Chapter 21 - Lymphatic & Immune System Flashcards
Lymphatic System
Structural basis of immune system, houses phagocytes and lymphocytes. Returns fluid that leaked from blood vessels back to blood. Includes: Tonsils, Thymus, Spleen, Aggregated Lymphoid, Appendix
3 Parts of Lymphatic System
- Network of Lymphatic Vessels
- Lymph - fluid in vessels
- Lymph nodes - cleanse lymph, checkpoints
Differences between lymphatic vessels and capillaries
- Permeable (proteins, debris, pathogens)
- Endothelia cells have one way mini valves (flaps)
- Increased extracellular fluid volume opens mini valves
Where are lymphatic vessels absent in body?
Bones, teeth, bone marrow, central nervous system
Lacteals
Specialized lymph capillaries in intestinal mucosa that absorbs digested fat and deliver fatty lymph to the blood.
Lymph delivered into blood stream via 2 large ducts
Thoracic duct - Left subclavian Vein and left internal jugular vein ( Rest of body)
Right Lymphatic Duct - Right Subclavian Vein (Right head and arm)
Lymphatic Collecting vessels are similar to veins except for:
Thinner walls, more intestinal valves, anastomose more frequently, nutrients supplied from vaso vasorum
What is Lymph Propelled By?
Milking action of skeletal muscle Pressure changes in thorax during breathing Valves to prevent backflow Pulsations of nearby arteries Contraction of smooth muscle in walls.
Lymphocytes
Main warrior of immune system that arise in red marrow, mature into 1 of 2 main varieties, T-Cell (thymus) or B-Cell (marrow)
Macrophage
Phagocyte foreign substances, help activate T-cells
Dendritic cells
capture antigens and deliver them to lymph nodes
Reticular cells
produce reticular fiber stroma; supports cells in lymphoid organs
Functions of Lymphoid Tissue
Houses and provides proliferation site for lymphocytes
Survellance vantage point for lymphocyte and macrophage
composed mainly of reticular connective tissue
Where are lymph nodes found
Principal lymphoid organs, embedded in CT, in clusters along lymphatic vessles, nearby surfaces in inguinal, axillary and cervical areas.
Functions of lymph nodes
Filter lymph: macrophages destroy microorganisms and debris
Immune system activation: lymphocytes activated and mount attack on antigens
Circulation of lymph
Lymph enters via afferent lymphatic vessels; to subcapsular sinus and smaller sinuses to medullary sinuses; exits at hilum via efferent vessels
Chyle
Fatty Lymph
Lymphoid follicles
solid, spherical bodies of tightly packed lymphoid cells and reticular fibers
• Germinal centers of proliferating B cells
• Isolated aggregations of Peyer’s patches and in appendix
Spleen
Largest lymphoid organ
Site of lymphocyte proliferation and immune surveillance and response
Cleanses blood of aged cells and platelets, macrophages remove debris
FUNCTIONS:
Stores breakdown products of RBCs
Stores blood platelets and monocytes
May be site of fetal erythrocyte production
Contains lymphocytes, macrophages, and huge numbers of erythrocytes
White pulp
around central arteries**
Mostly lymphocytes on reticular fibers
Red pulp
in venous sinuses and splenic cords
Rich in RBCs and macrophages
Thymus
increases in size, most active during childhood but stops growing during adolescence, then atrophies
-Slowly produces immunocompetent cells
Most thymic cells are lymphocytes
Cortex contains rapidly dividing lymphocytes and macrophages
Medulla contains fewer lymphocytes and thymic corpuscles (regulatory T cell dev.)
Thymus differs from other lymphoid organs:
-Has no follicles because it lacks B cells
-Functions strictly in T cell maturation
Stroma of epithelial cells provide place where T cells become immunocompetent
Mucosa-associated Lymphoid Tissue (MALT):
In mucous membranes
-Protects from pathogens entering body
Tonsils, Peyer’s patches, Appendix
Mucosa of respiratory, genitourinary organs; rest of digestive tract
Tonsils
Simplest lymphoid organs
Ring of lymphatic tissue around pharynx
Gather and remove pathogens in food or air
tonsillar crypts
Epithelium indents
Trap and destroy bacteria,particulate matter
Immune cells build memory for pathogens
Peyer’s patches
Clusters of lymphoid follicles in wall of small intestine
• Destroy bacteria, preventing them from breaching intestinal wall
• Generate “memory” lymphocytes
Innate Defense
Surface Barriers - Mucous Membranes and Skin. Internal defenses • Phagocytes • Natural killer cells • Inflammation • Antimicrobial proteins • Fever
Adaptive Defense
- Specific: recognizes specific antigens
- Systemic: not restricted to initial site
- Memory: stronger attacks to “known” antigens
Two separate, overlapping arms
Humoral (antibody-mediated) immunity
Cellular (cell-mediated) immunity
Humoral Immunity
B-Cells
Cellular Immunity
T-Cells
Skin
Physical barrier to microorganisms
Keratin resistant to weak acids and bases, bacterial enzymes, and toxins
Acidity of skin and secretions – acid mantle – inhibits growth
Enzymes - lysozyme of saliva, respiratory mucus, lacrimal fluid kill microorganisms
Defensins – antimicrobial peptides
Other- lipids (sebum), dermcidin (sweat)
Respiratory system modifications
Mucus-coated hairs in nose
Cilia of upper respiratory tract sweep dust/bacteria-laden mucus toward mouth
Internal Defenses: If deeper tissues invaded
Phagocytes
Natural killer (NK) cells
Interferons and complement proteins
Inflammatory response
Phagocytes
Neutrophils most abundant but die fighting
Macrophages chief phagocytic cells
-Free wander tissue spaces (alveolar)
-Fixed permanent residents (liver, brain)
Natural Killer (NK) Cells
Nonphagocytic large granular lymphocytes
Attack cells that lack “self” receptors
Induce apoptosis in cancer and virus-infected cells
Secrete chemicals that ↑ inflammation
Recognize Lack of class I MHC, antibody coating target cell, surface markers of stressed cells Use same key mechanisms as TC cells for killing their target cells
Inflammatory Response
Triggered whenever body tissues injured Prevents spread of damaging agents Disposes of cell debris and pathogens Alerts adaptive immune system Sets the stage for repair
Cardinal signs of acute inflammation
Redness Heat Swelling Pain Impairment of function
Inflammatory mediators
Kinins, prostaglandins, complement
Dilate local arterioles (hyperemia)
Make capillaries leaky
Many attract leukocytes to area
Innate Defense steps of Inflammatory response
Leukocytosis.Neutrophils enter blood from bone marrow.
Margination. Neutrophils cling to capillary wall.
Diapedesis.Neutrophils flatten and squeeze out of capillaries.
Chemotaxis.Neutrophils follow chemical trail.
Interferons
immune modulating proteins
Viral-infected cells secrete IFNs to “warn” neighboring cells
IFNs enter neighboring cells produce proteins that block viral reproduction and degrade viral RNA
Complement Proteins
Unleashes inflammatory chemicals that amplify all aspects of inflammatory response
Kills bacteria and other cell types by lysis
Enhances innate and adaptive defenses
Cell lysis begins when C3b binds to target cell insertion of complement proteins called membrane attack complex (MAC)
-MAC forms hole, influx of water lysis of cell
opsonization
pathogen is marked for ingestion by a phagocyte
Fever
Systemic response, leukocytes and macrophages secrete pyrogens whichact on body’s thermostat in hypothalamus
Benefits: liver and spleen sequester iron and zinc (needed by microorganisms) and increases metabolic rate faster repair
Antigens
Complex molecules not found in body
targets of all adaptive response
Immunogenicity
ability to stimulate proliferation of specific lymphocytes
Reactivity
ability to react with activated lymphocytes and antibodies
MHC (Major Histocompatibility Complex)
glycoproteins, unique to individual, have groove holding self- or foreign antigen
self-antigens
Protein molecules on surface of cells not antigenic to self but antigenic to others in transfusions or grafts
Three types of cells in Adaptive Response
B lymphocytes: humoral immunity T lymphocytes: cell-mediated immunity Antigen-presenting cells (APCs) Do not respond to specific antigens Play auxiliary roles in immunity
Positive Selection
T Cells must recognize a MHC. Failure to recognize MHC results in apoptosis, recognize results in survival.
Negative Selection
T Cells must not recognize self-antigens. Recognize self-antigen results in apoptosis. Gets rid of T Cells that could cause autoimmune diseases. Failure to recognize results in Survival
Steps of Lymphocyte Maturation
Seeding secondary lymphoid organs and circulation
• Immunocompetent but still naive lymphocytes leave the thymus and bone marrow.
• They “seed” the secondary lymphoid organs and circulate through blood and lymph.
Proliferation and differentiation
• Activated lymphocytes proliferate (multiply) and then differentiate into effector cells and memory cells.
• Memory cells and effector T cells circulate continuously in the blood and lymph and throughout the secondary lymphoid organs.
Antigen-presenting Cells (APCs)
Engulf antigens
Present fragments of antigens to T cells
Dendritic cells, Macrophages, B cells
Dendritic cells phagocytize pathogens, present antigens to T cells in lymph node
Macrophages present antigens to T cells to activate themselves into voracious phagocytes secreting bactericidals.
Humoral Immunity Primary Response and Proliferation
Most clone cells become plasma cells Secrete specific antibodies at rate of 2000 molecules per second for 4-5 days, die. Others become memory cells Provide immunological memory Response to exposures to same antigen
Active Humoral Immunity
B cells encounter antigens and produce specific antibodies
- Naturally acquired: response to bacterial or viral infection
- Artificially acquired: response to vaccine of dead or attenuated pathogens
Vaccines
Dead or attenuated pathogens
Provide antigenic determinants that are immunogenic and reactive
Humoral Immunity Passive vs Active
Passive
Naturally - Antibodies passed from mother to
fetus via placenta; or to infant in her milk
Artificially - Injection of exogenous antibodies (gamma globulin)
Active
Naturally - Infection; contact with pathogen
Artificially - Vaccine; dead or attenuated pathogens
IgM
First antibody released
Potent agglutinating agent
Fixes and activates complement
IgA (secretory IgA)
Monomer or dimer; secretions
Helps prevent entry of pathogens
IgD
Monomer on surface of B cells
IgG
Monomer; most of antibodies in plasma
Crosses placental barrier
IgE
Monomer active in some allergies and parasitic infections
Causes release of histamine
Neutralization
Antibodies block specific sites on viruses or bacterial exotoxins
Prevent these antigens from binding to receptors on tissue cells
Antigen-antibody complexes undergo phagocytosis
Agglutination
Antibodies bind same determinant on more than one cell-bound antigen
Cross-linked antigen-antibody complexes agglutinate
Precipitation
Soluble molecules are cross-linked then complexes are subject to phagocytosis
Complement Fixation and Activation
Main antibody defense against cellular antigens (bacteria, mismatched RBCs)
Several antibodies bind close together on a cellular antigen complement-binding Complement fixation into surface lysis
Two types of MHC proteins important to T cell activation
Class I MHC proteins – all cells except RBCs
Class II MHC proteins – APCs (dendritic cells, macrophages, and B cells)
Class I MHC
Bind with fragment of protein made in the cell (endogenous-antigen)
Crucial for CD8 cell activation
Inform cytotoxic T cells of microorganisms hiding in cells (cytotoxic T cells ignore displayed self-antigens)
Class II MHC
Bind with fragments of exogenous antigens that have been broken down in a phagolysosome
Recognized by helper T cells
Signal CD4 cells that help is required
T cell Activation: Antigen Binding
T cell antigen receptors (TCRs) bind to antigen-MHC complex on APC surface
TCR that recognizes the nonself-self complex linked to signaling pathways
T cell Activation: Co-stimulation
Requires T cell binding to other surface receptors on an APC – co-stimulation
Cytokines trigger proliferation and differentiation of activated T cell
T cell Activation Requires
Antigen Binding
Co-Stimulation
Cytokines
Cell development and differentiation
Include interferons and interleukins
IL-2 key growth factor, acting on cells that release it and other T cells
Helper T Cells
play central role in adaptive immune response
Once primed by APC presentation they Help activate, proliferate T and B cells
Cytokines recruit other immune cells
Without TH, there is no immune response
Amplify responses of innate immune system
Activate macrophages more potent killers
Mobilize lymphocytes and macrophages and attract other types of WBCs
Targets of Cytotoxic T Cells
Virus-infected cells
Cells with bacteria, parasites
Cancer cells
Foreign cells (transfusions, transplants)
SCID
Severe combined Immunodeficiency Syndrome (Boy in the Bubble)
Genetic Defect in B & T cells, treated with bone marrow transplant and gene therapy
Hodgkin’s Disease
Acquired immunodeficiency
Cancer of B cells
Leads to immunodeficiency by depressing lymph node cells, swollen lymph nodes
Acquired Immune Deficiency Syndrome (AIDS)
Cripples immune system by interfering with activity of helper T cells
-Weight loss, night sweats, swollen nodes
Opportunistic infections: pneumocystis pneumonia and Kaposi’s sarcoma
Caused by human immunodeficiency virus (HIV) transmitted via body fluids—blood, semen, and vaginal secretions
Blood transfusions; blood-contaminated needles; sex, mother to fetus
HIV
HIV multiplies in lymph nodes throughout asymptomatic period, ~10 years
HIV-coated glycoprotein complex attaches to CD4 receptor
Enters cell and uses reverse transcriptase to produce DNA from its RNA
Autoimmune Diseases
Immune system loses ability to distinguish self from foreign
Production of autoantibodies and sensitized TC cells that destroy tissues
MS, myasthenia gravis, Graves’ disease, type 1 diabetes mellitus, lupus, glomerulonephritis, rheumatoid arthritis
Treatment of Autoimmune Diseases
Suppress entire immune system Anti-inflammatory drugs, Blocking cytokine action Blocking co-stimulatory molecules Activating regulatory T cells; inducing self-tolerance using vaccines; directing antibodies against self-reactive immune cells
Hypersensitivities
Immune responses to perceived (harmless) threat cause tissue damage
Anaphylactic Shock
Systemic response to allergen that circulates rapidly
-Systemic histamine release may cause constriction of bronchioles; tongue swelling
-Vasodilation, fluid loss from bloodstream may hypotensive shock, death
Treatment: epinephrine
