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Immunity
Chapter 23
Smallpox Vaccine
• Before vaccines, smallpox had up to 50% death rates
• Now smallpox is practically eradicated
Immunity
• Body’s ability to resist and combat diseases
• Depends on mechanisms that recognize
proteins as self or nonself
• Antigen
– Any molecule the body recognizes as nonself and
provokes an immune response
Evolution of Defenses
• Innate immunity
– Preset responses to nonself cues
– Complement, phagocytes
• Adaptive immunity
– Prepares defenses to specific pathogens
encountered during an individual’s lifetime
– Cytokines, lymphocytes
Adaptive and Innate Immunity
Three Lines of Defense
• Physical barriers
– exclude pathogens
• Innate immunity
– begins as soon as antigen is detected
• Adaptive immunity
– forms cells that fight infection and prevent
later infection
White Blood Cells
• Form in bone marrow
• Participate in adaptive and innate responses
• Release cytokines and other cell-to-cell
signaling molecules
Chemical Weapons
White Blood Cells
basophil
mast cell
neutrophil
eosinophil
White Blood Cells
NK cell
B lymphocyte
T lymphocyte
White Blood Cells
dendritic cell
macrophage
Surface Barriers
• Physical barriers
– Intact skin
• Mechanical barriers
– Mucus, cilia, flushing
• Chemical barriers
– Protective secretions, low pH, lysozyme
Cilia in Airways
Bacterial Invaders
Table 23-3, p.385
Innate Immune Response
•
•
•
•
Phagocytosis
Complement
Fever
Acute inflammation
Complement
• Many types of circulating proteins
• Activated by binding to antigen
– Triggers reactions that activate more complement
• Attract phagocytic cells
Membrane Attack Complexes
antibody
lipid
bilayer of
pathogen
activated
complement
bacterial pathogen
Activation
Cascade
reactions
Formation of attack
complexes
Lysis
of target
one membrane
attack complex
(cutaway view)
lipid bilayer of one
kind of pathogen
hole in the plasma
membrane of an
unlucky baterium
Fig. 23-6, p.388
Acute Inflammation
• Nonspecific response to foreign invasion,
tissue damage
• Destroys invaders, removes debris
• Symptoms are redness, swelling, warmth,
and pain
Inflammation
•
•
•
•
Mast cells release histamine
Capillaries dilate and leak
Complement proteins attack bacteria
White cells attack invaders and clean up
b Mast cells in tissue release
histamines, which then trigger
arteriole vasodilation (hence
redness and warmth) as well as
increased capillary permeability.
a Bacteria invade a
tissue and directly
kill cells or release
metabolic products
that damage tissue.
c Fluid and plasma
proteins leak out of
capillaries; localized
edema (tissue
swelling) and pain
result.
d Complement
proteins attack
bacteria. Clotting
factors wall off
inflamed area.
e Neutrophils, macrophages,
engulf invaders and debris.Some
macrophage secretions kill targets,
attract more lymphocytes, and call
for fever.
Fig. 23-7, p.388
Fever
• Temperature up to 39°C (102°F)
• Enhances immunity, increases rates of enzyme
and phagocyte activity
• Accelerates tissue repair
Features of Adaptive Immunity
•
•
•
•
Self/nonself recognition
Specificity
Diversity
Memory
Antigens
• “Nonself” markers on foreign agents
and altered body cells such as
tumors
• Trigger division of B and T cells
Memory and Effector Cells
• When a B or T cell is stimulated to divide, it
produces 2 cell types
• Memory cells: set aside for future use
• Effector cells: engage and destroy the current
threat
Key Components of
Immune Response
•
•
•
•
•
MHC markers
Antigen-presenting cells
T cells
B cells
Natural killer (NK) cells
Formation of
Antigen–MHC
Complex
antigen
fragments
MHC
molecule
antigen–MHC
complex
fragments of
engulfed
antigen
MHC marker
that the cell
already made
antigen-MHC complex displayed at
surface of plasma membrane
Fig. 23-9, p.390
Key Interactions
Antibody-Mediated
Immune Response
Cell-Mediated
Immune Response
naive B cells
+
antigen
+
complement
antigen-presenting cells
activated
B cells
effector
helper T cells
+
memory
helper T cells
effector B cells
+
memory B cells
naive helper T cells
naive
cytotoxic T cells
effector cytotoxic T cells
+
memory cytotoxic cells
Fig. 23-10, p.390
Antigen Interception
• Antigen-presenting T cells are trapped
in lymph nodes
• Macrophages, dendritic cells,
and B cells bind, process and present
antigen
TONSILS
RIGHT LYMPHATIC DUCT
THYMUS GLAND
THORACIC DUCT
SPLEEN
SOME OF THE LYMPH
VESSELS
SOME OF THE LYMPH
NODES
BONE MARROW
Fig. 23-11a, p.391
arrays of
lymphocytes
valve (prevents backflow)
Fig. 23-11b, p.391
Antigen Receptors
• Antibodies
– Synthesized by B cells
– Bind to one specific antigen
• Mark pathogen for destruction by
phagocytes and complement proteins
Antibody Structure
• Consists of four
polypeptide chains
• Parts of each chain
are variable; provide
antigen specificity
antigen binding site
variable
region
constant
region
binding site for
antigen
variable region
(dark green)
of heavy chain
binding site for
antigen
variable region
of light chain
constant region (bright
green) of heavy chain, that
includes a hinged region
Fig. 23-12a, p.392
antigen on bacterial cell
(not to scale)
binding site on one kind of
antibody molecule for a
specific antigen
Fig. 23-12b, p.392
antigen on virus particle
binding site on another
kind of antibody molecule
For a different antigen
Fig. 23-12c, p.392
Immunoglobins (Igs)
• Five classes of antibodies
– IgG
– IgA
– IgE
– IgM
– IgD
Antigen Receptor Diversity
a As a B cell matures, different
segments of antibody-coding genes
recombine at random into a final gene
sequence.
b The final sequence is transcribed
into mRNA.
c Processing yields a mature mRNA
transcript (e.g., introns excised,
exons spliced).
d mRNA is translated into one of the
polypeptide chains of an antibody
molecule.
Stepped Art
Fig. 23-13, p.393
Antibody-Mediated Immune Response
• B cell responds to one particular extracellular
pathogen or toxin
• Activated B cell forms clones that differentiate
into effector and memory cells
• Effector B cells secrete antibodies that tag
antigens for destruction
Antibody-Mediated
Response
B Cell Division
antigen
Antigen binds only to antibody
specific to it on a naive B cell.
clonal
population
of effector
B cells
Effector B cells secrete antibodies.
Fig. 23-15a, p.395
First exposure to
antigen provokes
a
primary immune
response.
naive B cell
effector cells
Another
exposure
to the same
antigen
provokes
secondary
response.
effector cells
B Cell
Differentiation
memory cells
memory cells
Fig. 23-15b, p.395
Secondary Immune Response
Fig. 23-15c, p.395
Cell-Mediated Immune Response
• Cytotoxic T cells target altered body cells that
evade antibody-mediated immune response
• Antigen-presenting dendritic cells activate
helper T cells
Fig. 23-16, p.396
Cell-Mediated Immune Response
• Helper T cells secrete cytokines
– Induce formation of cytotoxic T cells
– Proliferate NK cells
– Enhance macrophage activity
• Destroy infected or altered cells
Cell-Mediated Immune Response
cytotoxic Tcell
tumor cell
Immunization
• Process that induces immunity
• Active immunization:
– Vaccination with antigen
– Long-lasting immunity
• Passive immunization:
– Purified antibody is injected
– Protection is short lived
Allergies
• Immune reaction to harmless proteins
(allergens)
• IgE binds to mast cells, causing inflammatory
response
• Histamine release causes symptoms
Anaphylactic Shock
• Life-threatening allergic reaction
• Caused by histamine released by many mast
cells
• Airways constrict
• Blood pressure drops as fluid leaks out of
capillaries
Autoimmune Disorders
• Failure of immune system to distinguish
between self and nonself
– produces antibodies against self
• Graves’ disease
• Multiple sclerosis
Deficient Immune Responses
• Primary immune deficiencies
– Present from birth
• Secondary immune deficiencies
– Acquired by exposure to agent such as HIV
HIV Replication
reverse
transcriptase
viral genes are
integrated
into the host DNA
viral RNA
enters
cell
viral
RNA
core proteins
(two layers)
reverse
transcription
of viral RNA
integrase
DNA is
transcribed
host cell
viral RNA
viral
DNA
viral
proteins
budding
viral enzyme
(reverse transcriptase)
viral coat
proteins
a viral RNA
enters a T cell.
c The viral
DNA becomes
integrated into
host cell’s DNA.
d DNA,
including the
viral genes,
is
transcribed
nucleus
25-30m
viral
RNA
lipid envelope
with proteins
b Viral DNA
forms by
reverse
transcription of
viral RNA.
f Virus particles
that bud from the
infected cell may
attack a new one.
Viral RNA
viral DNA
viral
proteins
e Some transcripts are new
viral RNA, others are
translated into proteins. Both
self-assemble as new virus
particles.
Fig. 23-20, p.396
HIV Infection
• HIV infects immune system cells
– Macrophages, dendritic cells, helper T cells
•
•
•
•
T cells are killed
Cytokine IL-4 is released
Immune system destroys itself
Secondary infections and tumors cause death
Table 23-4, p.399
HIV Transmission
• Virus transmitted by
– Sex
– Infected mothers
– Shared needles
• Not transmitted by causal contact
Treatment
• No cure
• AZT and other drugs slow disease and
increase life span
• Traditional vaccines do not work
• Researchers continue to work