Immunology Chapter 3

==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

1. ==Tight Binding==

• CXCL8R binds to CXCL8
• LFA-1 binds to ICAM-1
• this causes tight binding, stopping the rolling

1. ==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