450_Chapter 5: Soluble Mediators Of The Immune System

Front 1

LIst 3 characteristics common to the complement components

Back 1

- part of innate immune system
- Heat labile
- most components made in liver
- circulate in inactive form

Front 2

Explain where complement components are produced within the body

Back 2

- C4 is a glycoprotein made by macrophages
- C3 is a beta globulin from macrophages
- the rest is made in liver

Front 3

Classical pathway

Back 3

- C1 is a complex of 3 proteins (C1q, C1r, C1s) held together by Ca2+ ions
- C1q has 6 identical subunits. Binding to 2 Fc regions of Ig to be activated
- Activated C1q activates C1r, which then activates C1s
-Activated C1s has proteolytic properties and acts on C4
- C4 is cleaved into C4a and C4b
-C4b binds to the cell membrane adjacent to the Ab-Ag complex that initiated the process. interacts with C1s to induce cleavage of C2
- If C4b does not bind to membrane, it decays and is inactive.
- C2 cleaved by action of C1s and C4b into C2a and C2b
-C4b binds to C2a = C4b2a = C3 convertase
- C3 convertase cleaves C3 into C3a and C3b
- A single C4b2a can activate hundreds of C3 molecules= amplification
-C3b attaches to cell membrane in immediate vicinity of site of activation
- C3b combines with C4b2a = C4b2a3b = C5 convertase
- C5 convertase splits C5 into C5a and C5b.

Front 4

Membrane attack complex

Back 4

- C5b binds with C6, and C7 to form C5b67 on the cell membrane.
- This complex focuses the activity of C8 and C9 onto the target membrane.
- produced transmembrane channels
- Ions pass through, disturbs osmotic equilibrium... cell lyses

Front 5

Alternative pathway

Back 5

- Reactive C3b binds to pathogen surface
- protein B binds to stabilized C3b --> C3bB
- Protein D clips part of Protein B, resulting in C3bBb = C3 convertase
- Factor P = properdin stabilizes C3bBb complex
- C3b binds to C3bBb = C3bBbC3b= C5 convertase

Front 6

Mannin -binding Lectin (MBL) pathway

Back 6

- Ca2+ dependent
- MBL is homologous in structure to C1q
- MASP1 and MASP2 homologous to C1r and C1s
- Result is C3 convertase from bound C2a and C4b

Front 7

List the various inhibitors present to help control complement activation in each pathway and how each inhibitor works.

Back 7

- CD55: decay accelerating factor (DAF)
- CD59: protectin
- Factor I: results in inactive C3b (iC3b)
-Factor H: competes with factor B
- C1 INH

Front 8

Discuss how alterations in complement levels occur and how those alterations affect the body

Back 8

- persisten infections, autoimmune disorders, intravascular thrombosis, certain disease states, genetic disorders
- Elevated C' levels: inflammatory conditions
- Decreased C' levels: excessive activation (consumption) or genetic defect (decrease production)
- C' deficiency often leads to increased susceptibility to pyrogenic infections

Front 9

Categorize the types of diseases associated with a deficiency of a component with the 3 pathways

Back 9

- Classical pathway: pyrogenic infections
- MAC components: Neisserial infection
- MBL components: recurrent infections in infants/ young children

Front 10

Deficiencies of C' Components

Back 10

Paroxysmal nocturnal hemaglobinuria (PNH):
- Deficiency of DAF (CD55) on cell surface
- results in RBCs subject to be lysed when C' is activated
- Chronic intravascular hemolysis with or without blobinuria
- Hypochromic, microcytic anemia
- Neutropenia
- Thrombocytopenia
- Marrow failure- aplastic anemia

Front 11

Hereditary Angioedema

Back 11

- decrease levels or lack of C1 INH
- results in excess cleavage of C4 and C2
- localized swelling (edema) at site of antigen exposure
Maybe life-threating in Ag exposure is near oropharynx
- primary: genetic defect: normal levels of C1q and C3, reduced levels of C4 and C2
- secondary: acquired defect: reduced levels of C1q (not measure)

Front 12

C' Deficiencies

Back 12

C2:
- most common, autosomal recessive
- recurrent infecitons
- Lupus- like disorders (photosensitivity/rash)
C4:
- very sensitive indicator of disease activity
C6, C7, C8
- susceptible to infection with Neisseria spa.
Properdin
- susceptible to bacterial infection , X-linked recessive

Front 13

Briefly describe the assessment of complement levels

Back 13

- Qualitative testing: latex agglutination
- Quantitative testing: radial immunodiffusion, rocket immunoeletrophoresis, nephlometry
- Can measure individual C' components or ability of components to function
- CH50: hemolytic titration assay, measures funtional activity of C, quantitative endpoint of C activation, measured by lysis of sensitized antibody-coaated. CH50= amount of patient serum required to lyse 50% of sensitized cells, measures classical pathway.

Front 14

For the following types of nonspecific mediators of the immune system, including cytokines, interleukins, TNF, hematopoietic GF, and chemokines. Describes at least 2 functions and its association with innate or adaptive immunity

Back 14

Cytokines:
- In innate immunity: mediate early inflammatory rx to microbes and stimulate adaptive immune responses
- In adaptive immunity: proliferation, activation, differentiation of lymphoctes
IL:
- Mediate local interactions between leukocytes, but do not bind Ag
- Modulate inflammation and immunity: regulate growth, mobility, differentiation of lymphoid cells
- Each IL functions through a separate receptor system
TNF:
- Principle mediator in acute response to Gram negative bacteria
-Very potent systemic effects
- Secreted by macrophages and APCs
- Kills virally infected and tumor cells
- recruits and active of PMNs and monocytes

Front 15

Discuss the clinical applications of CRP

Back 15

- Produced by liver under influence of IL-6
- monitor of infection, autoimmune disorders, myocardial infract
- fastest and most sensitive response to acute inflammation
- used for screening
- measured using agglutination procedures.