Transcript Foundations in Microbiology

The Nature of Host Defenses
Nonspecific Defense
Chapter 14
Talaro
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Defenses can be classified as either (1) innate &
nonspecific or (2) acquired & specific
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• 1st Line of Defense
– Physical / anatomical barriers
– Chemical barriers
– Innate /genetic barriers
Nonspecific - innate
• 2nd Line of Defense
– Phagocytic white blood cells
– Inflammation
- Complement proteins
– Fever
- Interferon
• 3rd Line of Defense
– B cells
• Antibodies
– T cells
Specific - acquired
• Killer cells
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Physical or Anatomical Barriers
• Outermost layer of skin
– Epithelial cells
– Compacted, cemented together & impregnated with keratin
– Damaged cells are rapidly replaced
• Sweat glands
– Flushing effect
• Mucous membranes
– Impedes attachment & entry of bacteria- also keeps membranes moist
• Blinking & tear production –also keeps surfaces moist
• Nasal hair traps larger particles
• Ciliated epithelial cells in upper respiratory tract – keeps moving
small objects out on a continual basis…. (“ciliated escalator”)
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Chemical Defenses
• Sebaceous secretions – sebum and dead cells
– Inhibit attachment of bacteria & fungi to epithelial cells
• Antimicrobial peptides
• Lysozyme in tears
– Hydrolyzes the cell wall of bacteria
• Acidic pH of skin
– High lactic acid & electrolyte concentration in sweat
• HCl in stomach
• Digestive juices and bile of intestines
• Antimicrobial chemicals of semen – high pH
sperm-binding proteins (epididymis), prostasomes, cleavage
products of semenogelin I; also lysozyme, phospholipase 2 amd
lactoferrin
• Acidic pH of vagina – normal flora like Lactobacillus
• Urine – correlated with high concentrations of urea and ammonia
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Physical & Chemical Barriers
General protection mechanisms
that attempt to stop pathogens
from invading the body.
Evidence for the effectiveness of
physical & chemical barriers can
be deduced by observing
individuals who have lost or
never had them.
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Genetic Defenses
“Humans can’t acquire distemper
from cats & cats can’t get
mumps from humans.”
• Some hosts are genetically
immune to the diseases of other
Foundations in Microbiology (5 ) Talaro
hosts
• Some pathogens have great
specificity
• Some pathogens have a narrow
Possible Explanations
host range
- Absence of receptor on host cell
- Absence of a particular cell or tissue
“Shigella are pathogens of
humans and baboons but not - Inappropriate temperature for growth
- Missing nutritional requirement
chimpanzees.”
- Missing target for toxin
th
Why?
Todar’s On-Line Textbook of Bacteriology
Age, sex, stress, diet/malnutrition, trauma or other disease may
predispose the host to infection.
Todar’s On-Line Textbook of Bacteriology
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The Second Line of Host Defense
• Second line of defense is much more complex,
involves many different types of cells, many
levels
• Phagocytosis
• Inflammation – redness and increased
blood flow and increase in temperature,
edema
• Fever – increase in temperature of body
• Complement proteins
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Immunology: the study of the immune system
Immune system is responsible for…
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Surveillance of the body
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Immune cells constantly move throughout the body
searching for pathogens & infected / damaged cells
Recognition of foreign material
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Self versus non-self
Glycoproteins
Destruction of foreign entities or infected/damaged
cells
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Phagocytosis
Induce apotopsis
• Programmed Cell Death
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Some more
definitions
Epitope
Proteins produced by the immune
system that specifically binds to an
epitope and initiates its removal of
the antigen from the body
Ab recognize and
bind to a specific epitope
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Specialized WBC “touch” cells as they pass through tissues. The WBC
recognize surface glycoproteins to determine what is self and what is not.
An immune response is mounted if non-self glycoproteins are
recognized.
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Human Body & the Immune System
Network of cells & fluids that permeate every organ & tissue
Fluid-filled spaces that are interconnected
• Reticuloendothelial System (RES) – Very important part of
immune system – consists of monocytes and macrophages
– Fibrous support network enmeshing cells –reticular connective tissue
– This web connects one cell to another within a tissue or organ and provides
a niche for phagocytic WBC
• Reticulum = small net
• Endothelium = lining of a blood vessel
• Extracellular fluid (ECF)
– Spaces surrounding tissue cells
• Bloodstream
• Lymphatic System
– A system of vessels & organs that serve as sites for the development of
immune cells
• Spleen, thymus, lymph nodes & gut-associated lymphoid tissue
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Reticuloendothelial System
Dendritic Cells
An antigen-presenting leukocyte
that is found in the skin, mucosa,
and lymphoid tissues and that
initiates a primary immune
response.
Neutrophil Cell
An abundant type
of granular white blood
cell that is highly
destructive of
microorganisms.
Macrophage
Large phagocytic
cells found in the
reticuloendothelial
system
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Leukocytes or WBC
Classified according to staining reactions:
Granulocytes: granules in the cytoplasm & lobed nucleus
Agranulocytes: smaller granules & round nucleus
• Neutrophils or polymorphonuclear (PMNs)
Granulocytes
– Phagocytes in tissue – make up 55 to 90% of circulating leukocytes (25 billion
cells) – live for about 8 days
• Eosinophils
– Destroy eukaryotic pathogens such as Helminth worms & fungi – 1-3% of
total WBC
• Basophils
– Destroy eukaryotic pathogens - < 0.5% of circulating WBC
• Mast Cells
– Granules containing histamine & heparin
• Histamine dilates blood vessels and makes their walls permeable
• Heparin inhibits blood clotting
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– Mucous membranes & connective tissue
Polymorphonuclear
Neutrophil
Basophil
Eosinophils
Mast cell
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Process in which
phagocytes engulf and
digest microorganisms
and other cellular
debris
What is phagocytosis?
An important defense
against infection
Lysozymes fuse and release
digestive enzymes and reactive
oxygen compounds
Pseudopodium
Bacterial cells
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Agranulocytes
Lymphocytes - 20-35% of circ. WBC
Infected cell
– B cells – mature in bone marrow
– T cells – mature in thymus
– Involved in the specific immune
response
Monocytes –largest of all WBC (3-7%)
– Phagocytic
– Differentiate into macrophages
• Found in tissue
• Consume damaged host cells
• Present antigens
• Regulation of the immune systems
– Differentiate into dendritic cells
• Trap pathogens in the lymphatic tissue
• Present antigens
• Also important in specific immune response
T cell
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Inflammatory Response
Vasoconstriction
histamine & heparin
Vasodilation
Edema
Infiltration of neutrophils
Eliminate microbes, particulate matter
& dead or injured cells
Extract antigens
Macrophages &
Lymphocytes
Macrophages = phagocytosis
B cells = antibodies
T cell = killer & memory cells
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Tissue Repair
• Involves replacement of dead or damaged cells
• Begins during active phase of inflammation
• Extent of regeneration depends on tissue type, requires production of
new cells by STROMA (supportive connective tissue) or
PARENCHYMA (active part of tissue)
• Parenchymal regeneration restores skin to original form
• Stromal regeneration results
in scaring
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Fever
• Systemic nonspecific response to infection
• Higher than normal body temperature
• Pyrogen
• Exogenous
• LPS, pathogens, foreign cells, vaccines
• Endogenous
• Interleukin-1 (IL-1) & Tumor necrosis factor (TNF)
• Monocytes, neutrophils & macrophages
• Resets hypothalamus (in brain) thermostat to a higher setting
• Elevated temperature maintained until pyrogen is eliminated
• Low grade fever effective defense against disease
• Intensifies effects of antiviral agents (interferon)
• Inhibits microbial growth
• Speeds up physiological reactions (tissue repair)
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Complement: C proteins
Complements the Immune Reactions
• Consists of 26 blood proteins that work in concert to destroy
bacteria and viruses
• Nonspecific defense that any foreign cell can activate system
• Complement proteins are activated by cleavage
– Cascade reaction
• 1) Classical pathway
– C proteins bind to receptors on foreign cell membrane
• 2) Alternative pathway
- interaction with normal cell surface components
• 3) Lectin Pathway
- Direct interaction with polysaccharide that contains sugar called
mannan
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Classical Pathway
Collectively
they’re called C1
Initiation
Amplification & Cascade
Two complement components contribute to
inflammation - C3a and C5a
Both bind to mast cells, basophils, and platelets
- trigger release of histamines
C5a also a potent chemoattractant for
phagocytic cells
Series of cleavage rxns
C5 binds to membrane
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Polymerization
C5b attracts other C proteins
Form a ring that punctures the cell
Membrane attack
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Interferons (INFs)
• Originally described as interfering with viral infections
• Produced in response to a viruses & a variety of antigens
• RNA & products of immune cells
• Tumor suppressive effects
• Three types of human interferon
•a
lymphocytes & macrophages
•b
fibroblasts & epithelial cells
•g
T cells
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• a and b produced in infected cells, diffuse to uninfected cells
- Mediates transcription of antiviral protein in uninfected
cells
• Allows resistance to infection
- α activates “natural killer” cells (NK cells) (related to T cells
but lack specificity for Ag)
- β – maturation of B and T lymphocytes and has role in
inflammation
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• g interferon produced by T cells
- Inhibits cancer cells, activates macrophages, stimulates B
cells
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Defenses can be classified as either (1) innate &
nonspecific or (2) acquired & specific
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