Chapter 20 B Lymphatic System and Lymphoid Organs/Tissues
        Two functions: Circulatory, Immune

  Circulatory function: Lymphatic Vessels
        3 liters of fluid lost from (fenestrated) capillaries daily, returned to circulatory system
                 via lymph vessels.
        Lymphatic capillaries: dead ended in tissues. Cells of simple squam. E act like minivalves;
                allow in fluid, bacteria, etc. Distal ends of cells anchored by collagen fibers.
        Lymphatic trunks (veins): like circulatory veins; the same factors that aid venous return
                aid lymph transport (a pumpless system)
Know:  Lumbar, intestinal, bronchomediastinal, subclavian, jugular trunks; cisterna chyli,
        thoracic duct, right lymphatic duct (these dump lymph into circ. system at juncture of
        internal jugular vein and subclavian vein); also know lacteals

Immune Function:  Lymphoid Tissues -- framework of reticular CT
     Lymphoid Cells B Lymphocytes/macrophages/dendritic cells (See immune system, 
            below); reticular cells (secrete reticular fibers of stroma of lymphoid organs)
     Diffuse Lymphatic Tissue -- found throughout walls of most mucosal membranes
  Lymphoid Organs -- primary: where B & T cells mature -- bone marrow, thymus
            secondary: where lymphocytes encounter antigens and are activated.
      I.  Lymph nodes -- cortex (with lymphocytes [follicles, w/germinal centers]), medulla
                (with macrophages), capsule with trabeculae, stroma (reticular network)
         Found where many smaller (afferent) vessels come together; fewer efferent vessels 
               (exit at hilus) causes lymph to slowly percolate through sinuses of nodes, 
               which gives time for lymph to be cleaned.  ONLY lymph organs to clean lymph.
         Concentration where "appendages" attach to trunk (inguinal, axillary, cervical regions) 
    "Buboes":  Infected -- swollen and painful; Cancerous B swollen, with little pain initially

  Other lymphoid organs: all have supportive reticular networks, stored macrophages/
        lymphocytes, efferent (but no afferent) lymphatic vessels so cannot filter/clean lymph
    II.  Spleen -- left side beneath diaphragm; hilum -- main entry/exit point for nerves/vessels
            Functions: like lymph nodes, site of immune surveillance (macs./lymphs.) Also blood 
            filter (includes removing old RBC=s/platelets), stores (complexed) iron (from old 
            hemoglobin), stores platelets.  Produces RBC's in fetus.
        Anat.: red pulp - processes RBC's/platelets; white pulp - follicle "islands" in red pulp
    III. Tonsils -- pharyngeal (adenoids), palatine, lingual, tubal
            Obvious germinal centers for lymphocytes.
            Not fully encapsulated to allow entry of bacteria for activation of immune system;
                however, crypts may be easily infected
    IV.  Peyer=s Patches -- lymphoid nodules, at end of ileum (small intestine)
    V.  Appendix -- off of cecum (beginning of large intestine); many lymphoid follicles
           
Tonsils, Peyer=s Patches, and appendix, along with diffuse lymphatic tissue in the
            mucosal linings, make up the MALT (Mucosal Associated Lymphatic Tissue) 

     VI.  Thymus -- functions early in life; activates T lymphocytes
            Cortex/medulla, with epithelial tissue (star-shaped thymocytes) framework -- these 
                thymocytes are the source of the lymphocyte activating hormones.

Chapter 21 B Immune System:  Innate and Adaptive Defenses
    Functional System -- main components: lymphocytes (specific) and macrophages (non-
        specific) functions:  Direct cell attack, antibody production against foreign antigens.
    Innate defenses, though originally considered non-specific, do respond to some very
        specific chemicals, many of which are the same that the adaptive respond to, and many
        of which are released by both as well. Indeed, the innate is often responsible for alerting
        the adaptive defenses.  The adaptive defenses are very specific, but must be primed
        (by exposure).

    I.  Non-specific (Innate) defenses
        A. Surface membrane barriers: cutaneous/mucus membranes -- First Line of defense
            keratin of stratified squamous epithelium of skin, mucus (sticky) of mucus membs.    
            Chemical protection (of membs.): mucus, sebum, lysozyme (saliva, tears), acids,
            defensins, etc.
        B. Cellular/Chemical defenses (if surfaces breached) -- Second Line of defense
            1.  phagocytosis (macrophages, neutrophils, eosinophils)
            2.  natural killer cells (non-specific "lymphocytes") -- drop chemical "bombs" on
                tumor/viral-infected cells
            3.  Inflammatory response (initiated by chemicals [histamine, prostaglandins, kinins, 
                lymphokines, etc.] released by many different cells [basophils, etc.])
                    importance: prevents spread of "nasties" into nearby tisues, dilutes/loosens
                    cell debris/pathogens for disposal, alerts the immune sys., initiates repair
            4.  antimicrobial substances (interferons, complement)
            5.  fever (pyrogens) --  How does fever help?

    II. Specific Defenses -- The Immune response -- Third Line of defense
            (nice summary,  Focus Fig. 21.1, pgs. 808-809; Table 21.8, pg. 810)
        Characteristics: Specific, memory, systemic
     Immunity: 
                Humoral (antibodies [Ab=s], produced by B lymphoctyes)  
                Cell-mediated (T lymphocytes). 
                     Immunocompetence (mature and able to recognize antigens) in R-bone
                            marrow and thymus respectively

         Antigens activate certain pre-existing populations of B cells (free-floating antigens
        immunogenic and reactive) and T cells (through antigen-presenting macrophages) to
        divide, producing plasma cells, for current usage (lots of rER in B cells for making  
        Ab=s [2000 per second]) and memory cells (for secondary response). Antigens may
        have > one antigenic determinant (p. 791). Haptens (p. 791) and allergies (p. 811)

     Self-Antigens: Major Histocompatibility complex (MHC) proteins (see * below) 

     Antigen receptor and Ab diversity: involves genetic recombination -- Know basic idea
    Other cells of the immune response -- Macrophages, although non-specific, activate
        helper T lymphocytes by presenting antigens (APC's), which, in turn, activate more
        lymphocytes (both B & T cells) and macrophages, which also phagocytize Ab covered
        antigens (rough foreign particles). Dendritic cells and even B cells can also activate helper
        T cells by presenting antigens as well. 

       Humoral Response -- B-Cell Activation (free-floating antigens); B-cells release
            Antibodies: structure -- two heavy (±400 A.A.) and two light (±200 A.A.) chains,
            each with constant (between all Ab types) and variable (for attachment to Ag=s) 
            regions (Fig. 21.14, pg. 798). Some classes with multiple Ab units. Activation pro-
            duces plasma and memory cells, which give you protection with a second and future
            exposure.  See primary and secondary humoral response (Fig. 21.12, pg. 797).
             Active and Passive Humoral immunity; natural/artificial acquisition
         Antibody targets and functions: Complement fixation, neutralization, agglutination,
                promote phagocytosis by opsonization
      Cell-Mediated Response -- T-Cell Activation
            Most T cells require antigen-presentation -- recognition of combined self-antigens
                (Major Histocompatibility Complex [MHC] proteins) and pieces of antigens
            *MHC Classes I & II -- Know where found (see Table 21.6, p.803)
            Activation similar to B cells --
         Both B and T cells require costimulation from antigens and chemicals -- helper T  
            cells are major releasers of some of these costimulatory chemicals and are therefore 
            responsible for helping activate both arms of the immune system. Explains why HIV 
            (which targets helper T cells) and AIDS are so devastating.
         T cell types: cytotoxic (CD8), helper (CD4) (understand the functions), other classes
         Transplants and rejection.
    See summary Table 21.7, Table 21.8, and Focus Figure 21.1.

Chapter 22 -- Respiratory System
    Respiration -- exchange of O₂ and CO₂; system open to air
        Steps: pulmonary ventilation, external respiration, transport (blood), internal respiration
            (external and internal respiration [exchange] completely passive diffusion)
        (Fifth step:  Cellular Respiration [chapter 24])
Anatomy: 
  I. Conducting Zone
    A. Nose: humidifies & warms air, filters (air, mucus), olfaction
            bridge/septum (hyaline cart, bones), nostrils (nares), nasal cavities (surrounded by 
            bones [maxillae/palatine on floor]) with conchae/meati (for turbulence)
        Epithelium: P.C.C.E. with goblet cells (why?); sneezing
        Paranasal Sinuses
    B. Pharynx: naso- (with openings for auditory tubes), oro-, laryngopharynx 
            oro- and laryngopharynx shared with digestive system
        uvula/epiglottis (elastic cartilage, with taste buds) close off nasopharynx/larynx 
            respectively, when swallowing
         know appropriate epithelial linings; tonsils here (which in which part?)

    C. Larynx (Voice box, Adam=s apple): framework of hyaline cartilage (know thyroid,
            cricoid, arytenoid cartilages), cricothyroid ligament, laryngeal muscles; support
            and stretch vocal cords (elastic conn. tissue)
        Vocal cords avascular; vibrate to produce sound. Higher frequency vibration (pulled 
            tight) = higher pitch; forceful expiration = louder. Sound involves pharynx, tongue, 
            nasal cavities, sinuses, etc.
        Glottis = opening between vocal cords; Stratified Squamous above (including epiglottis),
             P.C.C.E. below glottis
        Valsalva maneuver, involves epiglottis
    D. Trachea: C-rings of hyaline cart., trachealis muscles (involved in coughing)
        Submucosa, with seromucous glands, P.C.C.E.: cilia move mucus up
    E. Major Bronchi, lobar bronchi, smaller bronchi, bronchioles (including terminal)
        Trends as tubes get smaller:
            1. cartilage rings replaced by irregular plates, and, in smallest, no cartilage
            2. epith. thins to simple cuboidal (non-ciliated) in terminal bronchioles
            3. relative amount of smooth muscle in wall increases (important in bronchioles for
                controlling air flow)
  II.  Respiratory Zone -- Gas exchange occurs here (diffusion) across moist membrane
    F.  Respiratory bronchioles and Alveoli -- @140m² of surface area
        Respiratory membrane = simple squamous layer (type I cells) of alveolus + simple
            squamous endothelium of capillaries + sparse basement membrane between
        Respiratory Surface.: Type II alveolar (H₂O + surfactant secreting) cells, keeps
            membrane moist; alveolar macrophages scour surfaces for pathogens

    Gross Anatomy of Lung- Stroma (elastic conn. tissue), apex, base (on diaphragm), 
        hilus, cardiac notch (left), bronchial arteries/veins
    Pleurae (visceral/parietal)

Physiology
        Breathing (inspiration [inhalation], active; expiration [exhalation], passive
    Intrapleural pressure (due to adhesiveness of serous fluid [water] between pleurae)
        must always be less than intrapulmonary pressure; holds pleurae together (i.e., holds
        lungs to chest wall/diaphragm) during inspiration and allows for stretching of stroma

    I. Pulmonary Ventilation: Boyle=s Law P₁V₁ = P₂V₂
         Inspiration: diaphragm and external intercostal muscles; generates negative pressure,
            increases volume 0.5 liters (during normal, at rest breath)
        Expiration: largely passive relaxation and elastic recoil of lungs; forced expiration 
            involves more muscles (and is therefore active, requiring energy)
        Energy used in inspiration needed to overcome: resistance (see pgs. 838-839), lung
            compliance/elasticity, alveolar surface tension (reason for surfactants)
        Respiratory Volumes/Capacities and dead space: tidal, inspiratory/expiratory reserve, 
            residual (volume); vital, total lung (capacity)
        Dead Space -- basically air in conducting zone (not involved in exchange)
        Measurements: Minute respiratory volume, alveolar ventilation rate (AVR which is 
            more precise measure of actual ventilation)
    II. Gas Exchanges in the Body
        Need to Know: Dalton=s Law of Partial Pressures, Henry=s Law
        Partial Pressures (Po₂ and Pco₂ directly proportional to concentrations; need to know
            typical partial pressures of gases in lungs (alveoli) and at tissues
        Gases (O₂ and CO₂) diffuse based on partial pressure gradients, and solubilities in 
            water (respiratory membrane/plasma) or attachment to Hb
        Blood usually completely oxygenated in .25s (blood in caps. for .75s at rest; fig. 22.21)
        Gas flow in bronchioles coupled to blood flow in alveolar capillaries (perfusion)
            (nervous/chemical control of smooth muscles in both tubes; Fig. 22.23, p. 846)
        External and internal respiration: partial pressure gradients opposite, but exchange
            mechanisms the same
    III. Gas Transport in the Blood -- Handout and page 833.
        A.  O₂ -- 1.5% in plasma, 98.5% to heme; know oxy-(HbO₂) and deoxy- (or reduced; 
                HHb) hemoglobin (Hb)
            Hb can hold four O₂ molecules; when one molecule attaches, easier for others to 
                attach, due to a conformational change. Same is true for O₂ release.
            Factors influencing Hb - O₂ affinity:  SEE curves, fig. 22.24, p. 850
                1. Po₂: saturation curves; venous blood usually only about 30% deoxygenated
                2. Temperature: As T_B 8, Hb - O₂ affinity 9 (why important?)
                3. pH: As pH 9, Hb - O₂ affinity 9 (why important?) ; called the Bohr effect.
                    typically, HHb can carry less O₂ than Hb.
                4.  NO -- also carried attached to Hb, unloaded when O₂ unloaded 
        B.  CO₂ -- > 20% bound to globin of Hb (carbaminohemoglobin), 7-10% dissolved
                directly in plasma, < 70% dissolved as HCO₃^- in plasma (catalyzed by carbonic
                anhydrase inside RBC=s) (remember, H₂O + CO₂ ø H₂CO₃ ø H⁺ + HCO₃^-). 
                HCO₃^- diffuses out of RBC=s once made; Cl^- moves in to offset negative ion loss --
                called the chloride shift. CO₂ doesn=t directly interfere with Hb - O₂ affinity, but 
                pH goes down, which does interfere with O₂ carrying capacity.  SEE fig. 22.23.
            Haldane effect -- tied to Bohr effect; reflects increased ability of reduced Hb to carry
                more CO₂, which means that CO₂ increases the ability of blood to carry CO_2.
            Everything that happens at the tissues happens in reverse at the lungs -- we blow off 
                CO₂ which drags the above chemical equation to the left, which reduces the acidity, 
                which allows more O₂ to load into the RBC's; in other words, everything happens 
                precisely in the manner we want it to!  (Chloride shift reverses as well).

Control of Respiration -- relatively complex
    Neural mechanisms: Medullary respiratory centers
            Ventral respiratory group (VRG) -- the apparent pace-setter (eupnea).
                involves phrenic and intercostal nerves, both of which contain neurons that fire during
                inspiration and others during expiration, with mutual inhibition working between them,
                with feedback from stretch receptors in the lungs as well (see DRG)
            Dorsal respiratory group (DRG) -- not well understood; appears to be involved in
                integrating stretch and chemoreceptor inputs and communicating this info to VRG

        Pontine respiratory center -- also not well understood; appear to smooth out the transition
                from inspiration to expiration and back; also appears to modify the normal VRG
                generated rate during activities such as talking, exercise, etc.
        Generation of normal ventilation -- requires interconnections (as describe above) between
                neuronal networks, with two basic sets to generate the rhythm (see under VRG) -->
                one for inspiration and one for expiration that inhibit each other

    Factors influencing rate & depth of breathing:
        1.  Chemical influences: most important in immediate air intake adjustments.
                connected to nervous system controls -- work through chemoreceptors in carotid
                    arteries; in the final analysis, adjustments during rest are aimed primarily at regulating
                    the H⁺ concentration in the brain.
            CO₂ levels most important (why?); O₂ and arterial pH influence air intake, too.
        2.  Stretch receptors

    Influence of Higher brain centers
        Hypothalamus (involuntary alterations in ventilation)
            emotional/pain responses; body temperature responses
        Cortical controls (voluntary)

    Reflexes altering/controlling ventilation         
            a.  pulmonary irritant reflexes
            b.  Hering-Breur (over inflation) reflex

Respiratory Adjustments during Exercise and at High Altitude (pg. 857-858)
    Understand basic changes that happen at beginning and during exercise
    Understand basic changes that happen over the course of a few weeks at high altitude