Integrated Biomedical Sciences – Lectures
Lecture 1: introduc7on to the course & history of biomedical sciences
Biomedicine: a branch of medical science that applies biological and physiological principles
to prac6ce à health and sickness are separated
17th century scien6fic revolu6on – body is a machine
- Boerhave: the body is a machine, the pa6ents is central, cu@ng pa6ents to see what
is in the body
- Harvey: the heart works like a pump
Early 19th century
- Percussion (technique of medical examina6on
- The laboratory gets prominence
o Cellular pathology (Virchow)
o The microscope improves (Ernst Abbe)
- Laboratory revolu6on
o Pasteur: discovered that microorganisms cause fermenta6on and disease
o Koch: Discovered tuberculosis bacteria
o Flemming: Discovered penicillin
Biomedicaliza6on
- Biomedicine is dominant in the system and signify ‘modern’ medicine
- Diagnosis is more focused on metrics rather than symptoms
- The development of the randomized clinical trial (RCT)
Reduc6onism
- Ontological claim that the whole organism is nothing more the sum of its parts
- Methodological claim that an organism is best inves6gated by its parts
- Evidence based medicine
Crisis in evidence based medicine?
- The volume of evidence has become unmanageable
- Sta6s6cally significant benefit may be marginal in clinical prac6ce à because every
treated individual is different
- Inflexible rules and technology driven prompts may produce care that is management
driven rather than pa6ent centred à money based
- Evidence based guidelines o]en map poorly to individuals, and complex
mul6morbidity
Interdisciplinarity
- Biomedical sciences aims to improve quality of life through medical innova6on
à this requires collabora6on
- Needed to prevent analy6cal and fragmented thinking
Scien6fic discipline has
- Ontology: the art of being
- Epistemology: the art of knowing (methodology)
- Conceptology: the art of understanding
What Is interdisciplinarity
, - Source of inspira6on à new combina6ons lead to innova6on
- Improve research quality
- Address interes6ng complex scien6fic ques6on or
topics you cannot answer from a monodisciplinary
Complex adap6ve system
- Biological process are complicated systems and more
factors influence the outcome, so interdisciplinarity is
necessary
Epidemiological triangle
- Host (suscep6bility), environment, agent (cause of
the disease)
Two ways of looking at knowledge
- Objec6vism (beta)
o presen6ng facts as the truth
o The reality is observed
o Knowledge van be formulated into laws
- Social construc6vism - interpre6vism (alfa, gamma)
o Truth and meaning are constructed by the person/researcher
o Interpreta6ons of the world
o Reality is experienced, so there are more reali6es, meaning is not stable
Meaning of interdisciplinarity
- Integra6on of discipline, more disciplinary perspec6ves by working on the same topic
- Different dimensions of different aspects
- How to work: get to know various interdisciplinary, working with others
- Challenges: 6me, effort and money; worlds are apart
- Integra6on of disciplines: working on the same complex problem/topics
,Lecture 2: Core concepts and processes in immunology
The immune system
- Response against the infec6ous pathogens
- Disturbed immunity: allergy, autoimmunity
- Ar6ficially induced immune responses à Vaccina6on
Different pathogens require different mechanism withing the immune system
Innate immune system:
Three pathways of complement ac6va6on
1. Alterna6ve route
- Spontaneous ac6va6on;
- Suppressed by ‘self’ proteins of the cell
2. Lec6n route
- Mannose binding lec6n (MBL) binds to carbohydrate on pathogen
3. Classical route
- ac6vates the complement system via IgM an6bodies, CRP via C1q
All complement ac6va6on routes converge on C3 ac6va6on
Complement ac6va6on results in death of the pathogen by:
- recruitment of inflammatory cells
- opsoniza6on of pathogens à killing by phagocytosis
- perfora6on of pathogen cell membranes
Pafern recogni6on receptors (PRRs)
- mediates the innate immune system
- Recognize PAMPs which are components of invading pathogens à DNA/RNA, cell
wall components such as lipids
- Contain extracellular and intracellular receptors
- Results in ac6va6on of cells and the produc6on of cytokines and induc6on of
pathogens
- Expressed by immune cells including macrophages, monocytes, granulocytes
Different types of PRRS
- Toll-like receptor
o Membrane bound receptors
, o TLR signaling results in pro-inflammatory cytokines and type 1 IFN
o Two types: cell surface TLRs and intracellular TLRs à bound to the membrane
of endosome
- NOD-like receptor
o Cytosolic recogni6on of various ligand
o Result in inflammatory cytokines and IL-1
- C-type lec6n receptor
o Ca2+ dependent recogni6on of carbohydrates
o Signaling
o An6gen uptake/phagocytosis
- Re6noic acid-inducible Macgene (RIG)-I-like receptors
o Cytosolic recogni6on of DNA and RNA
o Results in type 1 IFN
IFN-1: cytokines that play an important role in inflamma6on, T cell responses
Inflamma6on is caused by the recogni6on of innate immune system
Macrophages
- Express a lot of PRRs à recognizes various pathogens
- Alarm the immune system upon 6ssue damage and infec6on: cytokine produc6on
Neutrophils
- Important for bacterial and fungal infec6ons
- Efficient killer with a short-life span
- Expression of mul6ple receptors for pathogen recogni6on
- Expression of toxic granules for killing
- Innate soldiers: Reserves of neutrophils are stored in the bone
marrow and are released when needed to fight an infec6ons
à engulf and kill bacteria à degraded by macrophages à
‘one life’
Dendri6c cells (DCs)
- Present in all 6ssues
- Express PRRS and become ac6vated when s6mulated à
migrate to the lymphoid organs à ac6vated the adap6ve
immune system by an6gen presen6ng to T cells
Lecture 1: introduc7on to the course & history of biomedical sciences
Biomedicine: a branch of medical science that applies biological and physiological principles
to prac6ce à health and sickness are separated
17th century scien6fic revolu6on – body is a machine
- Boerhave: the body is a machine, the pa6ents is central, cu@ng pa6ents to see what
is in the body
- Harvey: the heart works like a pump
Early 19th century
- Percussion (technique of medical examina6on
- The laboratory gets prominence
o Cellular pathology (Virchow)
o The microscope improves (Ernst Abbe)
- Laboratory revolu6on
o Pasteur: discovered that microorganisms cause fermenta6on and disease
o Koch: Discovered tuberculosis bacteria
o Flemming: Discovered penicillin
Biomedicaliza6on
- Biomedicine is dominant in the system and signify ‘modern’ medicine
- Diagnosis is more focused on metrics rather than symptoms
- The development of the randomized clinical trial (RCT)
Reduc6onism
- Ontological claim that the whole organism is nothing more the sum of its parts
- Methodological claim that an organism is best inves6gated by its parts
- Evidence based medicine
Crisis in evidence based medicine?
- The volume of evidence has become unmanageable
- Sta6s6cally significant benefit may be marginal in clinical prac6ce à because every
treated individual is different
- Inflexible rules and technology driven prompts may produce care that is management
driven rather than pa6ent centred à money based
- Evidence based guidelines o]en map poorly to individuals, and complex
mul6morbidity
Interdisciplinarity
- Biomedical sciences aims to improve quality of life through medical innova6on
à this requires collabora6on
- Needed to prevent analy6cal and fragmented thinking
Scien6fic discipline has
- Ontology: the art of being
- Epistemology: the art of knowing (methodology)
- Conceptology: the art of understanding
What Is interdisciplinarity
, - Source of inspira6on à new combina6ons lead to innova6on
- Improve research quality
- Address interes6ng complex scien6fic ques6on or
topics you cannot answer from a monodisciplinary
Complex adap6ve system
- Biological process are complicated systems and more
factors influence the outcome, so interdisciplinarity is
necessary
Epidemiological triangle
- Host (suscep6bility), environment, agent (cause of
the disease)
Two ways of looking at knowledge
- Objec6vism (beta)
o presen6ng facts as the truth
o The reality is observed
o Knowledge van be formulated into laws
- Social construc6vism - interpre6vism (alfa, gamma)
o Truth and meaning are constructed by the person/researcher
o Interpreta6ons of the world
o Reality is experienced, so there are more reali6es, meaning is not stable
Meaning of interdisciplinarity
- Integra6on of discipline, more disciplinary perspec6ves by working on the same topic
- Different dimensions of different aspects
- How to work: get to know various interdisciplinary, working with others
- Challenges: 6me, effort and money; worlds are apart
- Integra6on of disciplines: working on the same complex problem/topics
,Lecture 2: Core concepts and processes in immunology
The immune system
- Response against the infec6ous pathogens
- Disturbed immunity: allergy, autoimmunity
- Ar6ficially induced immune responses à Vaccina6on
Different pathogens require different mechanism withing the immune system
Innate immune system:
Three pathways of complement ac6va6on
1. Alterna6ve route
- Spontaneous ac6va6on;
- Suppressed by ‘self’ proteins of the cell
2. Lec6n route
- Mannose binding lec6n (MBL) binds to carbohydrate on pathogen
3. Classical route
- ac6vates the complement system via IgM an6bodies, CRP via C1q
All complement ac6va6on routes converge on C3 ac6va6on
Complement ac6va6on results in death of the pathogen by:
- recruitment of inflammatory cells
- opsoniza6on of pathogens à killing by phagocytosis
- perfora6on of pathogen cell membranes
Pafern recogni6on receptors (PRRs)
- mediates the innate immune system
- Recognize PAMPs which are components of invading pathogens à DNA/RNA, cell
wall components such as lipids
- Contain extracellular and intracellular receptors
- Results in ac6va6on of cells and the produc6on of cytokines and induc6on of
pathogens
- Expressed by immune cells including macrophages, monocytes, granulocytes
Different types of PRRS
- Toll-like receptor
o Membrane bound receptors
, o TLR signaling results in pro-inflammatory cytokines and type 1 IFN
o Two types: cell surface TLRs and intracellular TLRs à bound to the membrane
of endosome
- NOD-like receptor
o Cytosolic recogni6on of various ligand
o Result in inflammatory cytokines and IL-1
- C-type lec6n receptor
o Ca2+ dependent recogni6on of carbohydrates
o Signaling
o An6gen uptake/phagocytosis
- Re6noic acid-inducible Macgene (RIG)-I-like receptors
o Cytosolic recogni6on of DNA and RNA
o Results in type 1 IFN
IFN-1: cytokines that play an important role in inflamma6on, T cell responses
Inflamma6on is caused by the recogni6on of innate immune system
Macrophages
- Express a lot of PRRs à recognizes various pathogens
- Alarm the immune system upon 6ssue damage and infec6on: cytokine produc6on
Neutrophils
- Important for bacterial and fungal infec6ons
- Efficient killer with a short-life span
- Expression of mul6ple receptors for pathogen recogni6on
- Expression of toxic granules for killing
- Innate soldiers: Reserves of neutrophils are stored in the bone
marrow and are released when needed to fight an infec6ons
à engulf and kill bacteria à degraded by macrophages à
‘one life’
Dendri6c cells (DCs)
- Present in all 6ssues
- Express PRRS and become ac6vated when s6mulated à
migrate to the lymphoid organs à ac6vated the adap6ve
immune system by an6gen presen6ng to T cells
