Complement component 3.

Most important.

Complement activation leads to the cleavage of C3 into small C3a and a large C3b.

High energy thioester bond within the glycoprotein.

Second pathway.

Induced by infection and requires some time before it gains strength.

Innate & Adaptive.

Requires the binding of an antibody or an innate immune-system protein called C-reactive protein to the pathogen's surface

Exposure and hydrolysis of the thioester bond of a small proportion of C3 molecules.

No cleavage of C3.

Catalyzed by certian pathogens in the environment (particularly bacteria)

Inactive complement of iC3.

Susceptivle to cleavage by protease.

Proteases taht cleave an activate C3.

i.e. iC3Bb

Fragment that is released from the cleavage of Factor B. has protease activity.

Remains bound to iC3

Alternative pathway

Potent C3 convertase.

Alternative C3 convertase.

Works at the surface of the pathogen.

Binds C3 and cleaves into C3b & Bb with activation of the thioester bond.

Plasma proteins.

Memberane proteins.

Properdin.

Increases the speed and power of complement activation by binding the C3 convertase C3bBb on microbial surfaces and preventing its degradation by proteases.

Plasma protein.

Binds to C3b and facilitates furthur cleavage to form iC3b by plasma serine protease, Factor I.

Plasma serine protease

The combined factors H & I reduces the number of C3 convertase molceules on the pathogens surface

Decay-accelerating factor.

Binds to the C3b component of the alternative C3 convertase (C3bBb), causing dissociation and inactivation.

In human cells.

Membrane co-factor protein.

MCP and C3b makes it also possible susceptible to cleavage by inactivation by Factor I.

Complement control protein modules.

Elongated structures built from varying numbers of structurally similar modules.

i.e. DAF, MCP, and Factor H

Regulators of complement activation.

Proteins made up of CCP modules.

Complement receptor 1.

A receptor that binds C3b fragments that have been deposited at high density on the surface of a pathogen through activation of the alternative pathway of complement.

Complement receptor 3 & 4.

Bind to iC3b fragments on microbial surfaces.

Alernative C5 convertase.

Consits of Bb plus two fragments.

C3b binds to the alternative C3 convertase to produce an enzyme that acts on the C5 component of complement.

Protectin.

w/ HRF prevent the recruitment of C9 by the complex of C5b, C6, C7, and C8.

DAF, HRF, and CD59 are all linked to the plasma membrane by glycosylphatidylinositol lipid tails.

Impaired synthesis of this tail.

Disease: episodes of complement mediated lysis of red blood cells that lack cell surface DAF, HRF, and CD59.

Plasma enzymes that form blood clots.

Immobilize microorganisms and prevent them from entering the blood and lymph.

Reduces the loss of blood a fluid.

Antimicrobial peptides made up of 35-40 amino acids that are rich in positivelt charged argnine residues and which characteristically have three intra-chain disulfide bonds.

Toll-like receptors.

A family of signaling receptors, each which is specific for a different set of microbial products

Specifity for the bacterial lipopolysaccharide (LPS) and related compounds present on the outside of G(-) bacteria.

Sends signals to the macrophage when infection is present to change the pattern of gene expression.

Proteins.

Acts as a co-receptor to TLR4.

CD14 and MD2 form a complex with the LPS; the complex generates intracellular signals via the cytoplasmic signaling domain of TLR4

Nuclear factor kB

Transcription factor which plays a major role in innate & adaptive immune responses

X-linked hypohydrotic ectodermal dysplasia and immunodeficiency

Disease: children lack one of the subunits of IKK and thus have impaired activation of NFkB; makes children susceptible to bacterial infection

Natural killer lymphocytes.

Enter infected sites soon after infection.

Specalize in defense against viral infections.

IL-1, IL-6, CXCL8, IL-12, and tumor necrosis factor-a (alpha) (TNF-a)

:These can be localized or systemic

Chemoattractant cytokines (chemokines); direct the flow of leukocytes during their development and during their recirculation through lymphoid tissues

Primary function: recruit neutrophils from the blood into infected areas

Disseminated intravascular coagulation

Exhausts the supply of clotting proteins

Pus-forming

i.e. S. aureus

A large family of adhesion molecules with a common structure of a-chain and B-chain polypeptides

i.e. C3 & C4

In a neutrophil.

Packed with proteins and peptides that can disrupt and digest microbes.

i.e. proteases

Contain unsaturated lactoferrin; which competes with pathogens for iron and copper by binding to proteins that contain these materials

Also contain: lysozyme and membrane proteins such as NADPH oxidase

Produces superoxide radicals that are converted into hydrogen peroxide by the enzyme superoxide dismutase

Raises the pH of the phagosome within 3 minutes of phagocytosis to ~8

Mannose-binding lectin.

A calcium-dependent lectin that binds to mannose-containing carbohydrates of bacteria, fungi, protozoans, and viruses.

Member of the protein family: collectins (collegen + lechtin properties)

C-reactive protein.

Member of the pentraxin family of proteins: contains 5 identical subunits that from a pentamer

Binds to the phosphocholine component of LPS in bacterial and fungal cell walls

Founded by binding to : Streptococcus pneumoniae

MBL- associated serine proteases.

Asssociate with the main stalk of the mannose-binding lectin

MASP-2 has an enzymatic role in lectin-mediated complement activation.

Anaphylatoxin that can recruit leukocytes to the site of C4b fixiation

Involved in the lectin and classical pathways

C4bC2a

Lectin related

C3 convertase

This convertase is where the lectin and classical pathways converge.

Cytokines that are produced when an infection enters a cell.

Interferons interfere with viral replication by the infected cell and to signal neighboring uninfected cells that they too should prepare to resist infection

Protein kinase R

Which phosphorylates and inhibits the protein synthesis initiation factor eIF2, preventing viral protein synthesis and the production of new infectious virons.

Interferon response factor 7.

Initiates the transcription of IFN-a which does not require the participation of NFkB and AP-1

(Natural) Interferon-producing cells.

These cells can produce up to 1000 times more interferon than other cells.

Conventional dendritic cells

Innnate

Type II interferon

Activates macrophages-- initiates adaptive immune response

Cell surface proteins that are produced in response to stress

Produced in intestinal epithelium