Cell Biology and Health
CBI-20306
Lecture 1 & 2
Innate immune processes
Immune system
▪ Protection against infectious microbes
• Intracellular; viruses, bacteria, parasites
• Extracellular; most bacteria and parasites, fungi
▪ Protection against modified self
• Cancer/tumour cells or transformed cells
Lymph nodes: drain certain areas of the body
▪ Kidney shaped organ of lymphatic system
▪ Part of adaptive immune system
▪ Linked by lymphatic vessels, part of circulatory system
▪ Act as filters for foreign particles and cancer/tumour cells
Lymphoid organs
▪ Primary
• Thymus “birth” and development of lymphatic T-cells
• Bone marrow “birth” and development of lymphatic B-cells
▪ Secondary
• Drain specific areas of the body
• Cells of immune system are ready to mount an immune response
• Examples: appendix, Peyer’s patches, tonsils, adenoids, spleen
Immune system in neck area
▪ Waldeyer’s ring: ringed arrangement of lymphoid tissue in the pharynx (keelholte)
• Adenoids (neusamandelen)
• Tubal tonsils (eileidersamandelen; located posterior to opening of the Eustachian tube)
• Palatine tonsils (palatine amandelen; back of the throat)
• Lingual tonsils (linguale amandelen; back of the tongue)
1 Waldeyer's ring
1 - 82
,Epithelial cell wall: one layer of cells on the outside of the
organism
▪ Goblet cells: produce a mucous layer
→ microbes stick to it and die
▪ AMPs: antimicrobial peptides; kill pathogens
Innate immune receptors
▪ Toll-like receptors: recognize pathogens
• Extracellular: on outer cell membrane
• Cytosolic
• Endosomal: in membrane of endosome
▪ Which TLR recognizes what?
→ see summary reader
2 Epithelial cell wall
Immune response
1. Epithelial cells infected/damaged by virus/bacteria
→ activation of acute phase proteins e.g. C-reactive protein
2. PAMP: pathogen associated molecular pattern recognized
3. Intracellular signalling cascade
4. Transcription of alarm molecules; cytokines/chemokines
5. Immune cells under epithelial layer alerted
3 Toll-like receptors: TLR
4 Cell types of the immune system
2 - 82
,Innate immunity
▪ Phagocytes; granulocytes
1. Extravasation: recruitment of cells to site of infection
- Due to chemotaxis: movement against chemo-gradient from site of infection
- From video: adhesion in leukocyte extravasation
- Inflammatory signal → endothelial cells exocytose P-selectin & synthesize platelet-activating factor
(PAF)
- P-selectin molecules bind to oligosaccharides on leukocyte cell membrane → leukocyte “rolls along”
endothelial cells
- PAF-receptor on leukocyte binds PAF → activation of integrins
- Integrins can bind to ICAM-1 molecules on endothelial cells → leukocyte stops rolling & tightly adheres
- Migration through two adjacent endothelial cells
2. Pattern recognition receptors; TLRs, NODs: recognition of and activation by microbes
- PRR: pattern recognition receptors on epithelial cells
- PAMPs: pathogen associated molecular patterns on microbe
3. Phagocytosis: ingestion of microbe
- Microbes bind to phagocyte receptors
- Phagocyte membrane zips up around microbe
- Microbe ingested in phagosome
- Fusion of phagosome with lysosome (contains digestion enzymes)
- killing of microbes by lysosomal enzymes
- killing of phagocytosed microbes by ROS (reactive oxygen species) and NO (nitrogen oxide)
4. Antigen presentation on MHC, secretion of cytokines, etc.: destruction and communication to adaptive
immune system
▪ Granulocytes, short-lived, fast responders made to destroy:
• Destruction by release of toxic substances to environment containing the microbe ór
• Phagocytosing microbe and destroying it inside itself
• Neutrophils
- Polymorpho-nuclear cells: lobular nucleus
- Produced in bone marrow
- Migrate very quickly to sites of infection
- More than 1 * 1011 neutrophils/day (6h half-life)
- Terminally differentiated; no further differentiation possible
- NETosis: neutrophil extracellular trap: network of fibers composed of neutrophil-DNA which binds
pathogens
→ killing extracellular pathogens while minimizing damage to the host cells
• Basophils
- Clearance of parasites
- Produced in bone marrow
Neutrophils Infections
- Directs T cell differentiation
- Defensive role against allergens
Allergic
- Release histamine, leukotrienes and prostaglandins Granulocytes Basophils reactions &
parasite defense
- Express receptors for IgE (allergy)
- Terminally differentiated Allergic
Eosinophils reactions &
• Eosinophils parasite defense
- Detects and kills parasites
- Produced in bone marrow
- Secretory vesicles with destructive proteins
- Express receptors for IgE and IgG (inflammation and allergy immunoglobins)
- Terminally differentiated
▪ Monocytes
• Become macrophages when leaving bloodstream
3 - 82
, • APCs: professional antigen presenting cells: kill pathogen → cut in into pieces and present these to
adaptive immune cells
• Molecules produced in activated macrophages - effector functions of activated macrophages
- ROS and nitric oxide → killing of microbes
- Cytokines → inflammation, enhanced adaptive immunity
- Growth factors → tissue remodelling “shutting down the inflammation”
▪ Dendritic cells
• APCs: kill pathogen → cut in into pieces and present these to adaptive immune cells
• Developed from a myeloid precursor; like monocytes
Kill and destroy
Granulocytes Short-lived
Fast response
Innate immunity
APCs
Macrophages &
Long-lived
dendritic cells
Phagocytose and
present to adaptive
immune system
Lecture 3 & 4
Adaptive immune processes
After 12-24 hours activated
Innate immunity Adaptive immunity
Pathogen Stays the same after repeated exposure to Matures over time; repeated exposure leads
recognition the same pathogen to faster responses
Early response Later response: lymphocyte generate
Pathogen
adaptive immune response & pathogen-
removal
specific memory
MHC-I presentation
▪ All nucleated cells have MHC-I
▪ Presents parts of all proteins that are broken down in the cell
▪ Signal to the rest of the body that the cell is alright
▪ Immune system scans presented peptides = NK cells and cytotoxic T cells
• NK cells scan for self MHC-I
• CTL cells scan for MHC-I + peptide; peptide not-self → kill and destroy
- Kill and destroy by: perforins and granzymes
▪ Virus enters cell → broken down → peptides shown → immune system recognizes it as foreign and destroys
host cell
MHC-II presentation
▪ On immune cells
4 - 82
CBI-20306
Lecture 1 & 2
Innate immune processes
Immune system
▪ Protection against infectious microbes
• Intracellular; viruses, bacteria, parasites
• Extracellular; most bacteria and parasites, fungi
▪ Protection against modified self
• Cancer/tumour cells or transformed cells
Lymph nodes: drain certain areas of the body
▪ Kidney shaped organ of lymphatic system
▪ Part of adaptive immune system
▪ Linked by lymphatic vessels, part of circulatory system
▪ Act as filters for foreign particles and cancer/tumour cells
Lymphoid organs
▪ Primary
• Thymus “birth” and development of lymphatic T-cells
• Bone marrow “birth” and development of lymphatic B-cells
▪ Secondary
• Drain specific areas of the body
• Cells of immune system are ready to mount an immune response
• Examples: appendix, Peyer’s patches, tonsils, adenoids, spleen
Immune system in neck area
▪ Waldeyer’s ring: ringed arrangement of lymphoid tissue in the pharynx (keelholte)
• Adenoids (neusamandelen)
• Tubal tonsils (eileidersamandelen; located posterior to opening of the Eustachian tube)
• Palatine tonsils (palatine amandelen; back of the throat)
• Lingual tonsils (linguale amandelen; back of the tongue)
1 Waldeyer's ring
1 - 82
,Epithelial cell wall: one layer of cells on the outside of the
organism
▪ Goblet cells: produce a mucous layer
→ microbes stick to it and die
▪ AMPs: antimicrobial peptides; kill pathogens
Innate immune receptors
▪ Toll-like receptors: recognize pathogens
• Extracellular: on outer cell membrane
• Cytosolic
• Endosomal: in membrane of endosome
▪ Which TLR recognizes what?
→ see summary reader
2 Epithelial cell wall
Immune response
1. Epithelial cells infected/damaged by virus/bacteria
→ activation of acute phase proteins e.g. C-reactive protein
2. PAMP: pathogen associated molecular pattern recognized
3. Intracellular signalling cascade
4. Transcription of alarm molecules; cytokines/chemokines
5. Immune cells under epithelial layer alerted
3 Toll-like receptors: TLR
4 Cell types of the immune system
2 - 82
,Innate immunity
▪ Phagocytes; granulocytes
1. Extravasation: recruitment of cells to site of infection
- Due to chemotaxis: movement against chemo-gradient from site of infection
- From video: adhesion in leukocyte extravasation
- Inflammatory signal → endothelial cells exocytose P-selectin & synthesize platelet-activating factor
(PAF)
- P-selectin molecules bind to oligosaccharides on leukocyte cell membrane → leukocyte “rolls along”
endothelial cells
- PAF-receptor on leukocyte binds PAF → activation of integrins
- Integrins can bind to ICAM-1 molecules on endothelial cells → leukocyte stops rolling & tightly adheres
- Migration through two adjacent endothelial cells
2. Pattern recognition receptors; TLRs, NODs: recognition of and activation by microbes
- PRR: pattern recognition receptors on epithelial cells
- PAMPs: pathogen associated molecular patterns on microbe
3. Phagocytosis: ingestion of microbe
- Microbes bind to phagocyte receptors
- Phagocyte membrane zips up around microbe
- Microbe ingested in phagosome
- Fusion of phagosome with lysosome (contains digestion enzymes)
- killing of microbes by lysosomal enzymes
- killing of phagocytosed microbes by ROS (reactive oxygen species) and NO (nitrogen oxide)
4. Antigen presentation on MHC, secretion of cytokines, etc.: destruction and communication to adaptive
immune system
▪ Granulocytes, short-lived, fast responders made to destroy:
• Destruction by release of toxic substances to environment containing the microbe ór
• Phagocytosing microbe and destroying it inside itself
• Neutrophils
- Polymorpho-nuclear cells: lobular nucleus
- Produced in bone marrow
- Migrate very quickly to sites of infection
- More than 1 * 1011 neutrophils/day (6h half-life)
- Terminally differentiated; no further differentiation possible
- NETosis: neutrophil extracellular trap: network of fibers composed of neutrophil-DNA which binds
pathogens
→ killing extracellular pathogens while minimizing damage to the host cells
• Basophils
- Clearance of parasites
- Produced in bone marrow
Neutrophils Infections
- Directs T cell differentiation
- Defensive role against allergens
Allergic
- Release histamine, leukotrienes and prostaglandins Granulocytes Basophils reactions &
parasite defense
- Express receptors for IgE (allergy)
- Terminally differentiated Allergic
Eosinophils reactions &
• Eosinophils parasite defense
- Detects and kills parasites
- Produced in bone marrow
- Secretory vesicles with destructive proteins
- Express receptors for IgE and IgG (inflammation and allergy immunoglobins)
- Terminally differentiated
▪ Monocytes
• Become macrophages when leaving bloodstream
3 - 82
, • APCs: professional antigen presenting cells: kill pathogen → cut in into pieces and present these to
adaptive immune cells
• Molecules produced in activated macrophages - effector functions of activated macrophages
- ROS and nitric oxide → killing of microbes
- Cytokines → inflammation, enhanced adaptive immunity
- Growth factors → tissue remodelling “shutting down the inflammation”
▪ Dendritic cells
• APCs: kill pathogen → cut in into pieces and present these to adaptive immune cells
• Developed from a myeloid precursor; like monocytes
Kill and destroy
Granulocytes Short-lived
Fast response
Innate immunity
APCs
Macrophages &
Long-lived
dendritic cells
Phagocytose and
present to adaptive
immune system
Lecture 3 & 4
Adaptive immune processes
After 12-24 hours activated
Innate immunity Adaptive immunity
Pathogen Stays the same after repeated exposure to Matures over time; repeated exposure leads
recognition the same pathogen to faster responses
Early response Later response: lymphocyte generate
Pathogen
adaptive immune response & pathogen-
removal
specific memory
MHC-I presentation
▪ All nucleated cells have MHC-I
▪ Presents parts of all proteins that are broken down in the cell
▪ Signal to the rest of the body that the cell is alright
▪ Immune system scans presented peptides = NK cells and cytotoxic T cells
• NK cells scan for self MHC-I
• CTL cells scan for MHC-I + peptide; peptide not-self → kill and destroy
- Kill and destroy by: perforins and granzymes
▪ Virus enters cell → broken down → peptides shown → immune system recognizes it as foreign and destroys
host cell
MHC-II presentation
▪ On immune cells
4 - 82
