Janeway 9 49 part 2
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Janeway 9.49 part 2. Roitt 12.22. Roitt 4.1. A Cascade of Proteases Is A Biological Amplifier. Protease cascades as biological amplifiers. Ucker, 2000. Classical Activation Pathway. C4b. C3b. The Classical Activation Pathway. The small fragments act as soluble mediators. C3a. C2b.

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Janeway 9.49 part 2

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Janeway 9 49 part 2

Janeway 9.49 part 2


Roitt 12 22

Roitt 12.22


Roitt 4 1

Roitt 4.1


Protease cascades as biological amplifiers

A Cascade of Proteases Is A Biological Amplifier

Protease cascades as biological amplifiers

Ucker, 2000


Classical activation pathway

Classical Activation Pathway

C4b

C3b

The Classical Activation Pathway

The small fragments act as soluble mediators

C3a

C2b

C5a

C4a

C3

C5

C6

C7

C8

C9

C2

C4

C1

MAC

Ab

C5b

C6

C7

C8

C9

C2a

Membrane

The large fragments function by binding to membranes

(esp. pathogen membranes)

Ucker, 2002


Roitt 4 2

Roitt 4.2


Janeway 9 36

Janeway 9.36


Janeway 9 34

Janeway 9.34


Janeway 9 35

Janeway 9.35


Janeway 9 32

Janeway 9.32


Janeway 9 37 i

Janeway 9.37(i)


Thioester mediated binding of c4b

Thioester mediated binding of C4b

THIOESTER-MEDIATED BINDING OF C4b

TO THE SURFACE OF APATHOGEN

C4a

C4

C4b

C4b

Pathogen

Ucker, 2000


Janeway 9 37 i iii

Janeway 9.37(i-iii)

Note C2a / C2b nomenclature is reversed here

(figure taken from Janeway et al.)


Roitt 4 7

Roitt 4.7


Thioester mediated binding of c3b

Thioester mediated binding of C3b

THIOESTER-MEDIATED BINDING OF C3b

TO THE SURFACE OF APATHOGEN

C3a

C3

C3b

C3b

Pathogen

Ucker, 2000


Roitt 4 16

Roitt 4.16


Roitt 4 8

Roitt 4.8


Roitt 12 10

Roitt 12.10


Amplification loop

Amplification Loop

Amplification Loop

B

C3b

C3a

C3bB

D

C3

Ba

Properdin

stabilization

C3

C3

C3bBb

(C3 convertase)

One C3 convertase molecule cleaves many C3 molecules.

C3b interacts with factor B, and more C3 convertase is generated.

Hanley, 1998


Roitt 12 13a

Roitt 12.13A


Roitt 12 13

Roitt 12.13


Two major pathways for complement activation

Two Major Pathways for Complement Activation

Classical Pathway

Alternative Pathway

C1 +

Ag-Ab, C4, C2

Factors

B, D, P

, C3, + Bacteria

C3

Initiation

(C4b2a) C3 Convertase

C3 Convertase (C3bBb)

Amplification

Loop

Amplification

(and production of

biologically active

fragments)

C3a

C3a

C3

C3b

C3b

b

(C4b2aC3b) C5 Convertase

C5 Convertase (C3bBbC3b)

C5 --> C5a + C5b

C5b + C5a <-- C5

Membrane

+ C6 + C7 + C8 + C9

attack

C5b6789 [MAC]

Hanley, 1998


Roitt 4 13 panel 1

Roitt 4.13 panel 1


Janeway 9 49 part 21

Janeway 9.49 part 2


Complement is a self limiting cycle

Complement is a self-limiting cycle

Ucker, 2000


Regulators of complement activation

Regulators Of Complement Activation

  • Regulators Of Complement Activation

  • Regulators of C3 convertase assembly and destruction:C4b-BP, MCP, CR1, Factor H, DAF (assembly),Factor I (destruction)

  • Regulators of the lytic pathway (MAC assembly inhibitors):HRF, MRL

  • Regulators of C1 esterase activity:C1INH(Deficiency = Hereditary Angioneurotic Edema)

Ucker, 2000


Roitt 4 71

Roitt 4.7


Roitt 4 12

Roitt 4.12


Roitt 12 11

Roitt 12.11


Roitt 4 13

Roitt 4.13


Complement control proteins adapted from janeway 9 50

Complement Control Proteins (adapted from Janeway 9.50)


Complement receptors adapted from roitt 4 15

Complement Receptors (adapted from Roitt 4.15)


Leukocyte adhesion deficiency

Leukocyte Adhesion Deficiency

  • Defects In Complement Receptor Proteins

  • Leukocyte Adhesion Deficiency Type I

  • Cells lack CR3 and CR4, which are Integrins (adhesion molecules) in addition to being Complement Receptors (CRs), hence the “LAD”phenotype.

  • CR3 and CR4 are composed of distinct  chains (CD11b and CD11c, respectively) complexed with a common 2 chain (CD18).

  • CR3 - M2- CD11b / CD18 (also known as Mac1)

  • CR4 - X2- CD11c / CD18

  • Type I LAD is a deficiency of the 2 chain.

  • The major functional manifestation of LAD is the defective vascular adhesion of PMNs, with consequent defective extravasation.

Ucker, 2000


Roitt 12 19

Roitt 12.19


Roitt 18 16

Roitt 18.16


Roitt 12 221

Roitt 12.22


Deficiencies of components within the same pathway result in similar clinical manifestations

Deficiencies of components within the same pathway result in similar clinical manifestations.

B

C1

C4

D

Properdin

C2

C3

(I, H)

Pyogenic infections

Immune Complex Disease

Neisserial infections

Severe pyogenic infections

Immune Complex Disease

C5

C6

C7

Neisserial infections

C8

C9

Hanley, 1998


Janeway 9 31

Janeway 9.31


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