Unit One - The Adversaries
Unit
One - Outline of Topics
I. Review of Microbes
(viruses, bacteria, fungi, protozoa, helminths,
arthropods, normal microbiota)
II. Host Defenses
A. Nonspecific Defenses
1. Defenses against entry
a. Physical
b. Chemical
c. Biological
2. Defenses of the interior
a. Complement cascade
b. Acute phase proteins
c. Interferons
d. Phagocytic cells
i.
polymorphonuclear
leukocytes
ii. monomorphonuclear leukocytes
e. Nonspecific cytolytic
cells
B. Specific Defenses
1. T lymphocytes
a. Recognition of specific
antigen (TCR and MHC)
b. Activation against a
specific antigen (role of APC and TH)
c. Response to specific
antigen
i.
T
helpers
ii.
T cytotoxic
iii.
T regs
2. B lymphocytes
a. Recognition of specific
antigen (BCR)
b. Activation against a
specific antigen (role of APC and TH)
c. Response to a specific
antigen
i. Plasma cells
ii. Memory cells (primary vs
secondary response)
Unit One - Background Terminology/Concepts
will not be covered in lecture
Obligatory Steps For
Infectious Microbes:
Phenomenon |
Step |
How |
1.
Entry |
attach
and enter into body |
evade
host's natural protective and cleansing mechanisms |
2.
Spread |
local
or general spread in body |
evade
natural barriers and immediate local defenses |
3.
Multiplication |
multiply |
but
many offspring will die in host |
4.
Evasion |
evade
host defenses |
evade
phagocytic and immune defenses long enough for full cycle in host to be
completed |
5.
Transmission |
exit
from body |
leave
body at a site and on a scale that ensures spread to fresh host |
6.
Pathology |
cause
damage in host |
not
strictly necessary but often occurs |
Pathogen - agent capable of
causing disease
Pathogenicity ability to cause
disease
Frank pathogen= obligate pathogen causes disease in a healthy host by
direct interaction
Opportunistic pathogen- may cause disease under the right conditions
Virulence degree or intensity
of pathogenicity.
Dependent
on:
1.
Invasiveness
ability of organism to spread
2.
Infectivity
ability of organism to leave point of entry
3.
Pathogenic
potential degree pathogen causes damage
Virulence
factors
individual characteristics of a specific strain of microbe that confer
virulence
Colonization (esp. by bacteria/yeast) establishment
of a site of replication dependent on attachment
Symbiosis - an association of two
different species of organisms.
Commensalism - one species uses the
body of another species as a habitat and possibly as a source of nutrition.
Mutualism - a reciprocal
relationship between two species.
Parasitism - one species in a
relationship benefits and the other does not.
------
Respiration - use electron
transport chain with an external e- acceptor (like O2 or NO3)
as the terminal e- acceptor
Fermentation - no external e-
acceptor, one of the substrates involved accepts the e-
Facultative
fermenter will respire in the presence of external
electron acceptors and ferment in their absence (Ex. Escherichia coli)
Obligate
aerobe
- must have O2 because only O2 can serve as the terminal
e- acceptor (Ex. Bacillus spp.)
Facultative
anaerobe
- will use O2 for aerobic respiration if its present but
will switch to fermentation or anaerobic respiration if no O2 (Ex. E. coli)
Aerotolerant anaerobe - can't use O2
as an external e- acceptor, but not killed by it.
Strict or obligate
anaerobe
- killed by exposure to O2 (Ex. Bacteroides
fragilis)
Microaerophilic - grows optimally in
presence of oxygen concentrations that are below atmospheric concentrations
(ex. the streptococci)
------
Inflammation
- the bodys response to injury or infection, which may be acute or chronic.
Acute
inflammation - the immediate defensive reactions to any
injury. It involves swelling, redness,
heat, and pain.
Edema
- excessive accumulation of fluid in the tissues.
Erythema
- abnormal flushing of the skin caused by dilation of the
blood capillaries.
Opsonin
- a molecule that attaches to cells, provides a bridge to receptors on
phagocytic cells, and enhances the rate of phagocytosis
Cells of
the Immune System
(White
Blood Cells = WBC = leukocytes)
Monocytes Mononuclear
Macrophages
(differentiated monocytes, found in tissues) leukocytes
(agranulocytes)
Phagocytes
Neutrophils
Eosinophils Polymorphonuclear
Basophils leukocytes
Mast cells
(differentiated basophils, found in tissues) (granulocytes)
Natural Killer (NK) cells Large Granular Lymphocytes (LGL)
Killer (K)
cells
Cytotoxic T
cell (TC)
Lymphocytes Helper T cell (TH) T
cells
Regulatory T
cell (Tregs)
Effector B cells/ Plasma cells
Memory B cells B cells
Origins of Cells of the Immune System
UNIT ONE
THE ADVERSARIES
I. The Microbes
Objectives:
To Review:
1.
important structural features of viruses
2.
sequence of steps during viral infection
3.
consequences of viral infections at a
cellular level
4.
important structural features of bacteria
5.
key differences between Gram positive and
Gram negative cell walls
6.
clinical significance of LPS, capsules,
flagella, fimbriae, and pili
7.
important features of eukaryotic
pathogens: fungi, protozoa, helminths, arthropods
8.
distribution and significance of normal
microbiota by way of clinical cases
A.
VIRUSES - Obligate intracellular parasites
Common structural features
1. Genetic material -
DNA or RNA, ss or ds
2. Outer coat - capsid
- composed of subunits called capsomers
Nucleic acid + capsid
= nucleocapsid
Only nucleocapsid = naked
Nucleocapsid surrounded by a lipid and protein
envelope = enveloped
*Outer surfaces (capsids
or envelopes) impt cause they 1st make contact
w/ host cells.
Viral infection of host proceeds through several
steps:
1. Entry
into body of host - 4 routes
1) inhalation of
droplets -
2) ingestion -
3) direct transfer -
4) bites of arthropod
vectors -
2.
Adsorption to target cell(s) in host specific interaction between
virus surface molecules and receptors on target cells ***
3. Entry into target cell - 3 mechanisms
1) Fusion
2) Receptor-mediated endocytosis (RME)
3) Translocation
Entry step ends with release of viral nucleic
acid inside host target cell.
4. Multiplication w/in the target cell (obligate
intracellular) complex process
1) synthesis of viral
mRNA
DNA viruses may use host RNA polymerase -- viral
DNAΰ
viral mRNA
RNA viruses have to use viral RNA polymerases
2) translation of viral
proteins in host cytoplasm using host ribosomes
viral mRNA can displace host mRNA
3) replication of viral
nucleic acid
4) assembly of nucleic acid
& capsomers into new nucleocapsids
(= viral progeny)
5.
Release from host cell (immediate or delayed) 2 mechanisms
1) lysis -
2) budding (acquisition
of envelope)
Pathology - effects of viral infection on the
targeted cell
1) lysis
2)
persistence
3) latency (ΰ
lytic)
4) transformation
CONCEPT CHECK - Viruses
In the space below, in your own words, describe in complete detail:
1) the significance of surface projection target cell receptor interactions in viral infections
2) the two mechanisms by which an enveloped virus may enter into a target host cell
B.
BACTERIA - prokaryotes
Common structural features
1. Genetic material ds,
circular DNA = chromosome
2. Ribosomes are only
organelle 70S (30S + 50S)
3. Cell membrane site of many metabolic
functions
4. Cell wall shape, rigidity, strength; impt in virulence and immunity
Compound responsible for strength of cell wall
is peptidoglycan (hexose sugars + amino acids)
unique to bacteria
Differences in cell wall structure - Gram
positive vs. Gram negative
Gram positive
peptidoglycan layer is thick
·
highly
polar ΰ
hydrophilic surface
·
Lipoteichoic acids = LTA
·
resists
activity of bile
·
digested
by lysozyme
·
synthesis
is disrupted by penicillin and cephalosporin antibiotics (more in Unit 4)
Gram negative
peptidoglycan layer is thin, overlaid
by outer membrane that contains lipopolysaccharide and lipoprotein
·
outer
membrane is polar, but lipids are hydrophilic
·
Lipopolysaccharide
= LPS
o
carbohydrates
ΰ
antigenicity
o
lipid
A is toxic = endotoxin ΰ induces fever, increases vascular
permeability, etc. (more Units 2 & 3)
5. Structures exterior to the cell wall in some
bacteria (more common in pathogens)
a. Capsule high
molecular weight polysaccharides ΰ slimy and sticky
clinically relevant for 2 reasons
1) attach
to a wide variety of surfaces *
2) more
resistant to engulfment by host defense cells **
b. Flagella
1) allow bacteria to
move
2) proteins are
strongly antigenic/immune stimulating
c. Fimbriae (aka common
pili, esp. in the Neisseria)
1) attachment (fimbriae
adhesins to target cell membranes)
2) evading engulfment
d. Pili
(aka sex pili)
1) exchange of genetic
info, incl. antibiotic resistance (more in Unit 4)
Bacterial infection of host proceeds through
several steps:
1. Entry into body of host 3 routes
1) direct
contact
2) ingestion
3) fomites (inanimate objects)
2. Adhere to, colonize,
(and possibly invade) host tissues or cells
3. Evasion of host defenses
(more in Unit 2)
4. Multiplication in the
host (extracellular or intracellular)
5. Pathology (more in Units
2 and 3)
1) toxins
2) host immune response
6. Transmission usually
passive in body fluids
EUKARYOTIC PATHOGENS
C. FUNGI
1. Morphology
hyphae mycelium
Dimorphic - 2 forms
yeast and mold
2. Reproduction mold vs yeast
spores division
budding
3 types of fungal infections = mycoses
1) superficial
2) subcutaneous
3) systemic or deep -
Infections are most serious in
immunocompromised.
D. PROTOZOA
1. Infection
extracellular or intracellular
2. Reproduction
asexual in humans, sexual
absent or in insect vector.
3. Evasion of host defenses
extracellular prevent or delay
recognition of antigens
intracellular - avoid intracellular
killing mechanisms
4. Transmission
bites of insects
ingestion
sexually transmitted
E. HELMINTHS multicellular
worms
1. Exs. tapeworms,
flukes, nematodes
2. Have complex life cycles
3. Transmission
fecal-oral
ingestion of larvae in tissues
active penetration by larvae
bites of insects
F. ARTHROPODS
1.
Exs.
mosquitoes, biting flies, fleas, ticks, lice
2.
increases
potential for infection with viruses and protozoa
NORMAL MICROBIOTA = Indigenous microbiota (= Normal flora)
·
1012
eukaryotic cells in adult human - 1013 prokaryotic
Clinical significance
1. common contaminants
of clinical specimens
Fig 8.1 and Fig 8.2
2. opportunistic
pathogens
In class
mini clinical cases