The Immune System
CAMPBELL and REECE
Chapter 43
Innate Immunity
nonspecific defense that is active
immediately upon infection
 found in all animals & plants
 includes:

◦ outer covering
 skin or shell
◦ chemical secretions
 @ openings to interior of body
Immune System
must be able to identify nonself from
self
 detection determined by molecular
recognition of receptor molecules

Adaptive Immunity
found only in vertebrates
 very specific
 aka acquired immune response
 activated after innate responses &
develops more slowly

Innate Immunity of Insects
only have innate immunity
 1st line of defense (barrier defenses)

◦ Exoskeletons: effective against most
pathogens: made of polysaccharide, chitin
Innate Immunity in Insects: Barrier
Defenses

lining of intestine:
◦ has chitin where it blocks infection by
pathogens ingested in food
◦ secretes lysozyme, enzyme that breaks
down bacterial cell walls
Insect’s Internal Immune
Responses
if pathogen gets by barrier defenses:
1. hemocytes: immune cells in
hemolymph

◦
◦
◦
some can phagocytose
others secrete chemicals that kill
pathogens & help entrap large parasites
(like Plasmodium)
interaction with pathogens  some
secrete antimicrobial peptides 
circulate in hemolymph
Phagocytosis
Insect Immune Cells

bind to molecules unique to outer
layers of fungi, or bacteria
◦ fungal cells: polysaccharides
◦ bacteria: combinations of sugars & a.a.
not found in animal cells
Innate Responses

unique for different classes of
pathogens
Innate Immunity in Vertebrates

coexists with adaptive immunity
mechanisms
◦ 2 are strongly interdependent
◦ basis same as innate immunity in
invertebrates but there are additions

most research done on mammals
Barrier Defenses

epithelial tissues block entry of many
pathogens
◦ skin
◦ mucous membranes
 line organs that have opening to outside of
body
 mucus: viscous fluid that blocks microbes &
other particles
 saliva, tears have “washing” action keeping
microbes from colonizing
Barrier Defenses

cellular secretions
◦
◦
◦
◦
lysozyme kills by breaking down cell walls
saliva, tears dilute & prevent colonization
sweat pH 3 – 4
stomach pH 2
Internal Innate Defenses
1. phagocytes

cells that can detect fungi & bacteria
 use several types of receptors:
◦
◦
Toll-like receptor (TLR) binds to fragments
of molecules characteristic of set of
pathogens
similar mechanism used in insects
TLR Signaling Pathway
TLR

TLR3
◦ sensor for dsRNA (viral)

TLR4
◦ recognizes lipopolysaccharide (surface of
many bacteria)

TLR5
◦ recognizes flagellin (bacterial flagella
protein)
Types of Phagocytic Cells
Neutrophils
1.
◦
◦
circulate in blood
attracted by signals sent from infected
cells
Macrophages
2.
◦
larger cells migrate thru tissues or reside
permanently in organs/tissues likely to
have invaders
Types of Phagocytic Cells
3. Dendritic cells

mainly found in tissues that contact
outside (skin)
◦ stimulate adaptive immunity after
engulfing pathogen
4. Eosinophils
◦ found beneath mucous membranes
◦ low phagocytic activity
◦ speciality: able to defend against parasitic
worms  secrete enzymes
Natural Killer Cells
circulate thru body detecting abnl
surface proteins of cells infected with
virus or cancer cells
 on detection  secrete chemicals that
kill affected cell

Lymphatic System

network of vessels that connect
lymphatic tissues thru out body
◦ ICF  lymph vessels  venous drainage

some macrophages in lymph nodes
Lymphatic System
dendritic cells migrate to lymph node
after interacting with pathogen 
interact with other immune cells
stimulating adaptive immunity attack
 aka APCs: Antigen-Presenting Cells

Lymphatic System
Pathogen Recognition Triggers:

release of peptides & proteins 
attack pathogens or impede their
reproduction
Interferons
proteins released in response to viral
infection
 vertebrates only
 now used in early treatment

Complement System
~30 proteins in plasma
 circulate in inactive state
 activated by substances on surfaces of
some microbes
 activation starts cascade of reactions
  lysis of invading cells

Inflammatory Response

innate immune defense triggered by
physical injury or infection of tissue
involving the release of substances
that promote swelling, enhance the
infiltration of WBCs, & aid in tissue
repair & destruction of invading
pathogens
Histamine
1 of inflammatory signaling molecules
 stored in granules of mast cells (in CT)

Cytokines

group of small protein secreted by # of
cell types:
◦ macrophages
◦ helper T cells
regulate function of other cells to
enhance immune response
 promote increased blood flow to
injured area

◦ causes redness & increased skin temp
◦ engorged capillaries leak fluid  localized
swelling
Inflammatory Response
Some Pathogens Evade Innate
Immunity

Bacteria:
◦ some have outer capsule that interferes
with recognition & phagocytosis
◦ Streptococcus pneumoniae
Adaptive Immunity
unique to
vertebrates
 relies on
lymphocytes

Thymus
organ in thoracic cavity
 some new lymphocytes travel from
bone marrow  thymus & are
“taught” how to respond in immune
attack  mature into T cells

B Cells
lymphocytes that stay in bone marrow
to mature
 become effector cells for humoral
immune response

Antigen (agn)

substance that elicits an immune
response by binding to receptors of B
cells, antibodies, or of T cells
◦ example: bacterial or viral protein

agn receptor: general term for a
surface protein, on B or T cells, that
binds to agns, initiating adaptive
immune responses
agn receptors
specific enough to bind to just one
part of 1 molecule from particular
pathogen
 1 B cell or 1 T cell makes only 1 specific
receptor

◦ ~ 100,000 agn receptors on 1 B or T cell
B Cell or T Cell Receptors
agns

usually large foreign molecules
(proteins or polysaccharides most
often)
◦ stick out surface of foreign cells or virus
◦ molecule of toxin secreted by bacteria
Epitopes
small, accesible region of agn to which
an agn receptor or antibody (aby)
binds
 aka: agn determinant

Epitopes
single agn typically has several
different epitopes each will bind to
receptor with different specificity
 agn receptors of B & T cells encounter
agns differently

Recognition of agn by B Cells
B cell agn receptors
“Y” shaped made of
4 polypeptide
chains
2 identical
heavy chains
2 identical light
chains
disulfide
bridges link them
B Cell Antigen Receptor
heavy chains extend into cytoplasm
anchor receptor
 light & heavy chains have
“constant”(C) region (nearly same on
all B cells) & “variable” (V) regions
(great amt variation from 1 B cell to
another)

◦ includes tail (heavy chain only)that
extends thru membrane & into cytoplasm
and all disulfide bridges
B Cell Activation
starts when agn binds to a B cell agn
receptor
 ends with B cell secreting soluble form
of its agn receptor = antibody (aby) or
immunoglobulin (Ig)
 abys have same “Y” shaped
organization as the B cell agn receptor

B Cell recognition of agn
T Cell Recognition of agn

agn receptors made of 2 chains: α
chain & a β chain linked by disulfide
bridges
◦ both chains pass thru plasma membrane
& into cytoplasm
◦ both have C regions & V regions
T Cell Antigen Receptors
fundamentally different from B Cell
 these bind only to fragments of agns
displayed or presented on surface of
host cells
 host protein that displays the
fragment called MHC (major
histocampatibility) molecule

T Cell Recognition of agns
begins when pathogen or part of one
either infects or is taken in by a host
cell
 enzymes in host cell break pathogen
 smaller peptides (each 1 called agn
fragment) which bind to MHC
molecule  combination moves to cell
membrane outer surface = agn
presentation

agn presentation
advertises fact that this cell has been
invaded by foreign substance
 when presenting cell meets T cell with
compatible agn receptor it will bind to
the agn fragment & the MHC molecule

4 Major Characteristics of
Adaptive Immunity
immense diversity of lymphocytes &
receptors
1.
◦
enables immune system to detect
pathogens never before encountered
adaptive immunity normally has
“self” tolerance
2.
◦
arises as B cell matures
4 Major Characteristics of
Adaptive Immunity
cell proliferation triggered by
activation greatly increases the # of B
and T cells
there is a stronger & more rapid
response to agn previously
encountered
3.
4.
◦
immunological memory occurs after
mature lymphocyte encounters & binds
to a specific agn
B & T Cell Diversity
everyone has ~ 20,000 protein-coding
genes but has ~1 million different B
cell agn receptors & ~ 10 million T cell
agn receptors
 manage this by making different
combinations

B Cell Diversity

3 genes code for light chain
1.
2.
3.
◦
V segment
J segment (joins)
C segment
V + J = variable region
◦
light chain gene contains 1 C segment,
40 different V segments & 5 different J
segments: these pieces can be combined
in 200 different ways
heavy chain segments have even more
combinations possible
◦
Enzyme complex called recombinase links 1
light chain gene segment to 1 J gene segment
forming single exon that is part V & part J
Recombinase
acts randomly linking any 1 of 40 V
gene segments with any 1 of 5 J
segments
 same random connections made in
heavy chains
 once rearrangements complete agn
receptors can be built

Origin of Self - Tolerance
because combinations are random
sometimes receptors will be made that
are specific for epitopes on own
cells/molecules
 as lymphocytes mature in bone
marrow or thymus their agn receptors
are tested for self reactivity  when
discovered are destroyed by apoptosis
or rendered nonfunctional

Proliferation of B & T Cells
successful match between epitope
with an agn receptor triggers a # of
changes in cell # & activity
 changes “activate” the lymphocyte 
# of cell divisions producing a clone
population

◦ some become effector cells
 Helper T Cells
 Cytotoxic T Cells
◦ rest become memory cells
 long-lived cells  effector cells should same
agn be encountered any time in animal’s life
Immunological Memory
gives individual long term protection
from an infection or vaccination
 Primary Immune Response

◦ produces effector cells from a clone of
lymphocytes
◦ peaks 10 -17 days after initial exposure
Immunological Memory

Secondary Immune Response
◦ if individual exposed again to same agn
there is a faster, larger & longer response
◦ peaks 2- 7 days after exposure
◦ is hallmark of adaptive (acquired)
immunity
Humoral Immune Response
occurs in blood &
lymph
 abys neutralize or
eliminate toxins &
pathogen in blood
or lymph
 includes a primary
& secondary
immune response

Cell-Mediated Immune Response
specialized T cells
destroy infected
host cells
 includes primary &
secondary immune
responses

Helper T Cells
triggers both humoral & cell-mediated
immune responses but does not
directly carry out these responses
 signals from helper Ts initiate
production of abys that neutralize
pathogens
 activate T killers

T Helper Cells
need 2 things to activate adaptive
immune responses
1. foreign molecule must bind to agn
receptor of T cell
2. agn must be displayed on surface of
an Agn-Presenting Cell (APC)

◦
APC must be a dendritic cell,
macrophage, or B cell
APCs

have a 2nd class of MHC molecules
◦ most body cells have Class I MHC
molecules
◦ APCs also have Class II MHC molecules
Class II MHC Molecules
provide molecular signature by which
APC is recognized
 complex interaction between T cell &
APC

T Cell Proliferation
follows agn presentation by dendritic
cell or macrophage
 forms clone of helper Ts

B cells present agn to activated helper
T cells
 these T cells then stimulate activate B
cells & cytotoxic T cells

Cytotoxic T Cells
in cell-mediated immune response
 role: effector cells

◦ synthesize toxic gene products that kill
infected cells

activated by signaling molecules from
helper T cells + interaction with APC
Activation of B Cells

when stimulated by both an agn &
cytokines secreted from helper Ts  B
cell differentiates into an abysecreting plasma cell
Activation of B Cells
Activated B Cells
give rise to thousands of plasma cells
 1 plasma cell secretes ~2,000 aby/s
 plasma cell lives 4 – 5 days

Antibody Function
do not kill pathogens
 bind to agns  inactivation or
destruction

Antibody-Mediated Mechanisms
of Antigen Disposal
Active Immunity

defenses that arise when a pathogen
infects the body & prompts a primary
or secondary immune response
Passive Immunity

pregnant mom’s IgG abys cross
placenta & protect fetus
◦ last few wks  few mos

newborn receives IgA abys in breast
milk
◦ give boost to baby’s immune system until
it fully develops
◦ Adults: IgA in tears, saliva, mucus
Artificial Active Immunity
Immunizations: introduce agns to
body  abys develop giving immunity
to person receiving vaccination
 Jenner: took cowpox virus to induce
adaptive immunity against small pox
(closely related viruses)

Small Pox Vaccination
Antibodies as Tools

Monoclonal Antibodies:
◦ made by clone of B cells in reaction to
single epitope
◦ used in medical diagnosis & treatment:
 Home pregnancy tests
 genetically engineered to use as
immunotherapy
Blood Groups
Tissue & Organ Transplants
MHC molecules stimulate the immune
response that  rejection
 MHC molecules have many alleles and
any 1 individual has many that vary in
shape & charge
 for most transplant recipients there
will be some MHC molecules seen as
foreign

Tissue & Organ Transplants
to decrease the chance of rejection the
donor & recipient are “matched” =
MHC molecules same is both as much
as possible
 also, recipient takes meds to suppress
immune response

◦ makes recipient more vulnerable to
infections
Moon Face
Graft Versus Host Rejection
seen in bone marrow transplants
 recipient’s bone marrow radiated b/4
to get rid of abnl cells  also wipes
out their immune system
 lymphocytes in donor’s marrow react
to “foreign” recipients tissues and cells

Allergies
exaggerated hypersensitivity reactions
to allergens: agn that triggers
exaggerated immune response
 most involve aby of IgE class
 example:

◦ hayfever
 agn on surface of pollen grains
Allergic Response


agn attaches to IgE
abys on mast cells
when cross linked 
release of histamine
 typical allergic
symptoms of itchy
eyes, sneezing, runny
nose, teary eyes,
smooth muscle
contraction 
constriction of
airways
Anaphylactic Shock
whole-body, life-threatening reaction
in response to allergen
 due to widespread release of
histamine by mast cells:

◦ abrupt dilation of peripheral blood vessels
 quick drop in BP & constriction of
bronchioles (smaller airways)
◦ death can occur w/in minutes due to
decreased blood flow and inability to
breathe
Autoimmune Diseases

Immune system reacts to some
molecules of self
Autoimmune Diseases
Exercise & the Immune System
moderate exercise boosts the immune
system & significantly reduces
susceptibility to colds & other URTI
 exercise to pt. of exhaustion  more
frequent infections
 psychological stress disrupts immune
system by altering interplay of

Stress & the Immune System
psychological stress disrupts immune
system by altering interplay of the
nervous system endocrine system &
immune system
 rest important for immunity

◦ adults with < 7 hrs sleep/nite : 3x more
likely to get sick when exposed to cold
virus as those who average 8 hrs
sleep/nite
Immunodeficiency Diseases

immune response to agns deficient or
absent
◦ frequent infections & increased risk of
certain cancers

Inborn Immunodeficiency:
◦ genetic or developmental defect in
immune system

Acquired Immunodeficiency:
◦ follows exposure to chemical or biological
agents
SCID
Severe Combines ImmunoDeficiency:
 missing one or more immune cells
 freq. die in infancy due to infections
 treatment:

◦ bone marrow transplant
◦ stem cell transplantation
◦ gene therapy
Immundeficiency Disease
Caused by Drugs

drugs used to fight against
autoimmune diseases or prevent
transplant rejection suppress immune
system  immunodeficiency state
Immunodeficiency Disease
Caused by Cancer

Hodgkins Lymphoma best known for
this
◦ possible genetic predisposition
AIDS
Acquired ImmunoDeficiency
Syndrome
 caused by HIV (Human
Immunodeficiency Virus)

HIV
escapes & attacks
adaptive immune
response
 infects helper Ts

◦ virus binds
specifically to the
CD4 accessory
protein
HIV

also infects cells with low levels of
CD4:
◦ macrophages
◦ brain cells
HIV RNA Genome
reverse transcribed
 product DNA
inserted into host
genome

◦ directs production of
new virus
Immune Response to HIV

immune system does respond to HIV
attack but some escape:
1. the virus has high rate of mutation
during its replication so has high agn
variation (each infected individual’s
population of the virus is evolving w/in
that individual)
2. viral DNA w/in host genome it is
protected from immune system (some
latent for period of time then activate)
Latent HIV

also protected from any anti-virals
used to treat patient
HIV over time
avoids adaptive immune system &
destroys it
 viral reproduction (lytic cycle) & cell
death  loss of helper T cells  loss
of humoral & cell-mediated immune
responses  progresses to AIDS

2º Infections

Pneumocystis carinii
◦ fungal pneumonia

Kaposi’s Sarcoma herpesvirus
◦ rare cancer except in AIDS

Candida
◦ fungal infection rare except in babies
Progress of Untreated HIV
Treatment Strategy
use combinations of anti-virals since
each round of HIV has mutations
 still get drug-resistant strains

Transmission of HIV

virus particles or infected cells person
to person in any body fluid
◦ semen
◦ blood
◦ breatmilk

most infections from unprotected sex
or tainted needles
◦ having another STD or some break in
mucous membranes increases likelihood
of HIV
Transmission of HIV
newly infected person can pass it on
even b/4 their blood test (+) for HIV
 blood test measures HIV abys
 10 – 50% new cases got it from
another newly infected person

Evolutionary Adaptations of
Pathogens that Avoid Immune
Responses
1. antigenic variation

immunologic memory is a record of
previous epitopes encountered
 pathogen may no longer express those
agns
◦ viruses
◦ parasites
Antigenic Variation in
Trypanosoma bruceii
Influenza Virus
mutates as spreads person to person
 exchanges genes with pigs, chickens
 Influenza outbreak 1918-1919:

◦ >20 million died worldwide
Latency
2nd way pathogens can change to avoid
immune system
 a largely inactive state
 dormant viruses quit making most
viral proteins and no free virus
particles so do not trigger adaptive
immune response
 viral genome still in host nuclei

Latency

typically persists until conditions arise
that are favorable for viral
transmission or unfavorable for host
survival or defense (currently fighting
another infection
Herpes Simplex Viruses
establish home in sensory neurons after
initial infection
 Type I: mostly oral herpes infections
 Type II: mostly genital herpes
 stimuli likely to cause recurrences:
 fever
 emotional stress
 menstruation

Cancer & Immunity
when adaptive immunity inactive,
incidence of certain cancers increases
 15 – 20% of human cancers involve
viruses

6 Viruses Known to Cause
Cancer
1.
2.
3.
4.
5.
6.
Herpesvirus
Hepatitis B
Human Papilloma Virus (HPV)
Hepatits C
Human T cell lymphotropic virus
Epstein-Barr virus
Vaccinations
Hepatitis B
 HPV
