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Colleges Mechanisms of Disease 1

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February 19, 2025
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Theme 1
HC2 – Introduction to the immune system
https://www.osmosis.org/learn/Introduction_to_the_immune_system

Osmosis
• Handige videos
• High yield notes (pdf)
• Flashcards (to test yourself)

Innate immunity (fast, not specific, no memory) Farfalle + tomaat
Pathogen enters body → anatomical lines of defence (skin, cilia in lungs) → dendritic cells
(or macrophage) recognize what the pathogen is by taking a piece of the pathogen → they
distribute cytokines (similar to ‘smell’ of the sauce) to recruit help = chemotaxis →
neutrophils (and macrophages) first arrive at the site, and they start eating (= phagocytosis)!
The coating of the pathogen (by cytokines (the sauce)) is done by the complement
system. This is opsonization; done by complement system (= cascade of proteins,
that whenever a pathogen enters, it starts rolling and produces C3b so that the
pathogens become easier to eat by neutrophils).
Complement system = soluble molecules in your blood that are always ready for
action.

Slide

The goal of this system is to start the immune response so that there is time to prepare an
adaptive immune response.


Adaptive immunity (slow, specific, memory) Trofie + pesto
Antigen-presenting cell (APC) eats the pathogen and recognizes it as complicated; it
produces cytokines but at the same time it presents the MHC-molecule (silver platter to
demonstrate the pathogen) → it enters a lymph node to have the highest chance of meeting
the cells they need → T-helper cell connects with the APC and starts proliferating and
helping the B-cell with activating → they undergo clonal proliferation → the B-cell will
differentiate into a plasma cell → the plasma cells secrete antibodies (takes a few weeks)
(the plasma cells (and T-cells) took part in the immune response now have immunologic
memory & the next response will be faster and better) → the antibodies coat the pathogen
and this makes it easier to eat → macrophages (and neutrophils) recognize the antibodies

Two systems together
Innate and adaptive immunity meet when the macrophage / dendritic cell (who engulfed the
first trofie) presents the MHC in the lymph node.
Also, another moment when the two systems meet has to do with the complement system.
This system is also activated when it sees an antibody bound to a pathogen. Antibody is part
of adaptive immunity, and complement system is part of innate immunity.


Bigger pathogens (like parasites) Tortellini + parmesan cheese
• Mast cell picks up the tortellini and tastes.
• It starts producing cytokines to call the eosinophil.

, • The eosinophil releases granules (parmesan cheese); to punch holes in the wall of the
bacterium.
• This triggers multiple responses to destroy the bigger pathogen.
We will see reactions like this in asthma and acute allergic reactions.




HC3 – Mechanisms of innate immunity
Immunity
(1) Innate
a. Fast
b. Less specific
c. Does not improve.
d. No memory
(2) Adaptive
a. Slow
b. Highly specific
c. Improves with time.
d. Memory

These systems work together!!

Together, all innate immune response causes inflammation:
- Redness
- Swelling
- Heat
- Pain
- (functional loss)
Reactions that bring cells and soluble molecules of the immune system to sites of infection or
tissue damage.

Innate immune system
• Bio-mechanical barriers
o Skin
o Mucosa
• Soluble proteins
o Anti-microbial peptides
o Complement
o Cytokines / chemokines
o Acute phase proteins
• Cells
o Granulocytes
o Macrophages

Innate defense system
Biomechanical barriers are very important. Located on the outside of the body; skin, gut,
lungs and eyes/nose/mouth.
- Mechanical processes for protection.

, - Chemical processes to produce an environment that is not favorable for pathogens to
grow.
- Microbiological processes by normal microbiota in our gut; by being there
(occupying the space and using the nutrients) they prevent other bacteria from entering
and growing in the gut etc.




Different locations/pathogens need different type of response
Different elements of the immune system are deployed depending on the type of infection and
the location.
When pathogens are in extracellular space, you can reach them via different ways than
when the pathogens are intracellular. Look at the graph.
Once pathogens make it to the inside of the cell, they are no longer reachable by
complement proteins. You need specialized systems: NK-cells become activated
because they have the capacity to kill pathogens that are inside the cell.
Remember that for different pathogens that are present at different locations in the body, you
need different immune response.




Complement system
= cascade of soluble proteins and cell-bound receptors and inhibitors.
Mainly present in serum (in blood, in circulation).
Produced by a variety of cell types (especially hepatocytes).

Functions of complement
(1) Innate immunity
a. Can directly kill bacteria.

, b. Induce process of inflammation (it can interact with many different cells; both
from innate and adaptive immunity)
(2) Adaptive immunity
a. It instructs what types of B- and T-cells are needed.




Background on complement activation
Cascade of enzymatic activation. Three different pathways because they have different
recognition molecules:
(1) Classical pathway
a. Recognition molecule = C1q
(2) Lectin pathway
a. Recognition molecule = MBL
(3) Alternative pathway
a. Activated spontaneously by interacting with water.
This produces molecules which have to capacity to cleave the important C3-molecule. This
gives rise to biological active molecules (C3a, C3b, etc).
This pathway is activated spontaneously. You don’t want that. That’s why we have inhibiting
factor H.
Bacteria do not have factor H so the alternative pathway will be very active on bacteria.




C3 produces C3a and C5a which leads to chemotaxis.
C3 also produces C3b and this leads to opsonization.

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