parham intro and pathogenesis ch1

7/30/2019 Parham Intro and Pathogenesis Ch1

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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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