Fighting the Enemy Within! phagocytic leukocyte Fighting the Enemy Within! The Immune System Innate Immune System lymph system

Avenues of attack Points of entry Routes of attack digestive system respiratory system urogenital tract break in skin Routes of attack circulatory system lymph system

What’s in your lunchbox? Why an immune system? Attack from outside lots of organisms want you for lunch! animals are a tasty nutrient- & vitamin-packed meal cells are packages of macromolecules no cell wall animals must defend themselves against invaders viruses HIV, flu, cold (rhinovirus), measles, chicken pox bacteria pneumonia, meningitis, tuberculosis, MRSA fungi yeast (“Athlete’s foot”…) protists amoeba, Lyme disease, malaria Attack from inside defend against abnormal body cells = cancers Mmmmm, What’s in your lunchbox?

Lymph system Production & transport of leukocytes Traps foreign invaders Lymph system lymph vessels (intertwined amongst blood vessels) lymph node

Development of Red & White blood cells Pluripotent = stem cell capable of giving rise to several different cell types Development of Red & White blood cells Red blood cells inflammatory response fight parasites (such as parasitic worms) develop into macrophages short-lived phagocytes 60-70% WBC

Bacteria & insects inherit resistance. Vertebrates acquire immunity! Lines of defense 1st line: Barriers broad, external defense “walls & moats” skin & mucus membranes 2nd line: Non-specific patrol broad, internal defense “patrolling soldiers” leukocytes = phagocytic WBC macrophages 3rd line: Immune system specific, acquired immunity “elite trained units” lymphocytes & antibodies B cells & T cells Bacteria & insects inherit resistance. Vertebrates acquire immunity!

1st Line of Defense BARRIERS

EXTERNAL DEFENSE Physical & chemical defenses external barrier non-specific defense external barrier epithelial cells & mucus membranes skin respiratory system digestive system uro-genital tract Lining of trachea: ciliated cells & mucus secreting cells

CHEMICAL BARRIERS ON EPITHELIUM Skin & mucous membrane secretions sweat pH 3-5 tears washing action mucus traps microbes saliva anti-bacterial = “lick your wounds” stomach acid pH 2 anti-microbial proteins lysozyme enzyme (in saliva, mucus, and tears) digests bacterial cell walls

CELLULAR INNATE DEFENSES 2nd Line of Defense CELLULAR INNATE DEFENSES

INTERNAL, BROAD RANGE CONTROL Innate, general defense RAPID response Patrolling cells & proteins attack invaders that penetrate body’s outer barriers leukocytes phagocytic white blood cells complement system ~20 anti-microbial proteins inflammatory response leukocytes

Leukocytes: Phagocytic WBCs Attracted by chemical signals released by damaged cells enter infected tissue, engulf & ingest microbes traps in a vacuole and fuses with a lysosome = nitric oxide poisons and enzymes degrade Neutrophils most abundant WBC (~70%) but short lived engulf & destroy microbe Macrophages “big eater”, long-lived some in spleen and lymph nodes Dendritic cells: stimulate the development of acquired immunity (dendri = tree like) Eosinophils low phagocytic activity defend against multicellular invaders (parasitic worms)

Phagocytes macrophage yeast

ANTIMICROBIAL PEPTIDES AND PROTEINS Interferons proteins provide innate defense against viruses Virus-infected body cells secrete interferons Nearby uninfected cells produce substances to “interfere” with the viral resproduction. Limits cell-to-cell spread of virus

ANTIMICROBIAL PEPTIDES AND PROTEINS Complement system ~20 proteins circulating in blood plasma attack bacterial & fungal cells form a membrane attack complex perforate target cell apoptosis cell lysis extracellular fluid complement proteins form cellular lesion plasma membrane of invading microbe complement proteins bacterial cell

INFLAMMATORY RESPONSE Damage to tissue triggers local non-specific inflammatory response release histamines & prostaglandins capillaries dilate, more permeable (leaky) increase blood supply delivers WBC, RBC, platelets, clotting factors fight pathogens clot formation accounts for swelling, redness & heat of inflammation & infection Histamine is a compound that is released by cells in response to injury and in allergic and inflammatory reactions, causing contraction of smooth muscle and dilation of capillaries. The prostaglandins (PG) are a group of physiologically active lipid compounds having diverse hormone-like effects in animals. Prostaglandins have been found in almost every tissue in humans and other animals.

Inflammatory response Reaction to tissue damage Pin or splinter Blood clot swelling Bacteria Chemical alarm signals Phagocytes Blood vessel

Fever When a local response is not enough systemic response to infection activated macrophages release interleukin-1 triggers hypothalamus in brain to readjust body thermostat to raise body temperature higher temperature helps defense inhibits bacterial growth stimulates phagocytosis speeds up repair of tissues causes liver & spleen to store iron, reducing blood iron levels bacteria need large amounts of iron to grow Certain bacterial infections can induce an overwhelming systemic inflammatory response leading to a condition known as septic shock. Characterized by high fever and low blood pressure, septic shock is the most common cause of death in U.S. critical care units. Clearly, while local inflammation is an essential step toward healing, widespread inflammation can be devastating.

Natural Killer Cells destroy virus-infected cells & cancer cells patrol body and attach to “sick” cells release chemicals that lead to cell death inhibit spread of viruses and cancer

Destroying cells gone bad! Natural Killer Cells perforate cells release perforin protein insert into membrane of target cell forms pore allowing fluid to flow into cell cell ruptures (lysis) apoptosis vesicle natural killer cell perforin cell membrane perforin punctures cell membrane cell membrane virus-infected cell