Download THE IMMUNE SYSTEM

THE IMMUNE SYSTEM
The Immune System
Bacteria or Viral
Invasion
1st Line of Defense
Skin
Mucosa
2nd Line of Defense
Phagocyte; Natural Killer Cells
Inflammation; Fever
Antimicrobial Proteins
3rd Line of Defense
Humoral (B cells)
Cell-Mediated (T cells)
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
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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:
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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
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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)
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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 lymph
 Can lyse and kill cancer cells and virusinfected body cells before the immune
system is activated and enlisted in the fight
 Part of large granular lymphocytes
 Not 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 function
 The inflammatory process begins with a
flood of inflammatory chemicals into the
ECF
 Injured tissue cells, phagocytes,
lymphocytes, mast cells, and blood proteins
are sources of these chemicals (see
following slide)
Inflammatory Chemicals
 Include histamine, kinins, prostaglandins,
complement, and cytokines
 Cause small blood vessels in the vicinity to
dilate and leads to hyperemia; redness and
heat
 Chemicals 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: Fever
 The 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 Cells
 Humoral 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 Cells
 The 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 Cells
 Active 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 Cells
 2 major populations of effector T cells
 T4 Cells: display cell differentiation
glycoprotein 4 (CD4); primarily helper T
cells
 T8 Cells: display cell differentiation
glycoprotein 8 (CD8); cytotoxic cells
 destroy any cells in the body that harbour
anything foreign
 the B cells prepare the antigen for disposal
by the T cells
3rd Line of Defense: T Cells
 T Cell Activation: (1) Antigen Binding: T
cell antigen receptors bind to an antigenMHC 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 Cells
 T 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
Summary
 T8 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