Innate Immunity Flashcards
What cells belong to myeloid lineage?
- neutrophils
- basophils
- macrophages
- eosinophils
What cells belong to lymphoid lineage?
- B cells
- T cells
Activated macrophages secrete a range of…
Cytokines
Which cytokines are responsible for fever?
IL-6, TNF-α, IL-1
Which type of cell is most important in the innate immune response?
Neutrophils
What are the functions of the innate immune system?
Phagocytes, complement, cytokines and NK cells:
1) Promote clearance of pathogens and other debris
2) Recruit immune cells to the site of infection
3) Activate adaptive immunity via antigen presentation
What are the three functions of complement?
1) Opsonization of bacteria
2) Formation of the Membrane Attack Complex
3) Recruitment of phagocytic cells
Describe the process of the MBL pathway.
1) MBL binds to pathogen
2) C4 and C2 complement proteins are cleaved into C4a, C4b and C2a, C2b
3) C2a and C4b join together to form C3 convertase
4) C3 convertase cleaves C3 to C3a and C3b
5) C3b acts as a powerful opsonin and helps with MAC formation
6) C3a recruits more phagocytes
How does the classical pathway differ from the MBL pathway?
Very similar, except it is C1 that binds to the pathogen - either directly or to antibodies on its surface.
How is C5 convertase created and what is its function?
- Formed from C3b when C3b joins C3 convertase
- Cleaves C5 to form C5a and C5b
- C5a is soluble; recruits immune cells/promotes inflammation
- C5b initiates formation of MAC
Which complement proteins are most important for formation of MAC?
C5-C9
Lacking C5-C9 (and thus the MAC defense mechanism) makes one more susceptible to…
Neisseria infections
What are the major players in the INDUCED innate response?
Neutrophils
How do dendritic cells differ from macrophages?
Both cells are professional APCs, but dendritic cells are not very good at killing
How do APCs tell the difference between pathogen and host cells?
APCs have PRRs (pattern recognition receptors) that recognize PAMPs (found on various pathogens) and DAMPs
What are the four types of PRRs?
1) Free receptors in serum (ex. MBL)
2) Membrane-bound phagocytic receptors
3) Membrane-bound signalling receptors (ex. TLRs, fMLP)
4) Cytoplasmic signalling receptors (NLRs)
What does NFkB do and how is it activated?
Activated via toll-like receptors and nod-like receptors, NFkB induces expression of proinflammatory cytokines and antimicrobial peptides
Which cytokine is most important for recruiting neutrophils/inducing chemotaxis?
IL-8 (aka CXCL8)
What are cytokines produced by?
Activated macrophages (after complement cascade)
In COVID-19, ____ could lead to excessive inflammation and tissue damage.
Complement activity and cytokines
After IL-8 (CXCL8) binds to neutrophils, ___ (adhesion molecule) allows neutrophils to squeeze through tight junctions and into tissue via diapedesis.
LFA-1
What does the F-Met-Leu-Phe receptor do?
- Example of a membrane-bound PRR
- Activate intracellular signalling pathways
- Induce production of ROS in the phagolysosome
- How neutrophils cells can kill
How do neutrophils kill?
- Engulf and kill microbes to which they bind
- Contain cytoplasmic granules that hold antimicrobial peptides and granules
- Bacterial peptides such as fMLP will bind fMLP receptors and initiate signalling via Rac2, inducing production of NADPH oxidase
- NADPH oxidase creates superoxide ions and free radicals
- Superoxide dismutase converts superoxide ions to hydrogen peroxide, killing the pathogen
Which cytokines activate NK cells?
IL-12, IFN-α, IFN-β
What is the importance of NK cells?
Kill virus-infection host cells by releasing cytotoxic granules
