,Lecture 1 – Introduction
3 phases of immune response :
1. Recognition phase → by APCs
- How is the antigen recognized?
- How does the structural diversity of receptors arise?
- How distinguished between self and non-self.
2. Induction phase
- Induction of an immune response or tolerance?
- Which type of response?
3. Effector phase
- How do the effector mechanisms operate?
- How is an immune response terminated?
- How is memory established and maintained?
2 signals required for activation of naive lymphocytes.
1. Signal 1 by recognition of antigen.
2. Second signal (co-stimulation / cytokines).
Lecture 2 – Innate immunity
Pathogen :
1. Gain access to body.
2. Attach to and/or enter cells of host via receptors.
3. Reproduce while avoiding immune system long enough to produce harmful changes.
Function of innate immune system :
- Prevents, controls or eliminated invading microbes.
- Elimination of damaged cells and initiation of process of tissue repair.
- Activation of adaptive immune system.
Components of innate immune system :
o Patrolling cells : attack pathogens without memory (phagocytes and NK cells)
o Innate immune receptors : recognizes features common to many pathogens.
o Proteins : complement, acute phase proteins and cytokines.
Induction of inflammation :
Leukocytes : white blood cells that help fight inflammation.
- Only adhere to veins, not arteries.
- Crawling along the walls → when attached, squeeze
between endothelial cells without rupturing the wall.
, Macrophages and neutrophils can engulf and digest bacteria.
- Macrophage has extensions to see if they can feel pathogens.
- Neutrophil search/smell for pathogens and when found engulfing.
- Important process → phagocytosis .
Recognition and pahocytosis mediated by PAMPs and PRRs.
o PAMPs : pathogen-associated molecular patterns.
- Expressed on large group of pathogens.
- Conserved and not subject to antigenic variability.
- Pathogens cannot change them because they are essential
for survival or pathogenicity.
- Distinct from self-antigens.
- Different pathogens have different kind of DNA/parts of
the cell that are not in our body → alarm signals for innate system.
o PRRs : pattern-recognition receptors.
- Expressed on pathocytes.
Toll-like receptors (TLRs) : leads to inflammatory response.
- Different receptors recognize different PAMPs.
o Cell surface TLRs : recognize bacterial cell wall structures.
o Intracellular TLRs recognize pathogen nucleic acids.
- When binding to PAMP → signaling cascade will form → depending on TLR can be different
signaling pathways → can activate transcription facto that lead to inflammatory signal /
activation of IRS (needed for anti-viral state).
Complement system
A set of circulating and cell surface proteins that act in a
cascade to :
1. Opsonize microbes.
2. Promote recruitment of phagocytes.
3. To attack and kill extracellular pathogens
Can be activated by 3 different pathways :
o Classical pathway : recognition of IgM antibody.
o Lectin pathway : recognition of Mannose structures on microbes.
o Alternative pathway : Ficolin → binding to N-acetylglucosamine on wall.
- All activate C3 protein
When activated compliment system → C3 is cleaved into C3a + C3b component.
- C3b coats microbes to promote binding of phagocyte (more easily recognized).
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