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Transcript
Microbiology: A Systems
Approach, 2nd ed.
Chapter 14: Host Defenses IOverview 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 glandsantimicrobial
• 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
(a)
Figure 14.9
(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 temperaturesensitive 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