Download and T cells

Innate Immunity
Dr. Hani Masaadeh, MD, PhD
Immunity: “Free from burden”. Ability of an
organism to recognize and defend itself
against specific pathogens or antigens.
Immune Response: Third line of defense.
Involves production of antibodies and
generation of specialized lymphocytes
against specific antigens.
Antigen: Molecules from a pathogen or
foreign organism that provoke a specific
immune response.
• immunity possessed by a group (as a species
or race) that is present in an individual at
birth prior to exposure to a pathogen or
antigen and that includes components (as
intact skin, salivary enzymes, neutrophils,
natural killer cells, and complement) which
provide an initial response against infection—
called also natural immunity;
compare ACQUIRED IMMUNITY, ACTIVE
IMMUNITY, PASSIVE IMMUNITY
Defensive mechanisms include :
1) Innate immunity (Natural or Non specific)
2) Acquired immunity (Adaptive or Specific)
Cell-mediated immunity
Humoral immunity
Innate or Genetic Immunity: Immunity an
organism is born with.
• Genetically determined.
• May be due to lack of receptors or other molecules required for
infection.
Acquired Immunity:Immunity that an
organism develops during lifetime.
• Not genetically determined.
• May be acquired naturally or artificially.
• Innate immunity is the first line of defense against infections.
The cells and soluble molecules of innate immunity either
exist in a fully functional state before encounter with
microbes or are rapidly activated by microbes, faster than
the development of adaptive immune responses
• Innate immunity is present before any exposure to
pathogens and is effective from the time of birth
• • It involves nonspecific responses to pathogens
• • Innate immunity consists of external barriers plus internal
cellular and chemical defenses
Components of Human Immune System
• Innate immunity is the initial response to microbes that
prevents, controls, or eliminates infection of the host by
many microbes.
• Innate immune mechanisms recognize the products of
damaged and dead host cells and serve to eliminate these
cells and to initiate the process of tissue repair.
• Innate immunity to microbes stimulates adaptive immune
responses and can influence the nature of the adaptive
responses to make them optimally effective against different
types of microbes.
• The two major types of responses of the innate immune
system that protect against microbes are inflammation and
antiviral defense.
• The innate immune system recognizes microbial products
that are often essential for survival of the microbes
• The innate immune system also recognizes endogenous
molecules that are produced by or released from damaged
and dying cells. These substances are called damageassociated molecular patterns (DAMPs)
• The innate immune system uses several types of cellular
receptors, present in different locations in cells, and soluble
molecules in the blood and mucosal secretions to recognize
PAMPs and DAMPs
• The receptors of the innate immune system are encoded in
the germline, whereas the receptors of adaptive immunity
are generated by somatic recombination of receptor genes in
the precursors of mature lymphocytes
• The innate immune system does not react against normal,
healthy cells and tissues.
• Most cell types express pattern recognition receptors and
therefore are capable of participating in innate immune
responses. Phagocytes, including neutrophils and
macrophages, and dendritic cells express the widest variety
and greatest amount of these receptors
• Toll-like Receptors
• The Toll-like receptors (TLRs), an evolutionarily conserved
family of pattern recognition receptors expressed on many
cell types, recognize products of a wide variety of microbes.
• Mammalian TLRs are involved in responses to a wide variety
of molecules that are expressed by microbial but not by
healthy mammalian cells.
• TLRs are also involved in response to endogenous molecules
whose expression or location indicates cell damage.
• The structural basis of TLR specificities resides in the multiple
extracellular leucine-rich modules of these receptors, which
bind directly to PAMPs or to adaptor molecules that bind the
PAMPs.
• TLRs are found on the cell surface and on intracellular
membranes and are thus able to recognize microbes in
different cellular locations
• TLR recognition of microbial ligands results in the activation
of several signaling pathways and ultimately transcription
factors, which induce the expression of genes whose
products are important for inflammatory and antiviral
responses
• RIG-like Receptors
• RIG-like receptors (RLRs) are cytosolic sensors of viral RNA
that respond to viral nucleic acids by inducing the production
of the antiviral type I interferons.
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Other Cell-Associated Pattern Recognition Receptors
Receptors for Carbohydrates
Scavenger Receptors
N-Formyl Met-Leu-Phe Receptors
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CELLULAR COMPONENTS OF THE INNATE IMMUNE SYSTEM
Epithelial Barriers
Phagocytes
Dendritic Cells
Natural Killer Cells
• Effector Functions of NK Cells
• The effector functions of NK cells are to kill infected cells and
to activate macrophages to destroy phagocytosed microbes
• Mast Cells
• Mast cells are present in the skin and mucosal epithelium
and rapidly secrete proinflammatory cytokines and lipid
mediators in response to infections and other stimuli.
• THE INFLAMMATORY RESPONSE
• The major way by which the innate immune system deals
with infections and tissue injury is to stimulate acute
inflammation, which is the accumulation of leukocytes,
plasma proteins, and fluid derived from the blood at an
extravascular tissue site of infection or injury.
• Acute inflammation can develop in minutes to hours and last
for days. Chronic inflammation is a process that takes over
from acute inflammation if the infection is not eliminated or
the tissue injury is prolonged. It usually involves recruitment
and activation of monocytes and lymphocytes.
• The Major Proinflammatory Cytokines TNF, IL-1, and IL-6
• One of the earliest responses of the innate immune system
to infection and tissue damage is the secretion of cytokines
by tissue cells, which is critical for the acute inflammatory
response. Three of the most important proinflammatory
cytokines of the innate immune system are TNF, IL-1and IL-6
• Tumor Necrosis Factor
• Tumor necrosis factor (TNF) is a mediator of the acute
inflammatory response to bacteria and other infectious
microbes.
• Interleukin-1 (IL-1) is also a mediator of the acute
inflammatory response and has many similar actions as TNF.
• Interleukin-6
• IL-6 is another important cytokine in acute inflammatory
responses that has both local and systemic effects, including
the induction of liver synthesis of a variety of other
inflammatory mediators, the stimulation of neutrophil
production in the bone marrow, and the differentiation of IL17–producing helper T cells.
• Recruitment of large numbers of neutrophils, followed by
monocytes, from blood into tissues typically occurs as part of
the acute inflammatory response to infections and tissue
injury. The cytokines TNF, IL-1, and IL-6 and chemokines,
which are secreted in the local sites of infection or tissue
injury.
• Recruitment of Leukocytes to Sites of Infection
• Phagocytosis and Killing of Microbes by Activated
Phagocytes
• Neutrophils and macrophages that are recruited into sites of
infections ingest microbes into vesicles by the process of
phagocytosis and destroy these microbes .
• Neutrophils and macrophages express receptors that
specifically recognize microbes, and binding of microbes to
these receptors is the first step in phagocytosis.
• Activated neutrophils and macrophages kill phagocytosed
microbes by the action of microbicidal molecules in
phagolysosomes
• A complication of severe bacterial sepsis is a syndrome
called septic shock
• Acute inflammation may cause tissue injury because the
effector mechanisms that phagocytes use to kill microbes are
also highly toxic to host tissues.
• THE ANTIVIRAL RESPONSE
• The major way by which the innate immune system deals
with viral infections is to induce the expression of type I
interferons, whose most important action is to inhibit viral
replication.
• Type I interferons are a large family of structurally related
cytokines that mediate the early innate immune response to
viral infections
• Type I interferons increase the cytotoxicity of NK cells and
CD8+ .
• Type I interferons upregulate expression of class I MHC
molecules and thereby increase the probability that virally
infected cells will be recognized and killed by CD8+ CTLs.
External Defenses
• Intact skin and mucous membranes
• Form physical barriers that bar the entry of microorganisms and viruses
• Certain cells of the mucous membranes produce mucus
• A viscous fluid that traps microbes and other particles
• In the trachea, ciliated epithelial cells
• Sweep mucus and any entrapped microbes upward,
m
preventing the microbes from entering the10lungs
Figure 43.3
• Secretions of the skin and mucous membranes
• Provide an environment that is often hostile to
microbes
• Secretions from the skin
• Give the skin a pH between 3 and 5, which is
acidic enough to prevent colonization of many
microbes
• Also include proteins such as lysozyme, an
enzyme that digests the cell walls of many
bacteria
• Phagocytes, types of white blood cells
• Ingest invading microorganisms
• Initiate the inflammatory response
• Macrophages, a specific type of phagocyte
• Can be found migrating through the body
• Can be found in various organs of the lymphatic system
Types of Acquired Immunity
I. Naturally Acquired Immunity: Obtained in the
course of daily life.
A. Naturally Acquired Active Immunity:
• Antigens or pathogens enter body naturally.
• Body generates an immune response to antigens.
• Immunity may be lifelong (chickenpox or mumps) or
temporary (influenza or intestinal infections).
B. Naturally Acquired Passive Immunity:
• Antibodies pass from mother to fetus via placenta or breast
feeding (colostrum).
• No immune response to antigens.
• Immunity is usually short-lived (weeks to months).
• Protection until child’s immune system develops.
Types of Acquired Immunity (Continued)
II. Artificially Acquired Immunity: Obtained by receiving
a vaccine or immune serum.
1. Artificially Acquired Active Immunity:
• Antigens are introduced in vaccines (immunization).
• Body generates an immune response to antigens.
• Immunity can be lifelong (oral polio vaccine) or temporary
(tetanus toxoid).
2. Artificially Acquired Passive Immunity:
• Preformed antibodies (antiserum) are introduced into body
by injection.
• Snake antivenom injection from horses or rabbits.
• Immunity is short lived (half life three weeks).
• Host immune system does not respond to antigens.
Aquired (specific) immunity
* The acquired immune response is more specialized
than innate immune response
* The acquired immune response involves a combination
of two mechanisms :
1) Humoral immune response
2) cell mediated immune response
* They interact with one another to destroy foreign body
(microorganisms, infected cells, tumor cells)
Aquired (specific) immunity
Two mechanisms
1) Humoral immune response:
- Antibodies are produced by B-lymphocytes
- These have the ability to recognize and bind
specifically to antigen that induced their formation
2) The cell mediated immune response (CMI)
- It is mediated by certain types of T-lymphocytes
- T-lymphocytes recognize foreign material by
means of surface receptors
- T-lymphocytes attack and destroy foreign material
directly or through release of soluble mediators
i.e. cytokines
Characters Of Acquired Immune Response
1) Highly specific for the invading organism
2) Discrimination between “self and “non self” molecules
The response only occurs to “non self” molecules
3) Diversity:
- It can respond to millions of different antigens
- Lymphoctes population consists of many different clones (one cell
and its progny)
- Each clone express an antigen receptor and responds only to one
antigenic epitope
Mechanism Of Acquired Immune Response
Acquired immune response is initiated by:
* Recognition of the antigen by specific lymphocytes
* Activation of these specific lymphocytes
* Proliferation and differentiation into effector cells;
-The effector cells eliminate the antigen
-Return of homeostasis and development of memory cells
* Memory cells evoke a more rapid and long response on re-exposure to
same antigen
Acquired Or Adaptive Immunity
I- Passive acquired immunity
a-Naturally passive acquired immunity
Antibodies are passed through placenta
to the fetus
b- Artificially passive acquired immunity
The injection of alredy prepared antibodies,
such as gamma globulin
(short-term immunization)
II- Active acquired immunity
a-Natural active acquired immunity :
- Following clinical or subclinical infections
- measles or mumps, in which immunity is
long lasting
b- Artificial active acquired immunity :
- Following vaccination with live or killed
infectious agents or their products
Mechanism of Humoral immunity
* Antibodies induce resistance through:
1) Antitoxin neutralize bacterial toxins (diphtheria,tetanus)
Antitoxin are developed actively as a result of:
a- Previous infection
b- Artificial immunization
c- Transferred passively as antiserum
* Neutralization of toxin with antitoxin prevents a combination with
tissue cells
Mechanism of Humoral immunity
2) Antibodies attach to the surface of bacteria and
a- act as opsonins and enhance phagocytosisd
b- prevent the adherence of microorganisms to
their target cells, e.g. IgA in the gut
c- Activate the complement and lead to bacterial lysis
d- Clump bacteria (agglutination) leading to
phagocytosis
Vaccination
* Vaccination prevents and control such diseases as cholera,
rabies, poliomyelitis, diphtheria, tetanus, measles, and typhoid
fever
* Vaccines can be:
a- prophylactic (e.g. to prevent the effects
of a future infection by any natural or
"wild" pathogen
b- Therapeupic (e.g. vaccines against cancer
are also being investigated)
Vaccination
Vaccination:
*Producing immunity against pathogens (viruses and
bacteria) by the introduction of live, killed, or altered
antigens that stimulate the body to produce antibodies
against more dangerous forms
*Vaccines work with the immune system's ability to
recognize and destroy foreign proteins (antigens)
Vaccination
Immunization of young children and adolescents:
- Hepatitis B (HepB) and Hepatitis A (HepA)
- Diphtheria, tetanus and pertussis (whooping cough) given together
as DTaP (formerly DTP)
- Haemophilus influenzae b (Hib)
- Poliomyelitis (IPV)
- Measles, Mumps, and Rubella, given together as MMR
- Chicken pox (Var)
- Neisseria meningitidis (meningococcal meningitis)
Cells Of Immune Response
Cells involved in specific immune mechanisms are:
I) Hematopoitic leucocytes
1- Lymphoid
* T-lymphocytes:
- Antigen specific cells carrying CD3 complex, CD4, CD8
- Dominant blood lymphocytes (70%)
- Produce cytokines
- Activation of other cells (Th CD4)
- Suppressors for others (Ts CD8)
Cells Of Immune Response
* B-lymphocytes:
- Antigen specific cells with surface receptor
- Less common lymphocytes (20%)
- Responsible for antibody production
* NK, K cells:
- Not antigen specific
- Carry Fc receptors , NK-target cell receptor
Cells of Immune Response (cont.)
2- Monocytic myeloid
a- Monocyte-tissue macrophages:
. Non specific
. Carry Fc receptors
. Phagocytic
. Antigen processing and presenting cells
. Produce cytokines
b- Neutrophils:
. Non specific
. Carrying Fc, complement molecules
Cells of Immune Response (cont.)
c- Eosinophils:
. Non specific
. Carrying Fc receptor
. Produce allergic mediators
d- Basophils and Mast cells:
. Non specifc
. Carrying Fc receptors
. Produce allergic mediators
Humoral Immunity (Continued)
Clonal Selection
• Clonal Selection: B cells (and T cells)
that encounter stimulating antigen will
proliferate into a large group of cells.
• Why don’t we produce antibodies
against our own antigens? We have
developed tolerance to them.
• Clonal Deletion: B and T cells that react
against self antigens appear to be
destroyed during fetal development.
Process is poorly understood.
Consequences of Antigen-Antibody Binding
Antigen-Antibody Complex: Formed when an antibody
binds to an antigen it recognizes.
Affinity: A measure of binding strength.
1. Agglutination: Antibodies cause antigens (microbes)
to clump together.
• IgM (decavalent) is more effective that IgG
(bivalent).
• Hemagglutination: Agglutination of red blood
cells. Used to determine ABO blood types and to
detect influenza and measles viruses.
2. Opsonization: Antigen (microbe) is covered with
antibodies that enhances its ingestion and lysis by
phagocytic cells.
Humoral Immunity (Continued)
3. Neutralization: IgG inactivates viruses by
binding to their surface and neutralize toxins
by blocking their active sites.
4. Antibody-dependent cell-mediated
cytotoxicity: Used to destroy large organisms
(e.g.: worms). Target organism is coated with
antibodies and bombarded with chemicals
from nonspecific immune cells.
5. Complement Activation: Both IgG and IgM
trigger the complement system which results
in cell lysis and inflammation.
Immunological Memory
Antibody Titer: The amount of antibody in the
serum.
Pattern of Antibody Levels During Infection
Primary Response:
• After initial exposure to antigen, no
antibodies are found in serum for several
days.
• A gradual increase in titer, first of IgM and
then of IgG is observed.
• Most B cells become plasma cells, but some B
cells become long living memory cells.
• Gradual decline of antibodies follows.
Immunological Memory (Continued)
Secondary Response:
• Subsequent exposure to the same antigen displays a faster and more
intense antibody response.
• Increased antibody response is due to the existence of memory cells,
which rapidly produce plasma cells upon antigen stimulation.
Duality of Immune System (Continued)
II. Cell Mediated Immunity
• Involves specialized set of lymphocytes called T cells that
recognize foreign antigens on the surface of cells,
organisms, or tissues:
• Helper T cells
• Cytotoxic T cells
• T cells regulate proliferation and activity of other cells of
the immune system: B cells, macrophages, neutrophils,
etc.
• Defense against:
• Bacteria and viruses that are inside host cells and are
inaccessible to antibodies.
• Fungi, protozoa, and helminths
• Cancer cells
• Transplanted tissue
T Cells and Cell Mediated Immunity
Antigens that stimulate this response are mainly intracellular.
Requires constant presence of antigen to remain effective.
Unlike humoral immunity, cell mediated immunity is not transferred to the
fetus.
Cytokines: Chemical messengers of immune cells.
• Over 100 have been identified.
• Stimulate and/or regulate immune responses.
• Interleukins: Communication between WBCs.
• Interferons: Protect against viral infections.
• Chemokines: Attract WBCs to infected areas.
T Cells and Cell Mediated Immunity
Types of T cells
1. T Helper (TH) Cells: Central role in immune response.
• Most are CD4+
• Recognize antigen on the surface of antigen presenting cells (e.g.:
macrophage).
• Activate macrophages
• Induce formation of cytotoxic T cells
• Stimulate B cells to produce antibodies.
Types of T cells (Continued)
2. Cytotoxic T (Tc) Cells: Destroy target cells.
• Most are CD4 negative (CD4 -).
• Recognize antigens on the surface of all cells:
• Kill host cells that are infected with viruses or bacteria.
• Recognize and kill cancer cells.
• Recognize and destroy transplanted tissue.
• Release protein called perforin which forms a pore in target cell, causing lysis
of infected cells.
• Undergo apoptosis when stimulating antigen is gone.
Types of T cells (Continued)
3. Delayed Hypersensitivity T (TD) Cells: Mostly T helper and a few
cytotoxic T cells that are involved in some allergic reactions (poison ivy)
and rejection of transplanted tissue.
4. T Suppressor (Ts) Cells: May shut down immune response.
Nonspecific Cellular Components
1. Activated Macrophages: Stimulated phagocytes.
• Stimulated by ingestion of antigen
• Larger and more effective phagocytes.
• Enhanced ability to eliminate intracellular bacteria, virus-infected and
cancerous cells.
2. Natural Killer (NK) Cells:
• Lymphocytes that destroy virus infected and tumor cells.
• Not specific. Don’t require antigen stimulation.
• Not phagocytic, but must contact cell in order to lyse it.
Relationship Between Cell-Mediated and Humoral Immunity
1. Antibody Production
T-Dependent Antigens:
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Antibody production requires assistance from T helper cells.
A macrophage cells ingest antigen and presents it to TH cell.
TH cell stimulates B cells specific for antigen to become plasma cells.
Antigens are mainly proteins on viruses, bacteria, foreign red blood
cells, and hapten-carrier molecules.
T-Independent Antigens:
• Antibody production does not require assistance from T cells.
• Antigens are mainly polysaccharides or lipopolysaccharides with
repeating subunits (bacterial capsules).
• Weaker immune response than for T-dependent antigens.
Relationship Between Cell-Mediated and Humoral Immunity
2. Antibody Dependent Cell Mediated
Cytotoxicity
• Target cell is covered with antibodies, leaving Fc
portion sticking outwards.
• Natural killer and other nonspecific cells that have
receptors for Fc region are stimulated to kill targeted
cells.
• Target organism is lysed by substances secreted by
attacking cells.
• Used to destroy large organisms that cannot be
phagocytosed.
• Humoral and cell-mediated immunity defend against different types of
threats
• Acquired immunity includes two branches
• The humoral immune response involves the activation and clonal selection
of B cells, resulting in the production of secreted antibodies
• The cell-mediated immune response involves the activation and clonal
selection of cytotoxic T cells
• Serum: Fluid that remains after blood has clotted and cells have been
removed.
• Antiserum: Serum containing antibodies to a specific antigen(s).
Obtained from injecting an animal (horse, rabbit, goat) with antigen
(snake venom, botulism or diphtheria toxin).
• Serology: The study of reactions between antibodies and antigens.
• Gamma Globulins: Fraction of serum that contains most of the
antibodies.
• Serum Sickness: Disease caused by multiple injections of antiserum.
Immune response to foreign proteins. May cause fever, kidney problems,
and joint pain. Rare today.
• Antibodies are circulating proteins that are produced in
vertebrates in response to exposure to foreign structures
known as antigens.
• The substances that generated or were recognized by
antibodies were then called antigens
• Antibodies can exist in two forms: membrane-bound
antibodies on the surface of B lymphocytes function as
receptors for antigen, and secreted antibodies that reside in
the circulation, tissues, and mucosal sites neutralize toxins,
prevent the entry and spread of pathogens, and eliminate
microbes.
• B lymphocytes are the only cells that synthesize antibody
molecules.
• Structural Features of Antibody Variable Regions
• Most of the sequence differences and variability among
different antibodies are confined to three short stretches in
the V region of the heavy chain and to three stretches in the
V region of the light chain. These diverse stretches are known
as hypervariable segments
Antibodies are Produced by B Lymphocytes
Antibodies are Proteins that Recognize Specific Antigens
Antibodies
Proteins that recognize and bind to a particular
antigen with very high specificity.
Made in response to exposure to the antigen.
One virus or microbe may have several antigenic
determinant sites, to which different antibodies
may bind.
Each antibody has at least two identical sites
that bind antigen: Antigen binding sites.
Valence of an antibody: Number of antigen
binding sites. Most are bivalent.
Belong to a group of serum proteins called
immunoglobulins (Igs).
Antibody Structure
Monomer: A flexible Y-shaped molecule with
four protein chains:
• 2 identical light chains
• 2 identical heavy chains
Variable Regions: Two sections at the end of Y’s
arms. Contain the antigen binding sites (Fab).
Identical on the same antibody, but vary from one
antibody to another.
Constant Regions: Stem of monomer and lower
parts of Y arms.
Fc region: Stem of monomer only. Important
because they can bind to complement or cells.
Properties of Immunoglobulins
Property
IgG
Heavy chain
symbol
γ
α
µ
ε
δ
Molecular
weight
150
KDa
170-400
KDa
900
KDa
190
KDa
180
KDa
Percentage
in serum
75 %
15 %
10 %
0.004 %
% 0.2
Complement
fixation
Yes
No
Yes
No
No
Transplacental
passage
Yes
No
No
No
No
Opsonization
Yes
No
No
No
No
IgA
IgM
IgE
IgD
Primary and Secondary antibody response
Secondary response
to Ag
Amount of
antibodies
in serum
Primary response
to Ag
1
2
3
4
5
6
Time (months)
1st injection of Ag
2nd injection of Ag
Immunoglobulin Classes
I. IgG
Structure: Monomer
Percentage serum antibodies: 80%
Location: Blood, lymph, intestine
Half-life in serum: 23 days
Complement Fixation: Yes
Placental Transfer: Yes
Known Functions: Enhances phagocytosis,
neutralizes toxins and viruses, protects fetus and
newborn.
Immunoglobulin Classes
II. IgM
Structure: Pentamer
Percentage serum antibodies: 5-10%
Location: Blood, lymph, B cell surface (monomer)
Half-life in serum: 5 days
Complement Fixation: Yes
Placental Transfer: No
Known Functions: First antibodies produced during
an infection. Effective against microbes and
agglutinating antigens.
Immunoglobulin Classes
III. IgA
Structure: Dimer
Percentage serum antibodies: 10-15%
Location: Secretions (tears, saliva, intestine, milk),
blood and lymph.
Half-life in serum: 6 days
Complement Fixation: No
Placental Transfer: No
Known Functions: Localized protection of mucosal
surfaces. Provides immunity to infant digestive tract
Immunoglobulin Classes
IV. IgD
Structure: Monomer
Percentage serum antibodies: 0.2%
Location: B-cell surface, blood, and lymph
Half-life in serum: 3 days
Complement Fixation: No
Placental Transfer: No
Known Functions: In serum function is unknown.
On B cell surface, initiate immune response.
Immunoglobulin Classes
V. IgE
Structure: Monomer
Percentage serum antibodies: 0.002%
Location: Bound to mast cells and basophils
throughout body. Blood.
Half-life in serum: 2 days
Complement Fixation: No
Placental Transfer: No
Known Functions: Allergic reactions. Possibly lysis
of worms.
Antibodies
Antibodies
Immunoglobulin G (IgG)
• Most abundant class (80%-85%)
• Transported across the placenta
• Four classes
• IgG1, IgG2, IgG3, and IgG4
Immunoglobulin A (IgA)
• Two classes
• IgA1 molecules are found predominantly in the blood
• IgA2 molecules are found predominantly in normal body
secretions
• IgAs found in body secretions are dimers anchored by a J chain
and a “secretory” piece
• Secretory piece may function to protect IgAs against enzyme
degradation
Immunoglobulin M (IgM)
• Largest of the immunoglobulins
• Pentamer stabilized by a J chain
• First antibody produced during the primary response to an
antigen
• Synthesized during fetal life
Immunoglobulin D (IgD)
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•
•
•
Limited information on IgD function
Low concentration in the blood
Located primarily on the surface of developing B lymphocytes
Function as one type of B cell antigen receptor
Immunoglobulin E (IgE)
• Least concentrated of the immunoglobulin classes in the
circulation
• Mediator of many common allergic responses
• Defender against parasites
IgE Function
• Provides protection from large parasites
• Initiates an inflammatory reaction to attract eosinophils
• When produced against innocuous environmental antigens,
they are a common cause of allergies
• Fc portions of IgEs are bound to mast cells
Primary and Secondary
Responses
• Primary response
• Initial exposure
• Latent period or lag phase
• B cell differentiation is occurring
• After 5 to 7 days, an IgM antibody for a specific antigen is
detected
• An IgG response equal or slightly less follows the IgM response
Primary and Secondary
Responses
• Secondary response
• More rapid
• Larger amounts of antibody are produced
• Rapidity is due to the presence of memory cells that do not have
to differentiate
• IgM is produced in similar quantities to the primary response, but
IgG is produced in considerably greater numbers
Antibody Response After Exposure to Antigen
Antigens
Most are proteins or large polysaccharides from
a foreign organism.
• Microbes: Capsules, cell walls, toxins, viral capsids,
flagella, etc.
• Nonmicrobes: Pollen, egg white , red blood cell surface
molecules, serum proteins, and surface molecules from
transplanted tissue.
Lipids and nucleic acids are only antigenic when
combined with proteins or polysaccharides.
Molecular weight of 10,000 or higher.
• Hapten: Small foreign molecule that is not antigenic. Must be
coupled to a carrier molecule to be antigenic. Once antibodies are
formed they will recognize hapten.
Part I Antigen and its characteristics
I. Definition of antigen
Antigen: Those substances that can induce a
specific immune response and specifically bind
products of immune response in vitro or in vivo.
. Antigen
. Tolerogen
. Allergen
II. Characteristics of Ag
1. Immunogenicity
The ability of antigen which can stimulate the
immune system of individual to induce a specific
immune response.
2. Immunoreactivity
The ability of antigen which can combine with
corresponding Ab or sensitized T lymphocyte.
III. Structure of antigen
 hapten
and carrier
Hapten: Only possess immunoreactivity
Carrier: Enhance the immunogenicity of hapten
• Immunogens :possess both characteristics
Hapten +carrier complete antigen(immunogens)
Part II Factors of affecting
immunogenicity of antigen
I. Factors related to antigen
1. Foreignness
According to Burnet clone selection theory ,
foreignness means substances that never contact
with lymphocytes in embryo period.
(2) Chemical composition and structure
Protein>polysaccharides, nucleic acids, lipids
(Protein containing aromatic amino acid,such as
tyrosine)
(3) Physical nature
Polymer > Monomer
Cycle molecule >linear molecule
Particulate Ag> soluble Ag
II. Factors related to host
1. Genetic backround (Species, Individual)
2. Age,Sex and healthy condition
II. Common antigen and
cross reaction
1. Common antigen
Different antigens which possess the same or similar epitopes
are called common antigen.
2. Mechanism of cross reaction
----Existence of common Ag determinant
Because there are some common antigen determinants existing in
different microbes, so the antiserum against one kind of microbe can also
react with another microbe,this called cross reaction.
3. Significance:
In clinic, existence of cross reaction may lead to
wrong diganosis.
Part IV Classification of Ag
I. According to immunogenicity of antigens:
 Antigen
 Hapten
II. According to the dependence of T cells
when Ags induce humoral immune response
TD-Ag (thymus dependent Ag )
TI-Ag (thymus independent Ag)
1.TD-Ag (thymus dependent Ag )
TD-Ag can stimulate B cell to produce Ab with
the help of T cell
 Most of TD-Ag are protein
 Have many kinds of determinants
 Can induce HI and CMI
 Stimulate B cell to produce :IgG, IgM, IgA
 Have immune memory
2. TI-Ag (thymus independent Ag)
TI-Ag can stimulate B cells to produce Ab without the help
of T cell
Most are polysaccharide
 Have more same or repeat determinants
 Only induce B cell to produce IgM
 Can not induce CMI
 No immune memory

III. According to source of antigen




Xenoantigen
Alloantigen
Autoantigen
Heterophile antigens(Forssman antigen)
The common antigen existing different species.
Part V Important antigens in medicine
I. Pathogens and their products
1. Pathogens:such as bacteria et al.
Surface antigen: “Vi” Ag
Somatic Ag: “O” Ag
Flagellar Ag: “H” Ag
Pillus Ag
2. Exotoxin and toxoid
(1) Exotoxin
Produced by G+ bacteria
Strong antigenicity and pathogenicity
(2) Toxoid
Under suitable conditions, exotoxin loss its
toxicity
without affecting its antigenicity, then the exotoxin
turned into toxoid
Antitoxin: The antibody produced by exotoxin or toxoid
stimulation was called antitoxin.
ABO system
Blood
type
A
B
AB
O
antigen
on RBC
A
B
A,B
-
antibody in
serum
anti-B
anti-A
anti-A, anti-B
• Recipient-donor combinations
• Can be fatal or safe
Table 43.1
• Another red blood cell antigen, the Rh factor
• Creates difficulties when an Rh-negative mother carries successive Rhpositive fetuses
Allergies
• Allergies are exaggerated (hypersensitive) responses
• To certain antigens called allergens
• In localized allergies such as hay fever
• IgE antibodies produced after first exposure to an allergen attach to
receptors on mast cells
• The next time the allergen enters the body
• It binds to mast cell–associated IgE molecules
• The mast cells then release histamine and other mediators
• That cause vascular changes and typical symptoms
• An acute allergic response sometimes leads to anaphylactic shock
• A whole-body, life-threatening reaction that can occur within seconds of
exposure to an allergen
Thanks