INTERACTIONS OF INNATE AND ADAPTIVE IMMUNE SYSTEMS WITH AGENTS OF INFECTIOUS DISEASES

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INTERACTIONS OF INNATE AND ADAPTIVE IMMUNE
SYSTEMS WITH AGENTS OF INFECTIOUS DISEASES

• PAUL A. GULIG, PH.D.
• Office - R1-250, 392-0050
• Lab R1-144, 392-0682
• email gulig_at_ufl.edu

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INTRODUCTION TO INFECTIOUS DISEASES
I. Wide variety of diseases with infectious
causes A. Severity self-limiting vs.
lethal B. Time course acute vs. chronic vs.
latent C. Where any organ system D. From the
environment or people or animals E. Highly
contagious vs. non-transmissible F. Relationship
with the infectious agent infection vs.
non-infection (toxin only)
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II. Wide variety of microorganisms that can cause
infectious disease in humans A. viruses -
parasitic nucleic acid 1. RNA vs. DNA
genomes 2. enveloped vs. non-enveloped
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II. Wide variety of microorganisms that can cause
infectious disease in humans B. bacteria -
prokaryotic 1. cell wall gram-positive vs.
gram- negative vs. acid-fast 2. physiology
aerobes vs. anaerobes
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II. Wide variety of microorganisms that can cause
infectious disease in humans C. fungi -
eukaryotic - yeasts vs. molds
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II. Wide variety of microorganisms that can cause
infectious disease in humans D. protozoans-
eukaryotic - unicellular organisms with complex
life cycles
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II. Wide variety of microorganisms that can cause
infectious disease in humans E. worms -
animals - large organisms with complex life
cycles
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• III. Microbial Pathogenesis
• Infectious disease usually constitutes a cycle of
  biological interactions.
• Intervention preventing ? physician.
• Understanding pathogenesis ? intervention
  prevention other than antibiotics or vaccines.

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III. Microbial Pathogenesis Functions/stages of
pathogens/disease A. Encounter 1. Exogenous
vs. endogenous infection and normal flora
a. Exogenous - disease initiated shortly after
encounter, no stable interaction b.
Endogenous - disease initiated after long-term
stable relationship
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Functions/stages of pathogens/disease 2.
sources food, water, air, body fluids, insects,
animals, fomites (things)
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2. Entry - where in/on the body do we initially
contact the microbes virulence function
adherence - to infect a mucosal surface or tract
bathed with moving fluid, microbes must stick or
be washed away
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Figure 2-2
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C. Spread - movement from surface through
tissues and body 1. not all microbes spread
to cause disease 2. microbes cannot penetrate
intact skin, require macro or microlesions 3.
mucosal surface is usually first barrier
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4. Spread - virulence functions a. cellular
invasion - invading into host cells to become
intracellular i. professional phagocytes
(macrophages and PMN) by phagocytosis ii.
non-professional phagocytes (epithelial cells,
endothelial cells, hepatocytes, etc.) by
microbial mediated endocytosis iii. some
microbes escape the phagosome into the cytoplasm
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Spread b. tissue invasion - through
tissues, either through cells or between
cells i. degrade extracellular matrix ii.
disrupt tight junctions 5. use of host cells
as vehicles to move through blood or lymph
(intracellular pathogens)
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D. Multiplication You will not normally
encounter enough microbes to cause damage and
disease without their increase in number in your
body, so multiplication in the host is essential
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5. Evasion of host defenses (later) consider
where the microbes are and which defenses they
will encounter a. Complement -beyond mucosal
surface b. Phagocytes - beyond mucosal
surface EXTRACELLULAR vs. INTRACELLULAR c.
Antibodies d. Cell-mediated immunity e. Latency
i. dormant in host ii. many viruses (e.g.,
Herpes)
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6. Damage a. cytotoxicity (kill host
cells) i. from outside - toxins ii. from
inside - intracellular growth b.
pharmacology/physiology (alter host cell
function) - toxins
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6. Damage c. host immune/inflammatory
response (host causes damage to itself) i.
nonspecific inflammation, abscess,
prostaglandins, cytokines ii. specific
immune response antibodies, cell-mediated
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Figure 10-5
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d. TOXINS i. Endotoxin vs. Exotoxin ii.
Endotoxin (LPS) from gram-negative bacteria
only - damage - macrophages producing
cytokines (TNF-a, IL-1, IL-6)
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d. TOXINS iii. Exotoxins (proteins) severa
l have A-B motif Aactive portion Bbinding
portion
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• c Exotoxins (proteins)
• lytic (pores or lipase activity)
• 2. cytotoxic (kill host cells by altering
  functions, e.g., protein synthesis)

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• c. Exotoxins (proteins)
• 3. pharmacological (alter host cell function,
  e.g., cAMP levels)
• 4. extracellular enzymes (degrade
  extracellular matrix, e.g., protease, DNase,
  hyaluronidase)

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c. Exotoxins (proteins) 5. superantigens
(stimulate host immune response in
antigen-independent manner resulting in cytokine
cascade - similar to endotoxin)
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7. Transmission to new host a. completes the
cycle to lead to new encounter virulence step
1 b. not all pathogens spread to new
human host (e.g., Legionella pneumophila) c.
not all pathogens are contagious - humans may
be dead end hosts
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G. Spread to new host 3. most bacterial
pathogens are contagious - some examples of
how a. fecal-oral b. sexually
transmitted c. droplet spread
(respiration) d. skin-skin e.
fomites f. vertical - in utero, at birth
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