Immunology week 1
- Distinction between harmless/harmful and self/non-self
- Activation is inflammation and inhibition is tolerance
This is all in balance. When you have a disease, this balance gets disturbed (disturbed immunity).
The balance between inflammation and tolerance is disturbed.
Circulatory system (blood):
- Red blood cells
- Platelets
- White blood cells
a. Neutrophils
b. Eosinophils
c. Basophils
d. Monocyte
e. Lymphocyte
- Plasma which contains molecules such as antibodies and complement molecules
These cells and molecules are subdivided into immunological categories: innate VS adaptive.
Haematopoiesis is the development of the immune cells with two common precursor cells. Macrophages and
dendritic cells belong to the innate immunity as well. Macrophages, dendritic cells and mast cells can be found
in our tissue, whereas the other immune cells are found in the blood. Epithelial barriers belong to the innate
immunity and are the first physical barriers that form the first line of defence against pathogens (skin). The cells
of the innate immunity are the second line of defence and the cells of the adaptive immunity are the third line
of defence.
- Immunity is subdivided into 3 lines of defence based on speed activation upon danger.
- We have innate and adaptive immunity which consist of white blood cells, antibodies, complement
and the lymphatic system.
The lymphatic system is subdivided into primary and secondary lymphoid organs with different functions.
Primary: development of adaptive immune cells secondary: activation of adaptive immune cells
- Bone marrow: B cells - lymph nodes
- Thymus: T cells - Gut Associated Lymphoid Tissues (GALT)
- spleen
,Secondary lymphoid organs are highly structured with specific sites for T cell and B cell activation.
Your innate and adaptive
immune systems differ in
speed and specificity of
inducing immunity.
Innate system:
Macrophages and neutrophils are fast responders upon bacterial infections and induce inflammation.
Macrophages are present in the tissue whereas neutrophils are present in the blood. These
macrophages give up/secrete cytokines when there is an invasion of bacteria to signal and recruit
other immune cells to the place of inflammation. The blood vessel dilates (increased vascular
permeability) which results that the neutrophils in the blood can come to the location of
inflammation.
, - Cytokine: signalling molecule for activation (inflammation)
- Chemokine: signalling molecule for migration. These are necessary for neutrophils to let
them know where they need to go.
Macrophages recruit neutrophils from the bone marrow to collaborate and clear bacterial infection
using phagocytosis (eating/up taking the bacteria). While this inflammation is ongoing, the dendritic
cells initiate adaptive immunity in secondary lymphoid organs. It is necessary to have a close
association between the innate and adaptive immunity systems!
The innate immune cells use pathogen recognition receptors to distinguish self from non-self and
get activated. These receptors can:
- Activate and take up the pathogen,
- There is an equal expression of these receptors in the immune cells.
- They can differentiate/distinguish between major pathogen species’
- They can bind to associated molecular patterns such as pathogen (PAMPS) and danger
(DAMPS) which the pathogens use.
There is NO specific response, so your pathogen will win
Adaptive immune cells
They use receptors to specifically detect danger and get activated. Adaptive immune receptors:
- used for activation and effector functions
a. B cell: B cell receptor (BCR) → become soluble: antibodies.
b. T cell: T cell receptor (TCR)
- They can differentiate/distinguish within major pathogen species.
- These receptors bind to antigens of the pathogen
a. Highly specific for each pathogen
b. Receptor is highly specific per cell
Antigens are specific for each pathogen and contain epitopes recognized by the receptors of your
adaptive immune system.
- Antigen: molecule/fragment of a pathogen recognized by T and B cells of the adaptive
immune system.
- Epitope: the minimal portion of an antigen bound by antibodies of the B cell receptors and
recognized by the T cell receptors. These minimal portions of the antigens that are bound to
these receptors are called epitopes. One antigen can have multiple epitopes.
After development, every T and B cell expresses a receptor which will bind a different epitope, thus
having different specificity. T and B cells:
- Express multiple TCR and BCR but all with one specificity per cell.
- Only the ones with a receptor specific for ongoing infection will be activated in the secondary
lymphoid organs.
- These will proliferate and become a clone of cells, all with the same receptor specific for one
epitope (thus one antigen)
a. Clonal expression takes approximately 1 week
b. One activated, they remember this specific infection.
B cell receptors (BCR) can bind to intact antigens, whereas T cell receptors can only bind to processed
antigens (so only the epitope) and induce different immune responses.
T cells:
, - TCR bind to epitopes (processed antigens)
- Then the T cells gets activated and the epitope get presented to other cells → cellular
response
B cells:
- BCR binds to epitopes of intact antigens
- They differentiate into plasma cells
- They produce antibodies → humoral response.
Antibodies produced during the humoral response have multiple functionalities against
infection. Antibodies:
- Broad range specific for the same pathogen (since a pathogen has multiple different
epitopes).
- They recognize different epitopes between antibodies
- One antibody recognizes one epitope
Functions of these antibodies:
- Neutralization: ‘counter act’
- Opsonization: ‘tagging’
- Complement activation
Activation of the innate cells happens via the antibody-receptor interaction (Fc-FcR).
a. Enhances phagocytosis
b. Activates granulocytes and NK cells.
Side note: Neutrophils are recruited by macrophages from the bone marrow by chemokines.
Complement system
The complement system complements ongoing
inflammation and consists of plasma proteins with
enzymatic activity.
Complement
Most important factor: C3.
Complement factor C3 is cleaved into C3a and C3B
(enzymatic reaction) by C3 convertase.
- C3a: anaphylatoxin (immune cell recruitment)
- C3b: complement fixation (pathogen binding
for phagocytosis and lysis).
Anaphylatoxins (c3a) enhance inflammation within
minutes through activation of
endothelium and immune cell
recruitment. They enhance the dilution of
the blood vessel so that neutrophils can
come to the location of inflammation. C3a
act on blood vessels to increase vascular
permeability.
- Distinction between harmless/harmful and self/non-self
- Activation is inflammation and inhibition is tolerance
This is all in balance. When you have a disease, this balance gets disturbed (disturbed immunity).
The balance between inflammation and tolerance is disturbed.
Circulatory system (blood):
- Red blood cells
- Platelets
- White blood cells
a. Neutrophils
b. Eosinophils
c. Basophils
d. Monocyte
e. Lymphocyte
- Plasma which contains molecules such as antibodies and complement molecules
These cells and molecules are subdivided into immunological categories: innate VS adaptive.
Haematopoiesis is the development of the immune cells with two common precursor cells. Macrophages and
dendritic cells belong to the innate immunity as well. Macrophages, dendritic cells and mast cells can be found
in our tissue, whereas the other immune cells are found in the blood. Epithelial barriers belong to the innate
immunity and are the first physical barriers that form the first line of defence against pathogens (skin). The cells
of the innate immunity are the second line of defence and the cells of the adaptive immunity are the third line
of defence.
- Immunity is subdivided into 3 lines of defence based on speed activation upon danger.
- We have innate and adaptive immunity which consist of white blood cells, antibodies, complement
and the lymphatic system.
The lymphatic system is subdivided into primary and secondary lymphoid organs with different functions.
Primary: development of adaptive immune cells secondary: activation of adaptive immune cells
- Bone marrow: B cells - lymph nodes
- Thymus: T cells - Gut Associated Lymphoid Tissues (GALT)
- spleen
,Secondary lymphoid organs are highly structured with specific sites for T cell and B cell activation.
Your innate and adaptive
immune systems differ in
speed and specificity of
inducing immunity.
Innate system:
Macrophages and neutrophils are fast responders upon bacterial infections and induce inflammation.
Macrophages are present in the tissue whereas neutrophils are present in the blood. These
macrophages give up/secrete cytokines when there is an invasion of bacteria to signal and recruit
other immune cells to the place of inflammation. The blood vessel dilates (increased vascular
permeability) which results that the neutrophils in the blood can come to the location of
inflammation.
, - Cytokine: signalling molecule for activation (inflammation)
- Chemokine: signalling molecule for migration. These are necessary for neutrophils to let
them know where they need to go.
Macrophages recruit neutrophils from the bone marrow to collaborate and clear bacterial infection
using phagocytosis (eating/up taking the bacteria). While this inflammation is ongoing, the dendritic
cells initiate adaptive immunity in secondary lymphoid organs. It is necessary to have a close
association between the innate and adaptive immunity systems!
The innate immune cells use pathogen recognition receptors to distinguish self from non-self and
get activated. These receptors can:
- Activate and take up the pathogen,
- There is an equal expression of these receptors in the immune cells.
- They can differentiate/distinguish between major pathogen species’
- They can bind to associated molecular patterns such as pathogen (PAMPS) and danger
(DAMPS) which the pathogens use.
There is NO specific response, so your pathogen will win
Adaptive immune cells
They use receptors to specifically detect danger and get activated. Adaptive immune receptors:
- used for activation and effector functions
a. B cell: B cell receptor (BCR) → become soluble: antibodies.
b. T cell: T cell receptor (TCR)
- They can differentiate/distinguish within major pathogen species.
- These receptors bind to antigens of the pathogen
a. Highly specific for each pathogen
b. Receptor is highly specific per cell
Antigens are specific for each pathogen and contain epitopes recognized by the receptors of your
adaptive immune system.
- Antigen: molecule/fragment of a pathogen recognized by T and B cells of the adaptive
immune system.
- Epitope: the minimal portion of an antigen bound by antibodies of the B cell receptors and
recognized by the T cell receptors. These minimal portions of the antigens that are bound to
these receptors are called epitopes. One antigen can have multiple epitopes.
After development, every T and B cell expresses a receptor which will bind a different epitope, thus
having different specificity. T and B cells:
- Express multiple TCR and BCR but all with one specificity per cell.
- Only the ones with a receptor specific for ongoing infection will be activated in the secondary
lymphoid organs.
- These will proliferate and become a clone of cells, all with the same receptor specific for one
epitope (thus one antigen)
a. Clonal expression takes approximately 1 week
b. One activated, they remember this specific infection.
B cell receptors (BCR) can bind to intact antigens, whereas T cell receptors can only bind to processed
antigens (so only the epitope) and induce different immune responses.
T cells:
, - TCR bind to epitopes (processed antigens)
- Then the T cells gets activated and the epitope get presented to other cells → cellular
response
B cells:
- BCR binds to epitopes of intact antigens
- They differentiate into plasma cells
- They produce antibodies → humoral response.
Antibodies produced during the humoral response have multiple functionalities against
infection. Antibodies:
- Broad range specific for the same pathogen (since a pathogen has multiple different
epitopes).
- They recognize different epitopes between antibodies
- One antibody recognizes one epitope
Functions of these antibodies:
- Neutralization: ‘counter act’
- Opsonization: ‘tagging’
- Complement activation
Activation of the innate cells happens via the antibody-receptor interaction (Fc-FcR).
a. Enhances phagocytosis
b. Activates granulocytes and NK cells.
Side note: Neutrophils are recruited by macrophages from the bone marrow by chemokines.
Complement system
The complement system complements ongoing
inflammation and consists of plasma proteins with
enzymatic activity.
Complement
Most important factor: C3.
Complement factor C3 is cleaved into C3a and C3B
(enzymatic reaction) by C3 convertase.
- C3a: anaphylatoxin (immune cell recruitment)
- C3b: complement fixation (pathogen binding
for phagocytosis and lysis).
Anaphylatoxins (c3a) enhance inflammation within
minutes through activation of
endothelium and immune cell
recruitment. They enhance the dilution of
the blood vessel so that neutrophils can
come to the location of inflammation. C3a
act on blood vessels to increase vascular
permeability.
