further sections of the immune system

3rd line of defense: adaptive/acquired immune response

• antigen: a foreign molecule that stimulates a response in the adaptive immune system
  • has a binding site known as an epitope
  • unique molecular shape; lock-and-key with binds
  • tends to be several variants for one antigen
• major histocompatibility complex proteins (MHC): proteins which bind to protein fragments inside the cell and transport them outside of the cell onto the cell surface
  • “displaying the antigen”/“antigen presentation”

lymphocytes

• 5th kind of leukocyte
• produced in bone marrow
• circulates through blood and lymph in an inactive form
• lymphocytes activate in the spleen and lymph nodes
  • swollen lymph nodes; lymphocytes activate and clone in lymph nodes

T-cells

• lymphocytes which mature in the thymus gland
• “thymus cells”
• only bind to antigens presented by the major histocoompatibility complex proteins from other cells
• bind to t-cell receptors on the cell surface
  • lower section: constant region
  • upper section: variable region
    • differentiates t-cell receptors; unique to one t cell
    • thousands of trillions (10^15) variations
    • uppermost region is the antigen binding site: very specific to epitopes

Helper T Cells (T subH)

• macrophages phagocyte antigens and present them on their surface to t cells
• a specific helper t cell whose receptor matches the epitope binds to the antigen presented
  • helper t-cell secretes cd-4 protein that keeps cells attached while activation continues
• t-cell activates → clonal expansion of helper t cells
• helper t-cells produce cytokines and activate other types of lymphocytes (cytotoxic t cells and b cells)
  • cytokine: a chemical that activates other lymphocytes

Cytotoxic T Cells (T subC, CD8, Killer T)

• kills native cells infected with an antigen
• infected presents antigen
• cytotoxic t cell binds to antigen on the infected cell on the variable region site
• cytotoxic t cell secretes cd-8 protein that keeps cell attached
• cytokine chemicals activate the cytotoxic t cell
• clonal expansion of cytotoxic t cells
• cloned cytotoxic t cells bind to an infecting antigen and secrete two chemicals:
  1. granzyme: enzyme inducing apoptosis
     • as specific killer cells, granzyme causes very specific cell death; only kills the infected cell and preserves the cytotoxic t cell
  2. perforin: protein which perforates the cell membrane

B-cells

• lymphocytes produced in and matured in the bone marrow
• “bursa fabricious cells”; found in bird cells
• produce antibodies that remove free-flowing antigens
• directly bind to and hold up antigens and present on the b-cell surface
• different shape; receptor has a y-shaped receptor with two pairs of heavy and two pairs of light chains

B-cell Activation

• known as the humoral response
• antigen binds to the variable region on one of the b cell receptors
• b cell phagocytes/ingests the antigen
• major histocompatibility complex proteins present antigen on b cell surface
• cloned helper t cell binds to the antigen presented by the major histocompatibility complex
• b cell activates; clonal expansion of undifferentiated clonal b cells
• undifferentiated clonal b cells mature/differentiate with helper t cell cytokines
  • floating cytokines cause sickly feeling
  • b cells differentiate into one of two types:
    1. plasma cells: short-lived immediate production of antibodies to remove free-floating antigens; causes the primary antibody response
    2. memory b cells: causes the secondary antibody response, or future infection response
       
• for an initial exposure, the primary immune response takes a week to begin and peaks at two weeks
• on a secondary exposure, the antibody production begins immediately (2-3 days with some initial), and a greater/larger reaction occurs
  • more effective antibodies are produced vs. initial exposure
  • note: memory t cells also exist: “immunological memory”

Vaccines

• rely on memory b cells; weakened or small/microscopic portions of the germ
  • mRNA: direct cell code for production of antibodies
• “initial exposure” is injection

Antibodies

• produced by plasma cells to remove free-floating antigens
• made from 5 classes of immunoglobulins
  • IgG (Immunoglobulin Type G): help with phagocytosis, cross the placenta
  • IgE (Type E): allergy responses
• antibody structure is based on parent b cell receptor shape, especially the variable region
• antibody-mediated disposal of antigens
  • antibodies mark antigens to be disposed of
  • neutrophils and macrophages see the signal and go to phagocytose the antibodies and antigens
  • antibodies bind to antigen, preventing activity from antigen
    • antibodies neutralize proteins protruding from antigens, so antigens are unable to adhere for infection

Clonal Expansion

• clonal selection theory
• occurs in both lymphocytes of the adaptive immune response
• lymphocyte activates when a matching epitope from an antigen binds
• activated lymphocyte goes through repeat cellular division, producing many clones of the activated parent cell
  • large aggregate of clones

muscle cells

• skeletal, cardiac, and smooth tissues
  • remember striation and multinucleated cells
• skeletal muscle
  • a single muscle cell (muscle fiber) is made of small myofibrils
  • myofibrils are made from thin filaments and thick filaments
    • thin filaments are made from 2 strands of actin and 2 strands of tropomyosin
      • both are proteins; tropomyosin is a regulatory protein which changes position and affects ability to contract and relax
      • twisted around one another
    • thick filaments are made from myosin proteins
      • myosin has a fibrous tail and a globular head
  • one unit of a myofibril is a sarcomere; it has thick and thin filaments arranged relative to each other in a specific pattern followed through the myofibril
    • a sarcomere is bound by z-lines/z-disks. thin filaments are bound to the z-lines, while the thick filaments are between the sarcomere-thin filament complex
    • sliding filament theory of muscle contraction
    • z-lines are the striations seen from microscopes

sliding filament theory

1. sarcomere is at rest; thick filaments and myosin head are at rest
2. atp binds to the myosin head
3. atp hydrolyzes chemical bond, releasing energy to the myosin head. head is excited, changing positions
4. when possible, myosin head forms a crossbridge on a myosin binding site on the actin; myosin-actin complex
5. adp + phosphate + adp-phosphate energy dissociates from the myosin head; myosin head falls to low-energy state, pulling crossbridge of the actin-tropomyosin-z-line towards the center
6. a new atp binds to the myosin, breaking the crossbridge

• step 5 occurring with multiple thick filament myosin heads causes contractions
• myosin heads are usually in active position (see #3 – #4) but tropomyosin is usually blocking myosin binding sites
• atp works to break the crossbridge when binding to the low energy myosin head and to be hydrolyzed to release energy for the myosin head to go to high energy configuration
• troponin: controls position of tropomyosin on the actin
  • muscle contraction is regulated by the presence of calcium ions; when calcium are present, calcium binds to the troponin, causing a confirmation shift that moves the tropomyosin

neuromuscular junction

• sarcoplasm: cytoplasm in a striated muscle cell
• sarcoplasmic reticulum: endoplasmic reticulum which pumps, stores, and releases calcium in the muscle cell
• chemical synapse between a motor neuron and a skeletal muscle cell
• action potential in the motor neuron releases acetylcholine into synaptic cleft: ridged area for binding of acetylcholine (ACh)
• sodium moves into the muscle cell and depolarizes the membrane, creating an action potential
• action potential propagates through the t-tubule and approaches the sarcoplasmic reticulum, opening several gates
  • not voltage-regulated, just ligand-regulated; signal transduction cascade
• action potential releases calcium ions from sarcoplasmic reticulum into sarcoplasm
• calcium binds to troponin; calcium is actively transported back into the sarcoplasmic reticulum

cardiac muscular cycle

• first sound (“lub”) is atrioventricular valve closing
• second sound (“dub”) is semilunar valves closing
• systole is contraction, diastole is relaxation
• autorhythmic regions of the heart: separate electrical signal generated that cause heart to contract
• similar mechanism to neuron and skeletal muscle cycles, except:
  • large plateau at depolarization phase
  • opens voltage regulated calcium channels and

tetrapods

• fish had the macroevolutionary origin of jaws; tetrapods had the origin of limbs And lungs due to the terrestrial advantage that warranted limbs and lack of gills
• common ancestor for tetrapods was a sarcopterygii (a lobe finned fish, not a ray finned fish) from 400 mya, during the devonian era
• the original trait for the lungs would have been a pouch drawn out of the pharynx that would evolve into the lungs
  • this kind of pouch is seen in lungfishes in modern day, a kind of sarcopterygii that can breath with a primitive lung pouch structure

amphibians

• earliest clade of vertebrata
• emerged proper ~360 million years ago
• amphibians have shellless eggs laid in the water or moist habitats; they don't need to avoid dessication
• skin-based gas exchange: pulmocutaneous gas exchange
• three-chambered heart (pulmocutaneous circuit vs. pulmonary circuit)

endangering amphibians

• 95% of california’s wetlands have been destroyed
• pesticides can disrupt endocrine systems in amphibians
  • produce all-male if mated
  • atrazine
• chytrid fungus
  • waterborne fungus that disrupts pulmocutaneous circuit
  • estimated ⅓ species risk extinction via chytrid fungus

amniota

• clade based on common amniotic egg
• reptilia and mammalia classes
• “shelled eggs”
• pores are large enough for gas exchange but small enough to prevent dessication
• 4 extra-embryonic membranes
  • 

reptilia