L11: Overview of Innate Immunity Flashcards
What activates the innate response?
PAMP receptors on innate immune cells
How do defensins work?
Amphipathic helical structures (polarized based on hydrophobic molecules). Can use electrical potential of bacterium to insert into membranes and create a pore.
What makes defensins?
neutrophils and macrophages. Gastrointestinal and repiratory tract cells.
some effector cells.
What does C5 initiate?
MAC (membrane attack complex)
What will recognition of a PAMP cause to change on the cell surface of an APC?
Initiate phagocytosis, inflammatory cytokine response and on the surface, expression of B7 on APCs
What will activation of a mannose receptor do?
promote phagocytosis by phagocyte without relaying an intracellular signal
What is a signaling PRR? What are the two main types?
membrane receptor that when activated will tell cell it has encountered a pathogen.
Two main types are Toll-like and NOD-like
What are Toll-like receptors?
membrane proteins that recognize microbial constituents and mediate signalling that initiates cytokine production
What are NOD-like receptors?
cytoplasmic proteins recognize microbial products and initiate signaling that results in production of inflammatory cytokines
What is TLR4 and what does it do?
It is a Toll-like receptor that recognizes gram negative bacteria and initiates cytokine production
What do TLR2 and TLR6 do?
It is a Toll-like receptor that recognizes gram positive bacteria and initiates cytokine production
What are secreted PRRs?
pattern recognition receptors that are secreted from host cells. (Ex: complement receptors, collectins, serum amyloid, CRP, mannose binding protein)
Most common are CRP and mannose-binding protein, which are both produced during the acute-phase response and can initiate complement activation
What does mannose-binding protein initiate?
lectin pathway
What does CRP initiate?
classical pathway in a nonspecific manner
What do C4 and C2 initiate?
classical pathway
What does C1 binding to CRP do?
initiate binding and cleavage of C4, which will produce a C4b that will bind to microbial membrane and initiate classical pathway
What does CRP bind to on microbial membranes?
phoshocholine
What cytokines will macrophages release during the innate response? What do they do?
IL-6, TNF-alpha, IL-1beta.
They initiate fever response.
TNF-alpha and IL1beta cause inflammation.
They also release IL-12 which activates NK cells.
How to IL-1, IL-6 and TNF-alpha released from macrophages affect liver?
promote production of acute phase proteins (CRP, mannose binding lectin), which will activate complement opsonization
How to IL-1, IL-6 and TNF-alpha released from macrophages affect bone marrow?
promotes neutrophil mobilization, which will promote phagocytosis
How to IL-1, IL-6 and TNF-alpha released from macrophages affect hypothalamus?
cause fever response
How to IL-1, IL-6 and TNF-alpha released from macrophages affect fat, muscle?
upregulates metabolism and activity to increase body temperature
What does TNF-alpha do?
contricts capillaries. (prevents dissemination of pathogens)
This can be problematic in sepsis because it will constrict blood vessels everywhere and potentially shut down organs
What are B1 B cells?
subset of B cells that respond to TI-2 antigens. They have a very limited Ig receptor repertoire, but specialize in recognizing carbs in bacterial pathogens
Could a 3 year old react to a TI-2 antigen?
No. The B1 B cell innate response system is not produced until about 5 years of age
What will a virus infected cell start secreting? What is the purpose?
IFN-alpha and beta. These make neighboring cells more resistant to infection. It also increases expression of ligands for receptors on NK cells. Also upregulates MHC class I and inhibitory ligand on neighboring cell surfaces.
What cell is the primary control of virus infected cell in an innate way?
NK cells that react to TNF-alpha and beta
What does an NK cell look for before killing a cell?
MHC class I. In virus infected cells it is not produced as much.
Can NK cells ever clear an infection?
No. They rely on MHC class I levels dropping, which doesnt occur until cell is already infected.
What is a MIC protein?
an activator on cell surfaces that will promote NK cell assassination
What does factor P do?
Properdin (protects). it binds to C3b in complement cascades and prevents factor H from marking it for degradation by factor I.
What would a mannorse or glucan PRR cause?
these are endocytic pattern recognition receptors and would promote endocytosis by phagocytes.
Which Toll-like receptor is important for binding flagellated pathogens?
TLR-5
What type of PRR is MBL?
Mannin-binding lectin is a secreted PRR. Will bind to variety of bacteria, viruses, fungi and protozoa. After binding, MASPs bind to it and become activated (they then cleave C2 and C4 to carry on lectin pathway.)
What does TNF-alpha do to capillaries near sites of infection?
it constricts them and causes clotting, preventing the pathogen from entering the blood stream and forcing it to enter the lymphatic system.
Which cytokines are associated with the acute-phase response?
IL-1, IL-6, TNF-alpha
Do B1 B cells undergo affinity maturation?
No. There is no memory response either.
Which of these are Type I interferons: IFN-alpha, IFN-beta, IFN-gamma?
IFN-alpha and beta.
Gamma is a beast of its own
