The Immune System
Chapter 43
A macrophage engulfing bacteria
The Body’s Defenses
Smallpox virus
The Body’s Defenses
Anthrax bacteria
The Body’s Defenses
Protozoan Trypanosoma
(African sleeping sickness)
The Body’s Defenses
Sac fungus Candida albicans
(yeast infections)
The Body’s Defenses
Heartworm nematodes...
How does the human body defend
against invaders?
INNATE IMMUNITY
Rapid responses to a
broad range of microbes
External defenses
Invading
microbes
(pathogens)
ACQUIRED IMMUNITY
Slower responses to
specific microbes
Internal defenses
Skin
Phagocytic cells
Mucous membranes
Antimicrobial proteins
Secretions
Inflammatory response
Natural killer cells
Humoral response
(antibodies)
Cell-mediated response
(cytotoxic
lymphocytes)
Figure 43.2
Skin is an inhospitable barrier of dead, dry
cells, & secretions containing oil & lactic acid
Mucous membranes in
respiratory, digestive & urogenital tracts secrete
mucus & antibiotic chemicals (e.g., lysozyme,
which digests bacterial cell walls)
How does the human body defend
against invaders?
INNATE IMMUNITY
Rapid responses to a
broad range of microbes
External defenses
Invading
microbes
(pathogens)
ACQUIRED IMMUNITY
Slower responses to
specific microbes
Internal defenses
Skin
Phagocytic cells
Mucous membranes
Antimicrobial proteins
Secretions
Inflammatory response
Natural killer cells
Humoral response
(antibodies)
Cell-mediated response
(cytotoxic
lymphocytes)
Figure 43.2
If external defenses are not effective –
nonspecific, innate response
Four types of phagocytic leucocytes
(WBCs) engulf invaders
E.g., macrophages, dendritic cells
If external defenses are not effective –
nonspecific, innate response
Microbes
Macrophage
Vacuole
Lysosome
Figure 43.4
If external defenses are not effective –
nonspecific, innate response
Natural killer cells (WBCs) – destroy
infected cells & cancer cells by inducing
apoptosis (programmed cell death)
If external defenses are not effective –
nonspecific, innate response
Antimicrobial proteins – (e.g., lysozyme)
produced by many cells of the body, often
in response to infection; actively destroy
microbes
If external defenses are not effective –
nonspecific, innate response
Local inflammatory response – injury or
pathogens can cause mast cells of
connective tissues to release histamine,
triggering dilation and increased
permeability of capillaries
Fever – systemic (widespread) response
that increases the body’s thermostat
How does the human body defend
against invaders?
INNATE IMMUNITY
Rapid responses to a
broad range of microbes
External defenses
Invading
microbes
(pathogens)
ACQUIRED IMMUNITY
Slower responses to
specific microbes
Internal defenses
Skin
Phagocytic cells
Mucous membranes
Antimicrobial proteins
Secretions
Inflammatory response
Natural killer cells
Humoral response
(antibodies)
Cell-mediated response
(cytotoxic
lymphocytes)
Figure 43.2
Immune system –
mounts attack on specific disease agents
Circulatory
System
Immune
System
Lymphatic
System
Immune system –
mounts attack on specific disease agents
2 main types of lymphocytes (WBCs):
B cells –
produced in bone marrow
differentiate in bone marrow
T cells –
produced in bone marrow
differentiate in thymus
Mature B and T cells are found throughout
the body in lymph and blood
Immune system –
mounts attack on specific disease agents
2 main types of lymphocytes (WBCs):
Lymphoid
stem cell
Bone
marrow
Thymus
B cell
T cell
Blood, lymph, and
lymphoid tissues
Figure 43.10
RECOGNITION
Lymphocytes recognize and respond to particular
microbes and foreign molecules, i.e.,
they display specificity
A foreign molecule
that induces an
immune response
is known as an
antigen
RECOGNITION
Multiple antibodies may recognize the same antigen
by different epitopes (small accessible portions
of the larger molecule)
Fig. 43.7
RECOGNITION
B cells produce antibodies, that are either secreted
out of the cells or remain embedded in the B cell
membranes, and that bind to antigens
RECOGNITION
B cells produce antibodies, that are either secreted
out of the cells or remain embedded in the B cell
membranes, and that bind to antigens
T cells have T-cell receptors, embedded in their
cell membranes, that bind to antigens
RECOGNITION
Even though many receptors (antibodies or T-cell
receptors) encounter a given type of antigen, only
the receptors that are compatible will bind to them
Illustrated here
for B cells, but
the process for
T cells is similar
Fig.
43.12
This process is known as clonal selection
RECOGNITION
Secreted antibodies constitute a group of proteins
called immunoglobulins
Antibodies have 2
heavy chain and 2 light
chain subunits
Each subunit has a
constant region and a
variable region
The variable region can
bind to an antigen
Fig. 43.8
RECOGNITION of non-self molecules
Construction of antibodies
(and T-cell receptors)
Millions of antigens are recognized by randomly
combining the protein products of hundreds of genes
Card analogy: although there are only 52 cards in the
deck, random combinations can produce an
enormous number of different hands
Construction of antibodies
B
Construction of antibodies
B
B
Construction of antibodies
B
B
B
RECOGNITION of self molecules
In a healthy immune system, as B and T cells mature
they are destroyed by apoptosis if they attack self
molecules
Healthy, mature B and T cells then have the capacity
to distinguish self from non-self molecules
RECOGNITION of self molecules
Almost all cells in an individual human’s body have
major histocompatibility complex (MHC)
glycoproteins embedded in their cell membranes
Class I MHC molecules are found on
almost every nucleated cell
Class II MHC molecules are restricted to a few
specialized cells, including macrophages,
dendritic cells, B cells, etc.
RECOGNITION of self molecules
MHC glycoproteins migrate to the cell
membrane after they are produced
MHC glycoproteins pick up molecules from the cytosol
that are presented at the cell’s surface
T cells bind to MHC glycoproteins and
the molecules they present
An individual’s own MHC glycoproteins, and
molecules of its own body that the MHC
glycoproteins present, are treated as self
RECOGNITION of non-self molecules
However, T cells treat foreign molecules presented
by MHC glycoproteins as antigens
Fig. 43.9
RECOGNITION of non-self molecules
Cytotoxic T cells bind to cells that carry
Class I MHC glycoproteins
Fig. 43.9
RECOGNITION of non-self molecules
Helper T cells bind to cells that carry
Class II MHC glycoproteins
Fig. 43.9
ATTACK & MEMORY
The B and T cells that recognize a given foreign
antigen produce two types of clones:
effector cells (attackers) and memory cells
Illustrated here
for B cells, but
the process for
T cells is similar
Fig.
43.12
ATTACK & MEMORY
The B and T cells that first recognize a given foreign
antigen are short lived, whereas immune memory
cells can have long lifetimes
Illustrated here
for B cells, but
the process for
T cells is similar
Fig.
43.12
ATTACK & MEMORY
Memory cells help produce a secondary immune
response that is faster, of greater magnitude, and of
longer duration than the primary immune response
Fig. 43.13
ATTACK & MEMORY
There are two types of immune response:
Humoral response
B cells and antibodies
Attack antigens that have not yet infected cells
(toxins, bacteria, and viruses in body fluids)
Deactivate, coat, and clump antigens (which are
then often engulfed and destroyed by
macrophages)
ATTACK & MEMORY
There are two types of immune response:
Cell-mediated response
T cells
Attack antigens after they have entered cells, as
well as fungi, protozoa, and parasitic worms
Activated T cells kill antigen-containing cells by
creating pores in their cell membranes
RECOGNITION, ATTACK, & MEMORY
Cell-mediated response
Humoral response
Involves the
activation and
clonal selection
of B cells
First exposure to antigen
Infected cells
Dendritic cells
MHC I
MHC II
Antigens
Activate
Results in the
production of
antibodies that
circulate in the
blood and
lymph
Activate
B cell Helper
T cell
Cytokines
activate
Memory
B cells
Active and
memory
helper
T cells
Secrete antibodies that defend against
pathogens and toxins in extracellular fluid
Cytotoxic
T cell
Gives rise to
Gives rise to
Gives rise to
Plasma
cells
Activate
Memory
cytotoxic
T cells
Active
cytotoxic
T cells
Defend against infected cells, cancer
cells, and transplanted tissues
Figure 43.14
RECOGNITION, ATTACK, & MEMORY
Cell-mediated response
Humoral response
First exposure to antigen
Infected cells
Dendritic cells
MHC I
MHC II
Antigens
Activate
Activate
B cell Helper
T cell
Plasma
cells
Activate
Cytokines
activate
Memory
B cells
Active and
memory
helper
T cells
Secrete antibodies that defend against
pathogens and toxins in extracellular fluid
Cytotoxic
T cell
Gives rise to
Gives rise to
Gives rise to
Involves the
activation and
clonal selection
of cytotoxic T
cells
Memory
cytotoxic
T cells
Active
cytotoxic
T cells
Defend against infected cells, cancer
cells, and transplanted tissues
Figure 43.14
Cytotoxic T
cells directly
destroy certain
target cells
RECOGNITION, ATTACK, & MEMORY
Cell-mediated response
Humoral response
First exposure to antigen
A primary
immune
response
begins with the
first exposure to
an antigen
Infected cells
Dendritic cells
MHC I
MHC II
Antigens
Activate
Activate
B cell Helper
T cell
Plasma
cells
Cytokines
activate
Memory
B cells
Active and
memory
helper
T cells
Secrete antibodies that defend against
pathogens and toxins in extracellular fluid
Cytotoxic
T cell
Gives rise to
Gives rise to
Gives rise to
A secondary
immune
response
begins with a
re-exposure to
an antigen, and
stimulates
memory cells
Activate
Memory
cytotoxic
T cells
Active
cytotoxic
T cells
Defend against infected cells, cancer
cells, and transplanted tissues
Figure 43.14
Medical practices can augment our
immune response by inhibiting invaders or
enhancing the immune response
Antibiotics
Inhibit microbial reproduction
Potent agents of natural selection
Vaccines (weakened or dead microbes, or their
toxins)
Stimulate development of memory cells = faster
response to invasion
Selectively effective
The immune system and blood types
antigen
Table 43.1
antigen
antigens
What happens when the immune system
malfunctions?
Allergies
Exaggerated immune responses to otherwise
benign substances
What happens when the immune system
malfunctions?
1. Antibodies are produced
Fig.
43.20
What happens when the immune system
malfunctions?
1. Antibodies are produced
2. Stems of antibodies
attach to mast cells,
especially in the respiratory
tract
Fig.
43.20
What happens when the immune system
malfunctions?
1. Antibodies are produced
2. Stems of antibodies
attach to mast cells,
especially in the respiratory
tract
Fig.
43.20
3. When
antibodies
attached to mast
cells bind antigens, the mast
cells release histamine, which causes inflammation
What happens when the immune system
malfunctions?
Autoimmune diseases
The immune system lacks or loses its ability to
distinguish self vs. non-self molecules, i.e., it
loses its self-tolerance and produces anti-self
antibodies
Rheumatoid arthritis (cartilage of joints)
Multiple sclerosis (mylein sheaths of
neurons)
Insulin-dependent diabetes mellitus (insulinsecreting cells of the pancreas)
What happens when the immune system
malfunctions?
Immunodeficiency diseases
Inhibit effective immune response; either
inherited or acquired
Severe Combined Immunodeficiency (SCID)
An inherited disorder
Acquired Immunodeficiency Syndrome (AIDS)
Caused by retroviruses (Human
Immunodeficiency Viruses – HIV) that
especially infect helper T cells
What happens when the immune system
malfunctions?
Adults and children estimated to be living
with HIV as of the end of 2001
North America
940,000
Caribbean
420,000
Latin America
1.4
million
Eastern Europe
Western Europe & Central Asia
560,000 1 millionEast Asia & Pacific
North Africa
1 million
& Middle East South
Asia
440,000 & South-East
6.1 million
Sub-Saharan
Africa
28.1
million
Total: 40 million
Australia
& New
Zealand
15,000
What happens when the immune system
malfunctions?
Estimated number of deaths
from AIDS during 2001
North America
20,000
Caribbean
30,000
Latin America
80,000
Eastern Europe &
Western Europe Central Asia
6,800
North Africa
& Middle East
23,000 East Asia & Pacific
35,000
South
30,000
& South-East Asia
Sub-Saharan
Africa
2.3
million
Total: 3 million
400,000
Australia
& New
Zealand
120
What happens when the immune system
malfunctions?
The global AIDS epidemic
HIV destroy helper T cells
– Victims die from other diseases
Transmission
– Direct contact between broken skin, mucous membranes & body
fluids
No cure
– Treatments = inhibitors of reverse-transcriptase and protease
– Problem = virus evolves quickly
How to reduce your risk
– Practice safe sex
– Avoid used needles
What happens when the immune system
malfunctions?
Cancer
Malfunction in cell production combined with a lack of recognition by the
immune system of aberrant cells or too many of them
Uncontrolled growth = tumor
Causes
Carcinogens, viruses, inheritance
No guaranteed cure
Most treatments also destroy healthy cells
How to reduce your risk
Reduce exposure to carcinogens