Microbiology: A Systems Approach, 2nd ed.

Chapter 14: Host Defenses I- Overview and Nonspecific Defenses

14.1 Defense Mechanisms of the Host in Perspective

Figure 14.1

Barriers at the Portal of Entry: A First Line of Defense

Figure 14.2

Figure 14.3

Nonspecific Chemical Defenses• Sebaceous secretions and specialized glands-

antimicrobial• Lysozyme in tears• Lactic acid and electrolyte concentrations of

sweat• Skin’s acidic pH and fatty acid content• HCl in the stomach• Digestive juices and bile in the intestine• Semen- antimicrobial chemical• Acidic pH in the vagina

Genetic Differences in Susceptibility

• Some hosts are genetically immune to the diseases of other hosts

• Particularly true of viruses

14.2 The Second and Third Lines of Defense: An Overview

• Immunology: the study of all features of the body’s second and third lines of defense

• Healthy functioning immune system is responsible for:– Surveillance of the body– Recognition of foreign material– Destruction of entities deemed to be foreign

Figure 14.4

Self and Nonself

• White blood cells must distinguish self from nonself cells

• Evaluates cells by examining markers on their surfaces

14.3 Systems Involved in Immune Defenses

• Body compartments– Intracellular– Extracellular– Lymphatic– Cerebrospinal– Circulatory

• Physically separated but have numerous connections

Body Compartments that Participate in Immune Function

• Reticuloendothelial system (RES)• Spaces containing extracellular fluid (ECF)• Bloodstream• Lymphatic system

The Communicating Body Compartments

Figure 14.5

Immune Functions of the Reticuloendothelial System

• Provides a passageway within and between tissues and organs

• Coexists with the mononuclear phagocyte system

Figure 14.6

Origin, Composition, and Functions of the Blood

• Circulatory system– Circulatory system proper– Lymphatic system

Figure 14.7

Fundamental Characteristics of Plasma

• Hundreds of different chemicals• Main component is water (92%)• Proteins such as albumin and globulins,

immunochemicals, fibrinogen and other clotting factors, hormones, nutrients, dissolved gases, and waste products

A Survey of Blood Cells

• Hematopoesis: production of blood cells• Relatively short life• Primary precursor of new blood cells:

pluripotential stem cells in the marrow– Red blood cells (erythrocytes)– White blood cells (leukocytes)– Platelets (thrombocytes)

• Differentiation

Figure 14.8

Figure 14.9

(a)

(b)

Leukocytes

• Granulocytes• Agranulocytes

Granulocytes

• Neutrophils – Phagocytosis

• Eosinophils– Attack and destroy large eukaryotic pathogens– Also involved in inflammation and allergic

reactions

• Basophils – Parallel eosinophils in many actions

Agranulocytes

• Monocytes• Lymphocytes

Monocytes

• Discharged by bone marrow into bloodstream, live as phagocytes for a few days, then differentiate into macrophages

• Responsible for– Many specific and nonspecific phagocytic and killing

functions– Processing foreign molecules and presenting them to

lymphocytes– Secreting biologically active compounds that assist,

mediate, attract, and inhibit immune cells and reactions• Dendritic cells

Lymphocytes• Key cells in the third line of defense and the specific

immune response• When stimulated by antigens, transform into activated

cells that neutralize and destroy that foreign substance• B cells

– Humoral immunity: protective molecules carried in the fluids of the body

– Produce specialized plasma cells which produce antibodies

• T cells– Cell-mediated immunity: T cells modulate immune

functions and kill foreign cells

Erythrocyte and Platelet Lines

• Erythrocytes– Develop from stem cells in the bone marrow– Lose their nucleus just prior to entering circulation– Transport oxygen and carbon dioxide to and from the

tissues• Platelets

– Formed elements in circulating blood– Not whole cells– Function primarily in hemostasis and in releasing

chemicals for blood clotting and inflammation

Components and Functions of the Lymphatic System

• Lymphatic system: compartmentalized network of vessels, cells, and specialized accessory organs

• Transports lymph through a system of vessels and lymph nodes

• Major functions– Provide an auxiliary route for the return of

extracellular fluid to the circulatory system proper– Act as a drain-off system for the inflammatory

response– Render surveillance, recognition, and protection

against foreign materials

Figure 14.10

Lymphatic Fluid

• Lymph• Plasmalike liquid formed when certain blood

components move out of blood vessels into the extracellular spaces and diffuse or migrate into the lymphatic capillaries

• Composition parallels that of plasma, but without red blood cells

Lymphatic Vessels

• Along the lines of blood vessels• Similar to thin-walled veins• High numbers in hands, feet, and around the

areola of the breast• Flow of lymph is in one direction only- from

extremities toward the heart• Lymph is moved through the contraction of

skeletal muscles through which the lymphatic ducts wend their way

Lymphoid Organs and Tissues

• Lymph nodes• Thymus• Spleen• Gut-associated lymphoid tissue (GALT)• Tonsils• Loose connective tissue framework that

houses aggregations of lymphocytes

Lymph Nodes

• Small, encapsulated, bean-shaped organs• Usually found in clusters along lymphatic

channels and large blood vessels of the thoracic and abdominal cavities

• Major aggregations: axillary nodes, inguinal nodes, cervical nodes

Spleen

• Similar to a lymph node except it filters blood instead of lymph

• Filters pathogens from the blood

The Thymus: Site of T-Cell Maturation

• Thymus originates in the embryo• High rates of activity and growth until puberty• Shrinks gradually through adulthood• Thymic hormones help thymocytes develop

specificity to be released as mature T cells

Figure 14.11

Miscellaneous Lymphoid Tissue• Bundles of lymphocytes lie at many sites on or just

beneath the mucosa of the gastrointestinal and respiratory tracts

• Tonsils• Breasts of pregnant and lactating women• GALT in the intestinal tract

– Appendix– Lacteals– Peyer’s patches

• Mucosal-associated lymphoid tissue (MALT)• Skin-associated lymphoid tissue (SALT)• Bronchial-associated lymphoid tissue (BALT)

14.2 The Second Line of Defense

• Inflammation• Phagocytosis• Interferon• Complement

The Inflammatory Response: A Complex Concert of Reactions to

Injury• Reaction to any traumatic event in the tissues• Classic signs and symptoms

– Rubor (redness)– Calor (warmth)– Tumor (swelling)– Dolor (pain)

• Fifth symptom has been added: loss of function

Figure 14.12

Chief Functions of Inflammation

• Chief functions of inflammation– Mobilize and attract immune components to the

site of the injury– Set in motion mechanisms to repair tissue damage

and localize and clear away harmful substances– Destroy microbes and block their further invasion

The Stages of Inflammation

Figure 14.13

Vascular Changes: Early Inflammatory Events

• Controlled by nervous stimulation, chemical mediators, and cytokines released by blood cells, tissue cells, and platelets in the injured area

• Vasoactive mediators affect the endothelial cells and smooth muscle cells of blood vessels

• Chemotactic factors (chemokines) affect white blood cells

• Cause fever, stimulate lymphocytes, prevent virus spread, and cause allergic symptoms

• Arterioles constricted at first but quickly vasodilation takes place

Edema: Leakage of Vascular Fluid into Tissues

• Exudates: the fluid that escapes through gaps in the walls of postcapillary venules

• Accumulation of exudates causes edema• Contains plasma proteins, blood cells, and

cellular debris• May be clear (serous) or may contain red blood

cells or pus• Diapedesis: how WBCs leave the blood vessels

and into tissue spaces• Chemotaxis: the tendency of WBCs to migrate in

response to a specific chemical stimulus

Benefits of Edema and Chemotaxis

• Dilutes toxic substances• Fibrin clot can trap microbes and prevent

further spreading• Phagocytosis occurs immediately

Figure 14.14

Late Reactions of Inflammation

• Long-lived inflammation attracts a collection of monocytes, lymphocytes, and macrophages to the reaction site

• Macrophages clear pus, cellular debris, dead neutrophils, and damaged tissue

• B lymphocytes produce antibodies• T lymphocytes kill intruders directly• Late in the process the tissue is repaired or

replaced by connective tissue (scar)

Fever: An Adjunct to Inflammation

• An abnormally elevated body temperature• FUO: fevers of unknown origin• Initiation of fever

– Pyrogen sets the hypothalamic “thermostat” to a higher setting

• Muscles increase heat production• Peripheral arterioles decrease heat loss through

vasoconstriction

– Pyrogens can be exogenous or endogenous

Benefits of Fever

• Inhibits multiplication of temperature-sensitive microorganisms

• Impedes the nutrition of bacteria by reducing the availability of iron

• Increases metabolism and stimulates immune reactions and naturally protective physiological processes

Phagocytosis: Cornerstone of Inflammation and Specific Immunity

• General activities of phagocytes– Survey the tissue compartments and discover

microbes, particulate matter, and injured or dead cells– Ingest and eliminate these materials– Extract immunogenic information (antigens) from

foreign matter• Three main types

– Neutrophils– Monocytes– Macrophages

Figure 14.15

Figure 14.16

Mechanisms of Phagocytic Recognition, Engulfment, and Killing

Figure 14.17

Interferon: Antiviral Cytokines and Immune Stimulants

• Interferon (IFN): involved against viruses, other microbes, in immune regulation and intercommunication

• Three major types– Interferon alpha– Interferon beta– Interferon gamma

• All three classes produced in response to viruses, RNA, immune products, and various antigens

• Bind to cell surfaces and induce changes in genetic expression

• Can inhibit the expression of cancer genes and have tumor suppressor effects

Figure 14.18

Complement: A Versatile Backup System

• At least 26 blood proteins that work in concert to destroy bacteria and certain viruses

• Cascade reaction• Three different pathways that all yield similar

end results– Classical pathway– Lectin pathway– Alternative pathway

Complement Cascade

• Initiation• Amplification and cascade• Polymerization• Membrane attack

Classical Pathway

Figure 14.19