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Chapter 43: Internal Defense
Immune Response – fight antigens
• Nonspecific (innate)– general
• Specific (adaptive or acquired) – tailor made
– Antibodies
Fig. 43-2
Pathogens
(microorganisms
and viruses)
INNATE IMMUNITY
• Recognition of traits
shared by broad ranges
of pathogens, using a
small set of receptors
• Rapid response
ACQUIRED IMMUNITY
• Recognition of traits
specific to particular
pathogens, using a vast
array of receptors
• Slower response
Barrier defenses:
Skin
Mucous membranes
Secretions
Internal defenses:
Phagocytic cells
Antimicrobial proteins
Inflammatory response
Natural killer cells
Humoral response:
Antibodies defend against
infection in body fluids.
Cell-mediated response:
Cytotoxic lymphocytes defend
against infection in body cells.
Nonspecific defense
•
•
•
•
•
Skin
Mucus membranes
Acid secretions / enzymes of stomach
Hairs in nose
Phagocytes
Cytokines – signaling molecules
• Interferons
• Interleukins
• Tumor necrosis factors
• Interferons
– Secreted by cells infected with viruses, parasites
– Produced by macrophages
– Type I interferons
• Inhibit viral replication
– Viruses exposed to Type I interferon can’t infect other cells as
well
• Activate natural killer cells
– Type II interferons
• Specific immune system
• Enhance activities of other immune cells
• Stimulate macrophages to destroy tumor cells and
virus-infected cells
• Interleukins
– Secreted by macrophages and lymphocytes
– Regulate actions between lymphocytes and other
body cells
– Interleukin-1 can reset body’s thermostat in
hypothalamus resulting in fever
• Tumor necrosis factors (TNFs)
– Secreted by macrophages and lymphocytes
– Stimulate immune cells for inflammation
– Kill tumor cells
Complement system
•
•
•
•
Complements actions of other defenses
20+ proteins in body fluids
Inactive until body exposed to antigen
Sometimes activated directly OR by binding of antigen
to antibody
• Nonspecific
• 4 actions:
–
–
–
–
Lyse pathogen cell wall
Coat pathogen (phagocytes can work more easily)
Attract WBCs to infected site
Increase inflammation by stimulating release of histamine
Phagocytosis
• Nonspecific
• Phagocytes =
– neutrophils (~20 bacteria)
– Macrophages (~100 bacteria)
• Endocytosis
Fig. 43-3
Microbes
PHAGOCYTIC CELL
Vacuole
Lysosome
containing
enzymes
Natural Killer (NK) Cells
•
•
•
•
Large, granular lymphocytes
Bone marrow
Nonspecific and specific
Release cytokines and enzymes to destroy
target cells
Inflammation
• Heat, redness, edema, pain
• Regulated by plasma proteins, cytokines, platelet
substances, basophils, mast cells
• Blood vessels dilate
• Increase capillary permeability
• Increase blood flow – lots neutrophils, phagocytes,
platelets, basophils, mast cells to infected area
• Mast cells release histamine, serotonin
• Increase blood flow  skin warm, appears red
• Phagocytes go out of capillaries to infected tissue
(phagocytosis)
• Edema – fluid and antibodies leave circulation
to enter tissues
• Swelling = increased volume of fluid in area
• Pain – from edema and action of enzymes in
plasma
Fig. 43-8-3
Pathogen
Splinter
Chemical Macrophage
signals
Mast cell
Capillary
Red blood cells Phagocytic cell
Fluid
Phagocytosis
Fever
• Body’s thermostat in hypothalamus reset
• Higher temp. interferes with growth and
replication of some pathogens
– Lysosomes break down, destroying cells infected
by viruses
• Increased temp. promotes T cell activity and
production of antibodies
• Increased phagocytosis
Specific immune response
• 2 types
– Antibody-mediated immunity
– Cell-mediated immunity
Fig. 43-16
Humoral (antibody-mediated) immune response
Cell-mediated immune response
Key
Antigen (1st exposure)
+
Engulfed by
Gives rise to
Antigenpresenting cell
+
Stimulates
+
+
B cell
Helper T cell
+
Cytotoxic T cell
+
Memory
Helper T cells
+
+
+
Antigen (2nd exposure)
Plasma cells
Memory B cells
+
Memory
Cytotoxic T cells
Active
Cytotoxic T cells
Secreted
antibodies
Defend against extracellular pathogens by binding to antigens,
thereby neutralizing pathogens or making them better targets
for phagocytes and complement proteins.
Defend against intracellular pathogens
and cancer by binding to and lysing the
infected cells or cancer cells.
Lymphocytes
• 3 types:
– T cells
– B Cells
– NK cells
Natural Killer cells
• Kill virally infected and tumor cells
B cells
• Antibody-mediated immunity
• Mature into plasma cells (produce specific
antibodies)
• Encode a receptor that binds to a specific
antigen
– B cell receptors bind to antigen  B cell activated
– Divides rapidly  differentiate into plasma cells
which produce antibody
– Antibody binds to antigen that originally activated
B cells
• Some become memory B cells
– Continue to make small amounts of antibody after
infection has been overcome
Fig. 43-19-3
Antigen-presenting cell
Bacterium
Peptide
antigen
B cell
Class II MHC
molecule
TCR
Clone of plasma cells
+
CD4
Helper T cell
Cytokines
Activated
helper T cell
Clone of memory
B cells
Secreted
antibody
molecules
Fig. 43-14
Antigen molecules
B cells that
differ in
antigen
specificity
Antigen
receptor
Antibody
molecules
Clone of memory cells
Clone of plasma cells
Role of B Cells Animation
T cells
•
•
•
•
Cell-mediated immunity
“T” = thymus-derived
Thymus make T cells immunocompetent
In thymus – cells divided many times, develop
specific surface proteins with distinctive
receptor sites
• Attack body cells infected by invading
pathogens, foreign cells, cancer cells
• T cell antigen receptor (TCR)
– Distinguishes T cells
– Allows T cells to recognize specific antigens
• 2 main types
– CD8 T cells (surface marker CD8)
• Cytotoxic T cells (killer T cells)
• Recognize/destroy foreign antigens
• Targets virus-infected cells, cancer cells, foreign
tissue grafts
• Kill by releasing variety of cytokines and enzymes to
lyse cells
Fig. 43-18-3
Released cytotoxic T cell
Cytotoxic T cell
Perforin
Granzymes
CD8
TCR
Class I MHC
molecule
Target
cell
Dying target cell
Pore
Peptide
antigen
– CD4 T cells (surface marker CD4)
• Helper T cells
• Secrete substances that activate or enhance immune
responses
• 2 subsets
– T helper 1 – cell-mediated
– T helper 2 – antibody- mediated : stimulate B cells divided and
produce antibodies
Fig. 43-17
Antigenpresenting
cell
Peptide antigen
Bacterium
Class II MHC molecule
CD4
TCR (T cell receptor)
Helper T cell
Humoral
immunity
(secretion of
antibodies by
plasma cells)
Cytokines
+
B cell
+
+
+
Cytotoxic T cell
Cell-mediated
immunity
(attack on
infected cells)
Fig. 43-12
Infected cell
Microbe
Antigenpresenting
cell
1 Antigen
associates
with MHC
molecule
Antigen
fragment
Antigen
fragment
1
Class I MHC
molecule
1
T cell
receptor
(a)
2
2
Cytotoxic T cell
Class II MHC
molecule
T cell
receptor
2 T cell
recognizes
combination
(b)
Helper T cell
Major Histocompatibility complex
• MHC antigens – cell surface proteins
– Help vertebrates distinguish self vs. nonself
– Coded for by set of closely linked genes = Major
histocompatibility complex (MHC)
• Humans MHC = HLA (human leukocyte antigen)
• Polymorphic
• Many combination  not likely for people to have
same combo (except identical twins)
Antibody-mediated Immunity
• (humoral immunity)
• B cells responsible
– Produce surface receptors
– Bind to particular antigen
– B cell activates
• Foreign antigen displayed on immune cell
surface
• Contacts helper T cell (has complementary
receptors)
• Macrophage secretes IL-1 – activated helper T
cells
• (T cells do not recognize an antigen presented
alone)
• Antibody receptor of B cell binds with
complementary antigen
• Inside B cell – antigen degraded  peptide
fragments
• B cells display fragments on surface
• Activated helper T binds with B cells
• Activated helper T releases interleukins which,
with antigen, activate B cell
• B cell increases in size  mitosis
• Each new cells makes antibodies specific to
antigen from original B cell
• Some cells of B cell clone  plasma cells
– Secrete antibody specific to antigen
– Plasma cells do not leave lymph nodes
– Antibodies can pass out of lymph tissue to
infected area
• Some B cells  memory B cells
– Live and make antibody after infection gone
– Same pathogen enters later  circulating
antibody targets it for destruction
– Same time  memory cells divided  plasma
cells
Helper T Cell Activation
Fig. 43-9
Antigenbinding
site
Antigenbinding site
Antigenbinding
site
Disulfide
bridge
C
C
Light
chain
Variable
regions
V
V
Constant
regions
C
C
Transmembrane
region
Plasma
membrane
Heavy chains
chain
chain
Disulfide bridge
B cell
(a) B cell receptor
Cytoplasm of B cell
Cytoplasm of T cell
(b) T cell receptor
T cell
Fig. 43-9a
Antigenbinding site
Antigenbinding
site
Disulfide
bridge
Variable
regions
C
C
Constant
regions
Light
chain
Transmembrane
region
Plasma
membrane
Heavy chains
B cell
(a) B cell receptor
Cytoplasm of B cell
Fig. 43-9b
Antigenbinding
site
Variable
regions
V
V
Constant
regions
C
C
Transmembrane
region
Plasma
membrane
chain
chain
Disulfide bridge
Cytoplasm of T cell
(b) T cell receptor
T cell
Antibodies
• (immunoglobulin, Ig)
• 2 main functions
– Combines with antigen
– Activate processes to destroy antigen
• Labels antigen for destruction
• Doesn’t destroy antigen directly
Structure of Antibody
• 4 polypeptide chains
– 2 identical long chains  heavy chains
– 2 identical short chains  light chains
• Can bind with different affinities
– During immune response, higher affinity
antibodies are made
Antigenic determinant
• Give antigen specific shape to be recognized
by antibody
• Usually antigen has many different antigenic
determinants
– Many antibodies can bind to antigen
Fig. 43-10
Antigenbinding
sites
Antigen-binding sites
Antibody A Antigen Antibody C
C
C
Antibody B
Epitopes
(antigenic
determinants)
5 Classes of Antibodies
• Unique AA sequences in heavy chain
• 1. IgG – human ~ 75%
– Gamma globulin fraction of plasma
– Interact with macrophages, activate complement
system
• 2. IgM
– Interact with macrophages, activate complement
system
– Defend against pathogens in blood
• 3. IgA
– Mucus, tears, saliva, milk
– Body openings
• 4. IgD
– Low concentration in plasma
– Helps activate B cells after antigen binding
• 5. IgE
– Low concentration in plasma
– Can bind to mast cells, cells with histamine
(allergy)
– Parasitic worms
Fig. 43-20a
Class of Immunoglobulin (Antibody)
IgM
(pentamer)
J chain
Distribution
First Ig class
produced after
initial exposure to
antigen; then its
concentration in
the blood declines
Function
Promotes neutralization and crosslinking of antigens;
very effective in
complement system
activation
Fig. 43-20b
Class of Immunoglobulin (Antibody)
IgG
(monomer)
Distribution
Most abundant Ig
class in blood;
also present in
tissue fluids
Function
Promotes opsonization, neutralization,
and cross-linking of
antigens; less effective in activation of
complement system
than IgM
Only Ig class that
crosses placenta,
thus conferring
passive immunity
on fetus
Fig. 43-20c
Class of Immunoglobulin (Antibody)
IgA
(dimer)
J chain
Secretory
component
Distribution
Present in
secretions such
as tears, saliva,
mucus, and
breast milk
Function
Provides localized
defense of mucous
membranes by
cross-linking and
neutralization of
antigens
Presence in breast
milk confers
passive immunity
on nursing infant
Fig. 43-20d
Class of Immunoglobulin (Antibody)
IgE
(monomer)
Distribution
Present in blood
at low concentrations
Function
Triggers release from
mast cells and
basophils of histamine and other
chemicals that cause
allergic reactions
Fig. 43-20e
Class of Immunoglobulin (Antibody)
IgD
(monomer)
Transmembrane
region
Distribution
Present primarily
on surface of
B cells that have
not been exposed
to antigens
Function
Acts as antigen
receptor in the
antigen-stimulated
proliferation and
differentiation of
B cells (clonal
selection)
Antibody + Antigen activates other
defense mechanisms
• 1. inactivate pathogen or its toxin
– Ex: virus may not be able to attach to host
• 2. stimulates phagocytic cells to ingest the
pathogen
• 3. complement proteins destroy pathogens
– IgG and IgM Fc fragments bind to phagocytes for
destruction
Monoclonal Antibodies
• = identical antibodies produced by cells cloned
from a single cell
• Steps:
– Inject specific antigen into mice
– Mice make antibodies
– Collect mice B cells
– Mix B cells (can only live in culture a few
generations) with lymphoma cells (can live in
tissue culture indefinitely)
– Cells induced to fuse  hybrid cells = hybridomas
• Have properties of 2 parent cells
• B cells – secrete antibodies
• Cancer cells – cultured indefinitely
– Select hybrid cells making specific antibody
• Clone them
• Cells of clone make large amounts of specific antibody
Antibodies Animation
Cell – Mediated Immunity
• T cells and APCs responsible
• T cells destroy virus-infected cells, altered cells
(cancer cells), foreign grafts
• Steps:
– Virus invades body cells
– Viral proteins displayed on cell surface of APC
– T cells with specific receptor to that antigen
become activated
– T cell grows in size  clone of helper T cells,
cytotoxic T cells and memory T cells
– Cytotoxic T cells leave lymph nodes  infected
area
– Combine with antigen on target cell
– Releases cytotoxic proteins to destroy cell
– Disengages from target and seeks new one
Cytotoxic T Cells animation
Long-term Immunity and
Immunological Memory
• Memory B and memory T cell responsible
• Primary Response vs. Secondary Response
Primary Response
•
•
•
•
1st exposure to antigen
3-14 days for specific antibodies
Injection of antigen
Brief latent period  antigen is recognized
and appropriated lymphocytes form clones
• Logarithmic phase  antibody concentration
rises rapidly for several days (mostly IgM)
• Decline phase  antibody concentration
decreases to very low level
Secondary Response
• 2nd injection of same antigen
• More rapid
• Shorter latent period  memory B and T cells already
bear antibodies to that antigen
• Less antigen needed for response
• More antibodies made with higher affinity (mostly IgG)
• Why we don’t usually suffer same disease many times
• No symptoms
• Booster shots – elicit secondary response to reinforce
immunological memory
Active immunity
• Developed after exposure to antigens
• Naturally or artificially induced
• Immunization - Exposed to vaccine
– Virus attenuated
• Sabin polio, measles
– Killed pathogens ( still have antigens)
• Whooping cough, Typhoid fever
– Toxins from pathogens (altered so no destruction,
same antigens)
• Tetanus, botulism
Passive Immunity
• Individual is given antibodies actively
produced by another organism
• “borrowed immunity” – effects don’t last
– Used to boost body’s defense temporarily
• Natural passive immunity
– Mom  baby
– Through placenta
– Until baby’s own immune system matures
– IgA in breast milk
Cancer
• Precancer cells – different surface proteins
(antigens)
• Dendritic cells recognize, present cancer antigen
to T cells
• T cell activates  clone cytotoxic T cells, make
interleukins to attract macrophages and NK cells
• Cytotoxic T cells make interferons for antitumor
effect
• Macrophages make TNF to inhibit tumor growth
Graft Rejection and Transplants
• MHC antigens same only for identical twins
• Hard to find matches because so many
possibilities for MHC antigens
• Graft rejection – immune response against a
foreign graft/transplant
– T cells attack transplanted tissue, destroy in a
week
• To prevent rejection
– Drugs – suppress immune system
• Xenotransplantation – process to transplant
animal parts to humans
– Genetic engineered pigs
– Artificial organs
Allergic reactions
• Hypersensitivity results in the manufacture of
antibodies against mild antigens, called
allergens, that normally do not stimulate an
immune response
• Ex: dust mites, pollen
Common allergic reaction:
Ex: hayfever to ragweed pollen
• Sensitization
• Activation of mast cells
• Allergic response prolonged (maybe)
Sensitization
• Macrophages degrade allergen, present
fragments of it to T cells
• Activated T cells stimulate B cells into plasma
cells and produce IgE
• IgE antibodies attach to receptors on mast
cells (at C region – V region is left open to
attach to allergen)
Activation of Mast cells
• Allergens attach to IgE on mast cells
stimulating mast cells to release histamine
and serotonin that cause inflammation
• Blood vessels dilate
• Capillaries more permeable  edema, red
• Nasal passages swollen, irritated
• Noses run, sneeze, eyes water
Allergic response is prolonged
(maybe)
• Chemical from mast cells lure certain WBCs to
inflamed area
• WBCs release compounds that damage tissue
and prolong reaction
Fig. 43-23
IgE
Histamine
Allergen
Granule
Mast cell
Hives
• Allergen/IgE reaction happens in skin
• Histamine released by mast cells causes
swollen red welts (hives)
Systemic anaphylaxis
• Dangerous allergic reaction that can occur
when a person develops an allergy to a
specific drug, venom or food
• In minutes  widespread reaction
• Mast cells give off much histamine 
vasodilation and permeability
• So much plasma may be last from blood that
circulatory shock and death can occur in
minutes
Antihistamines
• Drugs that block the effects of histamines
• Compete for same receptors on target cells as
histamine
• Not totally effective because mast cells release
substances other than histamine for reaction
Autoimmunity
• T cells react immunologically against self
• Ex:
– Rheumatoid arthritis
– Multiple sclerosis
– Systemic lupus erythematosus
– Insulin-dependent diabetes
– Psoriasis
– Scleroderma