODIES to own tissues & cytotoxic T-cells destroy own cells.
o Etiology unknown, but some hypothesize:
o Foreign antigens resemble self-antigens.
o T-reg cells don’t inhibit cell-mediated immunity.
o New self antigens appear (from mutations).
o Treat by using meds that suppress the entire immune system (e.g., prednisone).
Immunodeficiency Diseases:
o SCIDS: Severe Combined Immunodeficiency Disease.
o Bubble babies.
o Non-functioning T-cells or B-cells.
o AIDS: Acquired Immunodeficiency Syndrome.
o Caused by HIV (human immunodeficiency VIRUS = a retro virus).
o NOT an autoimmune disease, your immune system is attacking a VIRUS.
How HIV Spreads:
o Transmitted in body secretions. o Blood. o Dirty needles. o Hemophiliacs. o Tearing of mucous membranes with sexual intercourse. o Semen. o Vaginal secretions. o Saliva and tears—extremely rare transmission, although documented cases of oral sex transmission. o Breast milk from AIDS-infected mother.
AIDS:
o Virus loves to get inside T-Helper cells.
o AIDS victims don’t die of AIDS…they die of opportunistic infections (Kaposi’s sarcoma, pneumocystis pneumonia, etc.).
Invasion of HIV:
o Virus glycoprotein (gp120/gp4) docks on host cell membrane proteins.
o Requires a second docking receptor (CXCR4).
o Virus gains entry to cell.
o Virus uses it’s own reverse transcriptase enzyme to produce DNA that is inserted into host DNA.
o New DNA directs host cell to crank out new HIV.
Treatment of AIDS:
o Meds that prevent the virus from DOCKING on your body cells.
o Fusion inhibitors (e.g. Enfuvirtide).
o Meds that prevent the virus from replicating inside your cells.
o Reverse transcriptase inhibitors (e.g. AZT and ddC).
o Protease inhibitors (e.g., Saquinavir, Ritonavir).
o Meds that block viral integrase enzyme that puts provirus into cell’s DNA (new).
