The Immune System: Innate and Adaptive:Body Defenses: Part A 21 The Immune System: Innate and Adaptive:Body Defenses: Part A

Immunity: Two Intrinsic Defense Systems Innate (nonspecific) system responds quickly and consists of: First line of defense – skin and mucosae prevent entry of microorganisms Second line of defense – antimicrobial proteins, phagocytes, and other cells Inhibit spread of invaders throughout the body Inflammation is its most important mechanism Adaptive (specific) defense system Third line of defense – mounts attack against particular foreign substances Takes longer to react than the innate system Works in conjunction with the innate system

Types of Nonspecific Defenses Physical/surface barriers Internal Defenses: Cells and Chemicals Phagocytes Netural killer cells Inflammation Antimicrobial proteins Interferons Complement system fever

Surface Barriers Presents a physical barrier to most microorganisms Skin, mucous membranes, and their secretions make up the first line of defense Keratin in the skin: Presents a physical barrier to most microorganisms Is resistant to weak acids and bases, bacterial enzymes, and toxins

Epithelial Barriers Epithelial membranes produce protective chemicals that destroy microorganisms Skin acidity (pH of 3 to 5) inhibits bacterial growth Sebum contains chemicals toxic to bacteria Stomach mucosae secrete concentrated HCl and protein-digesting enzymes Saliva and lacrimal fluid contain lysozyme Mucus traps microorganisms that enter the digestive and respiratory systems Mucus-coated hairs in the nose trap inhaled particles Mucosa of the upper respiratory tract is ciliated Cilia sweep dust- and bacteria trapped by mucus away from lower respiratory passages

Internal Defenses: Cells and Chemicals The body uses nonspecific cellular and chemical devices to protect itself Phagocytes and natural killer (NK) cells Antimicrobial proteins in blood and tissue fluid Inflammatory response enlists macrophages, mast cells, WBCs, and chemicals

Phagocytes Macrophages are the main phagocytic cells Two general types: Macrophages – most derived from monocytes Fixed (ex. Kupffer cells in liver) Free/mobile - wander throughout a region in search of cellular debris Microphages – circulating neutrophils and eosinophils Figure 21.2a

Phagocytes Neutrophils become phagocytic when encountering infectious material Eosinophils are weakly phagocytic against parasitic worms Mast cells bind and ingest a wide range of bacteria Mast cells are found in the connective tissue and are similar to basophiles Originate in the bone marrow contain special cytoplasmic granules which store mediators of inflammation

Natural killer (NK) cells Are a small, distinct group of large granular lymphocytes React nonspecifically and eliminate cancerous and virus-infected cells Kill their target cells by releasing perforins and other cytolytic chemicals Secrete potent chemicals that enhance the inflammatory response NK cells Recognize cell surface markers on foreign/abnormal cells Recognize variety of antigens (less selective) Immediate response when contact abnormal cells Destroy cells with foreign antigens

How Natural Killer Cells Kill Cellular Targets Figure 22.11

Inflammation: Tissue Response to Injury The inflammatory response is triggered whenever body tissues are injured Prevents the spread of damaging agents to nearby tissues Disposes of cell debris and pathogens Initiate repair processes The four signs of acute inflammation are Swelling Redness Heat Pain

Inflammation Response Begins with chemical “alarm” a flood of inflammatory chemicals released into the extracellular fluid Macrophages and epithelial cells of boundary tissues have Toll-like receptors (TLRs) TLRs recognize specific classes of infecting microbes Activated TLRs trigger the release of cytokines that promote inflammation and attract WBC

Inflammatory Response Some of the inflammatory mediators Histamine – amino acid derivative produced by basophiles and must cell- promote vasodilation Kinins – plasma proteins that are activated by tissue injury and promote vasodilation prostaglandins (PGs) – promote neutrophil diapedesis Leukotrienes – stimulate vasodilation and netrophil cemotaxis Complement – set of proteins that promote phgocytosis, activates cells of the immune system Colony-Stimulating Factors – hormones that promote WBC count Cells that are involved WBC, helper T cells, platelets, endothelial cells

Vasodilation and Increased Vascular Permeability The most immediate requirement is to bring WBC to the injury site! Vasodilation – causes hyperemia (increased blood flow) (Which sign of inflammation?) Increase permeability of blood walls (cells separate slightly) – causes edema (leakage of exudate) (Which sign of inflammation?) Exudate—fluid containing proteins, clotting factors, and antibodies Exudate moves into tissue spaces causing local edema (swelling), which contributes to the sensation of pain

Vasodilation and Increased Vascular Permeability The surge of protein-rich fluids into tissue spaces (edema): Helps dilute harmful substances Brings in large quantities of oxygen and nutrients needed for repair Allows entry of clotting proteins, which prevents the spread of bacteria

Inflammatory Response: Phagocytic Mobilization Four main phases: Leukocytosis – neutrophils are released from the bone marrow in response to leukocytosis-inducing factors released by injured cells Margination – neutrophils cling to the walls of capillaries in the injured area Endothelial cells in the injury site produce cell-adhesion molecules that make the surface “sticky” to help in this process Diapedesis – neutrophils squeeze through capillary walls and begin phagocytosis Chemotaxis – inflammatory chemicals attract neutrophils to the injury site

Antimicrobial Proteins Enhance the innate defenses by: Attacking microorganisms directly Interfering with microorganisms’ ability to reproduce The most important antimicrobial proteins are: Interferon Complement proteins

Interferons Interferons (INF) provide rapid response. Produced by a variety of body cells Lymphocytes produce gamma (), or immune, interferon Most other WBCs produce alpha () interferon Fibroblasts produce beta () interferon INF alpha and beta are the most potent against viruses

Interferon (IFN) when a host cell is invaded by a virus it activates the genes that synthesize IFN Interferon molecules leave the infected cell and enter neighboring cells Interferon stimulates the neighboring cells to activate genes for PKR (an antiviral protein) PKR nonspecifically blocks viral reproduction in the neighboring cell Interferons also activate macrophages and mobilize NKs Interferon can not save the infected cell but can prevent the virus from infecting other cells

Complement – “complete the action of antibody” 30 or so proteins synthesized mainly by the liver circulate in the blood in an inactive form and activate in the presence of pathogen Proteins include C1 through C9, factors B, D, and P, and regulatory proteins

Complement system functions Destruction of target cells membrane (MAC) Stimulation of inflammation – C3a stimulates mast cells and basophils to secrete histamine Attraction of phagocytes Enhancement of phagocytosis – Phagocytes membrane carry receptors that can bind to the complex of the complement proteins and antibodies. The binding results in much more efficient phagocytosis. The antibodies in such a complex are called opsonins and the effect is called opsonization (enhanced attachment )

Complement Pathways Complement can be activated by two pathways: The classical pathway is activated by the binding of antibody molecules to a foreign particle. This pathway is antibody-dependent. The alternative pathway it is activated by invading microorganisms and does not require antibody. This pathway is antibody-independent.

Complement Pathways Each pathway involves a cascade in which complement proteins are activated in a sequence where each step catalyzes the next Both pathways converge on C3, which cleaves into C3a and C3b C3b initiates formation of a membrane attack complex (MAC) MAC causes cell lysis

Complement Pathways Figure 21.6

Fever Abnormally high body temperature in response to invading microorganisms Maintenance of a body temperature above 37.2oC (99oF) The body’s thermostat is reset upwards in response to pyrogens, chemicals secreted by leukocytes and macrophages exposed to bacteria and other foreign substances High fevers are dangerous because they can denature enzymes Moderate fever can be beneficial: Promotes INF activity May inhibit some viruses and bacteria reproduction Increase body metabolism so enzymatic reactions occur faster and so is tissue repair