Chap 17 Flashcards
Adaptive immunity
defenses that target a specific pathogen
adaptive immunity is acquired through
infection or vaccination
Primary response
first time the immune system combats a particular foreign substance
Secondary response
later interactions with the same foreign substance; faster and more effective due to “memory”
Humoral immunity
Produces antibodies that combat foreign molecules known as antigens
B cells
lymphocytes that are created and mature in red bone marrow
B cells functions
Recognize antigens and make antibodies
B cells named for
Named for bursa of Fabricius in birds
Cellular immunity (cell-mediated immunity) produces
T lymphocytes
T lymphocytes function
Recognize antigenic peptides processed by phagocytic cells
T lymphocytes mature in the
Thymus
T cell receptors (TCRs) located on
T cell surface
TCRs function
contact antigens, causing the T cells to secrete cytokines instead of antibodies
Pluripotent stem cells develop in
the red bone marrow or fetal liver
Stem cell
diverges into
two cell lines
Thymus
Differentiate to
T cells in thymus
Migrate to lymphoid
tissue such as spleen,
but especially lymph
nodes
both B and T cells
Differentiate to
B cells in
adult bone marrow
Cellular immunity attacks antigens that have already
entered cells
Cellular immunity attacks antigens that have already entered cells such as
some intracellular bacteria such as M. leprae and L. monocytogenes; viruses
Humoral immunity fights
invaders and threats outside cells
Humoral immunity fights invaders and threats outside cells such as
1.Extracellular bacteria and toxins
2.Viruses before they enter a host cell
Cytokines
chemical messengers produced in response to a stimulus
Interleukins (ILs)
cytokines between leukocytes
Chemokines
induce migration of leukocytes
Interferons (IFNs)
interfere with viral infections of host cells
Tumor necrosis factor alpha (TNF-α)
involved in the inflammation of autoimmune diseases
Hematopoietic cytokines
control stem cells that develop into red and white blood cells
Overproduction of cytokines leads to a
cytokine storm
Antigens
substances that cause the production of antibodies
Usually components of invading microbes or foreign substances
Antigens
Antibodies interact with
epitopes, or antigenic determinants, on the antigen
Haptens
antigens too small to provoke immune responses; attach to carrier molecules
Hapten-carrier conjugate
hapten molecules+ carrier molecules
Globular proteins called
immunoglobulins (Ig)
Valence
is the number of antigen-binding sites on an antibody
Bivalent antibodies have two
binding sites
Four protein chains form a
Y-shape
Two identical light chains and two identical heavy chains joined by
disulfide links
Variable (v) regions are at the ends of
the arms; bind epitopes
Constant (Fc) region is the
stem, which is identical for a particular Ig class
Five classes of Ig
IgG, IgM, IgA, IgD, IgE
IgG is a type of
monomer
80% of serum antibodies
IgG
IgG found in
blood, lymph, and intestine
Cross the placenta and protect the fetus; trigger complement; enhance phagocytosis; neutralize toxins and viruses
functions of IgG
Functions of IgG
- Cross the placenta and protect the fetus;
- trigger complement;
- enhance phagocytosis;
- neutralize toxins and viruses
Pentamer made of five monomers held with a J chain
IgM
6% of serum antibodies
IgM
Remain in blood vessels
IgM
Cause clumping of cells and viruses
IgM
First response to an infection; short-lived
IgM
Monomer in serum; dimer in secretions
IgA
13% of serum antibodies
IgA
Common in mucous membranes, saliva, tears, and breast milk
IgA
Prevent microbial attachment to mucous membranes
IgA
Monomer
0.02% of serum antibodies
IgD
Structure similar to IgG
IgD
In blood, in lymph, and on B cells
IgD
No well-defined function; assists in the immune response on B cells
IgD
Monomer
0.002% of serum antibodies
IgE
On mast cells, on basophils, and in blood
IgE
Cause the release of histamines when bound to antigen; lysis of parasitic worms
IgE
Major histocompatibility complex (MHC) genes encode
molecules on the cell surface
Class I MHC are on the membrane of
nucleated animal cells
Class I MHC identify
self
Class II MHC are on the surface of
antigen-presenting cells (APCs), including B cells
Inactive B cells contain surface Ig that
bind to antigen
B cell internalizes and
processes antigen
Antigen fragments are displayed on
MHC class II molecules
T helper cell (TH) contacts
the displayed antigen fragment and releases cytokines that activate B cells
B cell undergoes proliferation
clonal expansion
Activation of B Cells to Produce Antibodies step 1
APC receptors
recognize and
attach to antigen.
Activation of B Cells to Produce Antibodies step 2
Antigen is
phagocytized and
digested
Activation of B Cells to Produce Antibodies step 3
Antigen fragments are
displayed on the B cell
surface, attracting a
matching T helper cell.
Activation of B Cells to Produce Antibodies step 4
T helper cell
secretes cytokines,
activating a B cell.
Activation of B Cells to Produce Antibodies step 5
The activated B cell begins
clonal expansion, producing an
army of antibody-producing
plasma cells and memory cells
(not shown).
Clonal Selection and Differentiation of B Cells step 1
Stem cells differentiate into mature B cells,
each bearing surface immunoglobulins
against a specific antigen.
Clonal Selection and Differentiation of B Cells step 2
B cell II encounters its specific antigen
and proliferates.
Clonal Selection and Differentiation of B Cells step 3
Some B cells proliferate into long-lived
memory cells, which at a later date can be
stimulated to become antibody-
producing plasma cells.
Clonal Selection and Differentiation of B Cells step 4
Other B cells proliferate
into antibody-producing
plasma cells.
Clonal Selection and Differentiation of B Cells step 5
Plasma cells secrete antibodies
into circulation.
T-dependent antigen
Antigen that requires a TH cell to produce antibodies
T-independent antigens stimulate
the B cell without the help of T cells
T-independent antigens provoke
a weak immune response, usually producing IgM
T-independent antigens do not generate which cells?
memory cells
T-independent antigen is which type of molecule?
polysaccharide
17-10 On what part of the antibody molecule do we find the amino acid sequence that makes the huge genetic diversity of antibody production possible?
variable region
An antigen–antibody complex forms when
antibodies bind to antigens
affinity
strength of the bond in antigen-antibody complex
how does the antigen-antibody complex protect the host?
Protects the host by tagging foreign molecules or cells for destruction
What happens after the antigen antibody complex is formed?
1.Agglutination
2.Opsonization
3.Antibody-dependent cell-mediated cytotoxicity
4. Neutralization
5.Activation of the complement system
results of agglutination
Reduces number of infectious
units to be dealt with
Results of opsonization
Coating antigen with antibody
enhances phagocytosis
results of Neutralization
1.Blocks adhesion of bacteria
and viruses to mucosa
- Blocks attachment
of toxin
Results of Antibody-dependent cell-mediated cytotoxicity
Antibodies attached to target cell
cause destruction by macrophages,
eosinophils, and NK cells
Results of activation of complement
Causes inflammation and cell lysis
T cells combat
intracellular pathogens
Thymic selection
eliminates immature T cells
T cells migrate from
thymus to lymphoid tissues
T cells attach to antigens via
T-cell receptors (TCRs)
Pathogens entering the gastrointestinal tract pass through
microfold cells (M cells)
M cells located over
Peyer’s patches
Microfold cells
Cells that take up and transfer antigens to lymphocytes, on Peyer’s patches.
Peyer’s patches
Lymphoid organs on the intestinal wall
Transfer antigens to lymphocytes and antigen-presenting cells (APCs)
Peyer’s patches
M cells and epithelial cells form specialized
tissue structures called
Peyer’s patches
There are closely packed microvilli on the epithelial cells surrounding
Peyer’s patches
M cells facilitate contact between
antigens passing through the intestinal
tract and cells of the body’s immune system.
Dendritic cells (DCs)
Engulf and degrade microbes and display them toT cells
Dendritic cells found in
skin, genital tract, lymph nodes, spleen, thymus, and blood
Macrophages activated by
cytokines or the ingestion of antigenic material
Macrophages migrate to
the lymph tissue, presenting antigen to T cells
Clusters of differentiation
CD
CD4+
T helper cells (TH)
What do CD4+ T helper cells do?
Cytokine signaling with B cells; interact directly with antigens
CD4+ Bind
MHC class II molecules on B cells and APCs
CD8+
Cytoxic T lymphocytes (CTL)
Bind MHC class I molecules
TCR on the TH cell recognize and bind to
the antigen fragment and MHC class II on APC
APC or TH secretes a
costimulatory molecule, activating the TH cell
TH cells produce cytokines and differentiate into
TH1,TH2,TH17, memory cells
Activation of CD4+ T Helper Cells step 1
An APC encounters and ingests a microorganism. The antigen is enzymatically processed into short peptides, which combine with MHC class II molecules and are displayed on the surface of
the APC.
Activation of CD4+ T Helper Cells step 2
A receptor (TCR) on the surface of the CD4+ T helper cell (TH cell) binds to the MHC–antigen complex. The
TH cell or APC is stimulated to secrete a costimulatory molecule. These two signals activate the TH cell, which produces cytokines.
Activation of CD4+ T Helper Cells step 3
The cytokines cause the TH cell (which recognizes a dendritic cell
that is producing costimulatory molecules) to become activated.
TH 17 cells produce
IL-17 and contribute to inflammation
TH1 cells produce
IFN-y
IFN-Y activates
- Macrophages
- Complement
- Antibody production (phag)
macrophages, enhances complement, and stimulates antibody production that promotes phagocytosis
TH2 cells release
IL-4 cytokine
IL-4 cytokine activates
B cells to produce IgE; activate eosinophils
secrete cytokines that
promote inflammatory responses;
recruit neutrophils for protection
against extracellular bacteria
and fungi
TH 17 cells
Important in allergic responses,
especially by production of IgE.
Activate eosinophils to control
extracellular parasites such as
helminths (see ADCC discussion).
IL4 TH2 cells
cytokines (such as IFN-γ and IL-2) activate CD8+ T cells and NK cells, which control intracellular pathogens by killing infected host cells. They also enhance phagocytosis by antigen-presenting cells such as macrophages.
TH1
T regulatory cells
Lymphocytes that appear to suppress other T cells
Subset of CD4+ cells; carry an additional CD25 molecule
T regulatory cells
functions of T regulatory cells
1.Suppress T cells against self;
2.protect intestinal bacteria required for digestion;
3.protect fetus
Precursor T cytotoxic cells (CTLp) are activated to become
cytotoxic T lymphocytes (CTLs)
Activated into cytotoxic T lymphocyte (CTL) with the help of
TH cells and costimulatory signals
CTLs recognize and
kill self-cells altered by infection
Self-cells carry
endogenous antigens
endogenous antigens are carried on
surface presented with MHC class I molecules.
endogenous antigens
(1) infection caused by an opportunistic pathogen from an individual’s own normal microbiota. (2) Surface antigens on human cells produced as a result of infection.
CTL releases ________ and __________ that induce apoptosis in the infected cell
perforin and granzymes
releases perforin and granzymes that induce apoptosis in the infected cell
Cytotoxic T Lymphocytes (CD8+ T Cells)
A normal cell will not trigger a response
by a cytotoxic T lymphocyte (CTL), but
a
virus-infected cell or a cancer
cell produces abnormal endogenous antigens
The abnormal antigen is presented on
the cell surface in association with
MHC
class I molecules.
Binding of a TH1 cell
promotes
secretion of cytokines
cytokines activate a
precursor CTL (CTLp),
which
produces a clone
of CTLs.
CTL induces destruction of
virus-infected cell by apoptosis.
What prevents the spread of infectious viruses into other cells?
Apoptosis
During apoptosis, cells cut their genome into
fragments, causing the membranes to bulge outward via blebbing
Blebbing
bulging of plasma membranes as the cell dies
Natural Killer cells kill which cells?
Granular leukocytes destroy cells that don’t express MHC class I self-antigens
function of NK cells
Kill virus-infected and tumor cells and attack parasites
NK cells not always stimulated by
an antigen
NK cells form pores in the target cells leading to
lysis or apoptosis
Activates cells related to cell-mediated immunity; macrophages, CTLs, and natural killer cells
TH1 (THelper)
Stimulates production of eosinophils, IgM and IgE
T Helper TH2 cell
Recruits neutrophils; stimulates production of antimicrobial proteins
T helper TH17 cell
Destroys target cells on contact by inducing apoptosis
Cytotoxic T Lymphocyte CTL
Regulates immune response and helps maintain self-tolerance
T regulatory cell
Enhanced phagocytic activity; attacks cancer cells
Activated macrophage
Attacks and destroys target cells; participates in antibody-dependent cell-mediated cytotoxcicity
Natural Killer cell (NK)
are too large to be phagocytized
Protozoans and helminths
Protozoan or helminth target cell is coated with
antibodies
Immune system cells attach to which region of antibodies?
Fc regions of antibodies
Target cell is lysed by chemicals secreted by
the immune system cell
Antibody-Dependent Cell-Mediated Cytotoxicity
The killing of antibody-coated cells by natural killer cells and leukocytes.
too large for ingestion by phagocytic cells must be attacked externally
organisms and many parasites
Occurs after the second exposure to an antigen
Secondary (memory or anamnestic) response
Class switching
where initial IgM response shifts to IgG, IgE, or IgA, occurs
More rapid, lasts many days, greater in magnitude
Secondary (memory or anamnestic) response
Memory cells produced in response to the initial exposure are activated by the
secondary exposure
Antibody titer
relative amount of antibody in the serum
Antibody titer reflects
intensity of the humoral response
Resulting from infection
Naturally acquired active immunity
Transplacental or via colostrum
Naturally acquired passive immunity
Injection of vaccination (immunization)
Artificially acquired active immunity
Injection of antibodies
Artificially acquired passive immunity
The serum fraction containing immunoglobulins (antibodies); also called immune serum globulin.
gamma globulin
Gamma globulin
The serum fraction containing immunoglobulins (antibodies); also called immune serum globulin.
Control of freely circulating pathogens
humoral adaptive immunity
control of intracellular pathogens
Cellular immune system
Humoral immunity also called
antibody-mediated immunity
Humoral immunity is directed at
Freely circulating pathogens and depends on B cells
Cellular immunity, also called cell-mediated immunity, depends on
T cells to eliminate intracellular pathogens, reject foreign tissue, destroy tumor cells
The adaptive immune system provides
specificity, clonal expansion, and memory
Examples of innate nonspecific defenses
- first line (skin and mucous membranes)
- Phagocytosis
- inflammation
- complement system
Two main divisions of adaptive defense
humoral immunity, cell-mediated immunity
Humoral immune response
consists of B cells, and the antibodies they produce
cell-mediated immunity
fights intracellular pathogens and cancer cells
protagonists of cell-mediated immunity
T lymphocytes
types of T lymphocytes
- Helper T cells
- Cytotoxic T cells
secrete cytokines to activate other cells of the immune system
Helper T cells
Attack infected cells directly
cytotoxic T cells
the innate and adaptive immune system are interdependent, meaning
they work together to carry out host defenses
Humoral immune response
Activity of B cells and the antibodies they produce
antigen presenting cells
certain phagocytic cells of the immune system, show what is captured
Infected cell needs to show that it was
infected
Antigen processing and presentation
is a way for a cell to display information about its activities
The process of B cell activation is called
clonal selection
What happens during clonal selection?
B cell with a specific antigen receptor recognizes an antigen.
The B cell with the specific antigen proliferates to
a clone of cells with the same specificity. a lot of cells with the same specificity
The clones of B cells differentiate into
memory B cells and plasma cells
clonal expansion
making a lot of cell copies to fight a specific pathogen
plasma cells make
antibodies with several functions
The antibodies bind to antigens to produce the
humoral response
in the simplest form of B cell activation, an antigen called a T-independent antigen
enters the lymphatic tissues and binds to a B cell receptor on the surface of a B cell
B cell receptors on a particular B cell are identical and very specific to
just one antigen
once the BCR binds to the T-independent antigen, the B cell becomes
activated
When the B cell becomes activated, it is ready to
proliferate
most antigens are not potent enough to activate B cells themselves, so
the B cell will require a second opinion from a helper T cell to activate
T dependent antigens
B cell that needs second opinion from helper T cell to become activated
The helper T cell recognizes the antigen as its presented by the B cell and secretes
cytokines to tell the B cell to become activated
What happens to the B cell once it becomes activated?
it proliferates making a clone of cells specific to the same antigen
some B cells differentiate into
long-lived memory B cells
Most B cells differentiate into
plasma cells that secrete antibodies against the antigen that activated them
Antibodies can enter the blood stream and travel throughout
the body
Plasma cells only live for
a few days
Each plasma cell makes approximately how many antibodies per second
2000, enormous quantities of circulating antibodies
The antibodies produced by plasma cells have several
functions
Since each antibody has at least two antigen binding sites,
antibodies can bind to more than one microbial cell, resulting in agglutination, or clumping
helps remove microorganisms from the body
Agglutination
neutralize toxins, viruses and bacteria
antibodies
How do antibodies neutralize toxins, viruses and bacteria
by binding to critical portions of the toxin, or blocking proteins necessary for attachment to cells.
antibodies also act as _______ for phagocytosis
opsonins
can activate the complement system
antibodies
Have two classes of special proteins used to present antigens on their surfaces
APCs such as macrophages and dendritic cells
MHC
proteins used to present antigens on surfaces of APCs
Class I MHC proteins
used to present antigens produced within the cell
MHC II proteins
used to present antigens engulfed by antigen presenting cells
Most of the other cells in the body, including infected cells are also able to
present antigens
Most of the other cells in the body, including infected cells are also able to present antigens, however, these cells only have the
Class I MHC proteins
Each cytotoxic T cell produces a unique
T cell receptor which corresponds to a specific antigen
Each cytotoxic T cell also produces a receptor called
CD8
function of CD8
recognizes the MHC molecules of infected cells
When a cytotoxic T-cell encounters an infected cell with the specific antigen bound in an MHC molecule
the cytotoxic T cell produces receptors for IL-2 and other cytokines, and IFN-Y
The cytotoxic T cell can ten be activated by
cytokines from activated helper T cells
What happens when a cytotoxic T-cell becomes activated,
it proliferates, forming a clone of cells specific to the same antigen
some of these cytotoxic T cells differentiate into
long lived memory cells
Most cytotoxic T cells differentiate into
mature T cells and attack and destroy infected cells
cytotoxic T cells can destroy infected cells through multiple
pathways
perforin-granzyme cytotoxic pathway
when the cytotoxic T cell encounters an infected cell with the target antigen bound in an MHC molecule, the T cell secreted two types of proteins called perforin and granzyme
perforin forms a
pore in the membrane of the target cell, allowing granzyme to enter the cell.
granzyme activates
enzymes inside the cell leading to apoptosis
the humoral immune response experiences periods of
ramping up and gradual diminishing in response to a foreign invader
after the first exposure to an antigen, there is a lag period in which
the exposed person’s serum does not contain any detectable antibodies
after several days, the concentration of antibodies slowly
rises
after slowly rising, there is a gradual ________ of antibodies
decline
if memory b cells become stimulated by the original antigen, even years later
They rapidly produce antibody-secreting plasma cells
epitopes,
or antigenic determinants, on the antigen
Where to find IgA ?
1.mucous membranes,
2.saliva,
3.tears
4. breast milk
Where to find IgD ?
In blood, in lymph, and on B cells
IgE location
1.mast cells,
2.basophils,
3. blood
IgD function
No well-defined function; assists in the immune response on B cells
Function of IgM
- Clumping of cells and viruses
- First response to infection
- Remain in blood vessels
Function of IgA
Prevent microbial attachment to mucous membranes
IgE function
- Releases histamine
- lysis of parasitic worms
Cytoxic T lymphocytes (CTL)
Bind MHC class ___ molecules
I
Why do macrophages migrate to lymph tissue?
To present antigen to T cells
What causes endogenous antigens?
- Opportunistic normal microbes
- Antigens made by infection
infection caused by an opportunistic pathogen from an individual’s own normal microbiota. (2) Surface antigens on human cells produced as a result of infection.
