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Transcript
Immunity
Biology 2122
Chapter 21
Introduction
• Innate or nonspecific defense:
– First-line of defense
– Second-line of defense
• The adaptive or specific defense system
– lymphocytes, the production of antibodies specific to certain
antigens
• The immune system is a ‘functional’ system
Innate Defense System
Epidermis and keratin-cells provide a tough barrier to
penetrate
▫ Resistant to weak acids, bases, toxins
The mucous membranes
• physical barrier
▫
▫
▫
▫
3-5 pH
HCl in the stomach (pH 2)
Saliva contains lysozyme
Mucus
Internal Defense
If the surface defenses are broken, microorganisms will
invade deeper tissue areas.
Nonspecific cells and chemicals
– prevent the ‘invaders’ from penetrating deeper into the body
Cells involved- Nonspecific Cells:
– 1. Phagocytes- Neutrophils, Eosinophils
– 2. Natural Killer Cells
– 3. Mast cells
• When body tissues are damaged
– inflammatory response is set into motion which involves a series of chemicals
The Role of Phagocytes
Monocytes will leave the bloodstream and be converted into the ‘main’
phagocytes called macrophages.
They can be free (lungs) or fixed in position (Kupffer cells in the liver)
Other WBCs involved:
– 1. Neutrophils
– 2. Eosinophils
– 3. Mast cells
Phagocytosis
–
–
–
–
Phagosome
Phagolysosome
Opsonization
Respiratory Burst
– Animation
Natural Killer Cells
Large granular lymphocytes - non-specific
• Detect ‘non-self’ cells via the surface receptors.
• Eliminate cancerous or infected cells.
• The mode of killing is via the release of cytolytic chemicals
called perforins
• Not Phagocytic
What is an ‘inflammatory’ response?
When tissues are injured
– ‘healing process’ that eliminates debris and pathogens in the
affected area.
– Identifiable signs of an inflammation are redness, heat,
swelling and pain.
• Macrophages have surface membrane receptors called
Toll-like Receptors or TLRs.
▫ If activated, TLR triggers the release of chemicals called
cytokines that cause inflammation and attract WBCs to the
site of the injury
Histamines
Inflammatory
Chemicals
• released by basophils and mast cells, microorganism or
chemicals released by neutrophils
• Promotes vasodilation; permeability of capillaries
Kinins
• produced from the cleavage of a plasma protein called
kiniogen
• Induces chemotaxis of leukocytes; same roles as histamine
Prostaglandins or PGs
– fatty acid molecules
– generated by lysosomal enzymes of neutrophils and other
cells
– Production of free radicals
Inflammatory Chemicals - Effects
Most of the chemicals:
1. ‘Vasodilation’ of blood vessels
2. Increases the permeability of capillaries causing fluid
to leak out into the extracellular space
• exudate fluid and contains clotting factors and
antibodies
3. Causes swelling (edema), which causes pressure on
nerves, results in pain
• Dilutes harmful substances; brings oxygen and nutrients;
entrance of clotting proteins
Inflammatory Response
1. Release of Chemical
Mediators
2. Vasodilation, increased
permeability of
capillaries
3. Attraction of
neutrophils,
monocytes, leukocytes,
“chemotaxis”
4. Vasodilation leads to
“hyperemia”, redness
swelling
5. Capillary permeability
leads to exudate, pain,
swelling, clotting
Leukocytes migrate ----- Margination ---- Diapedesis ---- Phagocytosis of dead tissue and cells, etc.
Phagocyte Mobilization
Neutrophils are first followed by macrophages
1. Leukocytosis – injured cells release leukocytosis inducing factors which promote the fast
release of neutrophils from red marrow.
2. Margination – Blood flow slows in the injured region and the neutrophils will attach to CAMs
called selectins on the endothelial cells.
3. Diapedesis – Neutrophils are able to squeeze through the walls
4. Chemotaxis – chemotactic agents (inflammatory chemicals) attract neutrophils and other
WBCs to the injury site
Animation
Phagocyte Chemotaxis and the Inflammatory
Response
• Animation Link
• Leukocyte Migration Animation
Other Nonspecific Defense Systems
• Antimicrobial proteins attack pathogens directly or indirectly
– Interferon and complement proteins
• Complement Protein Animation
• Interferons (IFNs) are small proteins that are secreted by cells infected by
viruses to protect other cells which have not been infected.
– Stimulate synthesis of PKR protein that interfers with vial replication in
healthy cells
– Lymphocytes secrete gamma interferon; leukocytes secrete alpha interferon
– Also can activate NK cells and macrophages which have anti-cancer
capabilities (attack malignant cells)
Interferon
Animation
• Includes 20 plasma proteins which
circulate in their inactive form in the
blood. They are nonspecific!
Complement Proteins
• When activated they release chemical
mediators which:
– Amplify the inflammatory process
– Kill pathogens via lysis
– Complements both innate and
adaptive (specific responses)
– Activated via the classical pathway
or alternative pathway
Complement Protein Animation
Fever
This is a systemic response to invading microorganisms
Pyrogens (chemicals)
• released by leukocytes and macrophages exposed to a
pathogen
• cause the body’s temperature to be reset (hypothalamus)
Mild or moderate fevers cause the liver and spleen to hold
onto iron and zinc (necessary for bacteria to replicate)
Increases the metabolic rate of cells which increases healing.
▫ High temperature ‘denature’ enzymes