Bacterial infection:  At first: phagocytes, histamine release, inflammatory response  Inflammation brings phagocytes, plasma proteins (complement system,

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Bacterial infection:  At first: phagocytes, histamine release, inflammatory response  Inflammation brings phagocytes, plasma proteins (complement system, clotting proteins)  Bacteria antigen stimulates helper T cells, B cells get activated: antibodies  Bacteria get labeled w/antibodies, killed by complement, macrophages, killer cells. This slide is just another way to organize things for immune response to help study. I won’t use in lecture Combining non-specific and adaptive immune response

Viral infection:  Virus inside body cells do not trigger macrophages, B-cells, or complement.  Virus-infected or cancerous cells release interferon, signaling neighboring cells and attracting natural killer cells, macrophages, complement. Virus ‘out in the open’ can be attacked.  Antigen-self combination triggers T-helpers, which help stimulate killer T cells (takes days) and attract macrophages to the area. This slide is just another way to organize things for immune response to help study. I won’t use in lecture Combining non-specific and adaptive immune response

Systemic anaphylaxis- when large amounts of histamine and inflammatory signals are released all at once to blood.  Widespread dilation - hypotension. Airway constriction. Victim can die within minutes. Often due to penicillin, bee venom. Anaphylactic shock

Skin: Besides IgE response, can be a T-cell response to substance (ex: urushiol oil) Airway: besides histamine, leukotrienes are released – airway constricted Gut: traditional food allergies are IgE ( egg, milk, wheat, nuts, shellfish, etc.) Histamine dilation, leukotriene constriction. Some are T-cell allergies w/delayed effects ( gluten, milk ). Does the immune system react differently for different allergies?

 They generally reduce the histamine signal  They can be bronchodilators, reduce leukotrienes, decongestants (constrict capillaries), injectable epinephrine, anti IgE  Corticosteroids inhibit expression of cytokines and other signals of inflammation What do allergy medications do beside reduce inflammation?

Tolerance of substances develops early via clonal deletion of specific lymphocytes  Central tolerance: B and T cells that respond to self- antigen are destroyed  Error can result in autoimmune disease  Peripheral tolerance: regulatory cells inhibit response to environmental antigens  Error can result in allergies Allergies can have late onset, even in adulthood Development of ‘tolerance’

Hygiene hypothesis Recent study: Exposing ‘high-risk’ infants to peanuts reduced later allergies by 80% Keeping a child’s environment ‘too clean’ may prevent proper development of immune system

Immune system wrongly attacks body cells, often caused by production of autoantibodies  Rheumatoid arthritis – autoantibodies attach to joints and induce inflammation & attack by complement, and WBCs What are autoimmune diseases?

A few immune related disorders:  Diabetes Type I  Crohn’s Disease  Multiple Sclerosis  Pernicious anemia  Addison’s disease  Lupus

AI diseases often have an environmental trigger, those with certain genotypes can be more susceptible to it A trigger can be an infection w/antigen that is molecularly similar to markers on body cells Possible environmental agents: silica, mercury, nitrates in drinking water, groundwater pollutants, drugs, many other chemicals… Why do autoimmune diseases begin?

 A problem with apoptosis causes formation of autoantibodies  Apoptotic cells aren’t removed normally, they instead degrade, proteins left are engulfed by cells that present antigen. Autoantibodies created against these proteins. Question: Lupus

 Vitamin D – helps trigger T cell response  Zinc – if early in infection  Sleep  Diet  Exercise How can I boost my immune system?

Respiratory system External vs. cellular respiration

Respiratory system Bronchioles can dilate and constrict Airway: from nasal passages down to trachea, bronchioles and alveoli. The trachea and bronchi are reinforced with cartilage Larynx (voicebox) has vocal cords

bronchioles Alveolus Smooth muscle Pulmonarycapillaries Respiratory system

chest cavity

Lung wall Transmural pressure gradient lungs will always expand to fill pleural cavity Pleural cavity Lungs Chest wall

If lung pressure is less than atmospheric pressure, air enters the lungs. Increasing cavity volume, air enters

Inspiration and expiration: how we change chest volume

Puncture wound in chest wall 760 Pneumothorax: How a lung can ‘collapse’

F = P R Major determinant of resistance is radius of bronchioles Disease can increase resistance (asthma, bronchitis) What determines airflow? same equation as blood flow!

Surface tension – whenever water layer meets air – water molecules are attracted to each other. Surface tension along the lining of alveoli resists expansion of alveoli. Surfactant reduces surface tension. Surface tension at alveoli

Air is a mixture of gases Nitrogen is 79% of air. Its partial pressure: 0.79 x 760 = Gas exchange and partial pressure gradients AlveoliCapillaries P O P CO

Most O 2 is carried by Hb - some is dissolved in plasma and determines partial pressure Hb saturation is high where P O2 is high (lungs). Saturation remains high even P O2 is 60 Small decrease in P O2 makes Hb unload much more O 2 Hemoglobin saturation Oxygen saturation curve

Increase in CO 2 from tissue shifts the saturation curve to the right Increased acidity (H +, carbonic acid) and temperature has the same effect - Bohr effect Shifting the curve

Most O 2 carried on hemoglobin A teensy bit of O 2 is dissolved in plasma

Carotid and aortic bodies send info to the medulla P O2 and P CO2 and H + can be detected O 2 saturation is not detected Chemoreceptors sense O 2 dissolved in blood

Measures airflow and volume of inspiration and expiration Spirometry

 Aids homeostasis by removing cellular wastes and foreign compounds, and maintains salt and water balance of plasma Urinary system

Kidney anatomy Renal cortex Renal medulla Renal pelvis Ureter Medulla Cortex

Nephrons Each kidney has about one million nephrons Afferent arteriole brings blood to glomerulus and then forms efferent arteriole. Efferent arteriole branches to peritubular capillaries

Let’s make the filtrate... Blood is filtered at the glomerulus. Water and solutes leave the blood and enter Bowman’s capsule.

Glomerulus physiology Bowman’s capsule contains podocytes that encircle the glomerulus. Normally blood cells and plasma proteins are not filtered.

Glomerular filtration Glomerular filtration is similar to ultrafiltration of capillaries 20% of plasma becomes filtrate Capillary blood pressure Osmotic pressure Hydrostatic pressure Glomerular filtration rate (GFR) determined by: Net filtration pressure and glomerulus permeability

Adjusting GFR Blood pressure Radius of afferent arteriole Decreasing GFR helps retain fluid and salts

Filtrate is adjusted along the nephron Distal tubule Bowman’s capsule Proximal tubule Loop of Henle Cortex region Medulla region Juxtaglomerular apparatus - helps in adjustments to filtration rate

 180 liters per day are filtered, most is reabsorbed  Reabsorption: filtered substances leave the nephron and enter peritubular capillaries  Secretion: some substances from the peritubular capillaries enter the nephron Tubular reabsorption and secretion

Everything in the nephron that does not get reabsorbed into the blood leaves as ….urine!!! So what is urine, then?

Reabsorption physiology

Reabsorption of Na + (the key to it all…)

 Na + reabsorption (RA) drives the movement of many other substances in the tubule  Water will “follow” Na + movement Na + reabsorption

Figure Page 533 LumenProximal tubular cell Peritubular capillary Interstitial fluid Water channel Osmosis Hydrostatic pressure