MBS1201
Pathophysiology of disease
, Week 1; Overview of the immune system
History of immunity
Hippocrates was the first to believe that disease was not caused by supernatural forces or the
punishment of Gods. He believed diseases are caused by imbalance of bodily fluids of ‘’humores’’
which relates to humoral immunity. There should be focused on hygiene, diet and fresh air. He is the
father of the modern medicine.
Variola virus
- Causes smallpox
- Infection via lungs, spreads via the blood to organs and skin → Multiplication
- The earliest known case was around 3000 BC
- 10-30% of the global population died
- Most feared disease in human history
Variolation = Intentionally inducing a mild form of infection to induce immunity.
- Exposing healthy people to smallpox (variola virus) to develop a mild form. First performed in
China in 10th century.
- It has occasionally led to death or disfigurement
- Had limited acceptance back then
- Edward Jenner (1749-1823) observed that milkmaids did not get smallpox and he believed
they were infected with the cow pox before and therefore could not get the human variant.
- Vaccine and vaccination are derived from Variolae vaccinae (smallpox of the cow).
Germ theory of disease
- Disease is caused by micro-organisms
- Not spontaneous generation
- Girolamo fracastoro; ‘’diseases are caused by transferable seed-like entities that transmit
infection by direct and indirect contacts or even without contact over long distances’’.
- Louis Pasteur;
o Disproval of spontaneous generation hypothesis: without contamination, microbes
could not develop
o Pasteurization
o Vaccination
o Broth is boiled and if the lid was on it, it remained micro-organism free and when the
lid was opened micro-organisms were obtained by giving chickens this broth. Chicken
also received death microbes and it was found that attenuated chicken cholera does
not induce disease but renders animals immune. This was an important step for
vaccinations.
The immune system has cellular immunity
Elie Metchnikoff discovered Phagocytes and phagocytosis with an experiment of a splinter applied in
a transparent larva. It was hypothesized this was process by which bacteria were attacked and killed
by the white blood cells. This means the immune system is cellular
1
,But also, a humoral immunity
Von behring & Kitasto in 1890 did a transfer of immunity against Diphteria by a soluble anti-toxin in
the blood using serum a contaminated animal to a health animal. This means there must be
something in the serum (antibodies) and that immunity was specific for diphtheria. This means the
defense is humoral, so in the body fluids. Later on, it was discovered that antibodies were produced
by plasma cells, lymphocytes can be long-lived and move from blood to lymph and back. They are
also responsible for transplant rejections. It was found that the thymus is involved in cellular
immunity and that there is collaboration between t and B cells. Since 2000, there has been a revival
of research of non-specific immune system, mainly macrophages and neutrophils.
2
, The immune system
White blood cells
Leukocytes or white blood cells (WBCs), are the only formed elements that are complete cells, with
nuclei and the usual organelles. Accounting for less than 1% of total blood volume, leukocytes are far
less numerous than red blood cells. On average, there are 4800-10,800 WBCs/pl of blood. Leukocytes
are crucial to our defense against disease. They form a mobile army that helps protect the body from
damage by bacteria, viruses, parasites, toxins, and tumor cells. As such, they have special functional
characteristics. Red blood cells are confined to the bloodstream, and they carry out their functions in
the blood. But white blood cells are able to slip out of the capillary blood vessels—a process called
diapedesis. The circulatory system is simply their means of transport to areas of the body (mostly
loose connective tissues or lymphoid tissues) where they mount inflammatory or immune responses.
Leukocytes are grouped into two major categories on the basis of structural and chemical
characteristics:
Granulocytes
- Contain obvious membrane-bound cytoplasmic granules.
- Granulocytes are all roughly spherical in shape. They are larger and much shorter lived than
erythrocytes.
- Lobed nuclei (rounded nuclear masses connected by thinner strands of nuclear material),
and their membrane-bound cytoplasmic granules stain quite specifically with Wright’s stain.
- Functionally, all granulocytes are phagocytes to some degree.
Neutrophils
- Neutrophils, the most numerous white blood cells, account for 50- 70% of the WBC
population.
- Neutrophils are about twice as large as erythrocytes.
- The neutrophil cytoplasm contains very fine granules (of two varieties) that are difficult to
see.
- Neutrophils get their name (literally, “neutral-loving”) because their granules take up both
basic (blue) and acidic (red) dyes.
- Together, the two types of granules give the cytoplasm a lilac color.
- Some of these granules contain hydrolytic enzymes and are regarded as lysosomes.
- Others, especially the smaller granules, contain a potent “brew” of antimicrobial proteins,
called defensins. Neutrophil nuclei consist of three to six lobes. Because of this nuclear
variability, they are often called polymorphonuclear leukocytes (PMNs) or simply polys
(polymorphonuclear = many shapes of the nucleus).
- Neutrophils are our body’s bacteria slayers, and their numbers increase explosively during
acute bacterial infections such as meningitis and appendicitis. Neutrophils are the first to
arrive and secrete factors that kill and degrade pathogens.
- Neutrophils are chemically attracted to sites of inflammation and are active phagocytes.
- They are especially partial to bacteria and some fungi, and bacterial killing is promoted by a
process called a respiratory burst.
- In the respiratory burst, the cells metabolize oxygen to produce potent germ-killer oxidizing
substances such as bleach and hydrogen peroxide. In addition, defensin-mediated lysis
occurs when the granules containing defensins merge with a microbe containing phagosome.
- The defensins form peptide “spears” that pierce holes in the membrane of the ingested
“foe.”
- Light grey to pink cytoplasm.
3
Pathophysiology of disease
, Week 1; Overview of the immune system
History of immunity
Hippocrates was the first to believe that disease was not caused by supernatural forces or the
punishment of Gods. He believed diseases are caused by imbalance of bodily fluids of ‘’humores’’
which relates to humoral immunity. There should be focused on hygiene, diet and fresh air. He is the
father of the modern medicine.
Variola virus
- Causes smallpox
- Infection via lungs, spreads via the blood to organs and skin → Multiplication
- The earliest known case was around 3000 BC
- 10-30% of the global population died
- Most feared disease in human history
Variolation = Intentionally inducing a mild form of infection to induce immunity.
- Exposing healthy people to smallpox (variola virus) to develop a mild form. First performed in
China in 10th century.
- It has occasionally led to death or disfigurement
- Had limited acceptance back then
- Edward Jenner (1749-1823) observed that milkmaids did not get smallpox and he believed
they were infected with the cow pox before and therefore could not get the human variant.
- Vaccine and vaccination are derived from Variolae vaccinae (smallpox of the cow).
Germ theory of disease
- Disease is caused by micro-organisms
- Not spontaneous generation
- Girolamo fracastoro; ‘’diseases are caused by transferable seed-like entities that transmit
infection by direct and indirect contacts or even without contact over long distances’’.
- Louis Pasteur;
o Disproval of spontaneous generation hypothesis: without contamination, microbes
could not develop
o Pasteurization
o Vaccination
o Broth is boiled and if the lid was on it, it remained micro-organism free and when the
lid was opened micro-organisms were obtained by giving chickens this broth. Chicken
also received death microbes and it was found that attenuated chicken cholera does
not induce disease but renders animals immune. This was an important step for
vaccinations.
The immune system has cellular immunity
Elie Metchnikoff discovered Phagocytes and phagocytosis with an experiment of a splinter applied in
a transparent larva. It was hypothesized this was process by which bacteria were attacked and killed
by the white blood cells. This means the immune system is cellular
1
,But also, a humoral immunity
Von behring & Kitasto in 1890 did a transfer of immunity against Diphteria by a soluble anti-toxin in
the blood using serum a contaminated animal to a health animal. This means there must be
something in the serum (antibodies) and that immunity was specific for diphtheria. This means the
defense is humoral, so in the body fluids. Later on, it was discovered that antibodies were produced
by plasma cells, lymphocytes can be long-lived and move from blood to lymph and back. They are
also responsible for transplant rejections. It was found that the thymus is involved in cellular
immunity and that there is collaboration between t and B cells. Since 2000, there has been a revival
of research of non-specific immune system, mainly macrophages and neutrophils.
2
, The immune system
White blood cells
Leukocytes or white blood cells (WBCs), are the only formed elements that are complete cells, with
nuclei and the usual organelles. Accounting for less than 1% of total blood volume, leukocytes are far
less numerous than red blood cells. On average, there are 4800-10,800 WBCs/pl of blood. Leukocytes
are crucial to our defense against disease. They form a mobile army that helps protect the body from
damage by bacteria, viruses, parasites, toxins, and tumor cells. As such, they have special functional
characteristics. Red blood cells are confined to the bloodstream, and they carry out their functions in
the blood. But white blood cells are able to slip out of the capillary blood vessels—a process called
diapedesis. The circulatory system is simply their means of transport to areas of the body (mostly
loose connective tissues or lymphoid tissues) where they mount inflammatory or immune responses.
Leukocytes are grouped into two major categories on the basis of structural and chemical
characteristics:
Granulocytes
- Contain obvious membrane-bound cytoplasmic granules.
- Granulocytes are all roughly spherical in shape. They are larger and much shorter lived than
erythrocytes.
- Lobed nuclei (rounded nuclear masses connected by thinner strands of nuclear material),
and their membrane-bound cytoplasmic granules stain quite specifically with Wright’s stain.
- Functionally, all granulocytes are phagocytes to some degree.
Neutrophils
- Neutrophils, the most numerous white blood cells, account for 50- 70% of the WBC
population.
- Neutrophils are about twice as large as erythrocytes.
- The neutrophil cytoplasm contains very fine granules (of two varieties) that are difficult to
see.
- Neutrophils get their name (literally, “neutral-loving”) because their granules take up both
basic (blue) and acidic (red) dyes.
- Together, the two types of granules give the cytoplasm a lilac color.
- Some of these granules contain hydrolytic enzymes and are regarded as lysosomes.
- Others, especially the smaller granules, contain a potent “brew” of antimicrobial proteins,
called defensins. Neutrophil nuclei consist of three to six lobes. Because of this nuclear
variability, they are often called polymorphonuclear leukocytes (PMNs) or simply polys
(polymorphonuclear = many shapes of the nucleus).
- Neutrophils are our body’s bacteria slayers, and their numbers increase explosively during
acute bacterial infections such as meningitis and appendicitis. Neutrophils are the first to
arrive and secrete factors that kill and degrade pathogens.
- Neutrophils are chemically attracted to sites of inflammation and are active phagocytes.
- They are especially partial to bacteria and some fungi, and bacterial killing is promoted by a
process called a respiratory burst.
- In the respiratory burst, the cells metabolize oxygen to produce potent germ-killer oxidizing
substances such as bleach and hydrogen peroxide. In addition, defensin-mediated lysis
occurs when the granules containing defensins merge with a microbe containing phagosome.
- The defensins form peptide “spears” that pierce holes in the membrane of the ingested
“foe.”
- Light grey to pink cytoplasm.
3
