The Immune System
Chapter 21
The Immune System
Immune System – a “functional
system” consisting of many
disperse cells and molecules that
target pathogens, diseasecausing microbes
Innate defenses (nonspecific) –
inborn immunity that constantly
prevents infection of any target
Adaptive defenses (specific) –
form slower responses to specific
targets, improves through life
Figure 21.1
The Immune System
Innate defenses:
Surface barriers – skin and mucous
membranes that act as first line of
defense
• acidity and toxins of skin secretions
prevent bacterial growth
• acidic secretions in stomach kill
microbes
• enzymes in saliva and tears kill
bacteria
• mucous in digestive and respiratory
tracts trap microbes
Figure 21.1
The Immune System
Innate defenses:
Internal defenses – cells and
molecules that act as second line of
defense
• Phagocytes – cells that engulf
foreign cells and debris
• Fever – prevents bacterial growth
and encourages healing
• Natural killer cells – patrol tissues
and kill cells
• Antimicrobial proteins – kill
bacteria and prevent spread of viruses
• Inflammation – complex tissue
response to injury or infection
Figure 21.1
Phagocytes
Phagocytes – include macrophages,
dendritic cells, neutrophils, and
eosinophils
Steps of phagocytosis:
• Phagocyte attaches to and engulfs
microbe, forming a phagosome
•
The phagosome fuses with an
enzyme-filled lysosome, forming a
phagolysosome
•
The microbe is digested and waste
is removed
Figure 21.2b
Phagocytes
Image – a macrophage
engulfing E. coli
Opsonization – the
clinging of antimicrobial
proteins (antibodies or
complement) makes it
easier for phagocytes to
grab the microbes
(molecules act like
handles)
Figure 21.2a
Natural Killer Cells
Natural killer cells – important
cells of the innate immunity
• scan tissues for cells that are
cancerous or infected with a
virus
• they kill these cells by
triggering apoptosis, a
programmed cell death
• kill these cells before the
specific immune system is even
activated
Figure 21.2a
Inflammation
Inflammation – tissue response to
injury or infection in an effort to
prevent spread of pathogens, clear
foreign cells and debris, and promote
local healing. The four signs of
inflammation are redness, heat, pain
and swelling.
• begins when injured tissue releases
inflammatory chemicals, like
histamine, complement, etc.
• chemicals cause local hyperemia
due to vasodilation, causing heat and
redness
• chemicals cause increased vessel
permeability leaking exudate into local
tissues, causing swelling and pain
Figure 21.3
Inflammation
Phagocyte mobilization – inflammatory
chemicals also trigger leukocytosis,
recruiting white blood cells to the site of
inflammation
1. Leukocytosis – red bone marrow
releases neutrophils within hours
2. Margination – neutrophils roll along
capillary walls and bind to cell adhesion
molecules (CAM’s) on endothelial cells
near inflammation site
3. Diapedesis – neutrophils leave vessels
to enter inflamed tissue
4. Positive chemotaxis – neutrophils
follow inflammatory chemical gradient
to epicenter of inflammation and
perform phagocytosis
5. Macrophages - Monocytes arrive later
and become macrophages
Figure 21.4
Inflammation
Pus – a yellowish substance collecting
at a site of inflammation. Consists of
dead and dying neutrophils (short lived
cells) dead bacteria and other
pathogens, and cellular debris. Generally
does not include macrophages (long
lived cells)
Abcess – when collagen fibers and
clotting factors wall off an area of
infection, preventing spread
Fever – an elevated body temperature
triggered by pyrogen molecules secreted
by leukocytes and macrophages. Higher
body temp prevents bacterial growth and
promotes healing.
Figure 21.4
Antimicrobial Proteins
Interferons – communication molecules
that prevent the spread of viruses
• viruses take over cellular machinery to
make viral copies
• infected cells produce and release
interferons to chemically warn other cells
• Interferons trigger nearby cells to make
antiviral proteins, thereby preventing
spread
Figure 21.5
Antimicrobial Proteins
Complement system – a group of
circulating molecules that can destroy
pathogens and aide inflammation
• Opsonization – complement proteins
stick to pathogens, encouraging
phagocytosis
• Inflammatory chemical – promotes
vessel permeability and recruits cells
• Membrane Attack Complexes
(MAC’s) – groups of complement
proteins that kill pathogens by poking
holes in their cell membranes
Figure 21.6
The Immune System
Adaptive defenses – the slow but
highly specific method of targeting
pathogens, mainly via lymphocytes
• Specific – certain cells targeting
particular pathogens
• Systemic – full body, not one
infection site
• Memory – forms cells to prepare for
future encounters
1. Humoral Immunity (antibodymediated) – uses antibodies in body
fluids to target specific pathogens,
primarily bacteria
2. Cellular immunity (cell-mediated)
– uses whole cells to target specific
pathogens, primarily cancerous
cells and virally or parasitically
infected cells
Figure 21.1
Antigens
Antigens – any nonself molecule that can provoke an immune response
Complete antigens – large molecules with two major properties
1. Immunogenicity – ability to activate new B and T cells
2. Reactivity – ability to be recognized by already active B and T cells
Incomplete antigens (haptens) – small molecules with reactivity but not
immunogenicity, typically causing allergic reactions
Antigenic determinants – the immunogenic (recognizable) parts of a
whole antigen, can be many
Figure 21.7
Self-Antigens
Self-Antigens – any molecules located on our own cells’ surfaces
that should be ignored by the cells of our immune system, known
as self-tolerance
Major Histocompatibility Complex (MHC) – self-antigen
proteins on our cell surfaces used to communicate with immune
cells
MHC Class 1 – found on membranes of all body cells,
show self-antigens when healthy, but show nonself
antigens when infected or cancerous (alerts immune cells
to kill)
MHC Class 2 – found only on immune cells, used to
mobilize the immune system
Figure 21.7
Adaptive Immune Cells
B lymphocytes – oversee
humoral immunity
T lymphocytes - oversee cellular
immunity
B cells and T cells must have two
major abilities:
1.Immunocompetence – the
ability to bond to its specific
antigen
2.Self-tolerance – the ability to
ignore self-antigens
Figure 21.8
Adaptive Immune Cells
Lymphocyte movement:
1. B and T cells both develop in red
bone marrow
2. Both become immunocompetent
and self-tolerant in primary lymphoid
tissues (B cells in bone marrow & T
cells in the thymus)
3. Now “educated” but “naïve”, they
move to secondary lymphoid tissues
(like lymph nodes) to await
activation by their first encounter
with their specific antigens (called
an antigen challenge)
4. Once activated, B and T cells can
circulate and search for specific
targets
Figure 21.8
Lymphocyte Education
Positive selection – selects
lymphocytes whose receptors
can recognize the MHC
molecules that are used to
present antigens. Those that
can’t are eliminated by
apoptosis
Negative selection – those
lymphocytes that overreact to
the self-antigen are eliminated
by apoptosis
Somatic recombination – a
shuffling of the genes that
encode B and T cell receptors,
leading to huge receptor
diversity
Figure 21.9
Antigen Presenting Cells
Antigen Presenting Cells (APC’s) –
phagocytes that engulf antigen and then
display antigenic fragments (as warning
flags) to other immune cells (mainly T
cells)
• APC’s include macrophages and
dendritic cells and their function is the
bridge between innate and adaptive
immune responses
• The APC’s engulf antigen (innate
defense) then use the antigenic
fragments to activate lymphocytes
(adaptive defense)
Humoral Immunity
Humoral immune response –
an antibody-mediated
response triggered by the
antigen challenge of a B cell
Clonal selection – only B cells
challenged by antigen divide
into many identical copies
(also requires a helper T cell
signal…discussed later)
Plasma cells – the B cell
clones that specialize in
antibody production and
secretion, only a 4-5day
lifespan
Memory cells – long-lived
clones for future antigen
challenge
Figure 21.10
Immunological Memory
Immunological memory – the
increasing preparedness of the
immune system based on past
encounters with antigens
Primary immune response –
the first encounter with an
antigen, involving a 3-6 day lag
and peak antibody levels
reached in 10 days
Secondary immune response –
any additional encounter with an
antigen, where the response is
faster, longer, and more effective.
Almost no lag time, peak
antibody levels in 2-3 days, and
these levels stay high.
Figure 21.11
Active vs. Passive Humoral
Immunity
Active humoral immunity – a humoral
immune response involving a B cell
challenge, producing immunological
memory
• Naturally – bacterial or viral
infection
• Artificially – vaccine injection of
dead or weakened pathogen
Passive humoral immunity – a humoral
immune response not involving a B cell
challenge, and not memory
• Naturally – antibodies from mother
to child via placenta or breast milk
• Artificially – antibody injections, as
in rabies shots and antivenom
Figure 21.12
Antibodies
Antibodies (immunoglobulins) – proteins secreted by B cells that bind to
specific pathogens, a single y-shaped protein is called a monomer
• Heavy and light chains – inner and outer peptide chains, lengths vary
• Variable regions – unique area with antigen-specific binding sites
• Constant regions – large region that determines the ‘class’ of the antibody
Figure 21.13
Antibodies
Antibody Classes – the five types of antibody:
• IgD – found on b-cell surfaces acting as a B cell receptor
• IgM – can be a monomer on B cells, or as a pentamer which are
always the first antibodies secreted in a humoral response, many
antigen binding sites for effective agglutination
Table 21.3.1
Antibodies
Antibody Classes – the five
types of antibody:
• IgG – the most abundant
antibody type, and the only
type that can cross a placenta
• IgA – mostly a dimer, often
called secretory IgA since
found in body secretions
(saliva, sweat, etc.)
• IgE – a monomer that binds
to mast cells and basophils,
triggering histamine release.
Mediates inflammation and
allergic reactions
Table 21.3.2
Antibodies
Antigen-antibody complex – the binding of an antibody to its specific
antigen, marking the pathogen for destruction in these ways…
Neutralization – deactivation of a virus or toxin, and encourages phagocytosis
Agglutination – a clumping of foreign cells, encouraging their phagocytosis
Precipitation – solidifies dissolved antigens which encourages phagocytosis
Figure 21.14
Antibodies
Complement fixation – binding of antibodies to an antigen encourages the
binding of complement proteins which…
• Cause cell lysis via MAC’s
• Encourages phagocytosis via opsonization
Figure 21.14
Cellular Immunity
Cellular immune response – an cellmediated response triggered by the
antigen challenge of a T cell, where this
antigen must be presented. Their
primary targets are cancerous cells or
cells infected by virus or parasite
CD4 cells – called “Helper T cells”,
can only receive antigens presented by
MHC class 2
CD8 cells – called “Cytotoxic T cells”
because they can kill cells directly, can
only receive antigens presented by
MHC class 1
Figure 21.15
Cellular Immunity
MHC class 1 – antigen-presenting protein found on all body cells, only
presenting endogenous antigens to CD8 cells
• MHC displaying self-antigen means cell is healthy (leave it alone)
• MHC displaying antigen means cell is infected/cancerous (kill it)
Figure 21.16a
Cellular Immunity
MHC class 2 – antigen-presenting protein found on APC’s , only
presenting exogenous antigens to CD4 cells. APC’s must first engulf
and digest the pathogen, then present fragments to Helper T cells
Figure 21.16b
Cellular Immunity
T cell clonal selection:
• An APC uses its MHC class
2 to present antigen to T cell
receptors
• Only a T cell with a
matching receptor will divide
into many clones and begin
circulation
Figure 21.17
Helper T Cells
Helper T cells are necessary for both
humoral and cellular immunity!!
• Cytotoxic T cells can not perform
clonal selection without a Helper T cell
signal
• B cells cannot divide into plasma cells
without a Helper T cell signal
• HIV infection targets Helper T cells,
leading to the immunodeficiency of both
antibody and cellular immunity!!
• Helper T cells also help innate
immunity by increasing activity of
natural killer cells and macrophages!
Figure 21.18
Cytotoxic T Cells
Cytotoxic T cells – once activated by antigen and a Helper T cell, these cells can
kill infected cells directly. Find their target when a body cell’s MHC class 1 shows
its specific antigen.
• Cytotoxic T cell binds to target cell releasing perforin and granzymes
• Perforin forms holes in the target cell membrane, and granzymes begin to digest
the target cell, triggering apoptosis
Other T cells:
• Memory T cells –
long-lived clones for
secondary responses
• Regulatory T cells –
use chemicals to
dampen down
responses, preventing
autoimmunity
Figure 21.19
Immune System
Overview
Use this image to review
your understanding of the
divisions of the immune
system and their interactions
Figure 21.20
Immune System Disorders
Immunodeficiency – any condition causing impaired function of
immune cells, phagocytes or complement
• SCID (severe combined immunodeficiency) – genetic disorder
leading to nonfunctional B and T cells. Must live behind
protective barriers or a bone marrow transplant
• AIDS (acquired immunodeficiency syndrome) – series of
infections resulting from lack of B cell and Cytotoxic T cell
activation (due to loss of Helper T cells)
Autoimmunity – any condition where the body’s immune system
uses antibodies and Cytotoxic T cells to target self tissues
• Multiple Sclerosis - targets white matter of the CNS
• Rheumatoid arthritis – targets joints tissues
• Myasthenia gravis – targets ACh receptors at neuromuscular
junctions
Hypersensitivity
Hypersensitivities (allergic reactions) – when
the immune system responds to a nonpathogenic substance, now called an allergen
• Sensitization – first encounter with allergen
leads to the production of many, specific IgE
antibodies
• Secondary response – future encounters
activate the antibodies, triggering mast cells and
basophils to release histamine. Histamine
release causes vasodilation, mucus secretion,
bronchial constriction, etc.
Anaphylactic shock – when an allergic reaction
becomes systemic, can be fetal due to throat
swelling and bronchial constriction
Figure 21.21