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Lectures in Immunology 01 (Dr Hend)
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Definition
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The Immune ResponseImmunity: Free from burden. Ability of an
organism to recognize and defend itself against specificpathogens or antigens.
Immune Response:Th
ird 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.
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The Immune System is the Third
Line of Defense Against Infection
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Overview
What is an antigen?
What does an antigen do?
The Lymphatic System and
Body Defenses Nonspecific Defenses
Physical barriers
Phagocytes
Immunological surveillance
Interferons
Complement
Inflammation
Fever
Specific Defenses: The ImmuneResponse Overview of immune response
T cells and cell-mediatedimmunity
B cells and antibody-mediatedimmunity
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What is an antigen?
Antigen = antibody generating molecule any chemical substance that, when introduced into
the body, causes the body to produce specificantibodies that can react with the antigen
Properties of antigens: Foreign proteins or polysaccharides
Examples:
Cell membranes, flagella, viruses, toxins, enzymes,pollen, transplanted tissues & organs, markers on redblood cells
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AntigensMost 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 surfacemolecules from transplanted tissue.
Lipids and nucleic acids are only antigenic when
combined with proteins or polysaccharides.
Molecular weight of 10,000 orhigher. Hapten: Small foreign molecule that is not antigenic.
Must be coupled to a carriermolecule to be antigenic.Once antibodies are formed they will recognize hapten.
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AntigensEpitope:
Small part of an antigen that interacts withan antibody.
Any given antigen may have several
epitopes.
Each epitope is recognized by a different
antibody.
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Epitopes: Antigen Regions that
Interact with Antibodies
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Pathogens: microorganisms responsible
for human diseases
Bacteria Viruses
Fungi
Parasites
Lymphatic system
Keeps us alive and healthy
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What does an antigen do?
Antigen with its antigenic determinant stimulates
the formation of specific antibodies
The antigenic determinant, a portion of the
antigen, reacts with an antibody to form anantigen-antibody complex
The formation of the antigen-antibody complex
ultimately leads to inactivation and removal ofthe antigen
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Antigenic Determinants on an
Antigen
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Derivation and Distribution of
Lymphocytes
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The Lymphatic System and Body
Defenses Nonspecific Defenses Do not distinguish one
threat from another
Physical barriers
Phagocytic cells
Immunological surveillance
Interferons
Complement
Inflammation Fever
Specific Defenses
Protect against particular
threats
Develop after birth
Dependent on activity of
lymphocytes
B cells
T cells
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The Complement System
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Macrophage
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Specific Defense: The Immune
Response
Respond to specific antigens
T cells
Cell-mediated immunity (cellular immunity)
Provide defense against abnormal cells and
pathogens in living cells
B cells
Antibody-mediated immunity (humoral immunity)
Provide a defense against antigens and pathogens in
body fluids
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Lymphocytes and the
Immune Response
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T Cells and Cell-Mediated
Immunity
T cells recognize antigens when bound to
membranes of other cells
Membrane receptors called major
histocompatibility complex (MHC) proteins
2 classes
Class I MHC proteins
Class II MHC proteins
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Class I MHC Proteins
Found on the surfaces of all of our cells
MHC proteins bind small peptide
molecules normally present on cellmembrane
Normal peptides: T cell ignores
Abnormal, virus, or bacteria (nonself): T cell
activated
Destroys abnormal/infected cell
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Class II MHC Proteins
Found only on membranes of lymphocytes andphagocytic antigen-presenting cells (APCs) Such as monocyte-macrophage group, free and fixed
macrophages
Specialized for activating T cells against foreign cellsand proteins
Phagocytic APCs engulf and break down foreignantigens or pathogens Fragments of foreign antigens displayed on
phagocytic cells membrane Bind to Class II MHC proteins
T cells come in contact and become activated, starting theimmune response
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T Cells
T cell activation for both occur when MHCprotein contains specific antigen T cellprogrammed to detect
Once activated, T cells divide and differentiatein to cells with specific function in immuneresponse
Cytotoxic T cells
Helper T cells Memory T cells
Suppressor T cells
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T Cells Only Recognize Antigen
Associated with MHC Molecules on
Cell Surfaces
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Cytotoxic T Cells
Responsible for cell-mediated immunity
Activated by exposure to antigens bound
to Class IMH
C proteins Activated cells under cell division that produce
active cytotoxic T cells and memory cells
Track down and attack bacteria, fungi,
protozoa, or foreign transplanted tissue
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A TC Cell Lyses an Infected Cell
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Apoptosis and Macrophages
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Helper T Cells (TH
Cells)
Assist in the regulation and coordination of heimmune response
Steps of regulation
1. Processing Macrophage phagocytizes antigen, presents it on its surface
2. Recognition Appropriate TH cell binds to the macrophage
3. Stimulation Macrophage stimulates THcell to form a clone of TH cells
Cloned cells produce cytokines
Stimulate B cells and TC cells
4. Response TC cells kill infected cells, B cells produce antibodies
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The Role ofHelper T Cells as
Mediators of Immune Responses
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Central Role ofHelperT Cells
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Suppressor T Cells
When activated, depress responses of
other T and B cells
Does not occur immediately Takes much longer for these cells to become
activated
Act after initial immune response
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B Cell Activation
Activated B cells divide several times
Produce daughter cells that differentiate into:
Plasma cells
Synthesize and secrete large numbers of antibodies on
surface of sensitized B cells
Memory cells
Similar to memory T cells
If exposed to same antigen, will differentiate into plasmacells
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2 Methods of Antibody
Production T cell independent production B cells differentiate without the interaction of
TH
cells
T cell dependent production
B cells differentiate with the interaction of TH
cells
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T cell Independent Antigens
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T cell Dependent Antigens &
Antibody Production
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Outcome of Antibody
Production by B cells
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What is an antibody?
Large Proteins
Basic subunit has minimum of two binding sites
at which it combines with antigens
Also known as immunoglobulins
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Antibody Structure
Consist of short and heavy chains ofpolypeptides Each chain has constant and variable segments
Constant heavy chains form base of antibody molecule
B cells produce only 5 types of constant segments Specificity depends on variable segments of light and
heavy chains Free tips contain antigen binding sites (very specific for each
type of antigen)
Antigen-antibody complex Forms when antibody binds to proper antigen Binds to sites and leads to B cell sensitization and an
immune response
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Antibody Configuration
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Classes of Antibodies
(Immunoglobins Igs) IgG
Largest and most diverse
Resist many viruses, bacteria, bacterial toxins
Can cross placenta What type of immunity is that?
IgM Circulate; attack bacteria IgA
Found in exocrine secretions Ex?
Attack pathogens before they enter the body
IgE When bound to antigen, stimulates basophils and mast cells to releasechemicals to stimulate inflammation
IgD Attached to B cell and involved in their activation
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Antibody Function
Neutralization
Agglutination and Precipitation
Activation of a complement Attraction of phagocytes
Enhancement of phagocytosis
Stimulation of inflammation
C f A ib d
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Consequences of Antibody
Binding
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Primary and Secondary Responses
to Antigen Exposure
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Immunological Memory
Antibody Titer: The amount of antibody in the
serum.Pattern of Antibody Levels During Infection
Primary Response:
Afterinitialexposure to antigen, no
antibodies are found in serum for several
days.
A gradual increase in titer, first of IgM and
th
en of IgG is observed. Most B cells become plasma cells, but some
B cells become long living memorycells.
Gradual decline of antibodies follows.
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Immunological Memory (Continued)
Secondary Response:
Subsequent exposure to the same antigendisplays a faster and more intense antibody
response.
Increased antibody response is due to the
existence of memory cells, which rapidlyproduce plasma cells upon antigen
stimulation.
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Antibody Response After Exposure to
Antigen
Relationship Between Cell Mediated and
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Relationship Between Cell-Mediated and
Humoral Immunity
1. Antibody Production
T-Dependent Antigens:
Antibody production requires assistance fromThelper
cells.
A macrophage cells ingest antigen and presents it to TH cell.
TH cell stimulates B cells specific for antigen to becomeplasma 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 fromT
cells.
Antigens are mainly polysaccharides or
lipopolysaccharides with repeating subunits (bacterial
capsules).
Weaker immune response than forT-dependent antigens.
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Duality of the Immune System
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T Cells and Immunity
1000s of different types of T cells
When an antigen enters the body, only the particularT cell programmed to react with the antigen becomesactivated
Macrophages phagocytize the antigen Macrophages present it to the T cell
T cells increase in size, divide, differentiate Cytotoxic T cells
Helper T cells
Memory T cells
Delayed hypersensitivity T cells
Suppressor T cells
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B Cells
1000s of different kinds of B cells
Each type responds to a specific antigen
When an antigen enters the blood
B cells are activated Become plasma cells
Circulate in blood and lymph to reach site ofinvasion
B cells become memory B cells Respond more rapidly and forcefully should a
2nd invasion occur
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Humoral Response to T Dependent
Antigens
Humoral Response to T Dependent
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Humoral Response to T Dependent
Antigens
Overview of the Immune response
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Overview of the Immune response
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Disorders of the Immune
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Disorders of the Immune
System Allergy Person is overly reactive to an antigen
Autoimmune diseases
Body has difficulty in discriminating between its own antigens
and foreign antigens
Severe Combined Immunodeficiency (SCID)
Both T cells and B cells are absent or inactive
Acquired Immune Deficiency Syndrome (AIDS)
Human immunodeficiency virus (HIV) Primarily attacks helper T cells
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AntibodiesProteins that recognize and bind to a particular
antigen with very highspecificity.
Made in response to exposure to the antigen.
One virus or microbe may have several antigenic
determinantsites, to which different antibodies may
bind.Each antibody has at least two identical sites that
bind antigen: Antigen bindingsites.
Valence of an antibody: Number of antigen binding
sites. Most are bivalent.Belong to a group of serum proteins called
immunoglobulins (Igs).
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Antibody StructureMonomer: A flexible Y-shaped molecule with four
protein chains:
2 identical lightchains
2 identical heavychains
Variable Regions: Two sections at the end of Ys
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.
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Antibody Structure
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Immunoglobulin Classes
I. IgGStructure: 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.
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Immunoglobulin Classes
II. IgMStructure: 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.
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Immunoglobulin Classes
III. IgAStructure: 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 ofmucosal
surfaces. Provides immunity to infant digestive tract.
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Immunoglobulin Classes
IV. IgDStructure: 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.
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Immunoglobulin Classes
V. IgEStructure: 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.
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