Cytokines, Mediators, and the Complement Cascade

Microbiology innate immunity

cytokines

act as communication signals; secreted by WBCs that act on themselves or others

autocrine

same cell secretes and receives cytokine cell

paracrine

cytokine signal secreted to a nearby cell

interleukins (IL)

stimulate and modulate most functions of the immune system (innate and adaptive)

interferons (IFN)

type 1 alert cells to viral infection

type 2 activate macrophages

chemokines

recruit WBCs to infected area

TNF-alpha

stimulates production of adhesion proteins (selectins and ICAM1) on endothelial cells

histamine

promotes vasodilation, increased secretion and mucus production

prostaglandins

promote inflammation and fever; contribute to pain

leukotrienes

promote inflammation; stronger and longer lasting than histamine; contribute to pain

complement proteins (C#)

in the plasma; chemoattractant for phagocytes, promote degranulation of mast cells; opsonization

cardinal signs of acute inflammation

1. heat

2. erythema (redness)

3. edema (swelling)

4. pain

5. loss of function

pus

exudate, dead PMNs/WBCs, dead bacteria

complement system

• made in the liver, circulate in blood, enter tissue

• normally inactive

  • serum proteins are normally inactive and circulating

  • activated rapidly in a cascade

antigen antibody reaction

activates the complement system (classic)

proteins C3, B, D, P binding a pathogen

activates the complement system (alternative)

lectins binding to mannose on a pathogen

activates the complement system (lectin)

effects of complement system activation

opsonization, inflammation, and cell lysis

C3b

causes opsonization

C3a and C5a

cause inflammation

C5b, C6, C7, C8, C9

cause cell lysis

alternative pathway

triggered by C3b binding to microbial invaders

lectin pathway

triggered by mannose binding lectin (MBL) binding to microbial invaders

classical pathway

triggered by antibodies binding to microbial invaders

anaphylatoxins

bind and activate mast cells » degranulate » release histamine

ex. C3a and C5a

chemoattractant

attracts phagocytes (chemotactic)

ex. C5a

membrane attack complex (MAC)

C5b, C6, C7, C8, C9 » cause cytolysis

ONLY effective against gram negative bacteria

IFN-alpha and IFN-beta (TYPE 1)

• produced by virally in infected cells in small amounts

• diffuse locally and cause neighbor cells to produce antiviral proteins » enzymes that inhibit viral replication

IFN-gamma (TYPE 2)

• produced by lymphocytes

• activates macrophages