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Microsoft PowerPoint - Ch16_Lect.ppt []C H A P T E R
© 2016 Pearson Education, Ltd.
16
• White blood cell (WBC) counts measure leukocytes in the
blood
• High WBC counts may indicate bacterial infections, autoimmune
diseases, or side effects of medications
• Low WBC counts may indicate viral infections, pneumonia,
autoimmune diseases, or cancers
© 2016 Pearson Education, Ltd.
Plasma
White blood cells
Red blood cells
White blood cell count: 5,000–10,000 WBCs per cubic millimeter
(mm3) or 5.0–10.0 x 109 WBCs per liter.
Neutrophils: 60% to 70% Lymphocytes: 20% to 25% Monocytes: 3% to 8%
Eosinophils: 2% to 4% Basophils: 0.5% to 1%
NORMAL RANGES AND PERCENTAGES
Immunity: ability to ward off disease. Innate (nonspecific)
immunity: defenses against any
pathogen and are present at birth.
Adaptive (specific) immunity: defenses that involve specific
recognition of a microbe once it has breached the innate immunity
defenses.
Susceptibility: lack of resistance to a disease.
The Concept of Immunity
Toll-like receptors (TLRs) on host cells attach to
pathogen-associated molecular patterns (PAMPs).
TLRs bound to PAMPs induce the release of cytokines from the host
cell that regulate the intensity and duration of immune
responses.
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin
Cummings
Physical Factors
Skin: the largest organ of human body in terms of surface area.
Dermis: inner portion made of connective tissue
Epidermis: outer portion made of tightly packed epithelial cells
containing keratin, a protective protein
First line of defense: skin and mucous membrane
Figure 16.1 A section through human skin.
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Cummings
Mucous membranes: consist of an epithelial layer and an underlying
connective tissue layer
Lacrimal apparatus (): Washes eye.
Figure 16.2 The lacrimal apparatus.
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin
Cummings
Ciliary escalator: microbes trapped in mucus are transported away
from the lungs.
Earwax: prevents microbes from entering the ear. Urine: flows out.
Vaginal secretions: flow out.
Figure 16.3 The ciliary escalator.
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin
Cummings
Chemical Factors
Sebum (): produced by sebaceous (oil) glands of the skin
one of the components is unsaturated fatty acids, which inhibit the
grow of certain pathogenic bacteria and fungi
low pH (3-5) is caused in partly by fatty acid and lactic
acid
Perspiration (): produced by sweat glands of the skin
contain lysozyme can break peptidoglycan of cell walls of gram (+)
bacteria and
less gram (-) bacteria
is also found in tears, saliva, nasal secretions, tissue
fluids
Low pH (1.2-3.0) of gastric juice.
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin
Cummings
Normal Microbiota and Innate Immunity
Microbial antagonism/competitive exclusion: Normal microbiota
compete with pathogens. For example: (in Ch14) Normal microbiota vs
Candida albicans in vagina
E. coli vs Salmonella and Shigella in large intestine
Normal microbiota vs Clostridium difficiles in large
intestine
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin
Cummings
Formed Elements in Blood Second line of defense
Cells and cell fragments suspended in plasma. Erythrocytes (red
blood cells)
Leukocytes (white blood cells)
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Leukocytes are divided into: Granulocytes:
Neutrophils: highly phagocytic and motile
• commonly called polymorphonuclear leukocytes (PMNs), or
polymorphs
• activate in the initial stage of an infection
Basophils: produce histamine • important in inflammation and
allergic response
Eosinophils: produce toxic proteins against parasites and some
phagocytosis
© 2016 Pearson Education, Ltd.
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin
Cummings
Agranulocytes are leukocytes with granules in their cytoplasm that
are not visible with a light microscope. Monocytes: mature into
macrophages in tissues where
they are phagocytic
Dendritic cells: found in the skin, mucous membranes, and thymus;
phagocytic
Lymphocytes: T cells, B cells, and NK cells; play a role in
adaptive immunity
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin
Cummings
Agranulocytes:
Monocytes:
• are not actively phagocytic until they leave circulating blood
and mature macrophages
• fixed macrophages (or histiocytes) are found in lungs, liver, and
bronchi etc
• wandering macrophages roam the tissues
Dendritic cells:
• are belived to be derived from monocytes
• abundant in the epidermis of the skin, mucous membranes, the
thymus and lymph nodes
• initiate adaptive immune response
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin
Cummings
Lymphocytes: include natural killer (NK) cells, T cells and B
cells
• NK cells are found in blood, spleen, lymph nodes, and red bone
marrow, and attack abnormal body cells by perforins () and
granzymes ().
• B cells and T cells occur in lymphoid tissues of lymphoid system
and also circulate in the blood.
NK
T
B
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Cummings
The Lymphatic System
The lymphatic system: Consists of lymph, lymphatic vessels,
lymphoid tissue,
and red bone marrow.
Contains lymphocytes and phagocytic cells.
Lymph carries microbes to lymph nodes where lymphocytes and
macrophages destroy the pathogen.
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Thoracic (left lymphatic) duct
Interstitial fluid (between cells) Venule Tissue cell Lymph in
lymphatic capillary Lymphatic capillary
Blood capillary
Flow of fluid between arteriole, blood capillaries, lymphatic
capillaries, and venule
Lymph in lymphatic capillary
One-way opening
Phagocytosis
Fixed macrophages are residents in tissues and organs.
Free (wandering) macrophages roam tissues and gather at sites of
infection. Figure 16.7 A macrophage engulfing
rod-shaped bacteria.
Chemotaxis () Chemical signals attract phagocytes to
microorganisms.
Adherence Attachment of a phagocyte to the surface of the
microorganism. Ingestion Opsonization: microorganism is coated with
serum
proteins, making ingestion easier. Digestion Microorganism is
digested inside a phagolysosome.
The Mechanism of Phagocytosis
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Copyright © 2006 Pearson Education, Inc., publishing as Benjamin
Cummings
Inhibit adherence: M protein, capsules
Streptococcus pyogenes, S. pneumoniae
Lyse phagocytes: membrane attack complex Listeria
monocytogenes
Escape phagosome Shigella, Rickettsia
Survive in phagolysosome Coxiella burnetii
Microbial Evasion of Phagocytosis
Inflammation
Damage to the body’s tissue triggers a defensive response called
inflammation.
Inflammation is usually characterized by 4 signs and symptoms:
Redness
Pain
Heat
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Cummings
Inflammation has the following function: to destroy the injurious
agent, if possible, and to remove
it and its by-products from the body
if destruction is not possible, to limit the effects on the body by
confining or walling off the injurious agent and its
by-products
to repair or replace tissue damaged by the injurious agent or its
by-products
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Cummings
The process of inflammation into 3 stages: 1. Vasodilation and
increased permeability of blood
vessels
3. Tissue repair
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Cummings
During inflammation, there is an activation and increased
concentration of a group of proteins in the blood called
acute-phase proteins. Histamine
Kinins
Prostaglandins
Leukotrienes
Cytokines
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Tissue damage
Blood clot forms.
Chemical Function
Prostaglandins Intensity histamine and kinin effect
Leukotrienes Increased permeability of blood vessels, phagocytic
attachment
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Cummings
Margination is the sticking of phagocytes to blood vessels in
response to cytokines at the site of inflammation
Phagocytes squeeze between endothelial cells of blood vessels via
diapedesis
Phagocyte Migration and Phagocytosis
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Monocyte
Diapedesis—phagocytes squeeze between endothelial cells.
Phagocytosis of invading bacteria occurs.
NeutrophilMacrophage
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin
Cummings
Cannot be completed until all harmful substances are removed or
neutralized
Stroma is the supporting connective tissue that is repaired
Parenchyma is the functioning part of the tissue that is
repaired
Tissue Repair
Scab
Regenerated dermis (stroma)
(c) Tissue repair
Fever
Cytokines cause the hypothalamus to release prostaglandins that
reset the hypothalamus to a higher temperature
Body constricts the blood vessels, and shivering occurs (which
raises temperature)
As body temperature falls (crisis), vasodilation and sweating
occurs
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin
Cummings
Advantages
Antimicrobial Substances
consisting of over 30 proteins produced by liver found circulating
in blood serum destroy microbes by cytolysis inflammation
phagocytosis ( opsonization)
are inactive until they are split into fragments are numbered C1
through C9 activated in a cascade
The Complement System
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Cummings
The cascade of complement proteins that occurs during an infection
is called complement activation.
Complement activation may occur in 3 pathways: the classical
pathway the alternative pathway the lectin pathway
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin
Cummings
Antibodies bind to antigens, activating C1
C1 splits and activates C2 and C4
C2a and C4b combine and activate C3 C3a functions in
inflammation
C3b functions in cytolysis and opsonization
The Classical Pathway
pathway of complement activation
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin
Cummings
C3 present in the blood combines with factors B, D, and P on
microbe surface
C3 splits into C3a and C3b, functioning the same as in the
classical pathway
The Alternative Pathway
alternative
Macrophages ingest pathogens, releasing cytokines that stimulate
lectin production in the liver
Mannose-binding lectin (MBL) binds to mannose, activating C2 and
C4
C2a and C4b activate C3, which functions the same as in the
classical and alternative pathways
The Lectin Pathway
lectin
Cytolysis Activated complement proteins create a membrane
attack complex (MAC)
Opsonization () Promotes attachment of a phagocyte to a
microbe
Inflammation Activated complement proteins bind to mast
cells,
releasing histamine
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outcomes of complement activation C3
Splits into activated C3a and C3b
cytolysis opsonization inflammation
Microbes burst as extracellular fluid flows in through
transmembrane channel formed by membrane attack complex.
Coating microbes with C3b enhances phagocytosis.
Blood vessels become more permeable, and chemotactic agents attract
phagocytes to area.
The complement system is another way the body fights infection and
destroys pathogens. This component of innate immunity “complements”
other immune reactions. Complement is a group of over 30 proteins
circulating in serum that are activated in a cascade: one
complement protein triggers the next. The cascade can be activated
by a pathogen directly or by an antibody–antigen reaction. Together
these proteins destroy microbes by (1) cytolysis, (2) enhanced
phagocytosis, and (3) inflammation.
C5a
Histamine
Figure 16.13 Inflammation stimulated by complement.
C3a and C5a bound to mast cell, basophils, and platelets trigger
the release of histamine
C5a functions as a chemotactic factor that attracts phagocytes to
the site of complement activation
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Cummings
Regulatory proteins readily break down complement proteins,
minimizing host cell destruction
Regulation of complement
Lack of complement proteins causes susceptibility to
infections
Complement and disease
Interferons (IFNs)
IFN are a family of cytokines produced by cells; have antiviral
activity.
Human IFNs are of 3 principal types: Alpha IFN (IFN-) and Beta IFN
(IFN-): produced by
cells in response to viral infections; cause neighboring cells to
produce antiviral proteins (AVPs) that inhibit viral
replication.
Gamma IFN (IFN-): causes neutrophils and macrophages to phagocytize
bacteria.
© 2016 Pearson Education, Ltd.
Figure 16.14 Antiviral action of alpha and beta interferons
(IFNs).
New viruses replicated in host cell infect neighboring cells.
Transcription Translation
Viral RNA from an infecting virus enters the cell.
The virus induces the host cell to produce interferon mRNA
(IFN-mRNA), which is translated into alpha and beta
interferons.
Interferons make contact with uninfected neighboring host cells,
where they bind either to the plasma membrane or to nuclear
receptors. Interferons induce the cells to synthesize antiviral
proteins (AVPs).
AVPs degrade viral mRNA and inhibit protein synthesis—and thus
interfere with viral replication.
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin
Cummings
Transferrin () is found in blood and tissue fluids
Lactoferrin () is found in milk, saliva, and mucus
Ferritin () is found in the liver, spleen and red bone marrow
Hemoglobin is located within RBC
Function: inhibit bacterial growth by reducing the amount of
available iron siderophore
Iron-binding proteins
Short peptides produced in response to protein and
sugar molecules on microbes
Inhibit cell wall synthesis
Broad spectrum of activity
Table 16.2 Summary of Innate Immunity Defenses (1 of 2)
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Table 16.2 Summary of Innate Immunity Defenses (2 of 2)
© 2016 Pearson Education, Ltd.