Helps keep skin pliable and less likely to break or tear
Lowers the pH of the skin to a level inhibitory to many bacteria
Line all body cavities open to the outside environment
Two distinct layers
Deeper Connective Tissue layer that supports the Epithelium
Thin, outer covering of the Mucous Membranes
Unlike surface Epidermal Cells of Skin, Epithelial cells of Mucous Membranes are living.
Tightly packed to prevent entry of Pathogens
Continual shedding of cells carries attached microorganisms away.
Respiratory System Figure 15.2
Normal Microbiota help protect the body by competing with potential Pathogens.
Various activities of the Normal Microbiota make it hard for Pathogens to compete.
Consumption of nutrients makes them unavailable to Pathogens
Create an environment unfavorable to other microorganisms by changing pH
Helps stimulate the body’s Second Line of Defense
Promote overall health by providing vitamins to host
Other First-Line Defenses
Many body organs secrete chemicals with antimicrobial properties
Lacrimal (Tear) Glands that bathe the eye
Lacrimal Apparatus Figure 15.3
Second Line of Defense
Operates when pathogens succeed in penetrating the Skin or Mucous Membranes
Composed of cells, antimicrobial chemicals, and processes, but no physical barriers
Many of these components are contained or originate in the Blood.
Composed of cells and portions of cells within a fluid called Plasma
Plasma mostly water containing Electrolytes, dissolved gases, nutrients, and proteins
Serum – Plasma from which the Clotting Factors, a group of Plasma Proteins, have been removed
Include Iron-binding compounds
Other Plasma Proteins include Complement Proteins and Antibodies
Formed Elements -- the cells and cell fragments in the Plasma
Three types of Formed Elements
Erythrocytes (Red Blood Cells) – carry oxygen and carbon dioxide in the blood
Platelets (Thrombocytes) – cell fragments involved in Blood Clotting
Leukocytes (White Blood Cells) – involved in defending the body against invaders
Their cytoplasm contains visible granules that stain different colors based on the dye used
Basophils – stain dark blue or purple with the Basic Dye Methylene Blue
Eosinophils – stain red/orange with the Acidic Dye Eosin
Neutrophils – stain pink with a mixture of Acidic and Basic Dyes
Neutrophils and Eosinophils can phagocytize Pathogens
Neutrophils and Eosinophils are capable of Diapedesis – changing shape to squeeze through blood vessel walls
Diapedesis Figure 15.6
Cytoplasm appears uniform under a Light Microscope; lack visible cytoplasmic granules
Lymphocytes – most involved in Adaptive Immunity
Monocytes – leave the blood and mature into Macrophages which phagocytic and involved in Adaptive (Specific) Immunity
Phagocytic cells of the Second Line of Defense
Wandering Macrophages leave the blood via Diapedesis and phagocytize throughout the body.
Fixed Macrophages do not move throughout the body, and often phagocytize within a specific organ.
Include Alveolar Macrophages (in lungs), Microglia (in Central Nervous System), Küpffer Cells (in liver)
All Macrophages, plus Monocytes attached to Endothelial Cells; constitute the Mononuclear Phagocytic System
Lab Analysis of Leukocytes
Differential White Blood Cell Count test can signal signs of disease.
Increased Eosinophils can indicate allergies or parasitic worm infection.
Bacterial diseases often show increase in leukocytes and in Neutrophils
Viral infections show increase in Lymphocytes
Components of the Second Line of Defense
Extracellular killing by Leukocytes
Nonspecific Chemical Defenses
Phagocytes – cells capable of phagocytosis
Phagocytosis is not completely understood
Can be divided into five stages
PLAY Animation: Phagocytosis
Chemotaxis – movement in response to a chemical stimulus
Phagocytes move toward chemical stimulus (Positive Chemotaxis) via Pseudopodia
Phagocytes attracted to chemicals released by microbes, damaged host cells, activated Leukocytes, and components of Complement
Adherence –binding of Phagocyte to microbe by attaching to complementary molecules on its surface (such as Glycoproteins)
Bacterial Capsule or M Protein (in Streptococcus pyogenes ) may interfere with Adherence.
Opsonins (Antibodies or Complement Proteins) that coat microbe facilitate it; thus enhance Phagocytosis
Ingestion – envelopment of microbe by Phagocyte via its Pseudopodia, and taking it in by Endocytosis
Microbe contained within Phagosome (membrane of which was originally part of Phagocyte’s Cytoplasmic Membrane)
Killing – enzymatic destruction of microbe within Phagocyte’s Lysosomes which fuse with Phagosome forming Phagolysosome
Digestive Enzymes from Lysosomes usually kill and break down microbial cell.
M Protein (in S. pyogenes ) and waxy cell walls (in Mycobacterium tuberculosis ) may prevent Lysosome activity.
Elimination – excretion of microbial cell remnants from Phagocyte by Exocytosis
In some Phagocytes (Dendritic Cells and Macrophages) microbial cell surface markers may remain attached to phagocytic cell’s Cytoplasmic Membrane to help activate Lymphocytes.
Phagocytosis Figure 15.8
Host Cell Protection
The host’s cells are protected from destruction by the Phagocytes.
Some Phagocytes have receptors for bacterial surface components, such as flagellar proteins or cell wall components, that are lacking on the body’s cells.
Opsonins such as Complement and Antibody attached to microbial cell provide a signal to the Phagocyte.
Extracellular Killing by Leukocytes
Three Cell types that kill extracellularly
Mainly attack parasitic Helminths (worms) by attaching to their surface, or to Antibodies attached to worm’s surface
Secrete toxins that weaken or kill the Helminth
Eosinophilia -- elevated Eosinophil levels; often indicative of a Helminth infestation
Extracellular Killing by Leukocytes (cont.)
Natural Killer Lymphocytes (NK Cells) – large Lymphocytes that attack foreign (those that are not part of body) and abnormal body cells, but do not target specific microbes, as do other Lymphocytes
Secrete toxins onto the surface of virus-infected cells and tumors
Differentiate normal body cells because they have membrane proteins similar to the NK Cells
Extracellular Killing by Leukocytes (cont.)
Produce chemicals that kill nearby invaders
Enzymes that form Superoxide Radicals and Hydrogen Peroxide (Oxidants)
An Enzyme that converts these Oxidants into Hypochlorite (active ingredient in bleach)
Generate Extracellular Fibers that bind to and kill bacteria
Extracellular Fibers composed of DNA and Histones, and formed into NETs (Neutrophil Extracellular Traps) to bind microbes and expose them to high concentrations of antimicrobial chemicals
Nonspecific Chemical Defenses
Some attack Pathogens directly
Some enhance other features of Innate Immunity
Includes various chemicals
Complement System (Complement)
Set of Serum Proteins designated numerically according to the order of their discovery
Complement activation results in Lysis of the foreign cells
Complement can be activated in several ways
The Classical Pathway
Complement named for the events of this originally discovered pathway
Various complement proteins act nonspecifically to “complement” the action of Antibodies
In this Pathway: binding of Antibodies to Antigen activates Complement
Complement Enzymes split Complement Molecules into Fragments which 1) combine to form new enzymes, or 2) dilate blood vessels and increase their permeability, enhancing Diapedesis, or 3) increase Inflammation, or 4) attract Phagocytes by Chemotaxis, or 5) are Opsonins
The Classical Pathway (continued)
This Pathway followed by the Complement Cascade – sequence of reactions involving Complement Proteins in which product of one reaction is the enzyme that catalyzes the next reaction
Membrane Attack Complexes (MACs) – end products of Complement Cascade which punch holes in foreign cells’ cytoplasmic membrane, allowing water to flow into cells and lyse them
Gram (-) Bacteria more sensitive to MACs than Gram (+) due to their exposed Outer Membrane
The Alternate (Properdin) Pathway
Activation occurs independent of Antibodies; instead occurs when Complement Proteins (B, D, and Properdin) bind to Endotoxins or Glycoproteins in Cell of Bacteria or Fungi
Useful in early stages of infection before Antibodies have formed
Complement Cascade also follows this Pathway, resulting in formation of MACs and Cell Lysis
Complement – Two Pathways Figure 15.10
Classical Complement Cascade Figure 15.11
Inactivation of Complement
Complement System nonspecific and MACs can form on most cells’ exposed cell membrane
Body’s own cells can withstand Complement Cascade
Membrane-bound Proteins on normal body cells bind to and break down activated Complement Proteins
This stops Complement Cascade before cell damage occurs
PLAY Animation: The Complement System
Protein molecules secreted by virus-infected host cells to nonspecifically inhibit the spread of viral infections
Cause many symptoms typically associated with viral infections (malaise, headache, muscle aches, chills, and fever)
Three Classes produced by different cell types
Alpha Interferon from Monocytes, Macrophages, and some Lymphocytes
Beta Interferon from Fibroblasts
Gamma Interferon from activated T Lymphoytes and NK Lymphocytes (NK Cells)
Interferons do not protect virus-infected cells that secrete them, but neighboring cells by interfering with viral replication in them, and by activating NK Lymphocytes
Not specific; Interferon secretion stimulated by one type of virus can help protect against other viruses
Alpha and Beta Interferons have same action
They bind to receptors on other cells’ cytoplasmic membrane stimulating them to produce Antiviral Proteins (AVPs) which activated when they bind to viral nucleic acids
Some AVPs breakdown cells’ mRNA; others block protein synthesis at ribosomes – both preventing viral replication in cell
AVPs stop all protein synthesis in cell (for both virus and host cell) for 3-4 days.
This often enables cell to rid itself of virus, and yet survive brief period without protein synthesis.
Gamma Interferon (Macrophage Activating Factor) stimulates activity of Phagocytes – both Macrophages and Neutrophils
Alpha and Beta Interferons are present early in the infection.
Interferon Gamma appears later in the course of infection, since T Lymphocyte activation is part of the Specific Immune Response which occurs after the Nonspecific Response
The Characteristics of Human Interferons Table 15.3
It was thought that this might be a good antiviral treatment.
Recombinant DNA Technology used to produce various Interferons
Synthetic Genes for Human Interferons inserted into genomes of Escherichia coli and Saccharomyces cerevisiae
Interferons produced in this way are pure and can be made in large quantities.
Nonspecific Localized Response to tissue damage resulting from various causes – chemicals, heat, UV, trauma, and Pathogens
Characterized by Redness, Heat, Swelling, and Pain; sometimes also loss of function
PLAY Animation: Inflammation
Acute vs. Chronic Inflammation
Develops quickly and is short lived
Is usually beneficial, since results in elimination of what caused it
Important in the Second Line of Defense; it involves
Dilation and Increased Permeability of the Blood Vessels (due to release of Inflammatory Chemicals by Macrophages, Basophils, Mast Cells, Platelets, and damaged cells))
Migration of Phagocytes [involves Chemotaxis, Margination (sticking to blood walls), and Diapedesis (squeezing between cells in blood vessel wall)]