2- Innate Immunity Flashcards
How does an exotoxin damage host tissues?
binds to a specific cell surface receptor
How does an endotoxin damage host tissues?
It stimulates phagocytes to secrete cytokines and cause local or systemic symptoms
What is the direct cytopathic effect?
Intracellular destrction by an an intracellular bacteria or virus.
What is the complement system?
The first defense against pathogens using proteins that coat and kill the bacteria.
What is the most important protein for the complement system?
C3
How is the alternative pathway activated?
Triggered by microbial surface membranes or other innate immunity components.
How is the lectin pathway activated?
Mannose-binding lectin binding to the pathogen surface.
How is the innate classical pathway activated?
CRP
How is the adaptive classical pathway activated?
By the binding of antibodies to the bacterial surfaces.
Cleavage of C3 peptide yields what 2 important complement proteins?
C3a and C3b
What is the function of C3a?
It’s an anaphylatoxin
What is the function of C3b?
It’s an opsonin
What is the function of C4b?
It’s an opsonin
What is the function of C5a?
It’s both an anaphylatoxin and chemotractant
What is the cause of hereditary angioedema?
A lack of C1 inhibitor. This allows the complement process to continuously run and causes edema in various organs and tissues.
What is the end result of the complement system?
Membrane Attack Complex (MAC)
What is the C# convertase of the alternative complement pathway?
C3bBb
Why is C3bBb the amplification step of the alternative pathway?
Since it’s the C3 convertase and bound to the surface of the pathogen, lots of C3b is made and covers the pathogen for opsonization.
What is the function of CR1?
Since it’s on the macrophage, it binds to C3b on the pathogen and eats it.
What is the function of CR3 and CR4?
Same as CR1. On the macrophage, binds to C3b and allows the macrophage to feast.
What proteins compose the MAC?
C5-9
What infections might occur if there is a deficiency in any C5-9 proteins?
Neisseria infections
What does the MAC do?
Make holes in the membranes of the bacteria.
How do C3a and C5a act as anaphylatoxins?
They induce smooth muscle contraction and degrtanulation of basophils and mast cells.
What is the general function of defensins?
They are + charged molecules that attract the - charged proteins of the pathogens, penetrate the membranes of the pathogens and destroy them.
Where are α –defensins from?
Neutrophils and other cells of innate immunity like Paneth cells of the GI
Where are β-defensins from?
Most epithelial surfaces- skin, respiratory, and urogenital tract.
What is the process of macrophage activation and completion of phagocytosis?
Macrophage recognizes pathogen structures using various receptors –> M0 binds the pathogen –> internalize in a phagosome –> lysosome fuses with phagosome –> everything in the phagosome is destroyed
What are toll-like receptors (TLR’s)?
They are signalling receptors on cells that allows the body to detect pathogens based on pathogen structures. The “watchdogs” of the body.
What are the function of IL-1β from macrophages?
They locally activate the lymphocytes and tissue destruction.
What are the functions of TNF- α from macrophages?
Locally they increase vascular permability, systemically they induce fever.
What are the functions of IL-6 from macrophages?
Induce fever systemically
What is the function of CXCL8 (IL-8) from macrophages?
It’s a local chemotactic factor for PMN’s
What are the functions of IL-12 from macrophages?
Locally they activate NK cells to secrete IFN-γ
How does LSP activation of macrophages lead to septic shock?
LPS causes a widespread production of TNF- α, which dilates blood vessels and causes a massive leakage of fluids into tissues throughout the body.
What are the 1st type of WBC to a site of infection?
Neutrophils
How are neutrophils attracted to a site of infection?
CXCL8 from macrophages and C5a from the complement
What are the 4 steps of extravasation of neutrophils into tissues
- Rolling adhesion (selectins on neutrophil bind to vessel wall), 2. Tight binding (using integrin and CXCL8), 3. Diapedesis (sqeeze through the wall), 4. Migration (using CXCL8 gradient to infection)
What is the cause of the respiratory burst?
Neutrophils, when they eat, increase O2 consumption, subsequently making superoxide radicals and H2O2
What are the 3 proinflammatory cytokines?
IL-1, IL-6 and TNF-α
What occurs during the acute phase response?
Acute phase proteins like mannose-binding lectin and CRP are made to enhance fixation of the complement on pathogens.
What are the 2 functions of CRP?
Act as an opsonin and it triggers the classical complement pathway
What are the 2 main functions of IFNα and IFNβ?
- to interfere with viral replication and 2. activate NK cells to kill virus infected cells.
What are the 2 main functions of NK cells?
- to kill the infected cells using cytotoxic granules and 2. to release IFN-γ which recruits macrophages to the infection.
What receptor on NK cells bind to the MIC-A and B of infected cells?
NKG2D
