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Nonspecific Lines of Defense
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Innate Resistance Resistance to most plant and animal pathogens
Resistance due to physiological processes of humans that are incompatible with those of the pathogen Correct chemical receptors not present on human cells Temperature and pH may be incompatible with those necessary for the pathogen’s survival Number of pathogens for which humans don’t have innate resistance to that can cause disease
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First Line of Defense Structures, chemicals, processes that work to prevent pathogens from entering the body Nonspecific defenses Includes the skin and mucous membranes of the respiratory, digestive, urinary, and reproductive systems
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Skin –Physical Components of Defense
Two major layers Epidermis Outer layer composed of multiple layers of tightly packed cells Few pathogens can penetrate these layers Shedding of dead skin cells removes attached microorganisms Epidermal dendritic cells Also termed Langerhans cells Phagocytize pathogens
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Skin –Physical Components of Defense
Dermis Contains protein fibers called collagen Give skin strength and pliability to resist abrasions that could introduce microorganisms
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Skin –Chemical Components of Defense
Perspiration secreted by sweat glands Salt- inhibits growth of pathogen by drawing water from their cells Lysozyme- destroys cell wall of bacteria Sebum secreted by sebaceous (oil) glands Helps keep skin pliable and less likely to break or tear Lowers the pH of the skin to a level inhibitory to many bacteria
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Mucous Membranes Line all body cavities open to the outside environment Two distinct layers Epithelium Deeper connective layer that supports the epithelium
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Epithelium Thin, outer covering of the mucous membranes
Unlike surface epidermal cells, epithelial cells are living Tightly packed to prevent entry of pathogens Continual shedding of cells carries attached microorganisms away
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Microbial Antagonism Normal microbiota help protect the body by competing with potential pathogens Various activities of the normal microbiota make it hard for pathogens to compete Secrete antimicrobial substances that limit pathogen growth Consumption of nutrients makes them unavailable to pathogens Create an environment unfavorable to other microorganisms by changing pH
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Microbial Antagonism Helps stimulate the body’s second line of defense
Promote overall health by providing vitamins to host
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Other First-Line Defenses
Many body organs secrete chemicals with antimicrobial properties Lacrimal glands that bathe the eye
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Second Line of Defenses
Operates when pathogens succeed in penetrating the skin or mucous membranes Nonspecific defense Composed of cells, antimicrobial chemicals, and processes but no physical barriers Many of these components are contained or originate in the blood
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Blood Composed of cells and portions of cells within a fluid called plasma Plasma is mostly water containing electrolytes, dissolved gases, nutrients, and proteins When the clotting factors, a group of plasma proteins, are removed from plasma, the remaining fluid is called serum Other plasma proteins include complement proteins and antibodies The cells and cell fragments in plasma are called formed elements
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Formed Elements Three types of formed elements
Erythrocytes- carry oxygen and carbon dioxide in the blood Platelets- involved in blood clotting Leukocytes- involved in defending the body against invaders 2 groups Granulocytes Agranulocytes
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Granulocytes Contain large granules that stain different colors based on the dye used 3 types Basophils- stain blue with the basic dye methylene blue Eosinophils- stain red/orange with the acidic dye eosin Neutrophils- stain lilac with a mixture of acidic and basic dyes Neutrophils and eosinophils can phagocytize pathogens Neutrophils and eosinophils are capable of diapedesis
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Agranulocytes Cytoplasm appears uniform under a light microscope
2 types lymphocytes- most involved in specific immunity monocytes- leave the blood and mature into macrophages
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Macrophages 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 Langerhans cells (epidermis), alveolar macrophages (lungs), microglia (central nervous system), Küpffer cells (liver) All macrophages, plus monocytes attached to endothelial cells, constitute the mononuclear phagocytic system
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Lab Analysis of Leukocytes
The 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
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Components of the Second Line of Defense
Phagocytosis Extracellular killing by leukocytes Nonspecific chemical defenses Inflammation Fever
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Phagocytosis Cells capable of phagocytosis (certain leukocytes or their derivatives) are called phagocytes Phagocytosis is not completely understood Can be divided into 5 stages
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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 provide a signal to the phagocyte
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Extracellular Killing by Leukocytes
2 Cell types that kill extracellularly Eosinophils Mainly attack parasitic helminths (worms) by attaching to their surface Secrete toxins that weaken or kill the helminth Eosinophilia, or elevated eosinophil levels, is often indicative of a helminth infection
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Extracellular Killing by Leukocytes
Natural killer lymphocytes (NK cells) Secrete toxins onto the surface of virally infected cells and tumors Differentiate normal body cells because they have membrane proteins similar to the NK cells
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Nonspecific Chemical Defenses
Augment phagocytosis Some attack pathogens directly Some enhance other features of nonspecific resistance Includes various chemicals Lysozyme Complement Interferon
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Complement System Set of serum proteins designated numerically according to the order of their discovery Complement activation results in lysis of the foreign cell Complement can be activated in several ways Classical Pathway Alternate Pathway
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The Classical Pathway Complement named for the events of this originally discovered pathway Various complement proteins act nonspecifically to “complement” the action of antibodies
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The Alternate (Properdin) Pathway
Activation occurs independent of antibodies Less efficient than the classical pathway Useful in early stages of infection before antibodies have been made Initiated by interaction between properdin factors B, D, and P and the endotoxins and LPS from bacteria and fungi Stabilizes molecules of C3b that are normally in the blood in small quantities
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The Alternate (Properdin) Pathway
Stabilized C3b combines with the properdin factors to form an enzyme that cleaves C3 to produce more C3b C3b combines with properdin B to form a different enzyme which cleaves C5 molecules The complement cascade then continues as in the classical pathway
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Inactivation of Complement
Body’s own cells withstand complement cascade Membrane-bound proteins on many cells bind with and break down activated complement proteins High turnover rate for cell membranes means any bound membrane attack complexes are shed or endocytosed before any damage occurs
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Interferons Protein molecules released by host cells to nonspecifically inhibit the spread of viral infections Particularly effective against viruses with RNA genomes Cause many symptoms typically associated with viral infections 3 Classes Alpha Beta Gamma
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Interferons Alpha and beta interferons are present early in the infection Gamma interferon appears later in the course of infection
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Inflammation Nonspecific response to tissue damage resulting from various causes Characterized by redness, heat, swelling, and pain Two types Acute Chronic
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Acute Versus Chronic Inflammation
Acute inflammation Develops quickly and is short lived Is usually beneficial Important in the second line of defense Dilation and increased permeability of the blood vessels Migration of phagocytes Tissue repair Chronic inflammation Develops slowly and lasts a long time Can cause damage to tissues
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Fever A body temperature over 37C
Results when chemicals called pyrogens trigger the hypothalamus to increase the body’s core temperature Various types of pyrogens Bacterial toxins Cytoplasmic contents of bacteria released by lysis Antibody-antigen complexes Interleukin-I (IL-1)
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Fever Production IL-1 production causes the hypothalamus to secrete prostaglandin which resets the hypothalamic “thermostat” Communication with the brain initiates muscle contractions, increased metabolic activity, and constriction of blood vessels which raises the body’s temperature Chills associated with fever are due to the reduced blood flow of constricted vessels Decrease in IL-1 production results in the body’s temperature returning to normal
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Benefits of Fever Enhances the effects of interferons
Inhibits growth of some microorganisms May enhance the performance of phagocytes, cells of specific immunity, and the process of tissue repair
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