Immunology
Index:
Vaccines ———————————————————————————— page 2
Cell signaling —————————————————————————— page 3
Cell of the immune system ———————————————————— page 4
Cytokines ———————————————————————————— page 5
Cytokine signaling ———————————————————————— page 6
Differences ——————————————————————————— page 7
Innate immune system —————————————————————— page 8
Complement system ——————————————————————— page 9
Recognizing antigens —————————————————————— page 10
Lymphoid tissues ———————————————————————— page 12
Major histocompatibility complex (MHC) —————————————— page 14
Generation of B-cells ——————————————————————— page 16
Generation of T-cells ——————————————————————— page 18
Antibodies ——————————————————————————— page 19
T-cell activation ————————————————————————— page 21
B-cell activation ————————————————————————— page 23
T-cell differentiation ——————————————————————— page 25
Inhibitory signaling ——————————————————————— page 27
Removal of pathogens —————————————————————— page 28
Tolerance ————————————————————————————page 30
Organ rejection ————————————————————————— page 31
Page 1
,Immunology is the scientific disciple that studies the immune system, which serves to project the
body from infectious agents and cancer.
Infectious diseases can come from extracellular bacteria, intercellular bacteria, fungi, viruses and
parasites. Parasites are especially dangerous as they are multicellular and thus too big for
phagocytes to consume them, as is possible with unicellular bacteria.
Robert Koch was the first guy to understand that specific diseases are coupled to specific germs.
From this, he created the Koch postulate;
1. The microorganism must be founding abundance in a diseased organism, and not in a healthy
organism.
2. The microorganism must be isolated from the diseased organism and grown in a pure culture.
3. The cultured microorganism must cause disease when introduced into a healthy organism.
4. The microorganism must be re-isolated from the inoculated, diseased host and identified as
being identical to the original causative agent.
When all this is true, one can conclude that this specific microbe causes this specific
disease.
Vaccination:
They work. For most diseases, they reduce the number of cases by 99.99%. But
some people are stupid (most people are stupid from my experience) and don’t
believe in them, so infectious diseases are resurfacing.
Fun fact: vaccine comes from the latin word vaccinus, which means ‘from cows’. This
is because the first aver vaccine was derived from cow pox, after it was noticed that
the milkmaids who were exposed to cowpox, didn’t contract the more dangerous
smallpox.
Vaccines are effective. Look at the example of meningococcal disease. The number
of cases is shown in the figure on the left. When the vaccine was put on the market,
number of cases dropped. This vaccine concluded types; A, C, E, B, Y but not W.
And the graph also shows that type W increases around 2016, showing that when
limiting the other types, type W is able to outgrow them.
There is a difference between passive and active immunization. Passive immunization (serum
therapy), one is given antibodies to help fight a disease, though this does not give any memory.
Active immunization (regular vaccinations) uses dead or inactivated pathogens, this does give
memory.
Immune response:
1. Anatomic barriers, like; skin, mucosa, epithelium and intestine.
2. Complement/ antimicrobial proteins, like; defensins and C3.
3. Innate immunity, consists of macrophages, granulocytes and natural killer cells.
4. Adaptive immunity, consists of B- and T-cells.
Page 2
,Cell signaling:
Ofcourse, there are multiple types, of which I am sure you know most of them. So I will keep it
short.
Ligand binding:
Upon binding of a ligand to its receptor, protein-protein interactions in the cytosol often induce
activation of transcription factor that shuttles to the nucleus and induce gene transcription.
Examples:
The receptor can be membrane-bound or cytoplasmic.
It can harbor tyrosine kinase activity or activate this in a separate protein.
It might activate second messengers or be processed to release
an intracellular domain that mediates gene transcription itself.
In immune cells:
Signal transduction in immune cells is done by non-receptor
tyrosine kinases, like; Src family kinase, Syk family kinase and
Tec family kinase.
Immune cells also make use of scaffolding proteins. Scaffolding
proteins are large proteins that help bring multiple signaling
molecules together into a complex. They don’t perform the
signaling themselves but facilitate the process by holding the components in the right place.
An example of a scaffolding protein in the immune system is LAT (linker for activation of T-cells).
This protein is found in T-cells. When the T-cell receptor binds to the antigen peptide Lck kinase
activates ZAP-70, who can then phosphorylate LAT. LAT will then attract various signaling
proteins. More on this in the section ’T-cell activation’.
Page 3
,Cells of the immune system:
All cells in the immune system are derived from a pluripotent hematopoietic stem cell.
Leukocytes: (aka white blood cells), mature leukocytes circulate the blood or lymph system, but
there are also some specialized tissue-resident leukocytes, they are specific to one tissue. This is
the overarching term for; all that is below;
- Lymphocyte: they reside in the lymph nodes, examples are; NK cells, B- and T-cells.
Innate lymphoid cell (ILC): they secrete cytokines and regulate both the innate and
adaptive immune cells. Mostly found in lymphoid tissues. They are very similar to T-cells.
NK-cells are a type of ILC1.
Natural killer cell: a lymphocyte of the innate immune system. It destroys virus infected
cells and tumor cells without prior activation. They also produce cytokines.
- Granulocyte: category of leukocytes characterized by granules in their cytoplasm;
Eosinophilic granulocyte: fight parasitic infections and venom.
Basophilic granulocyte: release histamine and other chemicals in allergic and
inflammatory responses.
Neutrophilic granulocyte: most abundant, first responders to infection.
- Mast cell: closely related to basophilic granulocytes, but found in tissues rather than blood. It
releases histamine during allergic reactions and are involved in wound healing.
- Monocyte: circulates the blood, and differentiates into macrophages and dendritic cells. It does
phagocytosis and cytokine production.
Macrophage: differentiated monocyte in tissue. Phagocytes pathogens, dead cells and
debris, and present their antigens to T-cells. They also produce cytokines. It has 2 types;
• M1: pro-inflammatory response, with high ROS production.
• M2: anti-inflammatory response, initiates tissue repair.
Dendritic cell: antigen presenting cells that bridge the innate and adaptive immune
system. They phagocyte an antigen and then travel to a lymph node to activate naive T-
cells. Once they encounter a pathogen, they express CCR7, which guides them to the
lymph node, helps express MHC and co-stimulatory molecules for T-cell activation.
T-cells:
T cells are responsible for cell-mediated immunity, where they target and destroy infected or
abnormal cells, or help regulate the immune response. They can only recognize linear protein
fragments of pathogens, which needs to be presented to them on MHC.
There are 2 types; CD4+ are helper T-cells and regulatory T-cells, CD8+ are cytotoxic T-cells.
They get activated by dendritic cells, who present the antigen they captured on MHC, the type of
MHC depends on the type of T-cell. CD4+ listen to MHCII, and CD8+ listen to MHCI. The type of
receptors on T-cells are T-cell receptors (TCR).
Helper T-cells; do not directly kill antigen, but they help coordinate the immune response by
secreting cytokines that activate B-cells, cytotoxic T-cells and macrophages.
Cytotoxic T-cells; they directly kill infected or abnormal cells. When activated, they release
molecules like perforin (makes holes in target cells) and granzymes (induce apoptosis).
Regulatory T-cells; they suppress the activity of immune cells, ensuring that the immune system
doesn’t attack body’s own tissues and when stop the immune response once an infection is over.
Memory T-cells; provides quick immunity when encountering the same pathogen again in the
future.
B-cells:
B cells are primarily responsible for producing antibodies (immunoglobulins) that target specific
antigens. The type of receptor on B-cells are surface immunoglobulins (Ig). They can recognize
pathogens in their native form, by folded proteins and multi-subunit complexes.
They encounter an antigen and internalize it, then when activated by helper T-cells, they become;
Page 4
, Plasma cells; secrete large amounts of antibodies. Who are used for opsonization and activating
the complement system.
Memory B-cells; provides quick immunity when encountering the same pathogen again in the
future.
Page 5
Index:
Vaccines ———————————————————————————— page 2
Cell signaling —————————————————————————— page 3
Cell of the immune system ———————————————————— page 4
Cytokines ———————————————————————————— page 5
Cytokine signaling ———————————————————————— page 6
Differences ——————————————————————————— page 7
Innate immune system —————————————————————— page 8
Complement system ——————————————————————— page 9
Recognizing antigens —————————————————————— page 10
Lymphoid tissues ———————————————————————— page 12
Major histocompatibility complex (MHC) —————————————— page 14
Generation of B-cells ——————————————————————— page 16
Generation of T-cells ——————————————————————— page 18
Antibodies ——————————————————————————— page 19
T-cell activation ————————————————————————— page 21
B-cell activation ————————————————————————— page 23
T-cell differentiation ——————————————————————— page 25
Inhibitory signaling ——————————————————————— page 27
Removal of pathogens —————————————————————— page 28
Tolerance ————————————————————————————page 30
Organ rejection ————————————————————————— page 31
Page 1
,Immunology is the scientific disciple that studies the immune system, which serves to project the
body from infectious agents and cancer.
Infectious diseases can come from extracellular bacteria, intercellular bacteria, fungi, viruses and
parasites. Parasites are especially dangerous as they are multicellular and thus too big for
phagocytes to consume them, as is possible with unicellular bacteria.
Robert Koch was the first guy to understand that specific diseases are coupled to specific germs.
From this, he created the Koch postulate;
1. The microorganism must be founding abundance in a diseased organism, and not in a healthy
organism.
2. The microorganism must be isolated from the diseased organism and grown in a pure culture.
3. The cultured microorganism must cause disease when introduced into a healthy organism.
4. The microorganism must be re-isolated from the inoculated, diseased host and identified as
being identical to the original causative agent.
When all this is true, one can conclude that this specific microbe causes this specific
disease.
Vaccination:
They work. For most diseases, they reduce the number of cases by 99.99%. But
some people are stupid (most people are stupid from my experience) and don’t
believe in them, so infectious diseases are resurfacing.
Fun fact: vaccine comes from the latin word vaccinus, which means ‘from cows’. This
is because the first aver vaccine was derived from cow pox, after it was noticed that
the milkmaids who were exposed to cowpox, didn’t contract the more dangerous
smallpox.
Vaccines are effective. Look at the example of meningococcal disease. The number
of cases is shown in the figure on the left. When the vaccine was put on the market,
number of cases dropped. This vaccine concluded types; A, C, E, B, Y but not W.
And the graph also shows that type W increases around 2016, showing that when
limiting the other types, type W is able to outgrow them.
There is a difference between passive and active immunization. Passive immunization (serum
therapy), one is given antibodies to help fight a disease, though this does not give any memory.
Active immunization (regular vaccinations) uses dead or inactivated pathogens, this does give
memory.
Immune response:
1. Anatomic barriers, like; skin, mucosa, epithelium and intestine.
2. Complement/ antimicrobial proteins, like; defensins and C3.
3. Innate immunity, consists of macrophages, granulocytes and natural killer cells.
4. Adaptive immunity, consists of B- and T-cells.
Page 2
,Cell signaling:
Ofcourse, there are multiple types, of which I am sure you know most of them. So I will keep it
short.
Ligand binding:
Upon binding of a ligand to its receptor, protein-protein interactions in the cytosol often induce
activation of transcription factor that shuttles to the nucleus and induce gene transcription.
Examples:
The receptor can be membrane-bound or cytoplasmic.
It can harbor tyrosine kinase activity or activate this in a separate protein.
It might activate second messengers or be processed to release
an intracellular domain that mediates gene transcription itself.
In immune cells:
Signal transduction in immune cells is done by non-receptor
tyrosine kinases, like; Src family kinase, Syk family kinase and
Tec family kinase.
Immune cells also make use of scaffolding proteins. Scaffolding
proteins are large proteins that help bring multiple signaling
molecules together into a complex. They don’t perform the
signaling themselves but facilitate the process by holding the components in the right place.
An example of a scaffolding protein in the immune system is LAT (linker for activation of T-cells).
This protein is found in T-cells. When the T-cell receptor binds to the antigen peptide Lck kinase
activates ZAP-70, who can then phosphorylate LAT. LAT will then attract various signaling
proteins. More on this in the section ’T-cell activation’.
Page 3
,Cells of the immune system:
All cells in the immune system are derived from a pluripotent hematopoietic stem cell.
Leukocytes: (aka white blood cells), mature leukocytes circulate the blood or lymph system, but
there are also some specialized tissue-resident leukocytes, they are specific to one tissue. This is
the overarching term for; all that is below;
- Lymphocyte: they reside in the lymph nodes, examples are; NK cells, B- and T-cells.
Innate lymphoid cell (ILC): they secrete cytokines and regulate both the innate and
adaptive immune cells. Mostly found in lymphoid tissues. They are very similar to T-cells.
NK-cells are a type of ILC1.
Natural killer cell: a lymphocyte of the innate immune system. It destroys virus infected
cells and tumor cells without prior activation. They also produce cytokines.
- Granulocyte: category of leukocytes characterized by granules in their cytoplasm;
Eosinophilic granulocyte: fight parasitic infections and venom.
Basophilic granulocyte: release histamine and other chemicals in allergic and
inflammatory responses.
Neutrophilic granulocyte: most abundant, first responders to infection.
- Mast cell: closely related to basophilic granulocytes, but found in tissues rather than blood. It
releases histamine during allergic reactions and are involved in wound healing.
- Monocyte: circulates the blood, and differentiates into macrophages and dendritic cells. It does
phagocytosis and cytokine production.
Macrophage: differentiated monocyte in tissue. Phagocytes pathogens, dead cells and
debris, and present their antigens to T-cells. They also produce cytokines. It has 2 types;
• M1: pro-inflammatory response, with high ROS production.
• M2: anti-inflammatory response, initiates tissue repair.
Dendritic cell: antigen presenting cells that bridge the innate and adaptive immune
system. They phagocyte an antigen and then travel to a lymph node to activate naive T-
cells. Once they encounter a pathogen, they express CCR7, which guides them to the
lymph node, helps express MHC and co-stimulatory molecules for T-cell activation.
T-cells:
T cells are responsible for cell-mediated immunity, where they target and destroy infected or
abnormal cells, or help regulate the immune response. They can only recognize linear protein
fragments of pathogens, which needs to be presented to them on MHC.
There are 2 types; CD4+ are helper T-cells and regulatory T-cells, CD8+ are cytotoxic T-cells.
They get activated by dendritic cells, who present the antigen they captured on MHC, the type of
MHC depends on the type of T-cell. CD4+ listen to MHCII, and CD8+ listen to MHCI. The type of
receptors on T-cells are T-cell receptors (TCR).
Helper T-cells; do not directly kill antigen, but they help coordinate the immune response by
secreting cytokines that activate B-cells, cytotoxic T-cells and macrophages.
Cytotoxic T-cells; they directly kill infected or abnormal cells. When activated, they release
molecules like perforin (makes holes in target cells) and granzymes (induce apoptosis).
Regulatory T-cells; they suppress the activity of immune cells, ensuring that the immune system
doesn’t attack body’s own tissues and when stop the immune response once an infection is over.
Memory T-cells; provides quick immunity when encountering the same pathogen again in the
future.
B-cells:
B cells are primarily responsible for producing antibodies (immunoglobulins) that target specific
antigens. The type of receptor on B-cells are surface immunoglobulins (Ig). They can recognize
pathogens in their native form, by folded proteins and multi-subunit complexes.
They encounter an antigen and internalize it, then when activated by helper T-cells, they become;
Page 4
, Plasma cells; secrete large amounts of antibodies. Who are used for opsonization and activating
the complement system.
Memory B-cells; provides quick immunity when encountering the same pathogen again in the
future.
Page 5
