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Lymphatic & Immune Systems. Lymphatic System Reabsorbs about 15% of fluid filtered by blood capillaries & returns it to blood Provides immunity & protection from foreign cells & matter in the body Absorbs dietary lipids in small intestine & transports them to blood.

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Lymphatic & Immune Systems


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slide2

Lymphatic System

  • Reabsorbs about 15% of fluid filtered by blood capillaries & returns it to blood
  • Provides immunity & protection from foreign cells & matter in the body
  • Absorbs dietary lipids in small intestine & transports them to blood

p 809

slide3

Lymph = fluid in lymphatic vessels

  • Usually clear, colorless fluid
  • Originates in lymphatic capillaries

p 810

slide4
Lymphatic Vessels
  • Histology similar to veins
  • Thinner walls
  • More valves
  • Flow of Lymph
  • Like venous; low pressure & speed
  • Primary driving force is rhythmic contractions of vessels
  • Assisted by Milking & “Thoracic pump”

p 811

slide7
Lymph Nodes
  • In-line filters that cleanse the lymph as it passes through
  • Reticular fibers act as a filter and delay microbes & debris
  • Macrophages & reticular cells remove about 99% of impurities from lymph

p 817

lymphatic cells
Lymphatic Cells
  • Natural killer (NK) = lymphocytes that attack & destroy bacteria, transplanted cells, & host cells that are cancerous or viral-infected
  • Provide immune surveillance
  • T lymphocytes= mature in thymus & provide cell-mediated immunity
  • B lymphocytes = mature in bone marrow & provide antibody-mediated immunity
lymphatic cells1
Lymphatic Cells
  • Macrophages = develop from monocytes into large highly phagocytic cells that destroy foreign matter and dead tissues & cells
  • Act as antigen-presenting cells (APCs) by breaking down foreign matter & displaying parts of it on their cell membrane
lymphatic cells2
Lymphatic Cells
  • Dendritic cells = APCs that engulf foreign matter by endocytosis
  • Located in epidermis (Langerhans cells), mucous membranes, & lymphatic organs
  • Reticular cells = act as APCs in thymus
  • Form blood-thymus barrier that isolates lymphocytes from blood-borne antigens
  • Produce hormones that promote development & actions of T cells
lymphatic tissues
Lymphatic Tissues
  • Lymphatic Nodules = dense masses of lymphocytes & macrophages
  • Some appear temporarily to fight infections
  • Permanent nodules are found in;
  • Lymph nodes
  • Tonsils
  • Appendix
  • Ileum of Sm. Intestine (Peyer’s Patches)
slide13
Red Bone Marrow
  • Source of all blood cells which enter the blood through sinusoids
  • Site where
  • B lymphocytes mature

p 814

slide14
Thymus
  • Site where T lymphocytes mature
  • Shrinks to small size in adults
  • Secretes hormones that stimulate development and activities of T lymphocytes

p 815

slide15
Tonsils.
  • Patches of lymphatic tissue that guard entrances to the pharynx
  • Surface has deep pits called crypts that help trap foreign materials

p 819

slide16
Spleen:
  • Largest lymphatic organ
  • Acts as in-line filter for blood, with reticular fibers as filter and macrophages to ingest microbes & foreign material
  • “Erythrocyte graveyard” where worn out RBCs are phagocytized by macrophages

p 819

nonspecific defenses
Nonspecific Defenses
  • Protection against a wide range of pathogens
  • Pathogens = anything capable of causing disease
  • Bacteria
  • Viruses
  • Toxic chemicals
  • Radiation
nonspecific defenses1
Nonspecific Defenses
  • External Barriers
  • Leukocytes & Macrophages
  • Immunological Surveillance
  • Interferons
  • Complement System
  • Inflammatory Response
  • Fever
external barriers
External Barriers
  • Skin
  • Mucous Membranes
  • Secretions;
  • Tears, saliva, urine, vaginal secretions, perspiration
  • Lysozymes = antibacterial enzymes that breakdown cell walls
  • Stomach acid
leukocytes macrophages
Leukocytes & Macrophages
  • Neutrophils
  • Phagocytosis, plus
  • Lysozymes release enzymes that trigger the respiratory burst, which produces;
  • Superoxide (O2-)
  • Hydrogen peroxide (H2O2)
  • Hypochlorite (HClO)
  • All highly toxic, so form a killing zone, that kills many bacteria & neutrophils
slide21
Eosinophils
  • Phagocytosis
  • Release toxic chemicals
  • Particularly effective against allergens & parasites
  • Basophils
  • Secrete histamine (vasodilator)
  • Secrete heparin (anticoagulant)
  • Stimulated by Eosinophils
slide22
Monocytes
  • Leave blood and become macrophages
  • Wandering (Free) macrophages
  • Fixed macrophages
  • Includes;
  • Dendritic cells
  • Microglia
  • Alveolar macrophages
  • Hepatic macrophages (Kuppfer’s cells)
interferons
Interferons
  • Small proteins
  • Released from viral-infected cells & bind to receptors on surface of nearby cells causing them to make antiviral proteins that prevent viral replication, thereby protecting those cells
  • Act as cell to cell signals to stimulate activities of macrophages and NK cells
slide24
Complement System
  • Group of 30 or more proteins
  • Important role in both Specific and Nonspecific defenses

p 823

slide26

Immune SurveillanceNatural Killer (NK) Cellspatrol body looking to find & destroy bacteria, transplanted cells, viral-infected cells, & cancer cells.

p 824

inflammation
Inflammation
  • Inflammation is a local defensive response to injury, like trauma or infection
  • Purposes;
  • Limit spread of pathogens & eventually destroy them
  • Remove debris of damaged tissue
  • Start tissue repair
  • Words ending in itis denote inflammation of that tissue (arthritis, dermatitis, etc)
  • Signs = heat, redness, swelling, pain
inflammation1
Inflammation
  • Vasodilation triggered by histamine & other chemicals released from basophils, mast cells & damaged cells (flow=heat, redness)
  • These chemicals also cause Increased Blood Vessel Permeability as intercellular clefts widen & allow increased filtration of;
  • Fluids (swelling)
  • Leukocytes
  • Proteins (complement, antibodies, clotting factors)
slide29
Neutrophil Behavior
  • Margination = loose adhesion to vessel wall
  • Diapedesis = crawl thru gaps between cells
  • Chemotaxis = move toward chemical signals from damaged cells
  • Phagocytosis = engulf and digest foreign cells & molecules

p 826

slide30
Neutrophils release signaling molecules to attract more phagocytes (neutrophils & macrophages) through chemotaxis
  • Macrophages engulf & destroy pathogens, and casualties, like tissue cells & neutrophils
  • Macrophages secrete colony-stimulating factors, that trigger increased production of more leukocytes (reinforcements)
slide31
What remains is Pus which is the dead cells, tissue debris & fluid that are eventually absorbed
  • Pain receptors are stimulated by;
  • Direct injury
  • Pressure from edema
  • Chemicals released by damaged cells (like prostaglandins & bradykinin) and bacterial toxins
fever
Fever
  • Fever is an abnormal increase in body temp due to hypothalamus raising the set point for body temp.
  • Pyrogen (fever-causing agent) = interleukin-1, that triggers hypothalamus release of prostaglandin E (PGE) which raises set point for temp

p 827

specific immunity
Specific Immunity
  • Specific immunity is directed at
  • one and only one specific pathogen
  • An initial exposure to a pathogen will create a memory
  • When exposed again to the same pathogen the body reacts so quickly that there is no noticeable illness.
specific immunity1
Specific Immunity
  • Cellular (cell-mediated) immunity = lymphocytes directly attack & destroy foreign cells or diseased host cells where
  • Pathogen is inside human cells
  • Intracellular Viruses, Bacteria,
  • Protozoans, & Yeast
  • Cells of Transplanted Tissue & Cancer Cells
specific immunity2
Specific Immunity
  • Humoral (antibody-mediated) immunity = antibodies tag or mark the pathogen for destruction by other mechanisms
  • Indirect attack by antibodies,
  • instead of immune cells directly
  • Extracellular Viruses, Bacteria,
  • Protozoans, & Yeast
  • Molecular (noncellular) pathogens
  • like, toxins, venoms and allergens
antigens
Antigens
  • Antigen = any molecule that triggers an immune response, normally proteins, polysaccharides, glycoproteins, & glycolipids
  • Antigenic Determinant Sites (epitopes)
  • = portions of the exposed surface of the antigen that actually make it an antigen, (trigger an immune response)
  • = sites where antibodies bind
  • Immune system must distinguish between;
  • Self vs. Nonself molecules
haptens
Haptens
  • Too small to be an antigen
  • Bind host macromolecule = then antigenic
  • Second exposure may not require binding
  • Include many allergens;
    • Cosmetics
    • Detergents
    • Industrial chemicals
    • Poison ivy
    • Animal dander
t lymphocytes t cells
T Lymphocytes (T Cells)
  • “Born” in bone marrow, then to thymus where they become immunocompetent, meaning they get receptors on their surface for one antigen
  • Must pass a test to be sure they can recognize foreign antigens, but not attack self-antigens (only 2% pass)
  • Graduation = multiple & form clones of identical T cells that recognize that one specific antigen, then leave thymus as naive T lymphocytes
b lymphocytes b cells
B Lymphocytes (B Cells)
  • Born and become immunocompetent in bone marrow (develop receptors on surface for specific antigen)
  • Must pass same test to be sure they will tolerate “self” cells and recognize foreign or “nonself” cells
  • Then multiple & form clones of identical B cells that recognize that one specific antigen and leave marrow as naive B lymphcytes
major histocompatiblity complex mhc proteins
Major Histocompatiblity Complex (MHC) Proteins
  • Complex = genes are on chromosome #6
  • Glycoproteins on surface of cells (except RBC), about 200,000 per cell
  • Unique to each person
  • Shaped like hotdog bun, they pick up antigens from inside the cell, migrate to the surface & hold them in their central groove
  • Class I on all cells (except RBC)
slide41
. Acting like an information relay, the MHC Class I (MHC-I) molecules retrieve bits and pieces of the proteins from inside the cell and display them on the cell surface.
  • MHC complexes essentially give
  • a read out of what's inside the cell
slide42
Antigen-Presenting Cells (APCs)
  • Phagocytosis of antigen
  • Break down into molecular fragments
  • Display (present) the epitopes on its MHC proteins
  • Class II MHC proteins on APCs only
  • macrophages, B cells, reticular & dendritic cells

p 831

cellular immunity
Cellular Immunity
  • Cytotoxic T (TC) cells = carry out direct attack on enemy cells
  • Also known as T8, CD8, or CD8+ cells because they have a surface glycoprotein for binding to other cells called CD8
  • Helper T (TH) cells = promote actions of TC cells and play a key role in humoral immunity & nonspecific defenses
  • Also known as T4, CD4, or CD4+ cells due to CD4 glycoprotein
cellular immunity1
Cellular Immunity
  • Memory T (TM) cells = descended from cytotoxic T cells and provide memory of initial exposure to an antigen, providing for a very rapid response if exposed again
immunity as a three act play
Immunity as a Three Act Play
    • Act One = Recognition
    • Act Two = Attack
    • Act Three = Memory
  • OR
    • “the three Rs of immunity”
    • Recognize
    • React
    • Remember
slide46
Recognition
  • Naive T cells inspect cells MHC proteins & antigens
  • Self antigens = okay
  • Viral proteins, abnormal antigens made by cancer cells = Respond
  • Like a sign that says,
  • “I’m infected” or
  • “I’m a cancer cell”
  • TC cells only MHC-I
  • TH cells only MHC-II

p 833

slide47
T Cell Activation
  • Receptor on T cell surface must match foreign antigen on MHC
  • = binds MHC
  • Second binding called costimulation required for activation
  • Triggers clonal selection, repeated mitosis which produces a clone of T cells with receptors for same epitope

p 833

slide48
T Cell Attack
  • Helper T cells secrete interleukins that;
  • Attract neutrophils & natural killer cells
  • Atrract macrophages & stimulate phagocytosis
  • Stimulate T and B cell mitosis & maturation

p 833

slide50
T Cell Attack
  • Cytotoxic T cells attack & destroy cell with a release of chemicals
  • For example, Perforin creates pores in cell membrane that kill it
  • Recall the Membrane Attack Complex

p 833

memory
Memory
  • Some TC and TH cells become memory cells
  • Memory T cells are long-lived & much more numerous than naive T cells
  • They require fewer steps, so respond to antigens much more rapidly
  • If the body is exposed to that antigen again, the attack, called the T cell recall response is so quick that there are no symptoms
humoral immunity
Humoral Immunity
  • Instead of directly attacking enemy cells, the B lymphocytes produce antibodies that bind to antigens and tag them for destruction by other means.
  • Like cellular immunity, it also has 3 parts;
    • Recognition
    • Attack
    • Memory
slide54
Recognition
  • Immunocompetent B lymphocytes act as APCs
  • Receptor must bind to its specific antigen
  • Endocytosis
  • Digestion of antigen
  • Presentation of epitope in MHC-II on cell surface
  • Now called sensitized B lymphocyte

p 835

slide55
Recognition (cont’)
  • Sensitized B lymphocytes then must bind with a helper T cell, which secretes interleukins that complete activation
  • Activation triggers clonal selection – B cell mitosis giving rise to a battalion of identical B cells with receptors for the same antigen.

p 835

slide56
Recognition (cont’)
  • Most B cells become plasma cells that develop mainly in the germinal centers of the lymphatic nodules of the lymph nodes.
  • Plasma cells produce antibodies at a rate of 2,000 per second over 4 to 5 days until they die.

p 835

antibodies also called immunoglobulins ig have a monomer made of four polypeptides
Antibodies, also called immunoglobulins (Ig) have a monomer made of four polypeptides
  • Note the;
  • Variable region with a specific antigen-binding site
  • Constant region is the same for each class
  • 5 classes include; IgA, IgD, IgE, IgG, and IgM

p 837

slide60
An individual probably makes about
  • 2 million different antibodies.
  • The human immune system may be capable
  • of making at least 10 billion antibodies
  • and possibly 1 trillion antibodies.
how antibodies render antigens harmless
How Antibodies Render Antigens Harmless
  • 1) Neutralization Only the part of an antigen that binds human cells is pathogenic, so antibodies bind these active regions & neutralize them.

p 838

how antibodies render antigens harmless1
How Antibodies Render Antigens Harmless
  • 2) Complement Fixation
  • Antibodies IgM and IgG bind to foreign cells, particularly bacteria and mismatched RBCs, which allows complement to bind & trigger cytolysis.

p 837

how antibodies render antigens harmless2
How Antibodies Render Antigens Harmless
  • 3) Agglutination An antibody may have up to 10 binding sites; thus, it can bind to antigens on more than one cell at a time. This immobilizes microbes and prevents them from spreading.
  • Effective in mismatched
  • RBCs and more
  • importantly against
  • bacteria.

p 838

how antibodies render antigens harmless3
How Antibodies Render Antigens Harmless
  • 4) Precipitation Antibodies link antigen molecules (not whole cells) together.

p 838

how antibodies render antigens harmless4
How Antibodies Render Antigens Harmless
  • This creates large Ag-Ab complexes that come out of solution so they are available for complement to bind them to RBCs or be phagocytized by eosinophils .
  • As RBCs pass through the liver & spleen, the macrophages remove and destroy the Ag-Ab complexes.
  • This is the principle means of clearing foreign antigens from the blood.
memory1
Memory
  • During clonal selection memory B cells are also created in the germinal centers in lymph nodes. They form plasma cells within hours and mount a very quick secondary response, that prevents any symptoms.

p 838