Soluble Mediators

two major systems that provide immunity

1. innate

2. adaptive

type of immunity provided by humoral immunity

specific immunity → antibody production

type of immunity provided by natural immunity

nonspecific immunity → inflammation, fever, opsonization

complement

series of 18 heat-labile plasma proteins (enzymes)

three pathways of complement activation

1. classic pathway

2. alternative pathway

3. mannose-binding lectin pathway

three main physiologic activities of complement system

1. host defense against infection

2. connection between innate and adaptive immunity

3. disposal of immune system waste

purpose of control proteins in the complement system

control activity of complement and inhibit uncontrolled complement activation

how is the classic pathway of complement activation stimulated

by antigen binding to its specific antibody → humoral immunity

how is the alternative pathway of complement activation stimulated

when complement component contacts with the cell surfaces of foreign antigens → nonantibody-initiated and innate immunity

end result of complement activation

cell destruction

component the classic and alternative pathways converge at

C3

physiologic consequence of complement activation

blood vessel dilation and increased vascular permeability

cellular consequences of complement activation

1. inflammation

2. cytolysis/hemolysis

3. opsonization

three stages of classic pathway needed for complement activation

1. recognition

2. protein activation

3. membrane attack complex

why is nonspecific activation of complement a major advantage

host protection can be generated before the induction of a humoral response → allows immune system to react quicker

how does the mannose-binding lectin pathway activate complement

lectins are protiens tht bind the the mannose on the surface of foreign antigens

effects of increased complement

tissue damage

associated with intravascular thrombosis, inflammatory conditions, trauma, acute illness

indications of decreased complement

1. complement has been excessively activated

2. complement is currently being consumed

3. genetic defect causing absence of a complement component → pyogenic infection suceptibility

cytokines

protein products of activated cells that regulate the immune system:

1. mediate early inflammatory reactions

2. stimulate antigen-antibody complexes

3. activated effector cells

interleukins

33 proteins found in the blood that mediate local interactions between WBCs:

1. regulate growth, mobility, and differentiation of lymphs

interferons

group of cytokines that act as a natural defensive response to foreign substances

most broadly active regulators of the immune system:

1. enhance gene expression

2. inhibit cell proliferation

3. augment effector cells

4. antiviral agents

5. immunomodulators

6. antineoplastic agents

gamma interferon (IFN-gamma)

principle macrophage activating cytokine that stimulates expression of class I and II MHCs

tissue necrosis factor

principle regulator of the acute inflammaotry response to gram negative bacteria:

1. stimulates recruitment of segs and monos to infection site

2. activates these cells to destroy microbes

consequence of too much TNF elevation

septic shock

stem cell factor

cytokine that reacts on immature stem cells in the marrow:

1. makes bone marrow stem cells responsive to other colony-stimulating factors

2. role in sustaining proliferation of immature T lymps and mast cells

colony stimulating factors

stimulate hematopoietic stem cells to form cells that will differentiate into progenitor cells for WBC, RBC, and platelet production

transforming growth factor-beta

cytokines that inhibit the proliferation of T lymphs and the activation of macrophages

chemokines

large family of cytokines that stimulate WBC movement from the blood to the site of infection and regulate the migration of cells within tissues

acute phase reactants

proteins that are a nonspecific indicator of inflammation

increased production in response to tissue injury

applications of acute phase proteins

1. monitor progress of inflammatory disease

2. assess response to therapy of inflammatory disease

3. detect complications of a known disease

test used as an indirect measurement of inflammation

erythrocyte sedimentation test (ESR)

c reactive protein

protein produced by the liver that measures inflammatory activity

applications of CRP

1. monitor infection

2. autoimmune disorders

3. healing after MI

4. determine risk for cardiovascular disease (along with LPD)