Lecture 16 - Elimination of Extracellular Microbes and Toxins Flashcards
What generates the effector responses of Abs and what portion of the Ab mediates the response?
L16 S5
Effector functions of Abs are triggered by Ag binding.
Effector function is mediates by Fc region.
What are the effector functions of Abs?
L16 S6
Neutralization
Opsonization
-phagocytosis
Sensitization for Ab-dependent cellular cytotoxicity
Activation of complement
- inflammation
- lysis
- phagocytosis
How do antigens neutralize microbes and toxins?
L16 S11-13
Microbe neutralization:
-Ab bind/block functional portion of microbe preventing them from interacting with host cell
Toxin neutralization:
-Ab binds toxin preventing it from binding to host cell receptors
What are the types of Fc receptors, what is their affinity for Fc, what cells are they found on, and what function do they elicit?
L16 S15
FcγRI (CD64):
- high affinity (IgG3 > IgG1)
- Mφ, PMN, eosinophil
- phagocytosis/activation
FcγRII (CD32):
- low affinity
- APCs, PMN, and NK
- phagocytosis, activation, feedback inhibition
FcγRIII (CD16):
- low affinity
- NK
- Ab-dependents cell-mediated cytotoxicity
FcεRI:
- high
- Mast cells, basophils, and eosinophils
- activation (degranulation)
What is the mechanism of Ab-mediated phagocytosis?
L16 S17
- IgG binds antigen (opsonization)
- Ag-Ab complex binds FcγRI of phagocytic cell
- FcγRI stimulates phagocytosis
What is the mechanism of Ab helminth elimination?
L16 S21
-naïve T cell is activated by presentation of helminth antigen
Effector T cell:
- activates eosinophils with IL-4 and IL-5
- stimulates B cell isotype switching to IgE with IL-4 and IL-6
- activates mast cells with IL-4 and IL-13
IgE binds soluble and membrane bound Ag:
- membrane bound Ag bound IgE stimulates degranulation of activated eosinophil by binding FcεRI
- soluble Ag bound IgE stimulates degranulation of mast cells by binding FcεRI
What is the mechanism of Ab-dependent cellular cytotoxicity?
L16 S22
- Ab binds cell surface Ag
- Ab-Ag complex binds FcγRIII of NK cells activating them
- activated NK cells release pro-apoptotic factors killing target cell
What are the ligands of CR1, where is it located, and what are its functions?
L16 S44
Ligands:
- C3b
- C4b
- iC3b
Location:
-phagocytes, PMN, B/T cells, FDC, erythrocytes
Functions:
- phagocytosis
- clearance of immune complexes
- dissociation of C3 convertase via cleavage of C3b and C4b
What are the ligands of CR2, where is it located, and what are its functions?
L16 S45
Ligands:
- C3d
- C3dg
- iC3b
Location:
- B cells
- FDCs
- nasopharyngeal epithelium
Functions:
- signal 2 for B cell activation
- trapping of Ag in GC by FDC
- receptor for Epstein-Barr virus (EBV)
What are the ligands of CR3 and CR4, where are they located, and what are their functions?
L16 S46
CR3 is also know as Mac-1
Ligands:
- iC3b
- ICAM-1 (CR3 only)
Locations:
-phagocytes, PMNs, and NKs
Function:
- phagocytosis
- cell adhesion (leukocyte adhesion to endothelium via ICAM-1)
What are the soluble complement regulators, what are their lignads, and what pathway are they associated with?
FH, FI, FD, FP, C1-INH, Clusterin, and Vittronectin
L16 S48
Factor H:
- C3b and C3d
- AP (dissociation of Bb form C3 convertase
Factor I:
- C3b and C4b
- CP, LP, and AP (degrades C3b)
- CP and LP (degrades C4b)
Factor D:
- C3b, C3bB, and C3bBb
- AP (activates FB )
Properdin:
- C3b, C3bB, and C3bB
- AP (stabilizes C3 and C5 convertase)
C1-INH:
- C1r, C1s, and MASPs
- CP and LP (prevents activation)
Clusterin:
- C7, C8, C9, MAC
- CL, LP, and AP (prevents MAC assembly)
Vitronectin:
- C5b-C7 and MAC
- CL, LP, and AP (prevents MAC assembly)
What are the membrane associated complement receptors, what are their lignads, and what pathway are they associated with??
L16 S49
MCP (Membrane cofactor protein):
- C3b and C4b
- CP, LP, and AP (decays C3 convertase)
DAF (decay accelerating factor):
- C3b and C4b
- CP and LP (decays C3 convertase)
CR1:
- C3b and C4b
- CP, LP, and AP (decays C3 convertase)
CD59:
- C8 and MAC
- CP, LP, and AP (inhibits MAC)
What are the main complement deficiencies and their associated result?
L16 S57
C2:
-most common
