the immune system. the immune system 1st line of defense: surface barriers §the skin: heavily...
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THE IMMUNE SYSTEM
The Immune System
1 s t L in e o f D e fen seS k in
M u cosa
2 n d L in e o f D e fen seP h ag ocyte ; N a tu ra l K ille r C e lls
In flam m ation ; F ever A n tim ic rob ia l P ro te in s
3 rd L in e o f D e fen seH u m ora l (B ce lls )
C e ll-M ed ia ted (T ce lls )
B ac te ria o r V ira lIn vas ion
1st Line of Defense: Surface Barriers
The Skin: heavily keratinized epithelial membrane presents a physical barrier to most microorganisms that swarm on the skin; keratin is resistant to most weak acids and bases and to bacterial enzymes and toxins
1st Line of Defense (cont’d)
Mucous Membranes: serve as physical barriers and produce a variety of protective chemicals acidity of skin secretions (pH of 3-5) inhibits
bacterial growth and sebum contains chemicals that are toxic to bacteria
the stomach mucosa secretes a [ ]’d HCl solution and protein-digesting enzymes to kill microorganisms
1st Line of Defense (cont’d)
Mucous Membranes: saliva and lacrimal fluid (external eye) contain
lysozyme, an enzyme that destroys bacteria sticky mucous traps many microorganisms that
enter the digestive and respiratory passageways the respiratory tract mucosae also have
structural modifications such as vibrissae and cilia
2nd Line of Defense: Internal Defenses
Phagocytes the chief phagocytes are macrophages which derive
from circulating WBCs called monocytes search for cellular debris or foreign invaders; are called free (move about regions) or fixed (permanent to one organ)
neutrophils are the most abundant type of WBC and become phagocytic on encountering infectious material in the tissues; also contain the chemical, defensins, to kill
2nd Line of Defense: Internal Defenses
Phagocytes (cont’d) eosinophils are another type of WBC and are
weakly phagocytic but very important in defending the body against parasitic worms
mast cells, more associated with their role in allergies, have been shown to have an ability to bind with and ingest a wide range of bacteria, and then to kill the internalized bacteria
2nd Line of Defense: Natural Killer Cells
Police the body in the blood and lymphCan lyse and kill cancer cells and virus-infected
body cells before the immune system is activated and enlisted in the fight
Part of large granular lymphocytesNot phagocytic; attack the target cell’s
membrane and release cytolytic chemicals called perforins which causes the nucleus to disintegrate
2nd Line of Defense: Inflammation
Inflammation: tissue response to injury such as a physical trauma, intense heat, and irritating chemicals, as well as to infection by viruses, fungi, and bacteria
(1) prevents the spread of damaging agents to nearby tissues (2) Disposes of cell debris (3) Sets the stage for repair processes
2nd Line of Defense: Inflammation (cont’d)
5 Cardinal Signs of Acute Inflammation:(1) Redness (2) Heat (3) Swelling (4) Pain (5)
Loss of functionThe inflammatory process begins with a flood
of inflammatory chemicals into the ECFInjured tissue cells, phagocytes, lymphocytes,
mast cells, and blood proteins are sources of these chemicals (see following slide)
Inflammatory ChemicalsInclude histamine, kinins, prostaglandins,
complement, and cytokinesCause small blood vessels in the vicinity to
dilate and leads to hyperemia; redness and heatChemicals also increase the permeability of
local capillaries and allows exudate (fluid containing proteins such as clotting factors and antibodies) to seep from the bloodstream into the tissue spaces; swelling and pain (presses on nerve endings)
Inflammation (cont’d)Edema: (1) helps to dilute harmful
substances that may be present (2) brings in large quantities of oxygen and nutrients needed for repair (3) allows the entry of clotting proteins
If an epithelial barrier has been breached, -defensins (antibiotic-like chemicals) increases to help control bacterial and fungal colonization
Inflammation (cont’d): Phagocyte Mobilization
Leukocytosis: chemicals released by injured cells promote rapid release of neutrophils from red bone marrow
Margination: the neutrophils cling to the inner walls of the capillaries; also known as pavementing
Diapedesis: chemical signaling causes the neutrophils to squeeze through the capillary walls
Inflammation (cont’d): Phagocyte Mobilization
Chemotaxis: neutrophils and other WBCs are attracted to the site of injury by chemotactic agents and phagocytosis
2nd Line of Defense: Antimicrobial Proteins
Interferon: a virus-infected cell will help protect cells that have not yet been infected by secreting small proteins called interferons (IFNs); they interfere with viral replication in those cells by blocking protein synthesis at the ribosomes; also has an anti-cancer role by activating macrophages and natural killer cells
Inflammation (cont’d): Antimicrobial Proteins
Complement: a group of at least 20 plasma proteins that, when activated, amplify virtually all aspects of the inflammatory process, kill bacteria and other cell types by cell lysis
2nd Line of Defense: FeverThe body’s thermostat (in hypothalamus) is
normally set at 36.2 °C (98.2 °F) but resets upward in response to chemicals called pyrogens (pyro=fire), secreted by leukocytes and macrophages exposed to bacteria; moderate fever causes the liver and spleen to sequester iron and zinc, which bacteria need to multiply
3rd Line of Defense: Adaptive (Specific) Defenses
Antigens: substances that can mobilize the immune system and provoke an immune response; most are large, complex molecules (both natural and manmade) that are not normally present in the body; eg. bacteria, viruses, mismatched RBCs
Complete Antigens: foreign proteins, nucleic acids, some lipids, and many large polysaccharides; proteins are the strongest antigens
Antigens (cont’d)
Incomplete Antigens: Haptens; small molecules that link up with the body’s own proteins; haptens are reactive but not immunogenic unless attached to protein carriers; include penicillin, poison ivy, animal dander, some detergents, cosmetics
haptens can produce harmful reactions, called allergies
3rd Line of Defense: Adaptive (Specific) Defenses (cont’d)
Antibodies: also called immunoglobulins; soluble proteins secreted in response to an antigen, and they are capable of binding specifically with that antigen; they constitute the gamma globulin part of blood proteins
3rd Line of Defense: Adaptive (Specific) Defenses (cont’d)
Immunocompetent Lymphocytes: arise in red bone marrow and mature into T cells (T lymphocytes) or B cells (B lymphocytes)
T Cells: manage the immune response and some directly attack and destroy foreign cells; oversee cell-mediated immunity
B Cells: produce plasma cells, daughter cells that secrete antibodies into the blood or other body fluids; oversee humoral immunity
3rd Line of Defense: B CellsHumoral immune response (anti-body
mediated) occurs when antigens bind to the B cells
Clonal selection occurs to stimulate the B cell to grow and then to multiply rapidly
Most of the clone become plasma cells, which are antibody-secreting effector cells
B cells secrete limited amounts of antibodies, but plasma cells secrete 2000 molecules per second for 4 to 5 days
3rd Line of Defense: B CellsThe clone cells that do not become plasma
cells become long-lived memory cells which will mount an immediate humoral response if they encounter the same antigen again
Primary immune response occurs 3-6 days after the antigen challenge; secondary immune responses are faster, more prolonged, and more effective because the memory cells are already on alert
3rd Line of Defense: B CellsActive Humoral Immunity: (1) naturally
acquired during bacterial and viral infections (2) artificially acquired when we receive vaccines (contain dead or weakened pathogens); tetanus
Passive Humoral Immunity: antibodies obtained from a human or animal donor egs. breast milk, serum to treat snake bites, botulism, rabies (these would kill before active immunity could be established)
3rd Line of Defense: T Cells2 major populations of effector T cellsT4 Cells: display cell differentiation
glycoprotein 4 (CD4); primarily helper T cellsT8 Cells: display cell differentiation
glycoprotein 8 (CD8); cytotoxic cellsdestroy any cells in the body that harbour
anything foreignthe B cells prepare the antigen for disposal by
the T cells
3rd Line of Defense: T CellsT Cell Activation: (1) Antigen Binding: T cell
antigen receptors bind to an antigen-MHC protein (self body cell) complex on the surface of a body cell; not all T cells can bind to all antigen-MHC protein complexes (2) Costimulation: before a T cell can proliferate and form a clone, it must recognize on or more costimulatory signals; physical or chemical signals that nudge the T cells either to complete their activation process or to abort activation entirely
3rd Line of Defense: T CellsT Cell Activation: (3) Cloning: once
activated the T cells proliferate to form a clone of cells that differentiate and perform functions according to their T cell class; occurs within a week after a single exposure; death of T cells occurs between days 7 and 30; clone members become memory T cells for secondary responses
SummaryT8 cells prevent infectious microorganisms,
hidden within cells from antibody surveillance, from killing their cellular hosts
Helper T4 cells costimulate both other T cells and B cells and recruit nonspecific defenses; without them there is no adaptive immune response because they direct or help complete the activation of all other immune cells (AIDS)
Suppressor T cells prevent undesirable immune reactions
“and the Band Played On”Movie – To be shown in PMD lab
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