Ch. 22 The Lymphatic System and Immunity Above: macrophage (gray), T lymphocyte (pink), and bacteria (orange) The lymphatic system General functions: It acts with other organ systems to help provide immunity (= the ability to prevent and fight disease) It returns lost plasma (= interstitial fluid) to the blood It transports dietary lipids from the digestive tract to the blood (more in Ch. 24) Components: Lymph = interstitial fluid that gets absorbed and transported by Lymphatic vessels (lymphatics) = low pressure tubes that ultimately return lymph to the blood Lymphoid tissues and organs Lymphoid cells = lymphocytes and supporting cells Fig. 22-1, p. 787 1
Lymphatic capillaries Are different than typical blood capillaries, in part because they: Have larger diameters Have thinner walls Are more permeable Are composed of loosely bound, overlapping endothelial cells Which act as one-way valves for entry Fig. 22-2, p. 788 Lymphatic vessels Are a.k.a. lymphatics Are similar in structure to veins, but they have even thinner walls The larger ones have valves to prevent the backflow of lymph Fig. 22-3, p. 789 2
Lymphatic trunks and ducts Lymphatic vessels merge to form lymphatic trunks, which drain into either the Thoracic duct which empties into the left subclavian vein, or the Right lymphatic duct which empties into the right subclavian vein Fig. 22-4, p. 790 Types of lymphocytes Fig. 22-15, p. 806 3
Lymphocyte production Fig. 22-9, p. 798 Lymphocytes NK and T cells NK cells (natural killer cells) Are responsible for immune surveillance Function: nonspecifically attack foreign, virus-infected, and cancerous cells T cells (thymus-dependent cells) Are responsible for cell-mediated (cellular) immunity The main types of T cells include: Cytotoxic T cells (T C cells) Function: specifically attack foreign, virusinfected, and cancerous cells Helper T cells (T H cells) Function: stimulate T and B cells; coordinate cell- and antibody-mediated immunity Regulatory (suppressor) T cells Function: moderate/inhibit T and B cells Fig. 22-9, p. 798 4
Lymphocytes B cells B cells (bone marrow-derived cells) Are responsible for antibodymediated (humoral) immunity Function: when stimulated, they differentiate into plasma cells that secrete specific antibodies (immunoglobulins) Effects of antibodies include: Neutralizing viruses and toxins Agglutinating and precipitating antigens Activating complement proteins Attracting phagocytes Opsonizing antigens (making them easier to hang onto) to enhance phagocytosis Promoting inflammation By stimulating basophils and mast cells Interfering with bacterial/viral adhesion to body surfaces Fig. 22-9, p. 798 Lymphoid tissues = connective tissues (CTs) dominated by lymphocytes No external fibrous CT capsule is present (as opposed to lymphoid organs see the next slide) If the lymphocytes are densely packed, it s called a lymphoid nodule Examples: MALT (mucosaassociated lymphoid tissue) E.g. aggregated lymphoid nodules (Peyer s patches) in the digestive tract Tonsils = large lymphoid nodules in the walls of the pharynx E.g. the palatine tonsils (2), pharyngeal tonsil (1, a.k.a. the adenoid), and lingual tonsils (2) Fig. 22-5, p. 791 5
Lymphoid organs Have an external fibrous CT capsule separating the organ from other tissues (as opposed to lymphoid tissues see the previous slide) Include the: Lymph nodes Thymus Spleen Fig. 22-1, p. 787 Lymph nodes Functions: 1. They filter (purify) lymph before its return to the bloodstream They remove > 99% of the antigens in the lymph Antigen presentation is performed by macrophages and dendritic cells (which are examples of antigenpresenting cells, or APCs) This is the 1 st step in the activation of an immune response Reminder: antigens = substances that trigger an immune response 2. They serve as an early warning system, monitoring the condition of peripheral tissues via the interstitial fluid/lymph 3. They are strategically located in the axillae, groin, neck, and torso Fig. 22-6, p. 792 6
The thymus Is where lymphoid stem cells mature (differentiate) into T cells Is located in the mediastinum above the heart Reaches its maximum relative size (% of body weight) in the first 1 2 years of life Reaches its maximum absolute size just before puberty It gradually involutes (deteriorates into CT and shrinks) from then on Fig. 22-7a, p. 794 The thymus Is filled with lymphocytes and epithelial reticular cells (thymic epithelial cells); the epithelial reticular cells function to Maintain the blood thymus barrier Secrete thymic hormones (thymosins) that promote the division and maturation of T cells Fig. 22-7, p. 794 7
The spleen Note the non-intuitive orientation here! Is the largest lymphoid organ Fig. 22-8, p. 795 The spleen Functions: Its macrophages remove (via phagocytosis) abnormal or worn out blood cells It stores iron (recycled from RBCs) It initiates immune responses (via APCs) to antigens that are present in the blood The spleen is sort of like a lymph node for the blood! Fig. 22-8c, p. 795 8
Body defenses Function: provide resistance (= the ability to maintain immunity; i.e., the ability to fight infection, illness, and disease) The main types of body defenses: 1. Innate (nonspecific) defenses provide nonspecific resistance to disease; a.k.a. innate (nonspecific) immunity They provide general protection against a wide range of pathogens The response is the same regardless of the type of invader They are present at birth 2. Adaptive (specific) defenses provide specific resistance to disease; a.k.a. adaptive (specific) immunity They provide specific protection against a particular pathogen The response is specific to the particular antigen(s) associated with a particular pathogen They require functioning specific lymphocytes (T and B cells) and exposure to the pathogen Innate (nonspecific) defenses 1. Physical barriers = epithelium and its accessory structures and secretions, which keep hazardous organisms and materials outside the body 2. Phagocytes consume debris, foreign objects, and pathogens in peripheral tissues 3. Immune surveillance (by NK cells) destroys abnormal (foreign, bacterial, virus-infected, and cancerous) cells in peripheral tissues 4. Interferons cause the production of antiviral proteins 5. The complement system = circulating proteins that enhance the action of antibodies and phagocytes 6. Inflammation = a localized tissue response to limit the spread of an injury/damage and/or infection 7. Fever = a higher-than-normal body temperature that accelerates tissue metabolism and the activity of defenses 9
1. Physical barriers (and their accessory structures and secretions) Epithelial coverings Are often thick and/or keratinized, and sometimes hairy Are held together by desmosomes or tight junctions Have a dense, fibrous basement membrane Have an acidic ph in the skin, stomach, and vagina This inhibits pathogen growth, but is OK for friendly resident bacteria Tears and saliva are antimicrobial and may contain antibodies Mucous membranes and cilia Mucus traps pathogens, and can be swept away by cilia for removal Tears, saliva, and urine wash away pathogens Fig. 22-10, p. 799 Microphages include neutrophils and eosinophils Macrophages (most are derived from monocytes from the blood) include: Fixed macrophages permanently reside in specific tissues E.g. microglia in the CNS, stellate macrophages (Kupffer cells) in the liver Free (wandering) macrophages travel throughout various tissues Phagocyte movement and phagocytosis Emigration (diapedesis) they exit the bloodstream through the capillary walls Chemotaxis they are attracted to (or repelled by) chemical signals released by other body cells and pathogens Adhesion surface membrane receptors allow the attachment to a target Phagocytosis is followed by the fusion of the vesicle that contains the target with a lysosome or peroxisome for digestion/destruction 2. Phagocytes Fig. 22-10, p. 799 10
3. Immune surveillance Fig. 22-11, p. 801 Is carried out by NK cells, which Recognize a variety of abnormal antigens on bacteria, cancerous cells (tumorspecific antigens), and virus-infected cells When activated, release perforins, which cause the abnormal cell s membrane to rupture (lyse) Fig. 22-10, p. 799 4. Interferons Are examples of cytokines (chemical messenger proteins released by tissue cells that can act locally or system-wide as hormones) Are released by: Activated lymphocytes Macrophages Virus-infected cells Main effects of interferons: They cause the production of antiviral proteins that interfere with viral reproduction in nearby cells, slowing the spread of infection They stimulate NK cells and macrophages Fig. 22-10, p. 799 11
5. The complement system = a group of over 30 special plasma proteins that complement (enhance) the action of antibodies and phagocytes The activation of complement can occur via three different pathways (see the next slide for a figure that depicts these pathways): The classical pathway (which is fastest and most effective): C1 binds to antibodies that are already bound to the invader s membrane antigens A cascade is initiated, and eventually C3b forms and attaches to the invader The lectin pathway: The protein lectin binds to carbohydrates on the invader s membrane C3b forms and attaches to the invader The alternative (properdin) pathway: Factors P (properdin), B and D interact directly with the invader s membrane C3b forms and attaches to the invader See the next slide for some effects of activated and bound complement (C3b) Fig. 22-10, p. 799 Complement activation Some effects of activated and bound complement (C3b): Membrane attack complexes (MACs) are formed, causing lysis (similar to how perforins work) Inflammation is stimulated (due to histamine release) Phagocytes are attracted (chemotaxis) Phagocytosis is enhanced (opsonization) Fig. 22-13, p. 803 12
6. Inflammation Fig. 22-14, p. 804 = a localized tissue response to injury/damage Examples of damaging stimuli: impact, abrasion, chemical irritation, infection by pathogens, extreme temperatures Signs and symptoms: swelling (edema), redness, heat, pain Overall effects: It temporarily repairs the damage It walls off the damaged area to prevent or slow the spread and additional entry of pathogens It activates nonspecific and specific defenses to kill pathogens It initiates permanent tissue repair (regeneration) Fig. 22-10, p. 799 7. Fever = a regulated elevation of body temperature above 37.2 C (99 F) Pyrogen = a circulating chemical that can cause a fever Pyrogens may be produced by the human body in response to the presence of certain pathogens (bacteria, molds, viruses, etc.) Pyrogens may also be released by the pathogens themselves The benefits of a fever (as long as it s mild ): It leads to an overall increase in metabolic rate, so there is increased activity of WBCs and other body defenses It inhibits some viruses and bacteria Fig. 22-10, p. 799 13
Adaptive (specific) defenses Adaptive defenses = specific defenses = specific resistance = specific immunity = adaptive immunity Are provided by the activities of T cells and B cells Some properties of adaptive immunity: 1. Specificity the response is targeted to an antigen of a specific molecular size and shape 2. Versatility millions of different lymphocyte populations exist, each sensitive to a specific antigen 3. Memory activated lymphocytes divide to produce many, many daughter cells: Some are active cells that respond to a specific antigen immediately Others are memory cells = inactive reserve cells that recognize the same specific antigen if exposed to it at a later date 4. Tolerance normally, self-antigens do not stimulate an immune response Forms of immunity ( get sick ) (vaccine) Fig. 22-17, p. 808 14
Types of adaptive immunity 1. Cell-mediated (cellular) immunity Is directed against specific cellular and intracellular pathogens, such as Abnormal cells (e.g. cancerous cells) Foreign cells (e.g. bacteria, protozoa, and tissue graft cells) Pathogen-containing cells (e.g. virus-infected cells) Is carried out by T C cells that directly attack target ( bad ) cells T H cells that secrete cytokines, stimulating: Macrophages and NK cells to attack target ( bad ) cells The division and maturation of other T cells The activation of B cells (see below) 2. Antibody-mediated (humoral) immunity Is directed against specific antigens (both free and on the surface of pathogens) that are found in body fluids Is carried out by antibodies that attack these antigens Activated B cells differentiate into plasma cells, which then secrete antibodies An overview of adaptive immunity Fig. 22-16, p. 807 15
T cells and antigen presentation T cells need to be exposed to an antigen in order to be activated This most often occurs due to an antigen being presented on the surface of a cell s membrane in combination with a MHC (major histocompatibility complex) protein There are 2 types of MHC proteins: Class I MHC proteins are found on all nucleated cells Antigens bound to Class I MHC proteins stimulate T C cells (quickly, and in larger numbers) and regulatory (suppressor) T cells (slowly, and in smaller numbers) [both of which have CD8 markers]; the message to the T C cells = I m abnormal kill me! Class II MHC proteins are found on APCs (antigen-presenting cells; e.g. macrophages and dendritic cells) and lymphocytes only They are present on an APC only when it has engulfed and is processing an antigen Antigens bound to Class II MHC proteins stimulate T H cells [which have CD4 markers]; the message = This antigen is dangerous help me get rid of whatever it came from! The first binding of a T cell to an antigen-mhc complex (on a stimulating/presenting cell) prepares the T cell for activation Costimulation (= the binding of a T cell to the stimulating/presenting cell at a 2 nd site, OR additional chemical stimulation from the stimulating/presenting cell or other activated lymphocytes) is needed for complete activation Class I MHC antigen presentation (which can be any nucleated cell) Fig. 22-18a, p. 810 16
Class II MHC antigen presentation (remember, only APCs and lymphocytes can express Class II MHCs) Fig. 22-18c, p. 810 T C (cytotoxic T) cell activation Fig. 22-19, p. 812 17
Fig. 22-20, p. 813 T H (helper T) cell activation Some effects of cytokines secreted by T H cells: 1. Memory T H cell production and T C cell maturation 2. Attract macrophages and their activity 3. Attract T C cells and their activity 4. Activate B cells, and their division, maturation (into plasma cells), and antibody production; see Fig. 22-23 A summary of the pathways of T cell activation These processes can take a few days (found on any nucleated cell) (found on APCs and lymphocytes only) Fig. 22-22, p. 816 In which case, they will immediately respond! In which case, they will immediately respond! 18
Antibody structure and function B cell sensitization and activation Up to 100 million antibodies per plasma cell per hour! Fig. 22-23, p. 817 Fig. 22-24, p. 818 19
Table 22-1, p. 819 The classes and effects of antibodies (immunoglobulins) There are 5 classes (*denotes the biggest players): *IgG make up 80% of all antibodies; they are versatile and effective; they can cross the placenta IgE are found on basophils and mast cells IgD are found on B cells *IgM are secreted first (soonest) following antigen exposure; they are potent agglutinators IgA are found in secretions (e.g. mucus, tears, and saliva) Effects (repeated from earlier in the Ch. 22 notes): Neutralize viruses and toxins Agglutinate and precipitate antigens Activate complement proteins Attract phagocytes Opsonize antigens (making them easier to hang onto) to enhance phagocytosis Promote inflammation By stimulating basophils and mast cells Interfere with bacterial/viral adhesion to body surfaces Primary and secondary responses by B/plasma cells to antigen exposure A primary response will occur upon the initial (first) exposure to a specific antigen Thanks to memory cells, a secondary response will occur upon subsequent exposure to the same specific antigen as before There is a dropoff in antibody titer (= level of antibodies in the blood plasma) with time because: Plasma cells are short lived (they have a very high metabolic rate) Regulatory (suppressor) T cells eventually inhibit further plasma cell production Fig. 22-25, p. 820 20
A summary of the immune response Fig. 22-27, p. 823 The time course of an immune response to a bacterial infection Fig. 22-26, p. 821 21
Defenses against bacteria and viruses Fig. 22-28, p. 824 A summary table of the cells that participate in tissue defenses Table 22-2, p. 822 22