Life Science II

MOLECULAR PATHOLOGY & IMMUNOLOGY

MOLECULAR ONCOLOGY
Life Science II
MOLECULAR PATHOLOGY & IMMUNOLOGY
MOLECULAR ONCOLOGY
General
Aim of the lecture

In depth understanding of molecular based diseases

Focus on molecular oncology and immunology

Succesfull participation
Written exam of 90 minutes

Recommended literature
Janeway, Immunobiology
Molecular Biology: Bruce Alberts et al

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Content
PART I: Molecular Pathology PART II: Molecular Oncology

- General aspects - Cause of cancer

- Cell death - Frequent cancer
- Immunology - Molecular drugs fighting cancer
- Pathogen`s evasion
- Frequent diseases

Stefan Fischer Prof.Kappelmann-Fenzl

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Part I:
Molecular Pathology &
Immunology

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Pathology is….
…the study of the cause and effects of disease and injury

…using different kind of tools/knowledge (Histology, Anatomy, Chemical analysis,

Biochemistry, Molecular Biology and many others)

…one of the first life sciences

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 ◦ One root of Life sciences
◦ 1700 & 1550 BC: Egyptian papyrus showing ulcera, bone injuries,
parasite infection and others
◦ no systemic knowledge acquired

Short history of ◦ ~300 BC: Alexandrian Greeks

Pathology ◦ Hippocrates: humoural theory,

◦ Humoural theory: different liquids in the body are repsonsible
for different kind of disorders
Antiquity
◦ Black & yellow bile, phlegm, blood
◦ Lazy & fearful, bitter & daring, low spirited, freindly
Medieval
◦ Animal dissections, first human dissections
◦ Descirptions of inflammation, tumours, malaria, tuberculosis etc
◦ Knowledge inherited to Romans and arab / islamic physiciants
Enlightment
◦ 14th – 16th century: first scientific dissection of human bodies
◦ 17th century: microscopes invented
Modern medicine ◦ 1821-1902 Rudolf Virchow

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 ◦ One root of Life sciences
◦ 1700 & 1550 BC: Egyptian papyrus showing ulcera, bone injuries,
parasite infection and others
◦ no systemic knowledge acquired

Short history of ◦ ~300 BC: Alexandrian Greeks

Pathology ◦ Hippocrates: humoural theory,

◦ Humoural theory: different liquids in the body are repsonsible
for different kind of disorders
Antiquity
◦ Black & yellow bile, phlegm, blood
◦ Lazy & fearful, bitter & daring, low spirited, friendly
Medieval
◦ Animal dissections, first human dissections
◦ Descriptions of inflammation, tumours, malaria, tuberculosis etc
◦ Knowledge inherited to Romans and arab / islamic physiciants
Enlightment
◦ 14th – 16th century: first scientific dissection of human bodies
◦ 17th century: microscopes invented
Modern medicine ◦ 1821-1902 Rudolf Virchow

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 ◦ One root of Life sciences
◦ 1700 & 1550 BC: Egyptian papyrus showing ulcera, bone injuries,
parasite infection and others
◦ no systemic knowledge acquired

Short history of ◦ ~300 BC: Alexandrian Greeks

Pathology ◦ Hippocrates: humoural theory,

◦ Humoural theory: different liquids in the body are repsonsible
for different kind of disorders
Antiquity
◦ Black & yellow bile, phlegm, blood
◦ Lazy & fearful, bitter & daring, low spirited, freindly
Medieval
◦ Animal dissections, first human dissections
◦ Descirptions of inflammation, tumours, malaria, tuberculosis etc
◦ Knowledge inherited to Romans and arab / islamic physiciants
Enlightment
◦ 14th – 16th century: first scientific dissection of human bodies
◦ 17th century: microscopes invented
Modern medicine ◦ 1821-1902 Rudolf Virchow

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 ◦ 1821-1902 Rudolf Virchow
◦ „Omnis cellula e cellula“
◦ Founder of cellular Pathology
◦ – end of humoural theory

Short history of
Pathology ◦ End of 19th century-beginning of 20th:
Robert Koch: Germs as causal source for disease
Antiquity

Medieval

Enlightment

Modern medicine

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 Postulates by Robert Koch
Short history of 1. Sample from site of pathology are cultivated
Pathology 2.
3.
Colonies are characterised
Inoculation of animals
Antiquity 4. If animals are diseased a colony is isolated and
compared to the original colony

Medieval
- Sometimes culture were responsible for disease but
inoculated animals were not diseased
Enlightment
⇒ Species specificity

Modern medicine
- Sometimes no colony were growing but inoculated animals were diseased
⇒ Viridae / Virus

- Sometimes filtrated bacterial culture media were as well pathogenic

⇒ Bacterial toxins
Pathogenicity & Virulence
Both are synonyms for angloamericans

Pathogenicity (yes / no disease) Virulence = Poisonous (continuos degree of poisonous)

Virulence/pathogenetic factor = factor with poisonous/pathogenetic effect

Genetic islands of Virulence or pathogenesis

 ◦ 1821-1902 Rudolf Virchow
◦ „Omnis cellula e cellula“
◦ Founder of cellular Pathology
◦ – end of humoural theory

Short history of
Pathology ◦ End of 19th century-beginning of 20th:
Robert Koch: Germs as causal source for disease
Antiquity

Medieval

Knowledge / Understanding
Enlightment

Modern medicine

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Topics in Pathology
 Cause of disease (Germ, Mutation, etc)
 Mechanism of development: Pathogenesis
 Structural alterations of cell
 Consequences of changes: clinical manifestation

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 What is „ill“ and what is normal ?
The way from hypothesis to therapy:
1. Pre-analytic
2. Analytic
3. Postanalytic

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 What is „ill“ and what is normal ?
The way from hypothesis to therapy:
1. Pre-analytic - Medical history
2. Analytic - Physical examination
3. Postanalytic - By physiciant
=> Suspected diagnosis
- Decision about lab tests

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 What is „ill“ and what is normal ?
The way from hypothesis to therapy:
1. Pre-analytic - Taking samples
2. Analytic - Storage of sample
3. Postanalytic - Transport to lab
- diagnostic test
- Result analysis

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 What is „ill“ and what is normal ?
The way from hypothesis to therapy:
1. Pre-analytic - Result interpretation
2. Analytic - Reject or accept suspected diagnosis
3. Postanalytic - Choosing therapy

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Bioenergy Coupling of reactions

+∆G
-∆G
Bioenergy Coupling of reactions
Glucose

ATP

+∆G
-∆G

ADP + Pi
CO2
Diabetes mellitus

Heatlhy
- Constant blood sugar concentration in blood
- Leads to constant concentration gradient from
blood towards cytosol
- Leads to constant glucose flow into cell

- Glucose is for some tissue mandatory nutrient

Diseased: high blood sugar

Jakob Suckale, Michele Solimena,
https://upload.wikimedia.org/wikipedia/commons/4/4d/Suc
kale08_fig3_glucose_insulin_day.png
Diabetes mellitus
• Diabetes mellitus type I and type II

• Principal symptoms:
• high blood sugar (normal: 80-120 mg/dl = 4,5 – 6,7 mmol/l)
• Sugar in urine
• Patients can smell like aceton
 Diabetes mellitus
• Diabetes mellitus type I and type II

• Principal symptoms:
• high blood sugar (normal: 80-120 mg/dl = 4,5 – 6,7 mmol/l)
• Sugar in urine
• Patients can smell like aceton

• Type I:
• Juvenile onset (age 10-15)
• Multi-factor & -genetic disease (e.g.
chromosome 6/MHC alleles)
• Environmental conditions (virus infection, etc)
• Deletion of β-cells in pancreas => insulin
deficiency
 Diabetes mellitus
• Diabetes mellitus type I and type II

• Principal symptoms:
• high blood sugar (normal: 80-120 mg/dl = 4,5 – 6,7 mmol/l)
• Sugar in urine
• Patients can smell like aceton

• Type I: • Type II:

• Juvenile onset (age 10-15) • Late onset
• Multi-factor & -genetic disease (e.g. • Multi-factor & -genetic disease e.g. chromosome
chromosome 6/MHC alleles) 20/PTPN-1)
• Environmental conditions (virus infection, etc) • Environmental conditions (obesity, etc)
• Deletion of β-cells in pancreas => insulin • High insulin production but no effective signaling
deficiency => insulin resistance
 What is „ill“ and what is normal ?
Example: Blood sugar concentration
Mena value in human blood: 70-99 mg/dl Healthy population

Diseased population
frequency

95 %

97,5 %
„ill“ „ill“
„normal“
[Blood sugar]

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 What is „ill“ and what is normal ?
Example: Blood sugar concentration
Mena value in human blood: 70-99 mg/dl Healthy population

Diseased population
frequency

95 %

97,5 %
„ill“ „ill“
„normal“
[Blood sugar]
False negative results

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 What is „ill“ and what is normal ?
Example: Blood sugar concentration
Mena value in human blood: 70-99 mg/dl Healthy population

Diseased population
frequency

95 %

97,5 %
„ill“ „ill“
„normal“
[Blood sugar]
False negative results
False positive result
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 What is „ill“ and what is normal ?
Example: Blood sugar concentration
Mena value in human blood: 70-99 mg/dl Healthy population

Diseased population
frequency

Diagnostic test:
e.g. Specificity: 97% => 3 % are red area
95 % e.g. Sensitivity: 80% => 20 % are green area

97,5 %
„ill“ „ill“
„normal“
[Blood sugar]
False negative results
False positive result
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What kind of pathology can be
distinguished ?

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Disease
CLASSIFICATION, TERMS & DEFINITIONS

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How can diseases be classified
Disease = “not normal”, impaired body function

Classification by:
◦ Cause (e.g. genetic, metabolic, toxin-induced, viral infection, bacterial infection…)
◦ Pathogenesis (chronic autoimmune, cancer, demyelinating diseases,…)
◦ Symptoms (psychiatric, cerebral, musculoskeletal diseases)

In fact, no clear classification; i.e.:

- there are autoimmune disease with a genetic cause leading to impaired cerebral outcome…
- genetic disease leading to demyelination of nerve fibers affecting the muscles….
- viral infection which can induce a cancerous disease

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Inherited and genetic diseases/disorders
IMPORTANT: classification of diseases are different in every state!

In Germany, e.g. Cancer is a genetic disease which is of course not inherited (except of few
disorders, see below).
In U.S. genetic disease are all inherited diseases.

There is an international classification system which is adapted in each country:

ICD-11 by WHO

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