Section I
Immunology
Nonspecific Mechanisms To
Fight Infection
Skin & Mucous Membranes
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Sweat gland secretions (acidic)
Bacterial flora release acids
Saliva, tears and mucous secretion
Lysozyme in tears and perspiration
Nostril hairs
Stomach acid
Phagocytic White Cells and
Natural Killer Cells
Neutrophils ( majority of wbc’s)
- Released from bone marrow
– Enter by amoeboid mov’t; live only a few days
– Attracted by a chemical signal (i.e., pus)
– Capable of phagocytosis
or cell lysis (engulf)
– Arrive first, eliminate
microorganisms & die
Phagocyte ingesting polystyrene
beads
These phagosomes
deliver their contents
to lysosomes
Phagocytic White Cells and
Natural Killer Cells (cont.)
Monocytes migrate to the tissues (organ
& connective) where they enlarge and
become macrophages
– From bone marrow
– Use pseudopodia to phagocytize cells (e.g.
bacteria, viruses, & cell debris)
– Secrete lysozyme and interferon
– Expose molecules of digested bodies to more
specialized calls, such as B and Th
lymphocytes
Phagocytic White Cells (cont.)
Eosinophils: Understanding The
Immune System - Phagocytes and
Granulocytes
– Have digestive enzymes in granules which
are discharged against pathogen or parasitic
worms and Phagocyte antigen - antibody
complexes
Cells within the tissues of the
Immune System
Natural Killer Cells or NK
To attack, cytotoxic T cells need to
recognize a specific antigen,
whereas natural killer or NK cells
do not. Both types contain
granules filled with potent
chemicals, and both types
kill on contact. The killer binds
to its target, aims its weapons,
and delivers a burst of lethal chemicals.
Mature T cell & Macrophages
Bind to receptor on
target cells
Recruit other cells
Can serve as interleukins
in that they serve as a
messenger between
leukocytes or wbc’s
Antimicrobial Proteins
Complement System
– ~ 20 proteins which interact
– Attract phagocytes (call chemotaxis) to
foreign cells and help destroy by promoting
cell lysis
Antimicrobial Proteins (cont.)
Interferons
– Secreted & produced by virus-infected cells
– Types: alpha, beta, and gamma
– Stimulate production of proteins that inhibit viral
replication (including neighboring cells)
– Not a virus-specific defense
– Works best against short-term infections such as
colds and influenza
– Activates phagocytes which enhances their ability
to ingest and kill microorganisms
– Can be mass produced to be tested as treatments
for viral infections and cancer
Inflammatory Response
Occurs when there is damage to tissue
due to physical injury or entry of
microorganism
Vasodilation of small vessels increases
the blood supply to the area (redness)
Dilated vessels become more permeable,
allowing fluids to move in, resulting in a
localized edema
Inflammatory Response (cont.)
Chemical signals initiate the inflammatory
response
– Histamine released from cells called
Basophils and mast cells in connective
tissue
– Prostaglandins released from white blood
cells and damaged tissue (cause increased
blood flow)
– The increased blood flow delivers clotting
elements which help block the spread of
pathogenic microbes and begins the repair
process
Inflammatory Response (cont.)
Macrophages destroy pathogens and
clean up area
Pus may develop before absorbed by
the body
Bone marrow may release more
leukocytes
Fever develops due to toxins produced
or due to pyrogens released by
leukocytes
– Fever can inhibit growth of some micro’s
Complement System
These complement proteins
help the antibodies destroy
bacteria
The diagram shows the C1
encountering an antibody bound
to an antigen
The end product punctures the
cell membrane of the target cell
Complements illustrated
Section II
Immune System Defends the
Body Against Specific
Invaders
Antigen /Antibody Connection
Foreign molecules, or antigens, carry
distinctive markers, characteristic shapes
called epitopes that protrude from their surfaces.
Our Immune system has the ability to
recognize many millions of distinctive
non-self molecules, and to respond by
producing molecules, or antibodies
- also cells - that can match and counteract
each one of the non-self molecules.
Antigen/Antibody Continued (2)
An antigen can be a bacterium or a virus,
or even a portion or product of one of
these organisms. Tissues or cells from
another individual also act as antigens;
that's why transplanted tissues are
rejected as foreign.
How Antibodies are Produced
Third Line of Defense
Specificity: recognize and eliminate
microorganisms and foreign molecules
– Antigen: foreign substances that elicit an
immune response
Can be molecules exhibited on the surface of,
produced by, or released from bacteria, viruses,
fungi, protozoans, parasitic worms, pollen, insect
venom, transplanted organs, or worn-out cells
Each has a unique molecular shape
Stimulates production of an antibody that defends
specifically against the particular antigen
Third Line of Defense (cont.)
Antibody: antigen-binding
immunoglobulin (protein),
produced by B cells;
functions as the effector
in an immune response.
Third Line of Defense Continued:
Diversity: ability to respond to invaders
which are recognized by their antigenic
markers
– Based on a variety of lymphocyte pop’s
– Each antibody-producing lymphocyte is
stimulated by a specific antigen; lymphocytes
synthesize and secrete the appropriate
antibody
Third Line of Defense (cont.)
Memory: your immune system can
recognize previously encountered antigens
and react faster
Acquired immunity is a resistance to some
infection encountered earlier in life (e.g.
chicken pox)
Self/nonself recognition: the ability to
distinguish between the body’s own
molecules versus foreign molecules
– Failure leads to autoimmune disorders which
destroy body’s own tissue
Active Versus Passive Acquired
Immunity
Active Immunity: conferred by recovery
from an infectious disease
– Depends on each person’s immune system
– Acquired naturally from an infection or
artificially by vaccination
– Vaccines can be inactivated bacterial toxins,
killed microorganisms, or weakened living
microorganisms
Can no longer cause the disease
Can act as antigens and stimulate immune
response
Active Versus Passive
Acquired Immunity (cont.)
Passive immunity can be transferred from one
person to another by the transfer of antibodies
– Antibodies can cross the placenta to the fetus
– Some from nursing infants through milk
– Persists a few weeks or months until infant’s own
system defends its body
– Can be transferred artificially from an animal or
human already immune to the disease
Rabies is treated by injecting antibodies from people
vaccinated against rabies
Short in duration, but permits your body to begin to
produce antibodies against the virus
Humoral Immunity and CellMediated Immunity
Humoral Immunity: produces antibodies
in response to toxins, free bacteria, and
viruses
– Synthesized by certain lymphocytes and
circulate in blood plasma and lymph
Cell-mediated Immunity: the response to
intracellular bacteria and viruses, fungi,
protozoans, worms, transplanted tissues,
and cancer
Cells of the Immune System
Lymphocytes
– Responsible for both humoral and cellmediated immunity in that there are two main
classes; B cells and T cells
Develop from multipotent stem cells in bone
marrow, differentiate when they reach the site of
maturation
B cells (B lymphocytes): the humoral immune
and in the bone marrow until maturation
T cells (T lymphocytes): the cell-mediated
immune response; migrate to the thymus gland to
mature
Types of cells: B Cells
B cells (B lymphocytes): the humoral
immune and in the bone marrow until
maturation
Cells of the Immune System
(cont.)
– Mature cells (B and T) are concentrated in the
lymph nodes, spleen, and other lymphatic
organs
They are there to contact antigens
Antigen receptors are on the membranes of both
The receptors on a B cell are membrane-bound
antibody molecules which will recognize specific
antigens
The T cell antigen receptors are proteins (not
antibodies) embedded in the membrane which
recognize specific antigens
Cells of the Immune System
(cont.)
Effector Cells
– Actually defend the body during an immune
response
– Result from a division of lymphocytes when the
binding of antigens to their antigen receptors
– Activated B’s give rise to effector cells called
plasma cells which secrete antibodies that
eliminate the activating antigen
– Activated T cells produce two types:
Helper T cells: secrete cytokines
Cytotoxic T cells: destroy infected and cancer cells
Cells of the Immune System
(cont.)
Helper T cells:
secrete cytokines; carry the
T4 marker; essential
for turning on antibody
production; activate
cytotoxic T cells
Cytotoxic T cells:
destroy cells infected by
viruses or cancer; subset of
T cells
Cytokines
Cytokine: lymphokines can be
produced by lymphocytes &
monokines by monocytes &
macrophages
Section III
Clonal Selection of
Lymphocytes; Basis for
Immunological Specificity and
Diversity
Response Due to Diversity of
Antigen-Specific Lymphocytes
Each lymphocyte will respond to only one
antigen
Determined during embryonic
development before antigen are
encountered
Clonal Selection – antigenic-specific
selection of a lymphocyte that activates
clones of effector cells that eliminate the
antigen that provoked the initial immune
response
Response Due to Diversity of
Antigen-Specific Lymphocytes
(cont.)
When an antigen enters the body, it binds to
receptors on specific lymphocytes – those
lymphocytes are activated and begin dividing
– These divisions make identical effector cells or
clones that bind to the antigen that stimulated
the response
– e.g., a B cell when activated, will proliferate to
make plasma cells that secrete an antibody
which acts as a antigen receptor for the specific
antigen that activated the original B cell
Section IV
Memory Cells Action in a
Secondary Immune Response
Primary Immune Response
Primary Immune Response – the making
of lymphocytes to form clones of effector
cells specific to antigen
5 to 10 day lag between exposure and
effector cells
Lymphocytes to effector T cells & plasma
cells during this time period
B cell/Helper T cell/Plasma cell
2nd Immune Response
2nd immune response – when the body is
exposed to previously encountered
antigens
Response is faster and more prolonged
Antibodies more effective at binding to
antigen
2nd Immune Response (cont)
This is called immunological memory
– Based on memory cells produced during
clonal selection
Not active during primary response
New clones of effector and memory cells
are the 2nd response
Section V
Self/nonself Recognition with
Molecular Markers
Surface of Lymphocytes
Surfaces have antigen receptors that
detect foreign molecules that enter the
body
– No lymphocytes reactive against the body’s
own molecules under normal conditions
Surface of Lymphocytes (cont.)
Self-tolerance – lack of a destructive
immune response to the body’s won cells
– Develops (before birth) when T & B
lymphocytes begin to mature in the
thymus and bone marrow
– Any lymphocytes with receptors for
molecules present in the body at that time
are destroyed
Only has antigen receptors for foreign
molecules
Surface of Lymphocytes (cont.)
Mayor histocompatibility complex (MHC or HLA)
are glycoproteins within the plasma membrane;
Histocompatibility Molecules
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“Self-markers” coded by a family of genes
20 MHC genes & 100 alleles for each gene
No one has the same markers except identical twins
Two main classes of MHC molecules
Class 1 MHC molecules on nucleated cells (fig. 43.16)
Class 2 MHC molecules on specialized cells like (fig. 43.17)
macrophages, B, and active T cells
Section VI
The Humoral Response; B
Cells Defend against
Pathogens by Generating
Specific Antibodies
Background Facts
B cells differentiate into a clone of plasma
cells that secrete antibodies (fig. 43.17)
Most effective against pathogen is blood
or lymph
Memory cells produce and form the basis
for 2nd immune response
Activation of B Cells
First step: binding of the antigen to specific
antigen-receptors on the surface of B cells
2nd step is the B cell activation involving
macrophages & helper T cells; ends with
the production of plasma cells (p. 909 fig
43.14 & p. 911, fig 43.17)
– Macrophage phagocytes pathogens
Activation of B cells (cont.)
– Pieces of digested antigen bind to class 2
MHC molecules that are moved and present
on the surface of macrophage
– This is called an antigen-presenting cell
– Helper T cell specific of the presented antigen
binds to self/nonself MHC complex
– T cell is activated and forms a clone of helper
T cells
Activation of B cells (cont.)
– These T cells secrete cytokines which elicit
other B cells with the same antigen
(Fig. 43.17)
– T cell contact activates these B cells to form a
clone of plasma cells
– Each plasma cell (=effector cell) then
secretes antibodies specific for the antigen
Antibody and cell – mediated
Responses
Activation of B cells (cont.)
– Each macrophage can display a # of different
antigens depending on the type of pathogen
phagocytized
– B cells again are specific and can bind to and
display only one type of antigen
– Macrophages are nonspecific & can enhance
specific defense by selectively activating
helper T cells which in turn activate B cells
specific for the antigen
– Helper T cells are antigen-specific
T-dependent & T-independent
Antigens
T-dependent antigens – antigens that
evolve the cooperative response involving
macro’s, helper T’s, & B cells
T-independent antigens – antigens that
trigger humoral immune responses without
macrophage or T cell involvement
– Stimulated by the antigen which binds to
several antigen receptors on the B cells
surface
T-dependent & T-independent
Antigens (cont.)
– Usually weaker
– No memory cells are generated
Whether dependent or independent, a B
cell gives rise to a clone of plasma cells
– Each effector cell secretes up to 2000
antibodies / sec for 4 to 5 days
Molecular Basis of AntigenAntibody Specificity
Antigens are proteins or large
polysaccharides of the outer part of
pathogens or transplanted cells
– Can be coats of viruses, capsules, and cell
walls of bacteria
– Molecules of transplanted tissues and organ
or blood cells are recognized as foreign
Antibodies recognize the surface of an
antigen or the epitope, not the entire
antigen molecule (see fig. fig 43.10),
sometimes call the antigenic determinant
Molecular Basis of AntigenAntibody Specificity (cont)
Antibodies are Proteins in a Class Called
Immunoglobulins (lgs)
– See fig. 43.18
– Structure associated with its function
– Y-shaped with 4 polypeptide chains: two
identical light chains and two identical heavy
chains
– All 4 chains have constant C regions that vary
little in a.a. sequence
Molecular Basis of AntigenAntibody Specificity (cont)
– At the tips of the Y are variable (V) regions;
show extensive variation from antibody to
antibody
Functions as antigen-binding sites that result in
specific shapes that fit and bind to specific antigen
epitopes
This site is responsible for the antibody’s ability to
identify specific epitope and stem (constant)
regions through which the antibody inactivates or
destroys the antigenic invader
Molecular Basis of AntigenAntibody Specificity (cont)
– 5 types of constant regions which are the five
major classes of mammalian immunoglobins
(table 43.18)
IgM – 5 Y-shapes monomers; appear in the initial
exposure to an antigen
IgG – most abundant’ fights against bacteria, viruses,
and toxins in blood
IgA – in mucous membranes; prevent bacteria and
viruses from attaching to epithelial surfaces; in saliva,
tears, perspiration
IgD – found on B cells; initiates differentiation of B cells
IgE – stimulates basophils and mast cells to release
histamine and cause allergic reaction when triggered by
an antigen
Section VII
In the Cell-Mediated
Response, T Cells defend
Against Intracellular
Pathogens
The Cell-Mediated Immune
Response
It is the defense that combats pathogens
that have already entered cells
Key components are helper T cells (TH)
and cytotoxic T cells (TC)
T cells cannot detect free antigens in the
body fluids
The receptor of a helper T cell recognizes
the molecular combination of an antigen
fragment with a class 2 MHC
The Cell-Mediated Immune
Response (cont.)
The receptor of a cytotoxic T cell
recognizes the combination of an antigen
fragment with a class 1 MHC molecule
The MHC-antigen complex displayed on
an infected body cell stimulates T cells to
multiply and form clones of TH and TC
which recognized the pathogen
The Cell-Mediated Immune
Response (cont.)
(TH) cells stimulate B cells to secrete antibodies
against T-dependent antigens in a humoral
response
(TH) cells also activate other types of T cells to
mount cell-mediated responses to antigens
Helper T cells are able to stimulate other
lymphocytes by receiving and sending cytokines
such as interleuking-2. Increased levels of
cytokines also increase the cell-mediated
response by stimulating another class of T-cells
into cytotoxic cells (effector cells)
Section VIII
Complement Proteins
Participate in Both Nonspecific
and Specific Defenses
Complement Proteins circulate in
the Blood in Inactive Forms
Complement protein attaches to, and
bridges the gap between, two adjacent
antibody molecules
This antibody-complement activates
proteins to from a membrane attack
complex
Complement Proteins circulate in
the Blood in Inactive Forms (cont.)
This membrane attack complex lyses the
pathogen’s membrane producing a lesion and
the lyses of the cell
There is also a nonspecific defense mechanism
Complement and phagocytes work together two
ways
– Opsonization where the proteins attach to a foreign
cell and stimulate phagocytes to engulf the cell
– In immune adherence, where they coast a microbe
which causes to adhere to blood vessel walls and
sets it up for circulating phagocytes