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Notes 1-10 | 8TC00 Immunology and Infection
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Immunology and InfectionIntroduction
The biggest immunologic problems are allergies, which are heavy reactions of the body
towards certain non harmful objects. Immunologie is belangrijk in:
- Transplant rejections
- Immune deficiencies: primary & secondary
- Tumor immunology: defence & therapy
- Hypersensitivities: Allergy & autoimmune diseases
Het immuunsysteem
Het doel van het immuunsysteem is het afweren van (van groot naar klein):
- Fungi
- Parasieten
- Bacteriën
- Virussen
- Prionen
De omstandigheden die het immuunsysteem tegenwerken zijn:
- Tumoren
- Auto-immune responses
- Allergenen
- Voeding
- Toxines
- Stress
- Zenuwstelsel
- Genetische modificaties
Wanneer een pathogeen de barrière van de huid doordringt is de eerste respons van het
lichaam het activeren van “the innate immune system”. Dit systeem doet het volgende:
Innate system (response time = minutes)
- Phagocyten eten de meerderheid van de
pathogenen op
Adaptive specific memory system (rp = 1 week)
- Dendritic cells activeren T helper cells
→ activeren CTL → doden pathogenen
- T helper cells activeren B cells →
maken antibodies → maken doden
makkelijker voor phagocyten
,In short, there are two levels of immunity:
1. General immunity → global protection
- Barriers → Skin, epithelial cells in the GI tract
- Innate immunity → phagocytes
2. Adaptive immunity → recruited to sites of infection, effective in days to a
week
The innate immune system:
Constituents of this system are all called white blood cells or leukocytes:
- Dendritic cell → antigen presenting cells, bridge between the
innate and adaptive immune system.
- Macrophage → WBC that goes phagocytosis
- Helper T cell → CD4+ that helps others by cytokine release
- Natural killer cell → NKC that acts like CTL
- Natural killer T cell → combination of the above
- Complement protein → a group of serum proteins that are circulating
in inactive form. Once activated: membrane lysis of target cell (C9),
chemotaxis (C5a/C3a), opsonization (C3).
- Granulocytes → Consist of 4 different types:
1. Neutrophil → 60-65% WBC, phagocytosis
2. Eosinophil → 2-3% WBC acidophil kills parasites
3. Basophil → 0.5-1% WBC huge and inflammation
4. Mast cell → in connective tissue → wound healing & allergies
The adaptive immune system:
Constituents of this system are:
- B cell → creates antibodies
- Antibodies → help immune system
Lymphoid tissues
There are primary and secondary lymphoid tissues. The primary ones directly create T and
B cells. These tissues are:
1. Bone marrow → creates T cell precursors and B cells
2. Thymus → creates T cells
The secondary lymphoid tissues are:
1. Lymph nodes
2. Peyer’s patches (immune lymph node inside the
small intestine)
3. Spleen
Phagocytes and microorganism recognition
The main way in which phagocytes can determine whether
another microorganism is dangerous, is by pattern
recognition. This works as follows: PRRs (pattern
recognition receptors) are used to recognize certain
pathogens.
, The PAMP (pathogen associated molecular pattern) has a function…
The TLR (Toll-like receptor) can recognize different groups of pathogens.
When a macrophage detects a microbe, it can convert itself into two different states:
1. Activated state → mostly try to kill microbes, a little bit of repair.
2. Alternatively-activated state → mostly try to repair, a little bit of killing.
There are three different kinds of dealing with invaders:
1. Direct killing of the microbe → phagocytes
2. Killing of an infected cell → lymphoid cells like
NK or T cell
3. Expulsion or tissue repair → granulocytes like
eosinophils
Apoptosis
This mechanism is mostly induced by NK cells and cytotoxic
T cells. The mechanism works as follows:
1. The defending cell binds to the target cell
2. Granules filled with perforin and granzymes move towards the target cell
3. The perforin creates pores and the granzymes enter the target cell
4. The target cell will commence apoptosis
Alternative method:
1. The defending cell binds to the target cell through a Fas ligand
2. Upon binding of the Fas ligand, apoptosis is initiated
Antibodies AKA: immunoglobulin
These are always made of two heavy and
two light chains. All chains are connected
through disulfide bonds. The endings of
both sides are hypervariable. Antibodies
have four main functions:
1. Complement activation (IgM) →
Pentamer, initiate complement
activation.
2. Neutralisation (IgA) → Dimer, prevent infection by blocking binding sites.
3. Opsonization (IgG) → Monomer, makes phagocytosis much more efficient.
4. Allergic reactions (IgE) → Dimer, initiate allergic reactions through mast
cells or basophils.
Onthoudt: Ig MAGE
M - niet mono-, maar pentameer → complement activation.
A - 2e letter, dimeer → prevent infection.
G - gangsta, monomeer → opsonization
E - eeewwww, dimer → allergic reaction + clear parasites.
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