1. The Immune System: Innate and Adaptive:Body Defenses: Part A21
The Immune System: Innate and Adaptive:Body Defenses: Part A

2. 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

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

4. 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

5. 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

6. 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

7. 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

8. 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

9. 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

10. How Natural Killer Cells Kill Cellular Targets
Figure 22.11

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

12. 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

13. 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

14. 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

15. 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

16. 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

17. 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

18. 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

19. 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

20. 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

21. 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 )

22. 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.

23. 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

24. Complement Pathways
Figure 21.6

25. 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