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Lecture

BIOB32H3 Lecture Notes - Corticosteroid, Allergen, Antigen Processing


Department
Biological Sciences
Course Code
BIOB32H3
Professor
Kenneth Welch

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The Immune System: Innate and Adaptive Body Defenses
Immunity: Two Intrinsic Defense Systems
Innate (nonspecific) system responds quickly and consists of:
First line of defense intact skin and mucosae prevent entry of microorganisms
Second line of defense antimicrobial proteins, phagocytes, and other cells
Inhibit invaders spread throughout the body
Inflammation is its hallmark and most important mechanism
Immunity: Two Intrinsic Defense Systems
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
Surface Barriers
Skin, mucous membranes, and their secretions make up the first line of defense
Keratin in the skin:
Presents a formidable physical barrier to most microorganisms
Is resistant to weak acids and bases, bacterial enzymes, and toxins
Mucosae provide similar mechanical barriers
Epithelial Chemical 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
Respiratory Tract Mucosae
Mucus-coated hairs in the nose trap inhaled particles
Mucosa of the upper respiratory tract is ciliated
Cilia sweep dust- and bacteria-laden 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
Harmful substances are identified by surface carbohydrates unique to infectious organisms
Phagocytes
Macrophages are the chief phagocytic cells
Free macrophages wander throughout a region, in search of cellular debris
Kupffer cells (liver) and microglia (brain) are fixed macrophages
Neutrophils become phagocytic when encountering infectious material
Eosinophils are weakly phagocytic against parasitic worms
Mast cells bind and ingest a wide range of bacteria
Mechanism of Phagocytosis
Microbes adhere to the phagocyte
Pseudopods engulf the particle (antigen) into a phagosome
Phagosomes fuse with a lysosome to form a phagolysosome

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Microbes in the phagolysosome are enzymatically digested
Indigestible and residual material is removed by exocytosis
Natural Killer (NK) Cells
Cells that can lyse and kill cancer cells and virus-infected cells
Natural killer 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 cytolytic chemicals
Secrete potent chemicals that enhance the inflammatory response
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
Sets the stage for repair processes
The four cardinal signs of acute inflammation are redness, heat, swelling, and pain
Inflammatory Response
Begins with a flood of inflammatory chemicals released into the extracellular fluid
Inflammatory mediators:
Include kinins, prostaglandins (PGs), complement, and cytokines
Are released by injured tissue, phagocytes, lymphocytes, and mast cells
Cause local small blood vessels to dilate, resulting in hyperemia
Inflammatory Response: Vascular Permeability
Chemicals liberated by the inflammatory response
Increase the permeability of local capillaries
Exudate (fluid containing proteins, clotting factors, and antibodies):
Seeps into tissue spaces causing local edema (swelling)
The edema contributes to the sensation of pain
Inflammatory Response: Edema
The surge of protein-rich fluids into tissue spaces (edema):
Helps to dilute harmful substances
Brings in large quantities of oxygen and nutrients needed for repair
Allows entry of clotting proteins, which prevent the spread of bacteria
Inflammatory Response: Phagocytic Mobilization
Occurs in 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
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
Hindering microorganisms’ ability to reproduce
The most important antimicrobial proteins are:
Interferon
Complement proteins

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Interferon (IFN)
Genes that synthesize IFN are activated when a host cell is invaded by a virus
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
Interferon Family
Interferons are a family of related proteins each with slightly different physiological effects
Lymphocytes secrete gamma () interferon, but most other WBCs secrete alpha ()
interferon
Fibroblasts secrete beta () interferon
Interferons also activate macrophages and mobilize NKs
FDA-approve alpha IFN is used:
As an antiviral drug against hepatitis C virus
To treat genital warts caused by a herpes virus
Complement
20 or so proteins that circulate in the blood in an inactive form
Proteins include C1 through C9, factors B, D, and P, and regulatory proteins
Provides a major mechanism for destroying foreign substances in the body
Amplifies all aspects of the inflammatory response
Kills bacteria and certain other cell types (our cells are immune to complement)
Enhances the effectiveness of both nonspecific and specific defenses
Complement Pathways
Complement can be activated by two pathways: classical and alternative
Classical pathway is linked to the immune system
Depends upon the binding of antibodies to invading organisms
Subsequent binding of C1 to the antigen-antibody complexes (complement fixation)
Alternative pathway is triggered by interaction among factors B, D, and P, and
polysaccharide molecules present on microorganisms
Each pathway involves a cascade in which complement proteins are activated in an orderly
sequence and 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 by interfering with a cell’s ability to eject Ca2+
C3b also causes opsonization, and C3a causes inflammation
Fever
Abnormally high body temperature in response to invading microorganisms
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 as they can denature enzymes
Moderate fever can be beneficial, as it causes:
The liver and spleen to sequester iron and zinc (needed by microorganisms)
An increase in the metabolic rate, which speeds up tissue repair
Adaptive (Specific) Defenses
The adaptive immune system is a functional system that:
Recognizes specific foreign substances
Acts to immobilize, neutralize, or destroy them
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