PCB Immunology Exam 4

IgM & IgG

Binding to pathogen surface and initiating complement cascade (classical pathway)

Lectin Pathway (Mannose-binding)

binding to carbohydrates on microbial surface and initiating complement cascade

C1q (Bioactive fragment of C1)

initiates classical pathway by binding Ig binding to apoptotic blebs and starts phagocytosis of apoptotic cells

C1r (Bioactive fragment of C1)

Serine protease, cleaving C1r and C1s

C1s (Bioactive fragment of C1)

serine protease, cleaving C4 and C2

Anaphylatoxin

mediator of inflammation, degranulation (e.g. C3a/C5a —> Histamine

Classical Pathway

presence of specific Ab

Alternative Pathway

absence of specific Ab

Lectin Pathway

of specific Ab & presence of mannose

All pathways eventually make

Cb5 & Membrane Attack Complex (MAC)

L-929

Mouse Fibroblast cell line; often used in DNA transfection studies and to assay tumor necrosis factor (TNF)

SP2/0

Non-secreting mouse myeloma; often used as a fusion partner for hybridoma secretion

CTLL-2

Mouse t-cell line whose growth is dependent on IL-2; often used to assay IL-2 production

Jurkat

Human T-cell leukemia that secretes IL-2

P815

Mouse mastocytoma cells; often used as target to assess killing by cytotoxic T lymphocytes (CTLs)

Heterokaryon

multinucleate cell with genetically different nuclei

Hybridoma

clone with a single nucleus containing chromosomes from each fused cell

Zymogen (proenzyme)

remain inactive until proteolytic cleavage removes the inhibitory fragment, exposing the active site. Starts enzyme cascade.

Cascade function

activation of C3 leads to functioning of other components (C1-C9)

C2a (both pathways)

serine protease. With C1 and C4b, is a C3 convertase

C2b (Classical and lectin)

Inactive in complement pathway. Cleavage of plasmin releases C2 kinin, a peptide that stimulates vasodilation. Anaphylotoxin.

C4b (Classical and lectin)

Binds microbial cell membrane via thioester bond. With C1 and C2a, is a C3 convertase.

C4a (Classical and lectin)

Has weak anaphylatoxin activity

C4c, C4d (Classical and lectin)

Proteolytic cleavage products generated by factor I

C3a (Classical)

Anaphylatoxin. Mediates inflammation signals via C3aR.

C3b (classical)

Opsonization, tagging immune complexes, pathogens, and apoptotic cells for phagocytosis with C4b and C2a, forms the C5 convertase. With Bb, forms the C3 convertase.

C3c and C3d or C3dg (classical)

Proteolytic fragments of iC3b generated by factor I. C3d/dg bind antigen and to CR2, facilitating antigen-binding to B cells. C3c binds CRIg on fixed tissue macrophages.

C5a (all)

Anaphylatoxin binding to C5aR induce inflammation

C5b (all)

Component of MAC. Binds cell membrane and facilitates binding of other components of the MAC.

C6 (all)

Component of MAC. Stabilizes C5b. In the absence of C6, C5b is rapidly degraded.

C7 (all)

Component of MAC. Binds C5bC6 and induces conformational change allowing C7 to insert into interior of membrane

C8 (all)

Component of MAC. Binds C5bC6C7 and creates a small pore in membrane

C9 (all)

Component of MAC.10-19 molecules bind C5bC6C7C8 and create large pore in membrane

S protein (soluble)

binds C5b67 and prevents insertion into host cell membrane

CR1 (CD35)

binds C3b, C4b, C1q, iC3b - clearance of immune complexes, enhancement of phagocytosis, regulation of C3 breakdown. Blocks formation of C3 convertase, C4b2a and C3bBb.

CR2 (CD21)

binds C3d, C3dg (human), C3d (mouse), iC3b - B cells and FDCs

CR3 (CD11b/CD18, Mac-1)

binds iC3b and factor H - Monocytes, Macs, neutrophils, NK cells, FDCs, T cells

CR4 (CD11c/CD18)

iC3b-mediated phagocytosis

C3aR

binds C3a - induces degranulation

C5aR (CD88)

induces degranulation; chemoattraction acts with IL-1B and TNF-a to induce acute phase response; induces respiratory burst in neutrophils

C1INH (fluid)

C1 inhibitor binds C1r2s2, causing dissociation from C1q

Protectin (CD59)

binds C5b678 on host cells, blocking binding of C9 and the formation of the MAC complex

Systemic Lupus Erythematosus (SLE)

Deficiencies in C1, C2, C4 and CR1

Introns

non-coding regions

Poly-A Tail

Aids in mRNA stability, Translation termination