Inflammation

• means redness and swelling with heat and pain

• first response against infection = innate immune response

Stages in infection & response:

1. adherence to epithelium or other site = infection enter body

2. entry to body = organism gets passed body’s barriers to enter

3. local infection of tissues and innate immune system = local area around initial infection is the first site of immune system response (response = inflammation, complement activation, etc.)

4. activation of specific immune response = body mounts an effective humoral and cell mediated immune response

3 Roles in Fighting Infection

1.) deliver additional immune system cells to infection area

2.) induce local blood clotting

3.) promote repair of injured tissue

Inflammatory Process

• macrophage becomes activated = produces cytokines + chemokines

• blood vessels becomes dilated = increased blood flow → redness

• endothelial cells becomes activated = slow blood velocity

• cell adhesion molecules bind to leukocytes = extravasation occurs

• monocytes turn into macrophages

• eosinophil and lymphocytes move in

Endothelial cells during Inflammation

• activates kinin cascade

  • produces bradykinin = increases vascular permeability → leaks plasma and proteins out of blood vessels into tissue (causes swelling and pain)

• activates clotting cascade

  • forms clot in microvessels (prevents spread in bloodstream)

Chemokines

• they attract cells to an area through chemotaxis (function = chemoattraction)

• chemokines are a subset of cytokines

• cytokines = small proteins that affect

  • cell that produces them (autocrine effect)

  • cells nearby (paracrine effect)

  • distant cells (endocrine effect)

Types of chemokines produced:

1.) CC chemokines = binds to CCR-1 and CCR-9

• attracts monocytes and macrophages

2.) CXC chemokines = binds to CXCR-1 and CXCR-6

• attracts neutrophils

3.) CXXXC chemokines

Cytokines

1.) IL-1β

• activates endothelial cells and lymphocytes

• causes fever

2.) TNF-α

• activates endothelial cells

• increase vascular permeability

• causes fever

3.) IL-12

• activates NK cells

• T helper cells → TH1 cells = activates macrophages and B cells

4.) IL-6

• activates lymphocytes

• increase antibody production

• causes fever

Cell Adhesion Molecules

1.) selectins

• produce = P selectin and E selectin

• binds to carbohydrates

2.) integrins

• produce = LFA-1, CR3, CR4

• binds to ICAMS and extracellular proteins

3.) immunoglobulin superfamily

• produce = ICAM-1, ICAM-2, VCAM-1, PECAM

• binds to LFA-1

1. Rolling Adhesion

• location = blood vessel

• TNF-α, LPS, C5a, histamine, or leukotriene B4 = P selectin

• TNF-α and LPS = E selectin

• leukocytes have s-lex attached to it where it would roll from E selectin to another E selectin on the endothelial cells

• loose, and reversible binding

2. Tight Binding

• CXCL8R binds to CXCL8

• LFA-1 binds to ICAM-1

• this causes tight binding, stopping the rolling

3. Crossing Endothelial Wall

• leukocyte binds to PECAM to pull itself through the endothelial cell junction

4.) Diapedesis (crossing basement membrane)

• leukocyte must cross basement membrane before it is out of the blood vessel

• leukocyte produces enzymes that degrade the extracellular matrix so that it can move through