Lecture 1
Immune activation inflammation balance between inflammation and tolerance
Inhibition tolerance balance between inflammation and tolerance
Innate cells monocytes, granulocytes (basophils, eosinophils, neutrophils, mast
cells), complement proteins, NK-cells (derived from lymphocytes)
Innate response nonspecific and fast
Adaptive cells antibodies, T-cells and B-cells (both derived from lymphocytes)
Adaptive response slow and specific
Humoral (adaptive) B-cells and antibodies
Cellular (adaptive) T-lymphocytes and CD4+/CD8+
Haematopoiesis immune cell devefrom pluripotent haematopoietic stem cells
1. Common myeloid cell precursor > innate immune cells
2. Common lymphoid cell precursor > adaptive immune cells
Monocyte kidney-shaped; functions: differentiates into macrophages and den-
dritic cells to elicit an immune response; main targets: various
Macrophage derived from monocytes; functions: phagocytosis, antigen presenta-
tion to T-cells; main targets: various
Neutrophil granulocyte; functions: phagocytosis, degranulation (discharge of
contents of a cell); main targets: bacteria, fungi
Eosinophil granulocyte; functions: degranulation, release of enzymes, growth
factors and cytokines (activate the immune system); main targets:
parasites, various allergic tissues
Basophil granulocyte; functions: degranulation, release of histamine, enzymes
and cytokines; main targets: various allergic tissues
Mast cell common in various adult tissues; functions: degranulation, release of
histamine, enzymes, and cytokines; main targets: parasites, various
allergic tissues
,Lymphocytes (T) two variations: T-helper cells (CD4+) and cytotoxic T-cells (CD8+)
Function CD4+: mediates immune response
Main targets CD4+: intracellular bacteria
Function CD8+: cell destruction
Main targets CD8+: virus-infected cells, tumour cells
NK-cell natural killer cell (large granular lymphocyte); function: tumour re-
jection, destruction of infected cells, release of perforin and gran-
zymes which induce apoptosis; main targets: viruses, tumours cells
Lines of defence based on the speed of activation upon danger
1. Physical/chemical barriers (skin and mucosal surfaces)
2. Non-specific innate response
3. Specific adaptive responses
Circulatory system RBCs, platelets, plasma (containing antibodies and complement pro-
teins), and white blood cells:
• Lymphocytes (NK-cells, T-cells, B-cells)
• Granulocytes (neutrophil, basophil, eosinophil, mast cells)
• Monocytes (macrophages, dendritic cells)
Lymphatic system subdivided into primary and secondary lymphoid organs, according
to their differing functions:
Primary organs function: development of the immune cells
• Bone marrow > B-cells
• Thymus > T-cells
Secondary organs function: activation of the adaptive immune system, highly struc-
tured with specific sites for T-cell and B-cell activation (lymph nodes,
spleen, gut-associated lymphoid tissues GALT)
Cytokines signalling molecule for activation
Chemokines signalling molecule for migration
Inflammation upon infection by a bacterium in a surface wound, the effector cell is
activated to secrete cytokines. Vasodilation increases the permeabi-
, lity of the capillary wall: fluid, proteins, and cells leave the blood to
enter the wounded tissue. Numerous neutrophils are stored in the
bone marrow and released on demand to fight infection. Neutrophils
go the infected tissue and kill the bacteria. The neutrophils die and
are degraded by macrophages. While inflammation is ongoing, den-
dritic cells initiate adaptive immunity in secondary lymphoid organs.
Innate receptors to distinguish self from non-self and to get activated
• Used for activation and pathogen uptake
• Can differentiate between major pathogen species, using associ-
ated molecular patterns
- Pathogen > PAMPS
- Danger > DAMPS
Adaptive receptors to specifically detect danger and to get activated
• Used for activation and effector functions
- B-cell > BCR (becomes soluble: antibody, thus
plasma cell), can bind an intact antigen
- T-cell > TCR (only binds processed antigen), the
cellular response involves the activation
of other cells that present such epitopes
• Can differentiate within major pathogen species, using antigens
- Highly specific for each pathogen
- Adaptive receptors are highly specific per cell
Antigen molecule/pathogen fragment that is recognized by T-cells and B-cells
• Specific for each pathogen, contains epitopes
• Epitope: minimal portion of an antigen bound by antibodies or the
BCR, and recognized by TCRs
, B-cell the BCR binds epitopes on an intact antigen
Humoral response: production of antibodies by plasma cells. The an-
tibodies produced during the humoral response have different func-
tionalities against infection:
• Neutralization (ingestion and destruction by phagocytosis)
• Opsonization (opsonins tag pathogens for phagocytosis)
• Complement activation (complements opsonise pathogens)
1. Classical pathway
Activated when complement protein C1q binds to a pathogen,
or onto an antigen-antibody complex. This will trigger cleav-
age of the subsequent complement proteins in the cascade,
resulting in production of C3 convertase and its downstream
effects. Its involvement in antigen-antibody complexes means
it has a role in both the adaptive and innate immune response.
2. Mannose-binding lectin MBL pathway
MBL is a protein produced in the liver. Its function is to detect
carbohydrate-containing mannose on the surface of patho-
gens, activating a protease called MASP. This pattern cleaves
complement components, which activates a cascade that re-
sults in producing C3 convertase.
3. Alternative pathway
Usually activated by bacterial endotoxin (lipopolysaccharide
present on the outer membrane of gram negative bacteria).
This results in the spontaneous hydrolysis of C3 into small
amounts of factor C3b (opsonises pathogens), which com-
bines with other factors to produce C3 convertase.
• Innate cell activation via antibody-receptor mediation (Fc-FcR)
- Enhanced phagocytosis
- Activation of granulocytes and NK-cells
Immune activation inflammation balance between inflammation and tolerance
Inhibition tolerance balance between inflammation and tolerance
Innate cells monocytes, granulocytes (basophils, eosinophils, neutrophils, mast
cells), complement proteins, NK-cells (derived from lymphocytes)
Innate response nonspecific and fast
Adaptive cells antibodies, T-cells and B-cells (both derived from lymphocytes)
Adaptive response slow and specific
Humoral (adaptive) B-cells and antibodies
Cellular (adaptive) T-lymphocytes and CD4+/CD8+
Haematopoiesis immune cell devefrom pluripotent haematopoietic stem cells
1. Common myeloid cell precursor > innate immune cells
2. Common lymphoid cell precursor > adaptive immune cells
Monocyte kidney-shaped; functions: differentiates into macrophages and den-
dritic cells to elicit an immune response; main targets: various
Macrophage derived from monocytes; functions: phagocytosis, antigen presenta-
tion to T-cells; main targets: various
Neutrophil granulocyte; functions: phagocytosis, degranulation (discharge of
contents of a cell); main targets: bacteria, fungi
Eosinophil granulocyte; functions: degranulation, release of enzymes, growth
factors and cytokines (activate the immune system); main targets:
parasites, various allergic tissues
Basophil granulocyte; functions: degranulation, release of histamine, enzymes
and cytokines; main targets: various allergic tissues
Mast cell common in various adult tissues; functions: degranulation, release of
histamine, enzymes, and cytokines; main targets: parasites, various
allergic tissues
,Lymphocytes (T) two variations: T-helper cells (CD4+) and cytotoxic T-cells (CD8+)
Function CD4+: mediates immune response
Main targets CD4+: intracellular bacteria
Function CD8+: cell destruction
Main targets CD8+: virus-infected cells, tumour cells
NK-cell natural killer cell (large granular lymphocyte); function: tumour re-
jection, destruction of infected cells, release of perforin and gran-
zymes which induce apoptosis; main targets: viruses, tumours cells
Lines of defence based on the speed of activation upon danger
1. Physical/chemical barriers (skin and mucosal surfaces)
2. Non-specific innate response
3. Specific adaptive responses
Circulatory system RBCs, platelets, plasma (containing antibodies and complement pro-
teins), and white blood cells:
• Lymphocytes (NK-cells, T-cells, B-cells)
• Granulocytes (neutrophil, basophil, eosinophil, mast cells)
• Monocytes (macrophages, dendritic cells)
Lymphatic system subdivided into primary and secondary lymphoid organs, according
to their differing functions:
Primary organs function: development of the immune cells
• Bone marrow > B-cells
• Thymus > T-cells
Secondary organs function: activation of the adaptive immune system, highly struc-
tured with specific sites for T-cell and B-cell activation (lymph nodes,
spleen, gut-associated lymphoid tissues GALT)
Cytokines signalling molecule for activation
Chemokines signalling molecule for migration
Inflammation upon infection by a bacterium in a surface wound, the effector cell is
activated to secrete cytokines. Vasodilation increases the permeabi-
, lity of the capillary wall: fluid, proteins, and cells leave the blood to
enter the wounded tissue. Numerous neutrophils are stored in the
bone marrow and released on demand to fight infection. Neutrophils
go the infected tissue and kill the bacteria. The neutrophils die and
are degraded by macrophages. While inflammation is ongoing, den-
dritic cells initiate adaptive immunity in secondary lymphoid organs.
Innate receptors to distinguish self from non-self and to get activated
• Used for activation and pathogen uptake
• Can differentiate between major pathogen species, using associ-
ated molecular patterns
- Pathogen > PAMPS
- Danger > DAMPS
Adaptive receptors to specifically detect danger and to get activated
• Used for activation and effector functions
- B-cell > BCR (becomes soluble: antibody, thus
plasma cell), can bind an intact antigen
- T-cell > TCR (only binds processed antigen), the
cellular response involves the activation
of other cells that present such epitopes
• Can differentiate within major pathogen species, using antigens
- Highly specific for each pathogen
- Adaptive receptors are highly specific per cell
Antigen molecule/pathogen fragment that is recognized by T-cells and B-cells
• Specific for each pathogen, contains epitopes
• Epitope: minimal portion of an antigen bound by antibodies or the
BCR, and recognized by TCRs
, B-cell the BCR binds epitopes on an intact antigen
Humoral response: production of antibodies by plasma cells. The an-
tibodies produced during the humoral response have different func-
tionalities against infection:
• Neutralization (ingestion and destruction by phagocytosis)
• Opsonization (opsonins tag pathogens for phagocytosis)
• Complement activation (complements opsonise pathogens)
1. Classical pathway
Activated when complement protein C1q binds to a pathogen,
or onto an antigen-antibody complex. This will trigger cleav-
age of the subsequent complement proteins in the cascade,
resulting in production of C3 convertase and its downstream
effects. Its involvement in antigen-antibody complexes means
it has a role in both the adaptive and innate immune response.
2. Mannose-binding lectin MBL pathway
MBL is a protein produced in the liver. Its function is to detect
carbohydrate-containing mannose on the surface of patho-
gens, activating a protease called MASP. This pattern cleaves
complement components, which activates a cascade that re-
sults in producing C3 convertase.
3. Alternative pathway
Usually activated by bacterial endotoxin (lipopolysaccharide
present on the outer membrane of gram negative bacteria).
This results in the spontaneous hydrolysis of C3 into small
amounts of factor C3b (opsonises pathogens), which com-
bines with other factors to produce C3 convertase.
• Innate cell activation via antibody-receptor mediation (Fc-FcR)
- Enhanced phagocytosis
- Activation of granulocytes and NK-cells
