Summary of Immunopharmacology

IMMUNOPHARMACOLOGY
Rijksuniversiteit Groningen

,Contents
College 1: Introduction................................................................................................................................4
Things you need to know for the exam:...................................................................................................4
Case study - rheumatoid arthritis:...........................................................................................................4
Immune system.......................................................................................................................................4
Composition.........................................................................................................................................5
Immune system cells............................................................................................................................7
Solid lymphoid tissues.............................................................................................................................8
Lymph nodes:.......................................................................................................................................9
Spleen:...............................................................................................................................................10
Lymphoid tissues................................................................................................................................11
Additional information...........................................................................................................................13
Lecture 2: Innate immunity........................................................................................................................15
Cellular alarm systems...........................................................................................................................15
General information...........................................................................................................................15
Pattern recognition receptors kinds...................................................................................................16
Cytokines...........................................................................................................................................17
Epithelial barriers and lymphoid innate cells:........................................................................................18
The physical barrier:..........................................................................................................................19
Myeloid tissue-resident cells..............................................................................................................19
lymphoid innate cells:........................................................................................................................22
Help from the bone marrow..............................................................................................................24
The complement system and inflammation:..........................................................................................27
Additional information...............................................................................................................................28
Lecture 3: Adaptive immune system..........................................................................................................30
Composition...........................................................................................................................................30
Antigen presenting cells.....................................................................................................................31
Antigen presentation by MHC............................................................................................................32
How do T and B cells recognise antigens?.............................................................................................35
Types of immunoglobulins (antibodies):................................................................................................37
How do T and B cells develop?..............................................................................................................38
The development of B cells:...................................................................................................................38

, Development of T lymphocytes in thymus:............................................................................................40
Additional information...........................................................................................................................41
Lecture 4: T cell responses.........................................................................................................................48
Which signals and receptors are necessary for T cell activation?...........................................................48
How do we get from a few antigen-specific T cells to an enormous army of effector T cells?...........53
What do T cells produce for an effective response?..........................................................................54
T cell migration:.................................................................................................................................58
Contraction........................................................................................................................................58
Additional information...........................................................................................................................58
Lecture 5: B cell responses.........................................................................................................................61
B cell stimulation and T cell independent antibody responses (0production):......................................61
T cell independent:............................................................................................................................63
T cell dependent................................................................................................................................64
Effector mechanisms of antibodies:.......................................................................................................69
Neutralisation....................................................................................................................................69
Opsonisation:.....................................................................................................................................69
Antibody-directed cellular cytotoxicity (ADCC):.................................................................................69
Complement activation – immunoglobulins:.....................................................................................70
Vaccinations:..........................................................................................................................................73
Passive vaccination:...........................................................................................................................73
Active vaccination:.............................................................................................................................73
Additional information.......................................................................................................................75
Lecture 6: Tolerance in the immune system..............................................................................................76
Central tolerance...................................................................................................................................76
Peripheral tolerance..............................................................................................................................76
Anergy................................................................................................................................................76
Suppression.......................................................................................................................................77
Deletion.............................................................................................................................................77
Failing tolerance:....................................................................................................................................77
Asthma...............................................................................................................................................77
Too much tolerance – tumors:...............................................................................................................78
Cross presentation.............................................................................................................................78
Tumors can also downregulate MHCI expression...............................................................................78

, Important in central and peripheral tolerance.......................................................................................78
Regulatory T cells...............................................................................................................................78
Types of regulatory T cells..................................................................................................................79
Transplantations:...................................................................................................................................79
Bone marrow transplantation............................................................................................................80
Blood(cell) transfusion.......................................................................................................................81
Pregnancy – the perfect transplantation:..........................................................................................81
College 7: Drugs for and from the immune system....................................................................................83
Glucocorticosteroids:.............................................................................................................................83
Glucocorticosteroids has multiple functions:.....................................................................................84
Calcineurin inhibitors:............................................................................................................................85
Inhibitors of proliferation signals:..........................................................................................................86
Rapamycin:........................................................................................................................................86
Mycophenolate Mofetil (MMF):.........................................................................................................86
Other drugs:...........................................................................................................................................86
Cytotoxic drugs......................................................................................................................................87
Biologicals:.............................................................................................................................................88
Additional information...........................................................................................................................89
Development of CD4+ and CD8+........................................................................................................89
Lecture 8: USING IMMUNOLOGY FOR DIAGNOSTICS AND RESEARCH.......................................................91
ANTIBODIES...........................................................................................................................................91
MONOCLONAL AND POLYCLONAL ANTIBODIES.................................................................................92
LABELS OF ANTIBODIES......................................................................................................................93
DIRECT AND INDIRECT IMMUNODETECTION.....................................................................................94
TECHNIQUES USING ANTIBODIES......................................................................................................94
Flow cytometry analysis and use:....................................................................................................102

,College 1:
Introduction
Things you need to
know for the exam:
1. Basic immunology: chapter 1-11
2. Basic & Clinical Pharmacology: chapter 55
3. Paper: The 5 Rs of glucocorticoid action during inflammation – Busillo and Cidlowski in
4. Trends in Endocrinology and Metabolism 2013 (Nestor)
5. Paper: Flow Cytometry: basic principles and applications – Adan et al. 2016 (Nestor)
6. Paper: A short history, principle, and types of ELISA – Suleyman Aydin 2015 (Nestor)
7. Introduction to Western Blotting – Claire Moore (Nestor): chapter 14
8. Online classes on Nestor including the classes on SARS-CoV-2 and COVID19


Case study -
rheumatoid arthritis:
 What is rheumatoid arthritis?
 Rheumatoid arthritis is an auto-immune disease of the joints





Immune system
 Why is immune system important?
 The immune system tries to restore a balance (homeostasis)
 How is the balance disturbed?

,  Defence against invaders
 bacteria, virusses, fungi, parasites and objects.
 Removal of: dead cells, tumors and tumor cells, artificial objects and damaged molecules





 What are the requirements for effective immunity?
 Barriers for prevention
 Recognition
 Detection and identification of the foreign substance
 Communication and organization
 Coordination to mount the most optimal immune response
 Effector mechanisms
 To destruct or suppress the invading pathogen



Composition
 Innate immunity
 What is the innate immunity?
 the immunity you are born with.
 Why it innate immunity important? This protects you from before you were born.
 What are the characteristics of innate immunity?
 It can react fat
 How does the transformation of innate immunity to adaptive immunity work?
 There are epithelial barriers, but those are not enough. There are also tissue-resident
immune cells. If those cannot handle the bacteria, they call in the help from the bone
marrow. There are also cells from the bone marrow and tissues that clean up tissue damage.
If those cannot handle it, the adaptive immune systems is called in. This gives specialized
help from lymphocytes.
 What connects innate with adaptive?
 Antigen-presenting cells (APC) that present the antigen to T cells
 They are constantly sampling of antigens and decide if you need an immune
response or not.
 How is the antigen presenting work?
 They break the antigen down to little pieces and present it to T cells.
 What are the APC?
 Those are cells that phagocytoses stuff, strategically located in the
 tissues that are being exposed to the outside world a lot.
 Dendritic cells
 Travel through the body  major APC Importance
 Macrophages
 Stay in the tissue miner APC importance

,  The APCs patrol tissues, especially the ones that connect to the outside
world. Lymphocytes patrol the body looking for antigens they recognize.
They find each other in lymphoid structures and communicate with each
other there and exchange information.










 How does the innate immune system work?
 In case of skin mucosal, which it the first barrier in the innate immune system, barrier is
broken  innate immune system reacts fast by releasing compounds in the
 Humoral (in solutions): consists of complement.

 important
 Cellular: consists of granulocytes, macrophages,natural killer cells.


 Adaptive immunity
 What is adaptive immunity?
 the immunity you have to develop
 Why is innate adaptive important?






,  What are the characteristics of adaptive immunity?
 It reacts slow
 What are the phycological composition of adaptive immune system?
 Lymph nodes:
 Spleen:
 Langerhans cells
 Comparison between innate immune system and adaptive immune system







Immune system cells
 All leukocytes (= white blood cells) develop from stem cells in bone marrow OR yolk sac/fetal liver
 The stem cell develops into a progenitor cell that can differentiate into many types of cells
 A stem cell from bone marrow can become a myeloid progenitor (innate immune system) or a
lymphoid progenitor (adaptive immune system).
 What is meant with ‘myeloid’’?
 “myeloid” is an adjective meaning “relating to bone marrow”
 The myeloid progenitor can become a lot of different cells: red blood cells
(erythrocytes), platelets, basophils, eosinophils, neutrophils, monocytes and
macrophages. But macrophages can also develop from yolk sac cells and fetal liver cells.



 A lymphoid progenitor can become a B or T cell or a natural killer cell.
 All myeloid cells are innate immune cells, but not all lympoid cells are adaptive immune
cells. Because natural killer T cell and γδ-T cells are part of the innate immune system.

 There are two types of T-cells:
 Where are the t-cells developed?
 T cells develop in the bone marrow from the lymphoid progenitors. They
migrate to the thymus to develop into naïve T cells.
 what is the function of naïve T cells?
 They now know what is self and what is non-self.
 Naive T cells develop into effector T cells after recognition of
an antigen.



 T-helper cells:

,  What is the function of T-helper cells?
 they investigate and tell other cells what to do. They also help other cells
 Cytotoxic T cells
 What is the function of Cytotoxic T cells?
 they kill cells themselves.
 B cells
 What are the b cells?
 Where are the B cells developed?
 B cells develop in the bone marrow from the lymphoid progenitors and stay in bone
marrow to develop into naive B cells.
 What is the function of naïve b cell?
 Searching for antibody
 Why? To become into antibody-producing plasma cells.


 What is the function of B cells?
 help in protecting
 They make antibodies and spread them around (The B cell itself does not much, the
antibodies do the work.)








Solid lymphoid
tissues
 What the kinds of lymphoid tissues?
 Primary lymphoid tissues (generative lymphoid organs):
 these are the generative lymphoid organs like the bone marrow
(generation of all immune cells: myeloid cells and lymphoid cells)
and the thymus (maturation of T cells, selection for non-self-
reactive T cells). The immune cells develop and mature here.

, 
 Secondary lymphoid organs (sites for initiation of immune responses):
 These are on sites where immune responses are initiated. The immune cells can meet other
cells and antigens here.
 What is an antigen?
 Any molecule that is specifically recognized by lymphocytes or antibodies





Lymph nodes:
 The circulation drains (saheb) all the fluids in tissues from microbial antigens and dendritic cells and
delivers these to lymph nodes.
 The immune cells in the lymph node sense and intercept pathogens preventing their spread
throughout the body by initiating an immune response.
 The lymp nodes have specific areas.
 The T cells are more inside the lymph node (paracortex)
and the B cells are on the outside (cortex).
 The antigens and dendritic cells come in via lymphatic
vessels (afferent lymph vessel ). When they have traveled
through the lymph node they will leave again (efferent
lymph vessel).
 Cells come from blood veins






