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Defense Mechanisms of the Host in Perspective

Barriers at the Portal of Entry: First line of Defense

Self and Nonself


 White blood cells must distinguish self from nonself cells
 Evaluates cells by examining markers on their surfaces

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
Nonspecific Chemical Defenses
 Sebaceous secretions and specialized glands- antimicrobial The Communicating Body Compartments
 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

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

Immune Functions of the Reticuloendothelial System


 Provides a passageway within and between tissues and organs
 Coexists with the mononuclear phagocyte system
- Lymphocyte
 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
Origin, Composition, and Functions of the Blood
- Not whole cells
 Circulatory system - Function primarily in hemostasis and in releasing
- Circulatory system proper chemicals for blood clotting and inflammation
- Lymphatic system
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

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 w/o red blood cells
Fundamental Characteristics of Plasma
 Hundreds of different chemicals Lymphatic Vessels
 Main component is water (92%)  Along the lines of blood vessels
 Proteins such as albumin and globulins, immunochemicals, fibrinogen  Similar to thin-walled veins
and other clotting factors, hormones, nutrients, dissolved gases, and  High numbers in hands, feet, and around the areola of the breast
waste products  Flow of lymph is in one direction only- from extremities toward the
heart
A Survey of Blood Cells  Lymph is moved through the contraction of skeletal muscles through
which the lymphatic ducts wend their way
 Hematopoesis : production of blood cells
 Relatively short life Lymphoid Organs and Tissues
 Primary precursor of new blood cells: pluripotential stem cells in the  Lymph nodes
marrow  Thymus
 Red blood cells (erythrocytes)  Spleen
 White blood cells (leukocytes)  Gut-associated lymphoid tissue (GALT)
 Platelets (thrombocytes)  Tonsils
 Differentiation  Loose connective tissue framework that houses aggregations of
lymphocytes
Leukocytes
 Granulocytes Lymph Nodes
- Neutrophils > Phagocytosis  Small, encapsulated, bean-shaped organs
- Eosinophils > Attack & destroy large eukaryotic pathogens;  Usually found in clusters along lymphatic channels and large blood
Also involved in inflammation & allergic reactions vessels of the thoracic and abdominal cavities
- Basophils > Parallel eosinophils in many actions  Major aggregations: axillary nodes, inguinal nodes, cervical nodes
 Agranulocytes
- Monocytes Spleen
 Discharged by bone marrow into bloodstream,
 Similar to a lymph node except it filters blood instead of lymph
live as phagocytes for a few days, then
differentiate into macrophages  Filters pathogens from the blood
 Responsible for
 many specific & nonspecific The Thymus: Site of T-Cell Maturation
phagocytic & killing functions  Thymus originates in the embryo
 Processing foreign molecules &  High rates of activity and growth until puberty
presenting them to lymphocytes  Shrinks gradually through adulthood
 Secreting biologically active  Thymic hormones help thymocytes develop specificity to be released
compounds that assist, mediate,
as mature T cells
attract, & inhibit immune cells &
reactions
 Dendritic cells
Miscellaneous Lymphoid Tissue  May be clear (serous) or may contain red blood cells or pus
 Bundles of lymphocytes lie at many sites on or just beneath the  Diapedesis: how WBCs leave the blood vessels and into tissue spaces
mucosa of the gastrointestinal and respiratory tracts  Chemotaxis: the tendency of WBCs to migrate in response to a
 Tonsils specific chemical stimulus
 Breasts of pregnant and lactating women  Benefits:
 GALT in the intestinal tract - Dilutes toxic substances
- Appendix - Fibrin clot can trap microbes and prevent further
- Lacteals spreading
- Peyer’s patches - Phagocytosis occurs immediately
 Mucosal-associated lymphoid tissue (MALT)
 Skin-associated lymphoid tissue (SALT) Late Reactions of Inflammation
 Bronchial-associated lymphoid tissue (BALT)  Long-lived inflammation attracts a collection of monocytes,
lymphocytes, and macrophages to the reaction site
The Second Line of Defense  Macrophages clear pus, cellular debris, dead neutrophils, and
 Inflammation damaged tissue
 Phagocytosis  B lymphocytes produce antibodies
 Interferon  T lymphocytes kill intruders directly
 Complement  Late in the process the tissue is repaired or replaced by connective
tissue (scar)
The Inflammatory Response: A Complex Concert of Reactions to Injury Fever: An Adjunct to Inflammation
 Reaction to any traumatic event in the tissues  An abnormally elevated body temperature
 Classic signs and symptoms  FUO: fevers of unknown origin
- Rubor (redness)  Initiation of fever
- Calor (warmth) - Pyrogen sets the hypothalamic “thermostat” to a higher
- Tumor (swelling) setting
- Dolor (pain)  Muscles increase heat production
 Fifth symptom has been added: loss of function  Peripheral arterioles decrease heat loss
through vasoconstriction
Chief Functions of Inflammation - Pyrogens can be exogenous or endogenous
 Mobilize and attract immune components to the site of the injury  Benefits:
 Set in motion mechanisms to repair tissue damage and localize and - Inhibits
clear away harmful substances multiplication of
 Destroy microbes and block their further invasion temperature-
sensitive
Stages of Inflammation 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

Mechanisms of Phagocytic Recognition, Engulfment, and Killing

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
Interferon: Antiviral Cytokines and Immune Stimulants Classical Pathway
 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

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