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Non-specific defenses (does not distinguish)
1st line: physical and mechanical barriers

2nd line: biochemical barriers: mucous, perpiration, tears, saliva, ear wax

3rd line: phagocytosis

4th line: Inflammatory response

5th line: Fever (pyrogens)

6th line: Interferons
Neutrophils
12-15 um, multinucleated, phagocytic and granulocyte. first responders, life span hours to 3 days.
Eosinophils
10-12 um, granulocyte, parasitic infections, allergic responses, life span 10-12 days. Also regulates mast cell derived in inflammatory mediators
Basophils
Granulocyte, 11-14um, 2 lobed nucleus, life span hours to 3 days, very rare, has histamine and heparin
Monocytes
14-20um, kidney shaped nuclei, motile, phagocytic, lifespan: months. 2ndry responders.
Vascular response
1. blood vessel dilation
2. increased vascular permeability, leakage of fluid out of vessel
3. WBC adherence to endothelium of vessels and migration through vessel walls.
Inflammatory response
1. Destroy agent, get rid of them
2. confinement of agent to limit effects
3. stimulate and enhance adaptive response
4. promote healing.
mast cell, contents, location
contents: granules

location: loose connectie tissue, close to blood vessels in skin, lining of GI, respiratory tract (close to outside).
mast cell degranulation (and what it's stimulated by)
with Interleukin I, injury, bacteria or viruses, antibodies (IgE regulated) and activated compliment

(1st response)

Histamine
Chemotactive factors
Cytokines
Interleukin I
pyrogen, chemotaxis. Made my macrophages and monocytes.
Vasoactive Chemicals
mast cell long term response:

Leukotrienes, prostaglandins, platelet-activating factor (PAF), growth factors
Leukotrienes
similar effects to histamine: smooth muscle contraction, increasedvaccular permeability, leukocyte chemotaxis. Promote slower and more prolonged responses than do histamines.
Prostaglandins
Cause vascular permeability and neutrophil chemotaxis. Induce pain. LOTS of these and LOTS of different effects (some conflicting).
PAF
Endothelial cell retraction to increase vascular permeability, leukocyte adhesion to endothelial cells and platelet activation
Complement Activation
1. Classical: antibodies from immune system are bound to antigens
2. Lectin: by bacterial carbohydrates
3. Alternative: by gram(-) bacterial and fungal cell wall polysaccharides.
Complement's function
Any pathway can lead to the same results. It also works in tandom with the other inflammatory responses. Individual components of the system serve 4 key functions.

1. Opsonization - tag, you're dead
2. Anaphylatoxins - degranulate ye mast cell!
3. Leukocyte chemotaxis - get over here.
4. Cell Lysis - MAC (membrane attack complex) form on bacterial cell membranes and forms pores causing lysis. This is the end of the three pathways.
Clotting system functions
1. prevent the spread of infection
2. keeps foreigners at the scene of the crime
3. Stop the bleeding! Please!
4. Just laying the foundation... for healing.

Activated by numerous pathways, has intrinsic and extrinsic pathways that all lead to the same end: fibrin production.
Kinin System function
works closely with coagulation cascade.

primary kinin is Bradykinin
Bradykinin functions
1. Dilation of vessels
2. Acts with prostaglandins to stimulate pain
3. smooth muscle contraction
4. Increase vascular permeability
5. May increase leukocyte chemotaxis
6. Increase function at late stages of inflammation
Interleukins (in general)
produced mostly by macrophages and lymphocytes. Serve 4 main functions:

1. alteration of adhesion molecule expression on many types f cells
2. Leukocyte chemotaxis
3. Proliferation and maturation of leukocytes in bone marrow
4. General enhancement or suppression of inflammation
Chemokines
Mainly leukocyte chemotaxis. Produced by many cell types including: macrophagees, fibroblasts and endothelial cells. >40 human chemokines discovered.
Lymphokines
Interleukins 2-6 and a couple of other things. Typically produced by helper T cells for leukocyte chemotaxis.

Also increase phagocytosis by macrophages.

(a monokine)
Interferon
Produced by virally infected cells

Effects on nearby healthy cells to increase production of antiviral proteins.

antibody synthesis and enhancing acquired immune response.
Local vs. systemic manifestation
heat, swelling, pain and redness

vs.

fever, leukocytosis, plasma protein synthesis (via liver), increase in acute phase reactants (e.g. C reactive protein and fibrinogen)
Margination and Diapedesis
Sticking of neutrophils and macrophages to endothelium

and

emigration of these cells through retracted endothelium to area of involvement
Acute vs. Chronic Inflammation
Acute is fever, leukocytosis and increased levels of circulating plasma proteins

Chronic happens with inflammation lasting >2 weeks. Characterized by granuloma formation, epitheloid cells (former macrophages) for cleaning debris and small particles and giant cells, fused macrophages for engulfing larger particles.
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