Immunology
2nd year biology
Theme 1: Introduction immune system
Biology:
- Cell-cell interactions and communication
- Cell proliferation and (programmed) cell death
- Activation of cells via receptors and signal transduction
Medical:
- Diseases due to a failing immune system:
o Immunodeficiencies
o Allergic reactions (hypersensitivity reactions): oversensitive
o Autoimmune diseases: immune system is attacking your own body
- Health by manipulating the immune system
o Vaccination against infectious diseases
o Immunotherapy against cancer
o Immunosuppression after organ transplantation
Stem cell for all immune cells is coming from the bone marrow
Innate immune system: cells that react directly to the
trigger within seconds/hours. = First line of defence
Adaptive immune system: T cell and B cell. Takes about
4 days to respond to a specific thread. Specific.
Cellular components (cells) and humoral components (dissolved
molecules)
Recognition phase: by Antigen Presenting cells (APC)
- How is the antigen recognized?
- How does the structural diversity of receptors arise?
- How is distinguished between self and non-self?
Induction phase:
- Induction of an immune response or tolerance?
Tolerance required for self-cells.
- Which type of response? Humoral or cellular response.
Effector phase:
- How do the effector mechanisms operate?
1
, Immunology
2nd year biology
- How is an immune response terminated?
- How is memory established and maintained?
o Currently found that innate cells also have developed a kind of memory
Dendritic cells are a kind of master regulators in the immune system, decide whether you
induce tolerance or an immune response.
Antigen receptors of B and T lymphocytes
- Of B cells, first membrane bound and when
you have plasma cells you get soluble
antibodies
- T cell receptors are always membrane bound
Huge B and T cell repertoire: clonal selection of
lymphocytes
Naïve lymphocytes become effector lymphocytes
- Naïve B and T cells are completely
developed, but have never encounter an
antigen
- When they are activated, they start to
proliferate
- After proliferation, the cells can differentiate.
For B cells e.g. in plasma cells or memory cells.
And T cells into the possible subsets.
Two signals required for activation of lymphocytes:
1. Antigen recognition
2. Costimulation (often Th for B cells and for T
cells delivered by DC) or cytokines
Activation leads to:
- Proliferation (clonal expansion)
- Differentiation
2
, Immunology
2nd year biology
- Biological effect
Naïve B and T cells are generated in the
primary lymphoid organs (BM/Thymus) and
are transported to secondary lymphoid
organs (lymph nodes/spleen/mucosal and
cutaneous lymphoid tissues) when mature.
Induction phase part I: antigens activate
mature naïve lymphocytes
- DC (= kind of APC) under the skin is
activated by the antigen when that
has passed the epithelial layer of the skin and the DC brings the antigen to the lymph
nodes where it can meet lymphocytes.
- Spleen= blood filter, so when the antigens arrive in the blood it will be transferred to
the spleen where it can also meet the naïve lymphocytes.
Induction phase part II: Effector cells and mediators (antibodies)
- After full activation of the lymphocytes, formation of the effector cells and these
effector cells are transferred to the side of infections
Theme 2: innate immunity
After skin and mucous membrane, the defence.
A pathogen must:
- Gain access to the body
- Attach to, and/or enter cells of its host
- Receptors on pathogens must fit with receptor sites on host cell
- Reproduce while avoiding host’s immune system long enough to produce harmful
changes.
3
, Immunology
2nd year biology
Function of the innate immune system:
- Prevents, controls or eliminates invading microbes
- Elimination of damages cells and initiation of the process of tissue repair
- Activation of the adaptive immune system
Components of the innate immune system:
- Patrolling cells: attack pathogens, but don’t remember for the next time
o Phagocytes (macrophages, neutrophils and dendritic cells) and Natural Killer
cells
- Innate immune receptors: recognizes features common to many pathogens
- Proteins: complement, acute phase proteins and cytokines
Damage to tissue triggers local non-specific inflammatory response:
- Release chemical signals: histamine and prostaglandins
- Capillaries dilate, become more permeable (leaky)
o Delivers macrophages, RBC, platelets and clotting factors
- Increase temperature
o Decrease bacterial growth (optimum is 37 degrees)
o Stimulates phagocytosis
o Speeds up repair of tissue
Inflammation → endothelial cells in the blood vessel are stimulated by the secreted
cytokines that are released by the damaged tissue and start to express selectins, which are
adhesion molecules. The leukocytes that are travelling through the vessel will bind to the
adhesion molecules and they will slow down and will adhere. Then they can travel through
the vessel wall and migrate into the tissue to the side of inflammation to get rid of the
pathogen.
Macrophages and neutrophils can engulf and digest bacteria
- Macrophages have extensions to pull the bacteria towards it
- Neutrophil chases the bacteria and follows the bacteria
Events of phagocytosis (important):
1. Phagocyte adheres to pathogens or debris
2. Phagocyte forms pseudopods that eventually engulf the particles, forming a
phagosome (phagocytic vesicle)
3. Lysosome fuses with the phagocytic vesicle, forming a phagolysosome
4. Lysosomal enzymes digest the particles, leaving a residual body
5. Exocytosis of the vesicle removes indigestible and residual material
Innate immune receptors
Recognition and phagocytosis mediated by PAMPs and PRRs
PAMPs (=pathogen-associated molecular patterns) expressed on microbes:
- Shared by a large group of pathogens
- Conserved and not subject to antigenic variability (easy to recognize)
4
2nd year biology
Theme 1: Introduction immune system
Biology:
- Cell-cell interactions and communication
- Cell proliferation and (programmed) cell death
- Activation of cells via receptors and signal transduction
Medical:
- Diseases due to a failing immune system:
o Immunodeficiencies
o Allergic reactions (hypersensitivity reactions): oversensitive
o Autoimmune diseases: immune system is attacking your own body
- Health by manipulating the immune system
o Vaccination against infectious diseases
o Immunotherapy against cancer
o Immunosuppression after organ transplantation
Stem cell for all immune cells is coming from the bone marrow
Innate immune system: cells that react directly to the
trigger within seconds/hours. = First line of defence
Adaptive immune system: T cell and B cell. Takes about
4 days to respond to a specific thread. Specific.
Cellular components (cells) and humoral components (dissolved
molecules)
Recognition phase: by Antigen Presenting cells (APC)
- How is the antigen recognized?
- How does the structural diversity of receptors arise?
- How is distinguished between self and non-self?
Induction phase:
- Induction of an immune response or tolerance?
Tolerance required for self-cells.
- Which type of response? Humoral or cellular response.
Effector phase:
- How do the effector mechanisms operate?
1
, Immunology
2nd year biology
- How is an immune response terminated?
- How is memory established and maintained?
o Currently found that innate cells also have developed a kind of memory
Dendritic cells are a kind of master regulators in the immune system, decide whether you
induce tolerance or an immune response.
Antigen receptors of B and T lymphocytes
- Of B cells, first membrane bound and when
you have plasma cells you get soluble
antibodies
- T cell receptors are always membrane bound
Huge B and T cell repertoire: clonal selection of
lymphocytes
Naïve lymphocytes become effector lymphocytes
- Naïve B and T cells are completely
developed, but have never encounter an
antigen
- When they are activated, they start to
proliferate
- After proliferation, the cells can differentiate.
For B cells e.g. in plasma cells or memory cells.
And T cells into the possible subsets.
Two signals required for activation of lymphocytes:
1. Antigen recognition
2. Costimulation (often Th for B cells and for T
cells delivered by DC) or cytokines
Activation leads to:
- Proliferation (clonal expansion)
- Differentiation
2
, Immunology
2nd year biology
- Biological effect
Naïve B and T cells are generated in the
primary lymphoid organs (BM/Thymus) and
are transported to secondary lymphoid
organs (lymph nodes/spleen/mucosal and
cutaneous lymphoid tissues) when mature.
Induction phase part I: antigens activate
mature naïve lymphocytes
- DC (= kind of APC) under the skin is
activated by the antigen when that
has passed the epithelial layer of the skin and the DC brings the antigen to the lymph
nodes where it can meet lymphocytes.
- Spleen= blood filter, so when the antigens arrive in the blood it will be transferred to
the spleen where it can also meet the naïve lymphocytes.
Induction phase part II: Effector cells and mediators (antibodies)
- After full activation of the lymphocytes, formation of the effector cells and these
effector cells are transferred to the side of infections
Theme 2: innate immunity
After skin and mucous membrane, the defence.
A pathogen must:
- Gain access to the body
- Attach to, and/or enter cells of its host
- Receptors on pathogens must fit with receptor sites on host cell
- Reproduce while avoiding host’s immune system long enough to produce harmful
changes.
3
, Immunology
2nd year biology
Function of the innate immune system:
- Prevents, controls or eliminates invading microbes
- Elimination of damages cells and initiation of the process of tissue repair
- Activation of the adaptive immune system
Components of the innate immune system:
- Patrolling cells: attack pathogens, but don’t remember for the next time
o Phagocytes (macrophages, neutrophils and dendritic cells) and Natural Killer
cells
- Innate immune receptors: recognizes features common to many pathogens
- Proteins: complement, acute phase proteins and cytokines
Damage to tissue triggers local non-specific inflammatory response:
- Release chemical signals: histamine and prostaglandins
- Capillaries dilate, become more permeable (leaky)
o Delivers macrophages, RBC, platelets and clotting factors
- Increase temperature
o Decrease bacterial growth (optimum is 37 degrees)
o Stimulates phagocytosis
o Speeds up repair of tissue
Inflammation → endothelial cells in the blood vessel are stimulated by the secreted
cytokines that are released by the damaged tissue and start to express selectins, which are
adhesion molecules. The leukocytes that are travelling through the vessel will bind to the
adhesion molecules and they will slow down and will adhere. Then they can travel through
the vessel wall and migrate into the tissue to the side of inflammation to get rid of the
pathogen.
Macrophages and neutrophils can engulf and digest bacteria
- Macrophages have extensions to pull the bacteria towards it
- Neutrophil chases the bacteria and follows the bacteria
Events of phagocytosis (important):
1. Phagocyte adheres to pathogens or debris
2. Phagocyte forms pseudopods that eventually engulf the particles, forming a
phagosome (phagocytic vesicle)
3. Lysosome fuses with the phagocytic vesicle, forming a phagolysosome
4. Lysosomal enzymes digest the particles, leaving a residual body
5. Exocytosis of the vesicle removes indigestible and residual material
Innate immune receptors
Recognition and phagocytosis mediated by PAMPs and PRRs
PAMPs (=pathogen-associated molecular patterns) expressed on microbes:
- Shared by a large group of pathogens
- Conserved and not subject to antigenic variability (easy to recognize)
4
