Immunopharmacology
Day 1 – Chapter 1
Case study: rheumatoid arthritis → chronic disease→ autoimmune that involves the joints
Bones prevent from grinding at each other because of cartilage and fluid→ rheuma→ attacks bone and
cartilage
TNFalpha→ expressed in high quantities
Symptoms
- Pain in joints→ because of inflammation
- Stiffness→ edema
- Muscle weakness
- Weight loss
- Fatigue
- Fever
o All 3 because of TNFalpha
Goal of treatment
- RA is most progressive at the start of the disease→ start treatment quickly and effectively to
prevent damage to joints
Drugs used in RA
- Painkillers
- NSAIDs-→ pain and inflammation
- Corticosteroids
- DMARDs→ methotrexate, biologicals
o Methotrexate → prevents rapid proliferation of cells
o Biologicals directed at immune components
Case study→
- New symptoms→ painful and swollen fingers
- Paracetamol or NSAIDs
- See slide for the recommendations
- Adalimumab → blocks TNFalpha
- Combination of methotrexate and adalimumab → magnify each other
Innate vs adaptive immunity
- Ehrlich→ adaptive
- Mechnikov→ innate
Humoralist → people that study side chains
,Toll-like receptor→activating the immune system→ function like alarm system
Overview innate and adaptive immunity
- Cellular alarm systems
- Epithelial layers→ safety in numbers
o Tissue-resident immune cells→ patrol and deal with a
problem when it occurs
o Not enough? Get help from bone marrow
- Cleaning up tissue
- Specialized help from lymphocytes→ t-helper/cytotoxic t
cells
- B cells and antibodies→ extracellular defense
Characteristics innate vs adaptive
Immune cells and their origin
All leukocytes (white blood cells) develop from stem cells in bone marrow OR yolk sac/fetal liver
First immune cells come from yolk sac→ fetal liver take over→ once bone marrow is developed →
immune cells get developed there
Macrophages → either derived from monocytes or fetal liver cells
Most macrophages in CNS are coming from fetal liver cells→ because brain closes off and monocytes
can’t reach it
Mostly myeloid cells are innate
Mostly lymphocytes are adaptive
But sometimes both!
Immune cells communicate through APC→ macrophages and
dendritic cells
Present them to T-cells
Dendritic cells→ functions like a messenger → travel from tissues to lymph nodes to look for help from
more specialized cells: B and T cells
APC patrol tissues, especially the ones that connect to the outside world
Lymphocytes patrol the body looking for antigens they recognize
Lymphoid structures
- The immune system can be seen as a diffuse, body-spanning organ
- Solid tissues
- Fluid tissues
- Fluid molecules
,- Solid lymphoid tissues are everywhere
- Primary lymphoid tissues → where lymphoid tissue is born→ development, selection and
maturation
o Bone marrow
o Thymus
- Secondary → get educated → go from naïve to experienced → sites for initiation of immune
responses
o Spleen
o Lymph nodes
o MALT
Antigen= any molecule that is specifically recognized by lymphocytes or antibodies
T and B cell development
Lymphatic circulation→ drains organs from fluids and immune cells
Lymph vessels end up in lymph nodes
Dendritic cells carrying an antigen comes in to the nod via the afferent lymphatic vessel→ see if antigen
is recognized by B or T cells→ not recognized → go to the next lymph node via the efferent vessel
Spleen
- Lymph node of the blood
- Function of removing old blood cells
- Checks the blood for pathogens
- Leaf-like structure
- B-cells and follicles on outside
- T-cells in the middle
- Red pulp→ macrophages to remove damaged cells (RBC) and invaders/reservoirs of monocytes
- White pulp→ B and T cells, for adaptive response against blood-born antigens
Circulation of T cells
- Naïve and experienced cells
- Both present in blood
- Naïve cells get into lymph node looking for something to recognize
- Effector cells leave the lymph node and go to active site
Lymphoid structures in tissue
- Tissues connected to outside world have their own lymphoid structures
- For faster response against threats:
Gut has most specialized immune cells→ exposed the most to microbes
- Then the bronchi
- Lastly the skin → least organized
Lymph nodes at work→ lymphs will grow
, Day 2 – Chapter 2
Innate immune system
Cellular alarm systems
- Antigen recognition system
- Limited number of receptors
- Distribution of receptors is clonal → same type of receptors → recognize the same patterns
Characteristics of microorganisms → PAMPS
- Components of cell wall
- LPS
- PAMPS
RNA/DNA viruses
- Bacteria have specific patterns→ LPS
- DNA is also different
- Differences are being recognized
What are characteristics of tissue damage
DAMPS
- ATP/DNA leak out
- Components that are normally not exposed leak out of the cell
Cellular alarm systems→ pattern recognition receptors
- Toll-like receptors (TLR)
- C-type lectin receptors
- NOD-like receptors (nucleotide oligomerization domain)
- RIG-like receptors (retinoic acid-inducible gene)
TLR
- Most common receptors
o Outside of cells
o Endosome
o Cytosol
- NOD/RIG- like receptors
o RIG→ viruses
o NOD→bacteria
- TLR→ recognize bacterial cells
TLR
- Different components on different locations of the cell
- TLR mostly made out of RNA
- What happens when a TLR recognize a component in the cell?
Day 1 – Chapter 1
Case study: rheumatoid arthritis → chronic disease→ autoimmune that involves the joints
Bones prevent from grinding at each other because of cartilage and fluid→ rheuma→ attacks bone and
cartilage
TNFalpha→ expressed in high quantities
Symptoms
- Pain in joints→ because of inflammation
- Stiffness→ edema
- Muscle weakness
- Weight loss
- Fatigue
- Fever
o All 3 because of TNFalpha
Goal of treatment
- RA is most progressive at the start of the disease→ start treatment quickly and effectively to
prevent damage to joints
Drugs used in RA
- Painkillers
- NSAIDs-→ pain and inflammation
- Corticosteroids
- DMARDs→ methotrexate, biologicals
o Methotrexate → prevents rapid proliferation of cells
o Biologicals directed at immune components
Case study→
- New symptoms→ painful and swollen fingers
- Paracetamol or NSAIDs
- See slide for the recommendations
- Adalimumab → blocks TNFalpha
- Combination of methotrexate and adalimumab → magnify each other
Innate vs adaptive immunity
- Ehrlich→ adaptive
- Mechnikov→ innate
Humoralist → people that study side chains
,Toll-like receptor→activating the immune system→ function like alarm system
Overview innate and adaptive immunity
- Cellular alarm systems
- Epithelial layers→ safety in numbers
o Tissue-resident immune cells→ patrol and deal with a
problem when it occurs
o Not enough? Get help from bone marrow
- Cleaning up tissue
- Specialized help from lymphocytes→ t-helper/cytotoxic t
cells
- B cells and antibodies→ extracellular defense
Characteristics innate vs adaptive
Immune cells and their origin
All leukocytes (white blood cells) develop from stem cells in bone marrow OR yolk sac/fetal liver
First immune cells come from yolk sac→ fetal liver take over→ once bone marrow is developed →
immune cells get developed there
Macrophages → either derived from monocytes or fetal liver cells
Most macrophages in CNS are coming from fetal liver cells→ because brain closes off and monocytes
can’t reach it
Mostly myeloid cells are innate
Mostly lymphocytes are adaptive
But sometimes both!
Immune cells communicate through APC→ macrophages and
dendritic cells
Present them to T-cells
Dendritic cells→ functions like a messenger → travel from tissues to lymph nodes to look for help from
more specialized cells: B and T cells
APC patrol tissues, especially the ones that connect to the outside world
Lymphocytes patrol the body looking for antigens they recognize
Lymphoid structures
- The immune system can be seen as a diffuse, body-spanning organ
- Solid tissues
- Fluid tissues
- Fluid molecules
,- Solid lymphoid tissues are everywhere
- Primary lymphoid tissues → where lymphoid tissue is born→ development, selection and
maturation
o Bone marrow
o Thymus
- Secondary → get educated → go from naïve to experienced → sites for initiation of immune
responses
o Spleen
o Lymph nodes
o MALT
Antigen= any molecule that is specifically recognized by lymphocytes or antibodies
T and B cell development
Lymphatic circulation→ drains organs from fluids and immune cells
Lymph vessels end up in lymph nodes
Dendritic cells carrying an antigen comes in to the nod via the afferent lymphatic vessel→ see if antigen
is recognized by B or T cells→ not recognized → go to the next lymph node via the efferent vessel
Spleen
- Lymph node of the blood
- Function of removing old blood cells
- Checks the blood for pathogens
- Leaf-like structure
- B-cells and follicles on outside
- T-cells in the middle
- Red pulp→ macrophages to remove damaged cells (RBC) and invaders/reservoirs of monocytes
- White pulp→ B and T cells, for adaptive response against blood-born antigens
Circulation of T cells
- Naïve and experienced cells
- Both present in blood
- Naïve cells get into lymph node looking for something to recognize
- Effector cells leave the lymph node and go to active site
Lymphoid structures in tissue
- Tissues connected to outside world have their own lymphoid structures
- For faster response against threats:
Gut has most specialized immune cells→ exposed the most to microbes
- Then the bronchi
- Lastly the skin → least organized
Lymph nodes at work→ lymphs will grow
, Day 2 – Chapter 2
Innate immune system
Cellular alarm systems
- Antigen recognition system
- Limited number of receptors
- Distribution of receptors is clonal → same type of receptors → recognize the same patterns
Characteristics of microorganisms → PAMPS
- Components of cell wall
- LPS
- PAMPS
RNA/DNA viruses
- Bacteria have specific patterns→ LPS
- DNA is also different
- Differences are being recognized
What are characteristics of tissue damage
DAMPS
- ATP/DNA leak out
- Components that are normally not exposed leak out of the cell
Cellular alarm systems→ pattern recognition receptors
- Toll-like receptors (TLR)
- C-type lectin receptors
- NOD-like receptors (nucleotide oligomerization domain)
- RIG-like receptors (retinoic acid-inducible gene)
TLR
- Most common receptors
o Outside of cells
o Endosome
o Cytosol
- NOD/RIG- like receptors
o RIG→ viruses
o NOD→bacteria
- TLR→ recognize bacterial cells
TLR
- Different components on different locations of the cell
- TLR mostly made out of RNA
- What happens when a TLR recognize a component in the cell?
