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Yet Again another Pandemic
threat
http://www.who.int/csr/disease/avi
an_influenza/phase/en/index.html
• An influenza pandemic occurs when a
new influenza virus appears against
which the human population has no
immunity, resulting in epidemics
worldwide with enormous numbers of
deaths and illness.
• Outbreaks of influenza in animals,
especially when happening
simultaneously with annual
outbreaks of seasonal influenza in
humans, increase the chances of a
pandemic, through the merging of
animal and human influenza viruses.
• During the last few years, the world
has faced several threats with
pandemic potential, making the
occurrence of the next pandemic a
matter of time.
Some Links
• Timeline for vaccine
• A fact sheet on swine flue
• who Now list this a N1H1 post pandemic
period, N1H1 becomes pare of our
seasional flue
Some Numbers
• Many Millions get flue
• Each year 200,000 hospitalized
• 35,000 die
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Mortality rate 0.1%
SARS 10%
Bird flue up to 90%
Swine flue? Is it really 10%?
Nonspecific Immunity
Resistance  don’t get it
Susceptibility  get it
• Nonspecific immunity (innate immunity)
are the defenses that protect the body
against any pathogen.
– Are not normally set up against any particular
pathogen.
• Adaptive immunity: Immunity, resistance
to a specific pathogen
An Overview of the Body’s
Defenses
ANIMATION Host Defenses: The Big Picture
Figure 16.1
The Concept of Immunity
• Host Toll-like receptors (TLRs) attach to
Pathogen-associated molecular patterns
(PAMPs)
• TLRs induce cytokines that regulate the
intensity and duration of immune responses
The skin
• Mechanical
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Skin Structure
Saliva washes
Mucus traps and ciliary escalator
Urine, vaginal flows out
• Chemical
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Sebum w/ unsaturated fatty acids
Perspiration
Lysozyme
Acid conditions stomak(1.2-3pH) skin (3-5pH)
Normal microbiota
Transferrins, and NO
Physical Factors
• Skin
• Epidermis
consists of
tightly packed
cells with
– Keratin, a
protective
protein
Figure 16.2
Ciliary Escalator
Figure 24.7
Ciliary Escalator
Figure 16.4
Phagocytosis
• Define.
• What does this look like?
• What does this do?
Chemical Factors
• Fungistatic fatty acid in sebum
• Low pH (3–5) of skin
• Lysozyme in perspiration, tears, saliva, and
urine
• Low pH (1.2–3.0) of gastric juice
• Low pH (3–5) of vaginal secretions
Normal Microbiota and Innate
Immunity
• Microbial antagonism/competitive exclusion:
Normal microbiota compete with pathogens
or alter the environment
• Commensal microbiota: One organism
(microbe) benefits and the other (host) is
unharmed
– May be opportunistic pathogens
Formed Elements in Blood
Red Blood Cells
Transport O2 and CO2
White Blood Cells:
Neutrophils
Phagocytosis
Basophiles
Histamine
Eosinophils
Kill parasites
Formed Elements in Blood
Monocytes
Phagocytosis
Dendritic cells
Phagocytosis
Natural killer cells
Destroy target cells
Formed Elements in Blood
T cells
Cell-mediated
immunity
B cells
Produce antibodies
Platelets
Blood clotting
Differential White Cell Count
• Percentage of each type of white cell in a
sample of 100 white blood cells
Neutrophils
60–70%
Basophils
0.5–1%
Eosinophils
2–4%
Monocytes
3–8%
Lymphocytes
20–25%
White Blood Cells
• Neutrophils: Phagocytic
• Basophils: Produce histamine
• Eosinophils: Toxic to parasites, some
phagocytosis
• Monocytes: Phagocytic as mature
macrophages
• Fixed macrophages in lungs, liver, bronchi
• Wandering macrophages roam tissues
• Lymphocytes: Involved in specific immunity
Components of Lymphatic System
Figure 16.5a
The Lymphatic System
ANIMATION Host Defenses: Overview
Figure 16.5b–c
Phagocytosis
• Phago: From
Greek, meaning
eat
• Cyte: From
Greek, meaning
cell
• Ingestion of
microbes
or particles by a
cell, performed
by phagocytes
Figure 16.6
Phagocytosis
Figure 16.7
Phagocytosis
ANIMATION Phagocytosis: Overview
ANIMATION Phagocytosis: Mechanism
Microbial Evasion of Phagocytosis
Inhibit adherence: M
protein, capsules
Kill phagocytes:
Leukocidins
Lyse phagocytes:
Membrane attack
complex
Streptococcus pyogenes, S.
pneumoniae
Staphylococcus aureus
Escape phagosome
Shigella, Rickettsia
Prevent phagosomelysosome fusion
Survive in
phagolysosome
HIV, Mycobacterium tuberculosis
Listeria monocytogenes
Coxiella burnettii
Actions of phagocytic cells
• Neutrophils (granulocyte) phagocyte
• Increase in number during infection
(leukocytosis)
• Neutrophils are most important
• Can act as antigen presenting cells (APC)
– Important in specific resistance
Mechanism of phagocytosis
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Chemotaxis to pathogen
Adherence
Engulfment
Killing
• Resistance of microbes can be seen in
some ability to live even after
phagocytosis.
Inflammation
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Redness
Pain
Heat
Swelling (edema)
Acute-phase proteins activated
(complement, cytokine, kinins)
• Vasodilation (histamine, kinins,
prostaglandins, leukotrienes)
• Margination and emigration of WBCs
• Tissue repair
Chemicals Released by Damaged
Cells
• Histamine
Vasodilation, increased permeability
of blood vessels
• Kinins
Vasodilation, increased permeability
of blood vessels
• Prostaglandins
Intensity histamine and kinin effect
• Leukotrienes
Increased permeability of blood
vessels, phagocytic attachment
Fever
• Body temp is controlled by the brain
• High temp in response to IL-1
• Caused by
– Bacterial endotoxins
– Interleukin-1
– Chills indicate rising body temp (crisis)
Fever
• Advantages
– Increases
transferrins
– Increases IL–1
activity
– Produces Interferon
• Disadvantages
– Tachycardia
– Acidosis
– Dehydration
– 44–46°C fatal
Antimicrobial substances
• IFN- and IFN-: Cause cells to produce
antiviral proteins that inhibit viral
replication
• Gamma IFN: Causes neutrophils and
macrophages
to phagocytize bacteria
• Lysozyme
• Acids on skin
• Complement
Antiviral Actions of Interferons
(IFNs)
Figure 16.15
Innate Immunity
• Transferrins
– Bind serum iron
• Antimicrobial
peptides
– Lyse bacterial cells
• Deficiencies in complement can result in
an increased susceptibility to disease
The Complement System
• Serum proteins activated in a cascade
• Activated by
– Antigen-antibody reaction
– Proteins C3, B, D, P and a pathogen
ANIMATION Complement System: Overview
ANIMATION Complement System: Activation
The Complement System
• C3b causes opsonization
• C3a + C5a cause inflammation
• C5b + C6 + C7 + C8 + C9 cause cell lysis
ANIMATION Complement System: Results
The Complement System
Figure 16.9
Effects of Complement Activation
• Opsonization or immune adherence:
Enhanced phagocytosis
• Membrane attack complex: Cytolysis
• Attract phagocytes
Figure 16.10
Inflammation Stimulated by
Complement
Figure 16.11
Classical Pathway of Complement
Activation
Figure 16.12
Alternative Pathway of
Complement Activation
Figure 16.13
Lectin Pathway of Complement
Activation
Figure 16.14
Some Bacteria Evade
Complement
• Capsules prevent C activation
• Surface lipid-carbohydrates prevent
membrane attack complex (MAC) formation
• Enzymatic digestion of C5a