Chapter 15 Revised

MicrobiologyWith Diseases by Taxonomy

Second Edition

PowerPoint® Lecture Slides

Copyright © 2007 Pearson Education, Inc. publishing as Benjamin Cummings

15InnateImmunity


Innate Resistance

Innate (Immunity) Resistance – that which present at birth; before contact with microbes or their products

Nonspecific – not directed against a particular agent, but against anything foreign (not part of the body)

Resistance to most plant and animal PathogensResistance 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 Pathogens survival.

Pathogens for which humans don’t have Innate Resistance to can cause disease.


First Line of Defense

Structures, chemicals, processes that work to prevent pathogens entering the body

Nonspecific Defenses Includes the Skin and Mucous Membranes of the

Respiratory, Digestive, Urinary, and Reproductive Systems

PLAYPLAYAnimation: Host Defenses


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, and important in

Adaptive (Specific) Immunity


Skin – Physical Components of Defense

Dermis Contains protein fibers of Collagen

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


Skin – Chemical Components of Defense

Perspiration secreted by Sweat Glands Salt – inhibits growth of Pathogens by drawing water

from their cells Antimicrobial Peptides – Sweat Glands secret

Dermicidins Lysozyme – destroys cell wall of many 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


Mucous Membranes

Line all body cavities open to the outside environmentTwo distinct layers

Epithelium Deeper Connective Tissue layer that supports the

Epithelium


Epithelium

Thin, outer covering of the Mucous MembranesUnlike surface Epidermal Cells of Skin, Epithelial

cells of Mucous Membranes are living.Tightly packed to prevent entry of PathogensContinual shedding of cells carries attached

microorganisms away.


Respiratory System

Figure 15.2


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. 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


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

Nonspecific DefenseComposed of cells, antimicrobial chemicals, and

processes, but no physical barriers Many of these components are contained or originate

in the Blood.


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


Formed Elements

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 Two groups

Granulocytes Agranulocytes


Granulocytes

Their cytoplasm contains visible granules that stain different colors based on the dye used

Three types 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 DyesNeutrophils and Eosinophils can phagocytize

PathogensNeutrophils and Eosinophils are capable of Diapedesis

– changing shape to squeeze through blood vessel walls


Diapedesis

Figure 15.6


Agranulocytes

Cytoplasm appears uniform under a Light Microscope; lack visible cytoplasmic granules

Two types Lymphocytes – most involved in Adaptive Immunity Monocytes – leave the blood and mature into

Macrophages which phagocytic and involved in Adaptive (Specific) Immunity


Macrophages

Phagocytic cells of the Second Line of DefenseWandering 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

PhagocytosisExtracellular killing by LeukocytesNonspecific Chemical Defenses InflammationFever


Phagocytosis

Phagocytes – cells capable of phagocytosisPhagocytosis is not completely understoodCan be divided into five stages

Chemotaxis Adherence Ingestion Killing Elimination

PLAYPLAYAnimation: Phagocytosis


Phagocytosis (continued)

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 Eosinophils

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.)

Neutrophils 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

Augment Phagocytosis Some attack Pathogens directly Some enhance other features of Innate Immunity

Includes various chemicals Lysozyme Complement Interferon Defensins


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 Classical Pathway Alternate Pathway


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

PLAYPLAYAnimation: The Complement System


Interferons (IFNs)

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 (continued)

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


Interferon Therapy

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.


Inflammation

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

Two types Acute Inflammation Chronic Inflammation

PLAYPLAYAnimation: Inflammation


Acute vs. Chronic Inflammation

Acute 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)]

Tissue Repair (by Stem Cells or Fibroblasts) Chronic Inflammation

Develops slowly and lasts a long time Can cause damage to tissues, resulting in disease


Inflammatory Chemicals (Mediators)

Vasodilators: Histamine, Serotonin, Prostaglandins, Bradykinin

Increase Capillary Permeability: Prostaglandins and Leukotrienes

Chemotactic Factors: Collagen, Fibrin, Mast Cell secretions, Bacterial Peptides


Events in Inflammation

Figure 15.17.1


Events in Inflammation

Figure 15.17.2


Chemical Mediators of Inflammation

Table 15.4


Fever

A body core temperature over 37CResults when chemicals called Pyrogens trigger the

Hypothalamus to increase the body’s core temperatureVarious types of Pyrogens stimulate production of

Interleukin 1 (IL-1). These include: Bacterial Toxins Cytoplasmic contents of bacteria released by Lysis Antibody-Antigen Complexes


Fever Production

IL-1 production causes the Hypothalamus to secrete Prostaglandin which resets Hypothalamic “Thermostat”.

Communication with brain initiates temperature ↑ by 1) Muscle Contractions, 2) Increased Metabolic Activity, and 3) Constriction of Blood Vessels (reduce heat loss).

Chills associated with Fever are due to the reduced blood flow of constricted vessels – signal Fever onset.

↓ in IL-1 production results in the body’s temperature returning to normal by 1) Sweating, 2) Vasodilation, and 3) ↓ in Metabolic Rate

Aspirin & Acetaminophen ↓ Fever by blocking Prostaglandin Synthesis.


Benefits of Fever

Enhances the effects of Interferons Inhibits growth of some microorganisms (when above

their Optimum Temperature range)May enhance the performance of

1) Phagocytes, and 2) Cells of Specific ImmunityMay also accelerate the process of Tissue Repair

Adverse Effects of Fever: 1) Denature Proteins 2) Inhibit Nerve Impulses


A Summary of Some Nonspecific Components of the First and Second Lines of Defense

Table 15.5

Health & Medicine

Chapter 15 Revised