immunology exam 1 - complement system

come back to first powerpoint! ends at slide 10

what is the complement cascade important in?

• defense against microbial parasites

• homeostasis

• activation of the innate and adaptive immune system

• degranulation and phagocytosis

cells involved in the complement cascade

• neutrophils

• monocytes

• mast cells

• macrophages

• dendritic cells

• b-cells

• t-cells

complement cascade

• consists of over 30 proteins that are either structural, inflammatory, and enzymatic

• activated by three different mechanisms - classical, lectin, and alternative

• occurs in three stages - initiation, amplification, biological effects

what initiates the classical pathway

• C-reactive protein (CRP)

• serum amyloid protein (SAP)

• IgG or IgM (antibodies)

C4a

• forms when C4 is cleaved into two parts

• a modest inflammatory mediator

C3 convertase

• forms when C4b and C2a combine

• a major protein complex in the classical and lectin pathways

• purpose is to amplify the signal to initiate an immune response

IgG and IgM

• antibodies involved in the classical pathway

• bind to antigens on the pathogen’s surface

zymogens

• enzymatic proteins that must be modified to become active

• ex: a protein is cleaved into two pieces OR two proteins come together

describe the steps of the classical pathway

• IgG, IgM, CRP, or SAP bind to the pathogen’s surface

• C1 binds to antibody on the pathogen’s surface

• C1 cleaves C4 into C4a (modest inflammatory mediator) and C4b

• C4b binds to the pathogen’s surface

• C4b cleaves C2 into C2a and C2b

• C2a attaches to C4b to create C3 convertase

• C2a binds to C4b to create C3 convertase

• C3 convertase cleaves C3 into C3a (major inflammatory mediator) and C3b

• C5 convertase splits C5 into C5a (major inflammatory mediator) and C5b

• C5b attaches to the pathogen’s surface

• C6, C7, C8, and C9 attach to form a membrane attack complex to form a pore in the pathogen

describe the steps of the lectin pathway

• mannose-binding lectin (mbl), surfactant protein, or ficolin binds to the pathogen’s surface

• mbl-associated serine protein (masp) binds to the antibody on the pathogen’s surface

• masp cleaves C4 into C4a (modest inflammatory mediator) and C4b

• C4b cleaves C2 into C2a and C2b

• C2a binds to C4b to create C3 convertase

• C3 convertase cleaves C3 into C3a (major inflammatory mediator) and C3b

• C3b binds to C3 convertase to form C5 convertase

• C5 convertase cleaves C5 into C5a (major inflammatory mediator) and C5b

• C5b attaches to the pathogen’s surface

• C6, C7, C8, and C9 attach to form a membrane attack complex to form a pore in the pathogen

describe the steps of the alternative pathway

• hydrolysis cleaves C3 into C3a (major inflammatory mediator) and C3b OR C3 convertase cleaves C3 into C3a (major inflammatory mediator) and C3b

• C3b binds to the pathogen’s surface

• factor b binds to the pathogen’s surface

• factor d cleaves factor b into Ba and Bb

• Bb binds to the pathogen’s surface to create C3 convertase (unstable)

• properin binds to C3 convertase to stabilize it

• C3b binds to stable C3 convertase to form C5 convertase

• C5 convertase cleaves C5 into C5a (major inflammatory mediator) and C5b

• C6, C7, C8, and C9 attach to form a membrane attack complex to form a pore in the pathogen

initiation of complement system

involves binding to a pathogen or recognizing the pathogen

amplification of complement system

when one protein activates another, which then activates another protein, etc

biological effects of complement system

• what we can see/notice

• pro-inflammatory events

• opsonization

• induction of cell lysis

complement proteins that increase opsonization

• C4a

• C3a

• C5a

complement proteins that form the membrane attack complex

• C6

• C7

• C8

• C9

main differences between complement pathways

• what causes the protein to bind to the pathogen’s surface

• components from either the adaptive or innate response

what microbes is the classical pathway effective against?

• bacteria

• fungi

• virus

C5 convertase

• formed when C3b attaches to C3 convertase

• major protein in the classical and lectin pathways

• purpose is to amplify the signal to initiate an immune response

C3a

• major inflammatory mediator in complement cascade

• formed when C3 is cleaved

C5a

• major inflammatory mediator in complement cascade

• formed when C5 is cleaved

C3’s numerous functions

• C3b is a powerful opsonin that increases phagocytosis

• C3a and C3b help recruit and activate leukocytes to destroy microbes

• C3b helps to form the membrane attack complex which results in cell lysis

decay-accelerating factor (daf)

• found on the surface of host cells

• prevents C3b from binding to the host cell membrane and beginning the alternative pathway

membrane cofactor of proteolysis (mcp)

• found on the surface of host cells

• prevents C3b from binding to the host cell membrane and beginning the alternative pathway

where are complement cells created

• liver

• epithelial cells

• fibroblasts

amplification loop

the idea that the classical and lectin pathways can initiate the alternative pathway

draw the classical pathway

draw the lectin pathway

draw the alternative pathway