IMMUNOLOGY SUMMARY
INTRODUCTION DISEASES AND VACCINES
Specific germs can cause specific diseases, Robert Koch made a huge contribution to this understanding. He
did this by Koch’s postulate: the specific germ is found in diseases but not healthy organisms, and after
isolating this germ, it can cause disease when being transferred into a new animal. The germ can then be
isolated again (still commonly used)
- Polio: highly contagious virus, it paralysis and cause deformations in 1/200 patients
- Measles: highly contagious virus, with very severe complications and often resulting in death
- Diphtheria: bacterial infection, most common cause of paediatric death before a vaccine became
available. After diagnosis: 10% of patients with it will die and 50% die without treatment
➔ Mostly eradicated because of vaccinations
Infection and disease are not the same, COVID-19 is more common in elderly people and SARS is a common
side-effect, but the long-term symptoms (long COVID) is reported in all age groups. Elderly and people with a
high BMI are especially at risk due to that older people their immune system relays more on memory
responses and not on generating new immune responses
Meningococcal disease: found in immunosuppressed groups, such as students. It is caused by a bacteria that
can inhabit the mouth and throat. In rare occasions, the bacteria can enter the circulation leading to sepsis and
meningitis, with a death rate of around 10% and severe complications with the survivors including neurological
symptoms, deformations and amputations. This disease is nearly eradicated by a vaccine
MORE VACCINES ARE NEEDED
RSV: cause of common cold with yearly seasonal epidemics around the globe. In preterm infants, RSV can cause
severe complications. In susceptible children, also those carries to term, RSV infections in the first year
contribute to asthma inception. In non-western countries, RSV epidemics completely congest the healthcare
system. Most important cause of death in children
COVID-19: vaccine is mostly directed to the spike protein, the
protein that the virus uses to enter the cells in the nose or the
airway. Inactivated virions might be used as a vaccine. The
current vaccines seem effective in clinical studies
A successful SARS-CoV-2 vaccine triggers the innate immune
and adaptive immune system response → establishment of
memory B cells (antibody production) and memory T cells
(cell-mediated virus response). Clearly, a potent immune
response is of critical importance to combat infectious
disease
,SUMMARY OF THE TYPES OF IMMUNE CELLS
1. INNATE IMMUNE CELLS
Granulocytes (phagocytose):
1. Neutrophilic granulocytes: the most common leukocyte and are essential for the first response to
infection, they are short-lived and have high bactericidal activity. They are only found in the bloodstream
because of their toxic inside, only during infection they will migrate to the tissues
2. Eosinophilic granulocytes: are present in mucosa of the lung, the urogenital tract and the gastrointestinal
tract. Eosinophils can be recruited from the bloodstream during an inflammatory response, and contribute
to immunity against parasites
3. Basophilic granulocytes: are rare. In an inflammatory response, basophils can enter the inflamed tissue,
and through IgE bound on their cell surface contribute to immunity against parasites
Mast cells: tissue resident cells of barrier tissues such as the skin and the mucosa of the lung, urogenital and
gastrointestinal tract. Mast cells can also recognize parasites through IgE bound on their cell surface
Macrophages: can phagocytose microbes and dead cells. Monocytes can enter inflamed tissues from the
blood and differentiate to macrophages, to help clearance of an infection → long-lived an low bactericidal
activity. Two types: macrophages can be found in the blood and resident tissue macrophages (sentinels)
• (M1) Macrophages present antigens to T cells in the tissues, produce cytokines to induce
inflammation and chemokines to attract other cells and instruct adaptive immune responses
• (M2) Macrophages also have anti-inflammatory activities: tolerance of intestine bacteria, tissue
remodelling and wound repair, fibrosis
Innate lymphoid cells (ILCS): resemble T cells but do not have an antigen specific receptor. ILCs are activated
by cytokines and contribute to resistance to viruses and parasites
Subtype ILC1 → NK cells: type of innate lymphocytes that contribute to the killing of transformed or virus-
infected cells and produce IFN-gamma that stimulates macrophage activation. NK cells will only kill if
they don’t bind MHC-I (found
on all cells except red blood
cells) → So the inhibitory
receptors (MHC-I) block the NK
cell activation, activating
receptors (antibodies, viral
particles, MHC-I like proteins)
promote NK cell activation →
competition between the
activating and inhibitory
receptors
(monocytic) Dendritic cells: produce extracellular antigens though pinocytosis for presentation to T
cells in the lymph nodes, detect tissue damage and present pathogens such as viruses, bacteria or
fungi. Dendrites are the bridge between the innate and the adaptive immune response → move
from the tissue to the lymph nodes when macrophages stay in the tissues
,2. ADAPTIVE IMMUNE CELLS
B-lymphocytes: produce antibodies that can block infections and eliminate extracellular microbes.
Number of specificities of antigens on the B-cell surface is unlimited, but every lymphocyte is
monospecific
T-helper cells: active macrophages to kill phagocytosed microbes and can stimulate B-lymphocytes to
produce more antibodies, In the thymus there is negative selection (do they only recognize non-self)
and positive selection
Cytotoxic T-lymphocytes (CTL): kill infected cells and eliminate reservoirs of infection
(intracellular)
Regulatory T-lymphocytes: supress of the T cells (involved in allergies)
INNATE VERSUS ADAPTIVE IMMUNE SYSTEM
Innate immune response: nonspecific: targets different groups of micro-organisms. It gives a fast response
and is always active. It is encoded in the germline DNA and there is some memory response only by epigenetic
programming. Epithelia works as a barrier (tight junctions). There are aspects that help against infection:
- Mechanical → flow of movement of fluid such as tears and
mucus
- chemical → secretion of anti-microbial molecules
(enzymes, alfa-defensins)
- microbiological → normal microbiota
Our epidermis and our gut epithelium sheath a lot and this prevents
the annealing of microbes. In the gut, in addition, also produce
mucus. And the lungs they also produce mucus. If there is a breach
mostly neutrophilic granulocytes , macrophages and dendritic cells
attack the microbe
Adaptive immune response: is very specific to and is
induced by a single antigen. Can respond to a huge
number of antigens (diversity and universality by DNA
recombination). Its response is slow but powerful. It
requires DNA rearrangements. This immune response is
the source of specific of immunological memory and the
basis for vaccination.
Both immune systems collaborate with each other and
responding on NON-SELF
, THE IMMUNE SYSTEM
Humoral immune system: is mediated by antibodies produced by B lymphocytes and directed to extracellular
pathogens, such as the complement system, anti-microbial peptides and antibodies. Vaccines: can be
transferred directly by antibody transfer (passive immunization)
Cellular immune system: mediated by cells, such as phagocytes (granulocytes and macrophages), antigen
presentation (dendritic cells and macrophages, and cytotoxicity (lymphocytes). This is directed to intracellular
pathogens. Vaccines: requires active immunization (using dead or inactive microbes)
Immunisation: employs the cellular and/or humoral part of the adaptive immune system: active
immunisation induces memory, and passive immunisation only transfers antibodies (snake bite)
STEPS OF THE INNATE IMMUNE RESPONSE
RECOGNITION OF THE MICRO -ORGANISMS
Pattern recognition receptors (PRRs) on/in different immune cells and other type of cells and are present in
serum can recognize PAMPs and DAMPs:
- Pathogen-associated molecular patterns (PAMPs): molecular structures produced by groups/classes
of microbes (sugar residues, lipoproteins (LPS), nucleotides)
- Damage-associated molecular patterns (DAMPs): molecules secreted by damaged, dead cells (DNA,
RNA, chromatin, ATP, mitochondrial components) → normally not exposed to immune cells (sterile
inflammation)
- Types of membrane PRRs:
o Toll like receptors (TLRs): there are 10 different human TLRs and can distinguish between
self and non-self. Without these TLRs there is a weak immune responses and are used as
adjuvants for vaccines. TLRs recognize both PAMPs and DAMPs →all integral membrane
proteins, but their subset is kinda different, however similar structure
o C-type Lectin receptor: (CLR, e.g. mannose receptor and will bind to glycoproteins)
o Scavenger receptor: (e.g. CD36 and will bind to various DAMPs and PAMPs)
o N-formyl met-leu-phe receptors: (e.g. FPR, FPRL1 bind to peptides containing N-formyl
methionine that is found only in bacterial proteins)
- Types of cytosolic pattern recognition receptors:
o Present in the cytosol of phagocytes, epithelial cells and other cells
o NOD-like receptor: E.g. NOD1 and NOD2 that bind to bacterial and fungal cell wall
components
▪ Special example: inflammasome (NLRP = NOD-like receptor with pyrin domain) and
will bind to crystals, changes in cytosolic ATP and ion concentrations and lysosomal
damage
o Rig-like receptor and cytosolic DNA receptors (CDS): will bind to bacterial and viral DNA
▪ RIG-like receptors: activation of IRF3 and IRF7 and an anti-viral immune response
▪ Cytosolic DNA sensors: activate IRF3 or NF-kB. AIM2 can also activate the
inflammasome
- Extracellular Pattern recognition receptors in plasma (activation of complement system):
o Pentraxins: (e.g. CRP that bind to bacterial lipids)
o Collectins: (e.g. MBP that bind to microbial sugars)
o Ficolins: (e.g. N-acetylglucosamine binds to the wall gram-positive bacteria)
INTRODUCTION DISEASES AND VACCINES
Specific germs can cause specific diseases, Robert Koch made a huge contribution to this understanding. He
did this by Koch’s postulate: the specific germ is found in diseases but not healthy organisms, and after
isolating this germ, it can cause disease when being transferred into a new animal. The germ can then be
isolated again (still commonly used)
- Polio: highly contagious virus, it paralysis and cause deformations in 1/200 patients
- Measles: highly contagious virus, with very severe complications and often resulting in death
- Diphtheria: bacterial infection, most common cause of paediatric death before a vaccine became
available. After diagnosis: 10% of patients with it will die and 50% die without treatment
➔ Mostly eradicated because of vaccinations
Infection and disease are not the same, COVID-19 is more common in elderly people and SARS is a common
side-effect, but the long-term symptoms (long COVID) is reported in all age groups. Elderly and people with a
high BMI are especially at risk due to that older people their immune system relays more on memory
responses and not on generating new immune responses
Meningococcal disease: found in immunosuppressed groups, such as students. It is caused by a bacteria that
can inhabit the mouth and throat. In rare occasions, the bacteria can enter the circulation leading to sepsis and
meningitis, with a death rate of around 10% and severe complications with the survivors including neurological
symptoms, deformations and amputations. This disease is nearly eradicated by a vaccine
MORE VACCINES ARE NEEDED
RSV: cause of common cold with yearly seasonal epidemics around the globe. In preterm infants, RSV can cause
severe complications. In susceptible children, also those carries to term, RSV infections in the first year
contribute to asthma inception. In non-western countries, RSV epidemics completely congest the healthcare
system. Most important cause of death in children
COVID-19: vaccine is mostly directed to the spike protein, the
protein that the virus uses to enter the cells in the nose or the
airway. Inactivated virions might be used as a vaccine. The
current vaccines seem effective in clinical studies
A successful SARS-CoV-2 vaccine triggers the innate immune
and adaptive immune system response → establishment of
memory B cells (antibody production) and memory T cells
(cell-mediated virus response). Clearly, a potent immune
response is of critical importance to combat infectious
disease
,SUMMARY OF THE TYPES OF IMMUNE CELLS
1. INNATE IMMUNE CELLS
Granulocytes (phagocytose):
1. Neutrophilic granulocytes: the most common leukocyte and are essential for the first response to
infection, they are short-lived and have high bactericidal activity. They are only found in the bloodstream
because of their toxic inside, only during infection they will migrate to the tissues
2. Eosinophilic granulocytes: are present in mucosa of the lung, the urogenital tract and the gastrointestinal
tract. Eosinophils can be recruited from the bloodstream during an inflammatory response, and contribute
to immunity against parasites
3. Basophilic granulocytes: are rare. In an inflammatory response, basophils can enter the inflamed tissue,
and through IgE bound on their cell surface contribute to immunity against parasites
Mast cells: tissue resident cells of barrier tissues such as the skin and the mucosa of the lung, urogenital and
gastrointestinal tract. Mast cells can also recognize parasites through IgE bound on their cell surface
Macrophages: can phagocytose microbes and dead cells. Monocytes can enter inflamed tissues from the
blood and differentiate to macrophages, to help clearance of an infection → long-lived an low bactericidal
activity. Two types: macrophages can be found in the blood and resident tissue macrophages (sentinels)
• (M1) Macrophages present antigens to T cells in the tissues, produce cytokines to induce
inflammation and chemokines to attract other cells and instruct adaptive immune responses
• (M2) Macrophages also have anti-inflammatory activities: tolerance of intestine bacteria, tissue
remodelling and wound repair, fibrosis
Innate lymphoid cells (ILCS): resemble T cells but do not have an antigen specific receptor. ILCs are activated
by cytokines and contribute to resistance to viruses and parasites
Subtype ILC1 → NK cells: type of innate lymphocytes that contribute to the killing of transformed or virus-
infected cells and produce IFN-gamma that stimulates macrophage activation. NK cells will only kill if
they don’t bind MHC-I (found
on all cells except red blood
cells) → So the inhibitory
receptors (MHC-I) block the NK
cell activation, activating
receptors (antibodies, viral
particles, MHC-I like proteins)
promote NK cell activation →
competition between the
activating and inhibitory
receptors
(monocytic) Dendritic cells: produce extracellular antigens though pinocytosis for presentation to T
cells in the lymph nodes, detect tissue damage and present pathogens such as viruses, bacteria or
fungi. Dendrites are the bridge between the innate and the adaptive immune response → move
from the tissue to the lymph nodes when macrophages stay in the tissues
,2. ADAPTIVE IMMUNE CELLS
B-lymphocytes: produce antibodies that can block infections and eliminate extracellular microbes.
Number of specificities of antigens on the B-cell surface is unlimited, but every lymphocyte is
monospecific
T-helper cells: active macrophages to kill phagocytosed microbes and can stimulate B-lymphocytes to
produce more antibodies, In the thymus there is negative selection (do they only recognize non-self)
and positive selection
Cytotoxic T-lymphocytes (CTL): kill infected cells and eliminate reservoirs of infection
(intracellular)
Regulatory T-lymphocytes: supress of the T cells (involved in allergies)
INNATE VERSUS ADAPTIVE IMMUNE SYSTEM
Innate immune response: nonspecific: targets different groups of micro-organisms. It gives a fast response
and is always active. It is encoded in the germline DNA and there is some memory response only by epigenetic
programming. Epithelia works as a barrier (tight junctions). There are aspects that help against infection:
- Mechanical → flow of movement of fluid such as tears and
mucus
- chemical → secretion of anti-microbial molecules
(enzymes, alfa-defensins)
- microbiological → normal microbiota
Our epidermis and our gut epithelium sheath a lot and this prevents
the annealing of microbes. In the gut, in addition, also produce
mucus. And the lungs they also produce mucus. If there is a breach
mostly neutrophilic granulocytes , macrophages and dendritic cells
attack the microbe
Adaptive immune response: is very specific to and is
induced by a single antigen. Can respond to a huge
number of antigens (diversity and universality by DNA
recombination). Its response is slow but powerful. It
requires DNA rearrangements. This immune response is
the source of specific of immunological memory and the
basis for vaccination.
Both immune systems collaborate with each other and
responding on NON-SELF
, THE IMMUNE SYSTEM
Humoral immune system: is mediated by antibodies produced by B lymphocytes and directed to extracellular
pathogens, such as the complement system, anti-microbial peptides and antibodies. Vaccines: can be
transferred directly by antibody transfer (passive immunization)
Cellular immune system: mediated by cells, such as phagocytes (granulocytes and macrophages), antigen
presentation (dendritic cells and macrophages, and cytotoxicity (lymphocytes). This is directed to intracellular
pathogens. Vaccines: requires active immunization (using dead or inactive microbes)
Immunisation: employs the cellular and/or humoral part of the adaptive immune system: active
immunisation induces memory, and passive immunisation only transfers antibodies (snake bite)
STEPS OF THE INNATE IMMUNE RESPONSE
RECOGNITION OF THE MICRO -ORGANISMS
Pattern recognition receptors (PRRs) on/in different immune cells and other type of cells and are present in
serum can recognize PAMPs and DAMPs:
- Pathogen-associated molecular patterns (PAMPs): molecular structures produced by groups/classes
of microbes (sugar residues, lipoproteins (LPS), nucleotides)
- Damage-associated molecular patterns (DAMPs): molecules secreted by damaged, dead cells (DNA,
RNA, chromatin, ATP, mitochondrial components) → normally not exposed to immune cells (sterile
inflammation)
- Types of membrane PRRs:
o Toll like receptors (TLRs): there are 10 different human TLRs and can distinguish between
self and non-self. Without these TLRs there is a weak immune responses and are used as
adjuvants for vaccines. TLRs recognize both PAMPs and DAMPs →all integral membrane
proteins, but their subset is kinda different, however similar structure
o C-type Lectin receptor: (CLR, e.g. mannose receptor and will bind to glycoproteins)
o Scavenger receptor: (e.g. CD36 and will bind to various DAMPs and PAMPs)
o N-formyl met-leu-phe receptors: (e.g. FPR, FPRL1 bind to peptides containing N-formyl
methionine that is found only in bacterial proteins)
- Types of cytosolic pattern recognition receptors:
o Present in the cytosol of phagocytes, epithelial cells and other cells
o NOD-like receptor: E.g. NOD1 and NOD2 that bind to bacterial and fungal cell wall
components
▪ Special example: inflammasome (NLRP = NOD-like receptor with pyrin domain) and
will bind to crystals, changes in cytosolic ATP and ion concentrations and lysosomal
damage
o Rig-like receptor and cytosolic DNA receptors (CDS): will bind to bacterial and viral DNA
▪ RIG-like receptors: activation of IRF3 and IRF7 and an anti-viral immune response
▪ Cytosolic DNA sensors: activate IRF3 or NF-kB. AIM2 can also activate the
inflammasome
- Extracellular Pattern recognition receptors in plasma (activation of complement system):
o Pentraxins: (e.g. CRP that bind to bacterial lipids)
o Collectins: (e.g. MBP that bind to microbial sugars)
o Ficolins: (e.g. N-acetylglucosamine binds to the wall gram-positive bacteria)
