Immunology theme 1:
1. You can describe the global structure of the immune system.
The Immune system can be divided into 2 sub-categories:
Innate and Adaptive immunity. The innate immune system is a non-specific immune response that
can find and attack a microbe immediately. The adaptive immune system is specific, but only starts
to work after a few days.
Important parts of the innate immunity are:
Phagocytes (inflammation cells), Mast Cells,
NK cells (look for MHC I expression), DCs
(antigen presenting cell), complement
system
Important parts of the adaptive immunity:
B-cells (can proliferate and turn into antigen
producing cells), T-cells (Effector: CD4+ (Th1,
Th2, Th17) or CD8+, CTL, Regulator: Treg)
antibodies.
Another way to divide the immune system is into the
categories: Humoral and cellular. Humoral are components
(not cells) and are very effective against extracellular
microbes. Cellular are cell components that are very
effective against intra & extracellular microbes.
Humoral immune components:
Cytokines, antibodies (adaptive), complement (innate)
Cellular components are:
Macrophages, granulocytes, NK cells, DCs, T-cells, B-cells
Innate Adaptive
Response time Within a few hours Days/weeks
Specificity/Diversity Limited recognition of Very specific and diverse
pathogens, not very diverse.
Memory No Yes
Cells Phagocytes, dendritic, NK-cells, B & T-lymphocytes
mast cells.
Proteins Complement system, lectins & Antibodies
agglutines
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, 2. You know how cells are mobilized to initiate an immune response.
The immune system has 3 stages:
(1) Recognition phase – Recognition of antigen
(2) Induction phase – Which type of immune cells are induced
(3) Effector phase – Through what mechanism is the microbe induced.
(1) Recognition phase
During the first phase the microbes can be recognized by DCs because of specific PAMPs (Pathogen
associated-molecular pattern). The DC is able to phagocyte the microbe and put the peptides on an
MHC II molecule.
Thanks to the chemokines it the now mature DCs are migrated to the T-cell zones in the lymph
nodes, where they begin and look for the T-cell that recognizes the antigen on it’s MHC molecule.
(2) Induction Phase
A T-cell or B-cell that recognizes the microbe or peptide on the MHC molecule starts to proliferate.
This is called Clonal selection because only the cells that recognize the antigen are selected to
proliferate.
The type of T-cell that differentiates from the DC depends on the kind of MHC molecule it recognizes
(CD4+ for MHC II) (CD8+ for MHC I) and on the kind of cytokines they get (Th1, Th2, Th17)
The B-cell proliferates dependent on T-cells, and will the start
somatic hypermutations and Isotope switching (e.g. IgM for IgG)
(3) Effector Phase
- B-cells are able to produce specific antibodies against the
microbe, so they get opsonized for phagocytes and the
complement system.
- T-helper cells are able to move to the site of infection and recruit
specific inflammatory cells to the location.
- CTLs are able to recognize cells that are infected and send them
into apoptosis.
- Tregs are able to inhibit immune responses by other T-cells to
stop an immune reaction if needed.
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, 3. You understand how antigens can be recognized.
Antigens can be recognized by DCs If they present PAMPs (pathogen associated-molecular patterns)
the TLRs can recognize different PAMPs.
Another way for antigen to be recognized is if they are bound to the complement C3 protein or the
antibodies. The Fc side of antibodies can be recognized by several phagocytes.
4. You understand how ‘self’ and ‘non-self’ can be distinguished in general
Self and Non-self need to be distinguished by the immune system. The immune system needs to
avoid to respond to self-antigen.
The distinguishment for T-cells is done by negative selection in the thymus -> If a cell responds to the
self-antigen too heavily it will go into apoptosis.
Another way to distinguish is, are the macrophages who will not phagocyte cells if they do not
present PAMPs or DAMPs.
Another way is for NK-cells who only send apoptosis signals to cells that do not express MHC I
molecules on the membrane.
5. You know which immune cells are important for the specific immunity, which are
important for the non-specific immunity and how these cells can be distinguished from
each other.
Innate Immune cells are non-specific and travel all around the tissues and vessels. Adaptive immune
cells are created in the Bone Narrow and travel around the secondary lymphotic organs (lymph
nodes, Spleen).
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, Lecture 2:
1. You understand the role of the ‘innate immune response’ in the first defense against
infections. In particular, you know the principles of the complement system and the role of
cytokines in the early phase of the immune response.
The innate is the non-specific first line of defence. It consists of multiple inflammatory cells, antigen
presenting cells and the complement system.
Functions:
The main functions of the innate immune system are:
- Preventing microbes from invading (Or controlling the microbe that has invaded)
- Elimination of damaged cells, initiation of tissue repair
- Activation of the adaptive immune system (by recruiting immune cells to site of infection)
- Starting the protective reaction via inflammation
Innate components:
The innate immune system consists of a few important components:
(1) Phagocytes: (Macrophages, neutrophils, DCs)
These are important cell structures in the innate immune system. They are able to phagocytose
microbes and send signals to recruit specific lymphocytes to a site of inflammation.
Whenever they see a PAMP (such as lectin) or C3b on a microbe, they will
be able to bind to the PRR (Pattern recognition receptors) on the
macrophage. A bound microbe will go through the process of
phagocytosis.
With phagocytosis a microbe will enter a vesicle called: phagosome. This
phagosome is an internal extracellular vesicle.
This phagosome will fuse with a lysosome. When the macrophage is
activated (by IL-12 from NKs) it will kill the microbe with the use of
Reactive oxygen species (ROS). Which kills the microbe with Nitric oxide
(NO), ROS and lysosomal enzymes.
(See also figure 4.16 (pg. 87) in book)
These phagocytes are also carriers of MHC II molecules, and (especially DCs) are able to put them on
for presentation to CD4+ T-helper cells.
Neutrophils and macrophages are able to send signals (cytokines) for recruitment of immune cells.
(2) Innate Immune receptors.
Innate immune cells are able to recognize PAMPs and DAMPs (Pathogen/Damage associated
molecular pattern) With receptor groups called: PRR (Pattern recognition receptors). There are a few
different PRRs on innate immune cells, with TLRs (Toll-like receptors) as the most prominent ones.
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