Immunity
Human Immune Defenses
• Protection against foreign invaders
(bacteria, viruses, fungi, etc.)
• Three levels of defense:
– First line of defense = barrier to prevent entry
(skin, mucous membranes)
– Second line of defense = general reaction to
minimize infection via intruder (inflammation, etc.)
– Third line of defense = specific reaction to
minimize infection via intruder (MHC, antibodies,
T cells, etc.)
• Supplementary developments:
– Antibiotics, vaccines, and passive immunity
First Line of Defense
1. Skin – physical barrier, covered
with oily & acidic (pH 3-5)
secretions from sweat glands
2. Antimicrobial proteins (e.g.
lysozyme) – in saliva, tears, and
other mucosal secretions
3. Cilia – line the lungs to sweep
intruders up and out
4. Gastric juice – in stomach (pH
~2), kills most microbes
5. Symbiotic bacteria – in digestive
tract and vagina, outcompete
pathogenic organisms
Second Line of Defense
• Nonspecific mechanisms
• Phagocytes – white blood cells
(leukocytes) that phagocytose
pathogens, circulate constantly
• Complement – proteins (~20
different kinds) that attract
phagocytes to foreign cells &
promote lysis of pathogens,
precursors circulate constantly
• Interferons – secreted by
cells infected with viruses,
stimulate neighboring cells to
produce proteins to defend
against viral infection
• Inflammation – swelling in
response to tissue damage
Phagocytes: Neutrophils
• Neutrophils
–Engulf pathogens via phagocytosis
Travel to infection
site via chemotaxis
Neutrophils
Remember this
little guy from the
Inner Life of a Cell?
Phagocytes: Monocytes
– Mature into large macrophages
– Engulf pathogens via phagocytosis
Phagocytes: Natural Killer Cells
– Attack pathogen-infected body cells
– Attack abnormal body cells (tumors)
– Nonspecific attack on compromised cells
– Action based on activation and inhibitory
receptors
Granules
containing
digestive
enzymes
Phagocytes: Natural Killer Cells
Loss of “self” ID
tag, no longer
inhibits NK cell
Complement
Pathogen Detection
Antibodies bind pathogens and trigger
compliment-activating enzymes
Pathogen surface receptors trigger
complement-activating enzymes
Complement Activation
Inactive precursors in blood cleaved (by proteases) to become active compliment proteins
Amplification of Immune Response
Recruitment of Phagocytes
Enhancement of
Phagocytosis of Pathogens
Perforation of Pathogen
Cell Membrane (Lysis)
Complement:
Perforation of Pathogens
Interferons
Inflammatory Response
• Occurs when skin is damaged (damage allows
pathogens to enter body)
• Histamine secretion by basophils & mast cells
(WBC), stimulates vasodialation
• Vasodialation – increases blood supply to
damaged area, allows WBC and fluids (including
complement) to move easier through blood vessel
walls (increased permeability of blood vessels)
• Phagocytes attracted to site of injury by
complement, engulf pathogens
• Complement helps phagocytes, stimulates
basophil secretion of histamine, helps lyse
pathogens
Histamine Release
• Basophils (WBC)
normally circulate in
blood (recruited into
tissues when needed)
• Mast cells (WBC) exist
in tissues, particularly
near interface with
external environmental
(skin, lungs, digestive,
nose, mouth, eye)
• Release histamines in
response to pathogens
or allergens
Pathogen or
Vasodialation
• Dialation (widening) of blood vessels
• Causes redness, increase in temperature, and swelling
• Increases delivery of WBC & complement to site of
damage
• Increase in temperature may stimulate WBC and make
environment inhospitable to pathogens
Third Line of Defense
• Targets specific antigens (on pathogens)
• Major histocompatibility complex (MHC)
self vs. nonself proteins at surface of all cells
• Lymphocytes (WBC)
– B cells (make antibodies)
• respond to antigens on pathogens
• produce plasma & memory cells
– T cells
• respond to nonself cells
• produce cytotoxic/killer T cells
& helper T cells
Antigens
• Antigen = any molecule
(usually protein or
polysaccharide)
identified as foreign
– Part of protein coat of virus
– Unique molecule in plasma
membrane of bacteria,
protozoa, pollen, or other
foreign cells
– Toxin injected by insect
sting
Antigen Presenting Cells:
Macrophages & Dendritic Cells
Phagocytosis of
pathogen
Presentation of
antigens to
other immune
cells
Major histocompatibility complex (MHC)
• Collection of glycoproteins (proteins with
carbohydrate groups) on the membranes of all body
cells (ID tag)
• Each individual has unique MHC proteins
• Self vs. Non-self recognition
Carbohydrate groups
Polypeptide
chains
MHC Class I & MHC Class II
MHC Class I
>Found in all nucleated cells
>Function as “ID tag”
>Present antigens when cell is
infected or malignant
MHC Class II
>Found in antigen presenting cells
>Activate other immune cells
>Present antigens after phagocytosis
of pathogen
Antibodies
• On surface of B cells
(antigen receptors)
• Specific to particular
antigens
• Y-shaped proteins with
constant and variable
regions (variable
provides antigen
specificity)
• 5 classes
(immunoglobulins):
IgA, IgD, IgE, IgG, IgM
(different particular
activities)
Antibodies
• Inactivate antigens by binding to them
(phagocyte)
Agglutination and
inactivation of
pathogen
Antibodies
• Binding “flags” cells for death (macrophage
phagocytosis, compliment protein lysis) Response
to parasites
Macrophage
Flagged “foreign” cells
Antibodies
• Binding leads to B cell proliferation (by division):
– Plasma cells – release antibodies to circulate through the body
– Memory cells – long-lived, circulate & release antibodies with
subsequent infection of same pathogen (immunity)
T cell Lymphocytes
• Work with MHC to identify/destroy non-self cells
• Infected cell displays a combo of self and nonself markers (T cell interprets as non-self)
• Cancer cells & transplant cells also interpreted
as non-self
T cell
Cancer
cell
T cell Lyphocytes
• T cells encounter non-self cells, divide & produce:
– Cytotoxic/killer T cells – recognize & destroy nonself cells by puncturing them (lysis) and activating
apoptosis, induced by antigen-presenting cells
– Helper T cells – stimulate production of B cells
and cytotoxic T cells by secreting interleukins
Cytotoxic/Killer T cells
Lysis
Cytotoxic
T cell
Apoptosis
Don’t confuse your KILLERS!
Natural Killer Cells
Killer (Cytotoxic) T Cells
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Second line of defense
Non-specific response
No APC activation
Circulate constantly
(INNATE immunity)
Innate immunity is a non-specific
and immediate response,
responding in a general way that
does not confer long-lasting
immunity
Third line of defense
Specific response
Require APC activation
Proliferate in response to
an infection
(ADAPTIVE immunity)
Adaptive immunity is a specific
and acquired response, producing
antibodies and conferring longlasting immunity through memory
cells
Helper T cells
Immune Reactions
Cell-mediated Response
• Response to any non-self
cells (including infected
body cells and tumor cells)
– Non-self cell binds to T cell
– T cells produce cytotoxic T
cells (destroy nonself cells)
and helper T cells
– Helper T cells bind to
macrophages (that
engulfed pathogens and are
now presenting antigens)
– Helper T cells produce
interleukins (stimulate
production of T cells and B
cells)
Humoral Response
• Response to antigens or
pathogens circulating in
lymph/blood
– B cells produce plasma cells
and memory cells
– Plasma cells release
antibodies (bind to antigens)
– Memory cells provide future
immunity
– Macrophage & helper T cells
stimulate B cell production
(helper T cells bind to
macrophages that have
engulfed pathogens, then
secrete interleukins)
Supplementation of Immunity
• Antibiotics – derived from bacteria & fungi,
harmful to pathogenic microorganisms
• Vaccines – inactivated pathogens (or
fragments of pathogens), stimulate production
of memory cells (prevent disease if pathogen
introduced)
• Passive immunity – transferred antibodies
from immune person to non-immune and
infected person (ex: newborns get mom’s
antibodies through placenta and via breastmilk)
Antibiotics
Vaccines
Produces memory cells for
subsequent antigen exposures
Herd immunity reduces spread of infectious diseases
Passive Immunity
(placenta)
pathogen, etc.
Natural – placenta (IgG only),
breast milk (IgA only)
Artificial – serum infusion
(used for infection, poisoning,
immunodeficiency therapy)