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Outline of Intro to Immunology
Definition
History
Immunologys connection to Microbiology
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Immunology
The study of the physiological
mechanisms that (humans)
use to defend their bodiesfrom invasion by other
organisms
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Immunology
Based on observations that survivors of a
disease were untouched (immune) whenchallenged with the agent again
Researchers noted that the immune response(IR)
-critical to survival as evidenced by adverseeffects of immune deficiency
-complex, interconnected, redundant
- over-activity may cause problems.. e.g.
Hypersensitivity, autoimmune disease B/C of immunology -> in the only example of
eradication of a disease ( smallpox)
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Historically microbiology is linked
to immunology Outgrowth of observations that noted people were
seldom sickened by the same agent twice
Outgrowth of the desire to prevent infectious
diseases Jenners smallpox vaccine
Immunologys infancy is part of the GoldenAge ofMicrobiology
- e.g. Pasteurs chicken cholera & rabies vaccineetc.
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Story of smallpox eradication:Note the two types of smallpox
Variola Minor
CFR 2%
Variola major
CFR 30%
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Smallpox pustules
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Lesions on hands & feet helped
differentiate smallpox from other diseases
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Edward Jenner (1749-1823)
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Important observations that lead to
Jenners Discovery
Those with scarred faces did not come
down with smallpox
Those variolated did not come down withsmallpox
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Inoculation (Variolation)
Used in China and Mid East for centuries
Scratch material from smallpox lesions into a skinor vein (or nose) of a healthy person
This would cause a lesion at the site etc., &hopefully, if live thru this, PX smallpox in the future
Problems: Risk of death (1-5%)
Safer if
- used old scrapings
-injected when person was healthy
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Lady Wortley Montagu
Wife of English Ambassador to Turkey
Wrote about inoculation practice that
prevented smallpox ( 1716-1718) Strongly suggested that English use this to
prevent smallpox (as she had lost family
members to the disease). Eventually this became accepted medical
practice although not that widespread
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Jenners use of scientific method
English smallpox outbreak in 1778 kept Jenner
busy inoculating (variolating) people to PX disease
Observations:
-Many developed lesions at site while some didnt
-Those who did not have a lesion told him they
once had cowpox
-Recalled prior statements of milkmaids who werenever infected with smallpox during epidemics
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Jenners experiment
Had to acquire ability to recognize cowpox in cattle
Waited for next cowpox outbreak (1796)
On a farm, he found a person who had cowpox
lesions (Sarah Helmes)
Asked strategic questions about the problem:
Could he transmit cowpox from human to human?
Could cowpox infection protect someone fromsmallpox?
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Jenners Expt.
Collected pustularmaterial from Sarahscowpox lesion
On May 14, 1796, he scratched this into the
arm of James Phipps, an 8 year old boy.
7 days later James had a pain under hisarm, head ache, fever, refused to eat & then
felt better the next day In July, inoculated James with smallpox---
James never became ill with smallpox !!!!
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Jenners Next Expt.
Had to wait two years for another cowpox
outbreak (March 1798)
Inoculated several more children
Waited weeks & then scratched them with
smallpox scrapings
None of these ever became ill Published the paper in June 1798
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Smallpox Vaccination
Success ofJenners vaccination technique,
vaccination against smallpox becoming
accepted as standard medical practice-Smallpox officially declared eradicated in
1979 ( two years after the last naturally
transmitted case)
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Figure 1.1
Smallpox is the
ONLY disease
ever eradicated.
This was possible
because of Jenners
vaccine studies
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Fig. 1-26
Although the smallpox
vaccine was
developed before
much was know aboutimmunology,
knowing details of the
IR has lead to
development of many
vaccines.
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A few other vaccine success
stories Figure 1-27
All three of these
disease have not been
eradicated but we areclose to this goal for
polio.
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Fig. 1-28
AIDS, caused by HIV,
is an example of an
acquired
immunodeficiencydisease.
Many efforts are being
made to develop a
vaccine to protect the
world from HIV.
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Host-parasite Interactions
(~ecology)
Difficult to study medical microbiology
without understanding immunology
Difficult to study medical immunologywithout understanding medical
microbiology (pathogenesis)
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Section 1-2Diversity of pathogens and their effects
Diverse types of pathogens.. Fungi,bacteria, viruses, parasites (Fig 1.4)
Each agent has its preferred location of
replication: extracellular or intracellular(Fig.2-2)
Tissue damage can be direct or indirect
(Fig. 2-1) Type of IR is determined by location
infected, agent, host etc
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Figure 1-3
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Figure 1-4
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Figure 1-4
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Figure 1-4
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Figure 2-2
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Figure 2-1
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Host parasite Interactions
Outline Bacteria and how they cause disease
1. Bacterial structures involved in IR
A. Cell wall types:
A.1. gram positive & negative bact.
A.2. Impacts of cell wall on IR
B. Capsule
C. Other structures2. Pathogenesis (mode of transmission, attachment,evasion/invasion, toxigenicity, hypersensitivity )
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The Procaryotic Cell Wall
rigid structure that lies
just outside the plasma
membrane
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Functions of cell wall
provides characteristic shape to cell
protects the cell from osmotic lysis
may also protect cell from toxic substances may also contribute to pathogenicity*
Cell wall components (& other products)
determine type of IR*
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Cell walls of bacteria
Bacteria are divided into two major groups
based on the response to Gram-stain
procedure.
gram-positive bacteria stain purple
gram-negative bacteria stain pink
This staining reaction due to cell wall
structure
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Figure 3.15
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Peptidoglycan Structure
important component of both gram-positive and gram-negative bacteria
polysaccharide formed from
peptidoglycan subunits two alternating sugars form backbone
N-acetylglucosamine
N-acetylmuramic acid
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some aminoacids are not
observed in
proteins
Prescott et al.
Figure 3.16
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Prescott et al.
Figure 3.18
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Precott et al.
Figure 3.19
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Gram-Positive Cell Walls
composed primarily ofpeptidoglycan
may also contain largeamounts ofteichoic
acids some gram-positive
bacteria have a layer ofproteins on surface ofpeptidoglycan
Prescott et al.
Figure 3.20
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Prescott et al
.Figure 3.22
teichoic acids
polymers of glycerol
or ribitol joined by
phosphate groups
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Prescott et al.
Fig. 3.21 of Gram positive cell wall
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Gram-Negative Cell Walls
consist of a thin layer of peptidoglycan
surrounded by an outer membrane
outer membrane composed of lipids,
lipoproteins, and lipopolysaccharide (LPS)
no teichoic acids
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Lipopolysaccharides (LPSs)
consist of three parts
lipid A
core polysaccharide O side chain (O antigen)
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Prescott et al.
Figure 3.25
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Prescott et al.
Fig. 3.23 of Gram Negative Cell Wall
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Importance of LPS (endotoxin)
protection from host defenses (O antigen)
contributes to negative charge on cell
surface (core polysaccharide)
helps stabilize outer membrane structure
(lipid A)
can act as a toxin which is called endotoxin(endotoxin = lipid A component of LPS)
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Figure 2-29
Note impact of LPS from
a local gram negativeinfection (left column )
Note impact of LPS b/c of
systemic gram negative
infection
endotoxicshock (right column )
Figure 8 5 (Old Book)
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Figure 8-5 (Old Book)
Brief Summary of Host-Parasite Interactions
when host is successful
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Figure 1.11
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