• 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

Innate Resistance

• 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

First Line 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

Skin –Physical Components of Defense

– Dermis• Contains protein fibers called collagen

– Give skin strength and pliability to resist abrasions that could introduce microorganisms

Skin –Physical 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

Skin –Chemical Components of Defense

• Line all body cavities open to the outside environment

• Two distinct layers– Epithelium– Deeper connective layer that supports the epithelium

Mucous Membranes

• 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

Epithelium

• 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

Microbial Antagonism

– Helps stimulate the body’s second line of defense– Promote overall health by providing vitamins to host

Microbial Antagonism

• Many body organs secrete chemicals with antimicrobial properties

• Lacrimal glands that bathe the eye

Other First-Line 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

Second Line of Defenses

• 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

Blood

• 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

Formed Elements

• 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

Granulocytes

• Cytoplasm appears uniform under a light microscope

• 2 types– lymphocytes- most involved in specific immunity– monocytes- leave the blood and mature into

macrophages

Agranulocytes

• 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

Macrophages

• 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

Lab Analysis of Leukocytes

• Phagocytosis

• Extracellular killing by leukocytes

• Nonspecific chemical defenses

• Inflammation

• Fever

Components of the Second Line of Defense

• Cells capable of phagocytosis (certain leukocytes or their derivatives) are called phagocytes

• Phagocytosis is not completely understood• Can be divided into 5 stages

Phagocytosis

• 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

Host Cell Protection

• 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

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

Extracellular Killing by Leukocytes

• Augment phagocytosis– Some attack pathogens directly– Some enhance other features of nonspecific

resistance

• Includes various chemicals– Lysozyme– Complement– Interferon

Nonspecific Chemical Defenses

• 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

Complement System

• Complement named for the events of this originally discovered pathway

• Various complement proteins act nonspecifically to “complement” the action of antibodies

The Classical 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

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

The Alternate (Properdin) Pathway

• 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

Inactivation of Complement

• 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

Interferons

• Alpha and beta interferons are present early in the infection

• Gamma interferon appears later in the course of infection

Interferons

• Nonspecific response to tissue damage resulting from various causes

• Characterized by redness, heat, swelling, and pain

• Two types– Acute– 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

Acute Versus Chronic Inflammation

• 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)

Fever

• 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

Fever Production

• 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

Benefits of Fever