Download Immunity

Introduction to The Immune
System
• Mohamed Farouk Elshal, Ph.D.
Bldg.: 71 / Room:2008;
[email protected]
References:
1. Abbas, A, K. et.al, Cellular and Molecular
Immunology, 6th ed., 2007
2. Male D., J. Brostoff, D. B Roth, and I. Roitt
Immunology, 7th ed., 2006.
Dr. Mohamed Farouk Elshal
Keys toward Learning Immunology
•
Lectures => Deliver the key concepts of
Immunology.
•
Workbook => Apply the knowledge from
Immunology to the solution of clinical
problems.
•
Textbook reading => Help learn the
details and build up comprehensive
knowledge of immunology
Dr. Mohamed Farouk Elshal
Evaluation
For the Immunology Section:
• Examination => 70 %
• Attendance & Class performance
=> 30%
Dr. Mohamed Farouk Elshal
What is
Immunity?
Dr. Mohamed Farouk Elshal
Immunity
• Immunity
– The ability of the body to fight infection and/or foreign invaders by
producing antibodies or killing infected cells.
• Immune System
– The system in the body responsible for maintaining homeostasis
by recognizing harmful from nonharmful organisms and produces
an appropriate response.
Dr. Mohamed Farouk Elshal
Foreign Invaders
• Called Pathogens
– Viruses, bacteria or other living thing
that causes disease/immune response.
• Antigens
– Toxins that pathogens produce that
cause harm to an organism.
– A molecule which elicits a specific
immune response when introduced into
an animal.
More specifically, antigenic (immunogenic)
substances are:
– Generally large molecules (>10,000
daltons in molecular weight),
– Structurally complex (proteins are
usually very antigenic),
– Accessible (the immune system must be
able to contact the molecule), and
– Foreign (not recognizable as "self").
Dr. Mohamed Farouk Elshal
Epitopes: Antigen Regions that Interact with
Antibodies
Dr. Mohamed Farouk Elshal
Components of Human Immune System
Dr. Mohamed Farouk Elshal
Components of Human Immune System
CELLS OF THE IMMUNE RESPONSE
Cells:
Blood - White Blood Cells in particular.
1. B-cells
2. T-cells [Helper T-cells (TH), Suppressor T-cells
(TS), Cytotoxic T-cells (CTL) ]
3. Accessory cells [Macrophages, Dendritic cells,
Polymorphonuclear cells (PMNs)]
4. Killer cells [NK cells, K cells]
5. Mast cells
Dr. Mohamed Farouk Elshal
Components of Human Immune System
Lymphoid Tissues:
•
Thymus Gland – Produces T
Lymphocytes
•
Bone Marrow – Produces B
Lymphocytes
•
Lymph nodes
•
Spleen
Dr. Mohamed Farouk Elshal
LYMPHOID TISSUES
Dr. Mohamed Farouk Elshal
LYMPHOID TISSUES
Dr. Mohamed Farouk Elshal
How does the body fight
infection/foreign invaders?
Types of Immunity
Examples
Nonspecific (innate)
•
•
•
•
•
Specific (acquired) Naturally
acquired
• Placental transfer of antibody
(passive)
• Recovery from disease (active)
Artificially acquired
• Administration of antitoxin (passive)
• Vaccination (active)
Intact skin
Mucous membranes
Phagocytic cells
Enzymes in secretions
Cytokines (Interferon)
Dr. Mohamed Farouk Elshal
How does the body fight
infection/foreign invaders?
The Body’s THREE lines of Defense
First Line of Defense – The Skin
•
Provides Physical and Chemical barriers
•
•
Physical – hard to penetrate, made of indigestible keratin
Chemical – tears, sweat
Dr. Mohamed Farouk Elshal
Second Line of Defense –
Nonspecific Immune Response
These are defenses the body uses no matter what the invader
may be. These defenses include:
–
–
–
–
Phagocytosis – done by Macrophages
Natural Cell Killers
Inflammation - caused by release of Histamine from leukocytes
Fever – caused by histamines. The fever (high temp) kills invaders by
denaturing their proteins.
Macrophage: A phagocytic cell found in the liver, spleen, brain and lungs. Travels
to all areas of the body to find and eat pathogens.
Dr. Mohamed Farouk Elshal
Third Line of Defense –
Specific Immune Response
This is a specific response to a specific
pathogen/antigen.
• The response involves the creation of Antibodies.
Dr. Mohamed Farouk Elshal
Innate Immunity
Dr. Mohamed Farouk Elshal
Innate immunity
Innate immunity is the older host defense system:
- Existed in both Invertebrates & Vertebrates
- Provides the initial defense against infections
- Activates and shapes adaptive immune responses
Dr. Mohamed Farouk Elshal
Inflammation
=>A hallmark of innate immunity
=>Local accumulation of immune cells & molecules
against microbes
=>Function to eliminate infections but often cause
tissue damage & disease
Dr. Mohamed Farouk Elshal
Dr. Mohamed Farouk Elshal
Epithelial barriers prevent the
entry of microbes
Dr. Mohamed Farouk Elshal
Movements of phagocytic cells
• Ameboid movement.
Phagocytic cells
migrate in and out of
blood vessels and
throughout the
tissues.
• The process of
cellular emigration
from capillaries is
called diapedesis.
Dr. Mohamed Farouk Elshal
Dr. Mohamed Farouk Elshal
Phagocytosis during innate immunity
Stages in phagocytosis
A. Phagocyte detects chemicals released by a foreign
intruder (e.g. bacteria)
B. Phagocyte moves up the concentration gradient
towards the intruder
C. The phagocyte adheres to the foreign cell and engulfs it
in a vacuole by an infolding of the cell membrane.
D. Lysosomes (organelles which are rich in digestive
enzymes & found in the phagocytes cytoplasm) fuse
with the vacuole & release their contents into it leading
to killing the bacterium by the enzymes, and the
breakdown products are absorbed by the phagocyte.
Dr. Mohamed Farouk Elshal
Phagocytosis during innate immunity
Dr. Mohamed Farouk Elshal
Phagocytosis during innate immunity
Dr. Mohamed Farouk Elshal
Adaptive Immunity
Dr. Mohamed Farouk Elshal
Adaptive Immunity
Immunity that an organism develops during
lifetime.
– Not genetically determined.
– May be acquired naturally or artificially.
• Development of immunity to measles in
response to infection or vaccination.
Dr. Mohamed Farouk Elshal
Naturally Acquired Immunity
I. 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).
Dr. Mohamed Farouk Elshal
Naturally Acquired Immunity (Continued)
I. Obtained in the course of daily life.
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.
Dr. Mohamed Farouk Elshal
Artificially Acquired Immunity
II. Obtained by receiving a vaccine or immune
serum.
1. 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).
Dr. Mohamed Farouk Elshal
Vaccination (also called Immunization)
• The scientific view of immunity => Edward
Jenner (1796)
• Observation => Milkmaids generally get No
smallpox
• Hypothesis => Pus from vaccinia (cowpox)
•
=> Protect milkmaids from smallpox
• Test => Inoculate materials from cowpox pus
•
=> Protect a young boy from smallpox
•
(Protective immunity)
Dr. Mohamed Farouk Elshal
Eradication of smallpox
Edward Jenner
Dr. Mohamed Farouk Elshal
Vaccines for common infectious diseases
Still no effective vaccines for many infectious microbes,
ex. HCV, HIV, …..etc
Dr. Mohamed Farouk Elshal
Artificially Acquired Immunity (Continued)
II. Obtained by receiving a vaccine or immune
serum.
2. 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.
Dr. Mohamed Farouk Elshal
Artificially Acquired Immunity (Continued)
– 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.
Dr. Mohamed Farouk Elshal
Active vs. Passive immunity
Active immunity => A host response to a microbe (Ag)
=> specific and long-term immune defense (memory)
Passive immunity => Adoptive transfer of Ab or lymphocytes
specific for a microbe (or Ag)
=> specific, instant but transient immune defense
Dr. Mohamed Farouk Elshal
Interaction between innate and
& adaptive immunity
1. Innate immunity
=> Ag presentation
(by infected cells)
2. Adaptive immunity
=> Ag recognition
(by T & B lymphocytes)
Dr. Mohamed Farouk Elshal
Innate vs Adaptive immunity
Dr. Mohamed Farouk Elshal
Epitopes: Antigen Regions that Interact with
Antibodies
Dr. Mohamed Farouk Elshal
Innate vs Adaptive immunity
Dr. Mohamed Farouk Elshal
Features of Adaptive immunity
Dr. Mohamed Farouk Elshal
Types of adaptive
immunity
1. Humoral immunity
=> Molecules in body fluid,
ex. Antibody (Ab)
=> Key player => B cells
=> Target extracellular
microbes & toxins
2. Cell-mediated immunity
=> Key player => T cells =>
regulate other immune
cells
=> Target intracellular
microbes, ex. viruses,
bacteria
For innate immunity, it also includes Humoral & Cellular
components for immune defense
Dr. Mohamed Farouk Elshal
Cellular Immunity .vs. Antibody
Immunity
Cellular Immunity
• Carried out by T-Cells
• Infected cells are killed by
Cytotoxic T –Cells.
Antibody or Humoral Immunity
• Carried out by B-cells
• Antibodies are
produced and
dumped into blood
stream.
• Antibodies bind to
antigens and
deactivate them.
Dr. Mohamed Farouk Elshal
Humoral Immunity
Dr. Mohamed Farouk Elshal
Adaptive Humoral (AntibodyMediated) Immunity
I. Humoral (Antibody-Mediated) Immunity
– Involves production of antibodies against foreign antigens.
– Antibodies are produced by a subset of lymphocytes called B
cells.
– B cells that are stimulated will actively secrete antibodies and
are called plasma cells.
– Antibodies are found in extracellular fluids (blood plasma, lymph,
mucus, etc.) and the surface of B cells.
– Defense against bacteria, bacterial toxins, and viruses that
circulate freely in body fluids, before they enter cells.
– Also cause certain reactions against transplanted tissue.
Dr. Mohamed Farouk Elshal
How Do B Cells Produce Antibodies?
B cells develop from stem cells in the bone
marrow of adults (liver of fetuses).
– After maturation B cells migrate to lymphoid organs
(lymph node or spleen).
– Clonal Selection: When a B cell encounters an
antigen it recognizes, it is stimulated and divides into
many clones called plasma cells, which actively
secrete antibodies.
– Each B cell produces antibodies that will recognize
only one antigenic determinant.
Dr. Mohamed Farouk Elshal
Clonal Selection of
B Cells is Caused
by Antigenic
Stimulation
Dr. Mohamed Farouk Elshal
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.
Dr. Mohamed Farouk Elshal
Humoral Immunity (Continued)
Apoptosis
– Programmed cell death (“Falling away”).
– Human body makes 100 million lymphocytes every
day. If an equivalent number doesn’t die, will
develop leukemia.
– B cells that do not encounter stimulating antigen
will self-destruct and send signals to phagocytes to
dispose of their remains.
– Many virus infected cells will undergo apoptosis, to
help prevent spread of the infection.
Dr. Mohamed Farouk Elshal
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.
Dr. Mohamed Farouk Elshal
Antigens
Epitope:
Small part of an antigen that interacts with an
antibody.
Any given antigen may have several epitopes.
Each epitope is recognized by a different
antibody.
Dr. Mohamed Farouk Elshal
Epitopes: Antigen Regions that Interact
with Antibodies
Dr. Mohamed Farouk Elshal
Antibodies
• Y-shaped protein
molecule.
• Made up of variable and
constant regions.
• Made up of Heavy and
Light chains.
• Produced by BLymphocytes
• Function: Recognize
antigens, bind to and
deactivate them.
– Note: Variable region
recognizes the anitgens.
Dr. Mohamed Farouk Elshal
Antibodies
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.
Affinity: A measure of binding strength.
Belong to a group of serum proteins called
immunoglobulins (Igs).
There are five classes of antibodies: IgD, IgM, IgG, IgA,
and IgE
Dr. Mohamed Farouk Elshal
Classes of Antibodies
IgM – pentamer released by plasma cells during the
primary immune response
IgA – dimer that helps prevent attachment of
pathogens to epithelial cell surfaces
IgG – monomer that is the most abundant and
diverse antibody in primary and secondary
response; crosses the placenta and confers
passive immunity
IgE – monomer that binds to mast cells and
basophils, causing histamine release when
activated
IgD – monomer attached to the surface of B cells,
important in B cell activation
Dr. Mohamed Farouk Elshal
Antibody mechanisms of action
•
•
•
Antibodies themselves do not destroy antigen;
they inactivate and tag it for destruction
All antibodies form an antigen-antibody
(immune) complex
Defensive mechanisms used by antibodies
are:
1.
2.
3.
4.
neutralization,
agglutination,
precipitation, and
complement fixation
Dr. Mohamed Farouk Elshal
Consequences of Antigen-Antibody Binding
1. Agglutination: Antibodies
cause antigens (microbes) to
clump together.
•
•
•
•
Enhances phagocytosis
Reduces number of infectious
units to be dealt with
IgM (decavalent) is more
effective than IgG (bivalent).
Hemagglutination:
Agglutination of red blood cells.
Used to determine ABO blood
types and to detect influenza
and measles viruses.
Dr. Mohamed Farouk Elshal
Consequences of Antigen-Antibody Binding
2. Opsonization: Antigen
(microbe) is covered
with antibodies that
enhances its ingestion
and lysis by phagocytic
cells.
3. Neutralization: IgG
inactivates viruses by
binding to their surface
and neutralize toxins by
blocking their active
sites.
Dr. Mohamed Farouk Elshal
Humoral Immunity (Continued)
4. Antibody-dependent
cell-mediated
cytotoxicity (ADCC):
– Used to destroy large
organisms (e.g.: worms).
– Target organism is coated
with antibodies and
bombarded with
chemicals from
nonspecific immune cells.
Dr. Mohamed Farouk Elshal
Humoral Immunity (Continued)
5. Complement
Activation: Both IgG
and IgM trigger the
complement system
which results in cell lysis
and inflammation.
Dr. Mohamed Farouk Elshal
Humoral Immunity (Continued)
6. Disruption of cell by
complement/reactive
protein attracts
phagocytic and other
defensive immune
system cells
Dr. Mohamed Farouk Elshal
Dr. Mohamed Farouk Elshal
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.
Dr. Mohamed Farouk Elshal
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.
Dr. Mohamed Farouk Elshal
Antibody Response After Exposure to Antigen
Dr. Mohamed Farouk Elshal
Cellular Immunity
Dr. Mohamed Farouk Elshal
Specific Immune Response
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.
Dr. Mohamed Farouk Elshal
Importance of Cellular Response
• T cells recognize and respond only to
processed fragments of antigen displayed
on the surface of body cells (exogenous
antigens)
• T cells are also recognize and target
intracellular antigens like:
– Cells infected with viruses, bacteria, or
intracellular parasites
– Abnormal or cancerous cells
– Cells of infused or transplanted foreign tissue
Dr. Mohamed Farouk Elshal
Cell Mediated Immunity
• 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.
Dr. Mohamed Farouk Elshal
Antigen Recognition and MHC
Restriction
• Immunocompetent T cells are activated
when the V regions of their surface
receptors bind to a recognized antigen
• T cells must simultaneously recognize:
– Nonself (the antigen)
– Self (a MHC protein of a body cell)
Dr. Mohamed Farouk Elshal
MAJOR HISTOCOMPATIBILITY
COMPLEX
• The Major Histocompatibility Complex (MHC) is
a set of molecules displayed on cell surfaces
that are responsible for lymphocyte recognition
and "antigen presentation".
• The MHC molecules control the immune
response through recognition of "self" and "nonself" and, consequently, serve as targets in
transplantation rejection.
Dr. Mohamed Farouk Elshal
MAJOR HISTOCOMPATIBILITY
COMPLEX
• The Class I and Class II MHC molecules
belong to a group of molecules known as
the Immunoglobulin Supergene Family,
which includes immunoglobulins
• Both types of MHC proteins are important
to T cell activation
Dr. Mohamed Farouk Elshal
Class I MHC Proteins
• Class I MHC proteins
– Always recognized by CD8 cytotoxic T cells
(CTL)
– Display peptides from endogenous antigens
• Endogenous antigens are:
– Degraded by proteases and enter the
endoplasmic reticulum
– Loaded onto class I MHC molecules
– Displayed on the cell surface in association
with a class I MHC molecule
Dr. Mohamed Farouk Elshal
Class II MHC Proteins
• Class II MHC proteins are found only on
mature B cells, some T cells, and antigenpresenting cells
• Loaded Class II MHC molecules then
migrate to the cell membrane and display
antigenic peptide for recognition by CD4 T
helper cells (Th-cells).
Dr. Mohamed Farouk Elshal
MHC Proteins and antigen recognition
Dr. Mohamed Farouk Elshal
T Cells Only Recognize Antigen Associated with
MHC Molecules on Cell Surfaces
Dr. Mohamed Farouk Elshal
Cell Mediated Immunity
• Immune responsive cells can be divided
into five groups based on the presence of
specific surface components and function
into:
1. lymphocytes (B-cells, and T-cells).
2. Accessory cells (Macrophages and other antigenpresenting cells),
3. Killer cells (NK and K cells), and
4. Mast cells.
Dr. Mohamed Farouk Elshal
B-lymphocytes
Surface components
• Surface immunoglobulin (Ag recognition)
• Immunoglobulin Fc receptor
• Class II Major Histocompatability Complex
(MHC) molecule (Ag presentation)
Function
• Direct antigen recognition
• Differentiation into antibody-producing plasma
cells
• Antigen presentation within Class II MHC
Dr. Mohamed Farouk Elshal
T-lymphocytes
Surface components
• CD3 molecule
Function
• T-cell receptor (TCR, Ag recognition)
• Involved in both humoral and cellmediated responses
Dr. Mohamed Farouk Elshal
T-lymphocytes
– T cells are key cellular component of immunity.
– T cells have an antigen receptor that recognizes
and reacts to a specific antigen (T cell receptor).
– T cell receptor only recognize antigens combined
with major histocompatability (MHC) proteins on
the surface of cells.
• MHC Class I: Found on all cells.
• MHC Class II: Found on phagocytes.
– Clonal selection increases number of T cells.
Dr. Mohamed Farouk Elshal
Dr. Mohamed Farouk Elshal
Major Types of T Cells
Helper T-cells (TH)
Surface components
• CD4 molecule
Function
• Recognizes antigen presented within
Class II MHC
• Promotes differentiation of B-cells and
cytotoxic T-cells
• Activates macrophages
• Stimulate B cells to produce antibodies.
Dr. Mohamed Farouk Elshal
Central Role of Helper T Cells
Dr. Mohamed Farouk Elshal
Suppressor T-cells (TS)
Surface components
• CD8 molecule
Function
• Downregulates the activities of other cells
Dr. Mohamed Farouk Elshal
Cytotoxic T-cells (CTL)
Surface components
• CD8 molecule
Function
• Recognizes antigen presented within Class I
MHC
• Release protein called perforin which forms a
pore in target cell, causing lysis of infected cells.
• Undergo apoptosis when stimulating antigen is
gone.
Dr. Mohamed Farouk Elshal
Cytotoxic T Cells Lyse Infected Cells
Dr. Mohamed Farouk Elshal
Types of T cells (Continued)
• 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.
• T Suppressor (Ts) Cells: May shut down
immune response.
Dr. Mohamed Farouk Elshal
Nonspecific Cellular Components
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.
• Surface components
– Variable
• Function
– Direct cell killing
– Kills variety of target cells (e.g. tumor cells, virusinfected cells, transplanted cells)
Dr. Mohamed Farouk Elshal
Nonspecific Cellular Components
Polymorphonuclear cells (PMNs)
• Surface components
– Immunoglobulin Fc receptor
– Complement component C3b receptor
• Function
– Bind Fc portion of immunoglobulin (enhances
phagocytosis)
– Bind complement component C3b (enhances
phagocytosis)
Dr. Mohamed Farouk Elshal
Nonspecific Cellular Components
Macrophages
• Surface components
–
–
–
–
Variable
Immunoglobulin Fc receptor
Complement component C3b receptor
Class II MHC molecule
• Function
–
–
–
–
Bind Fc portion of immunoglobulin (enhances phagocytosis)
Bind complement component C3b (enhances phagocytosis)
Antigen presentation within Class II MHC
Secrete IL-1 (macrokine) promoting T-cell differentiation and
proliferation
– Can be "activated" by T-cell lymphokines
Dr. Mohamed Farouk Elshal
Nonspecific Cellular Components
Dendritic cells
• Surface components
– Class II MHC molecule
• Function
– Antigen presentation within Class II MHC
Dr. Mohamed Farouk Elshal
Nonspecific Cellular Components
Mast cells
• Surface components
– High affinity IgE Fc receptors
• Function
– Bind IgE and initiate allergic responses by
release of histamine
Dr. Mohamed Farouk Elshal
Relationship Between Cell-Mediated
and Humoral Immunity
1. Antibody Production
T-Dependent Antigens:
– 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.
Dr. Mohamed Farouk Elshal
Humoral Response to T Dependent
Antigens
Dr. Mohamed Farouk Elshal
The Pathway of Specific Immune
Response
Step 1
Pathogens eaten by Macrophage
Step 2
Displays portion of Pathogen
on surface
Step 3
Pathogens
Helper-T cell recognizes
Pathogen
Dr. Mohamed Farouk Elshal
Activates B- Cell
Activates Cytotoxic
T- Cell
Memory T-Cell
Memory B-Cell
Antibodies
Kills Infected Cells
Dr. Mohamed Farouk Elshal
Immune Response Explained
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
Antigen infects cells.
Macrophage ingests antigen and displays portion on its surface.
Helper T- Cell recognizes antigen on the surface of the
macrophage and becomes active.
Active Helper T-Cell activates Cytotoxic T-Cells and B-Cells.
Cytotoxic T-Cells divide into Active Cytotoxic T-cells and Memory
T – Cells.
Active Cytotoxic T-Cells kill infected cells.
At the same time, B-Cells divide into Plasma Cells and Memory
B- Cells.
Plasma cells produce antibodies that deactivate pathogen.
Memory T and Memory B cells remain in the body to speed up the
response if the same antigen reappears.
Supressor T-Cells stop the immune response when all antigens
have been destroyed.
Dr. Mohamed Farouk Elshal
Immune Response Summary
Displays copy of antigen
on surface of cell
Antigen
Macrophage
Antibody Immunity
Helper T - Cell
Cellular Immunity
Active Cytotoxic T-Cell
Kills Infected Cells
Memory T- Cell
Active B - Cell
Plasma Cell
Memory B-Cell
Antibodies
Deactivates Antigens
Dr. Mohamed Farouk Elshal
Overview of the Immune Response
Dr. Mohamed Farouk Elshal
Primary .vs. Secondary Immune
Response
• Primary Immune Response
– This is a response to an invader the First time the
invader infects the body.
• No measurable immune response for first few days.
• Next 10 – 15 days antibody production grows steadily
• Secondary Immune Response
– A more rapid response to an invader the 2nd time it
invades the body.
• Antibody production increases dramatically and in a much
shorter time period..
Dr. Mohamed Farouk Elshal
Primary .vs. Secondary Immune
Response
Dr. Mohamed Farouk Elshal
SUMMARY
1. Protective immunity against microbes is mediated by the
early response of innate immunity and the later response of
adaptive immunity.
2. Innate immune responses are initiated by recognition of
common microbial structures by
- Provide the first line of host defense
- Activate and regulate the adaptive immunity
3. Adaptive immune responses are initiated by recognition of
foreign antigens by specific lymphocytes.
- Provide more potent, specific (Ag), & broad protection
- Develop immune memory for next exposure
- Feedback regulate innate immunity
Dr. Mohamed Farouk Elshal
Failure of the immune system
Ineffective response
-Immunodeficiency
Overactive response
-Hypersensitivity
Auto-reactive response
-Autoimmunity
Dr. Mohamed Farouk Elshal
Autoimmune Disease
• Autoimmune diseases are diseases where the immune
system begins to attack itself.
– Ex:
• Rheumatoid Arthritis – crippling disease of the
joints.
• Lupus – disease of blood and organs.
• Multiple Sclerosis – disease of nervous system
• Cause(s):
unknown
• Cures/Treatments: No known cures. Usually treated
with drugs.
Dr. Mohamed Farouk Elshal
Allergies
Allergy
- An exaggerated response by the immune system to an allergen.
Allergen: a normally harmless substance that causes an allergic
reaction.
ex: dust, pollen, mould, food, insect stings
Types of Allergic reactions
There are two types of allergic reactions.
a. Immediate – occurs within seconds and normally lasts for about
30 mins.
b. Delayed – takes longer to react and can last for a much longer
time.
Dr. Mohamed Farouk Elshal
What happens during an allergic
reaction?
• During an allergic reaction antibodies cause histamines to be
released from certain cells.
Histamines cause:
a. Swelling of tissues
b. Release of fluids (runny noses and eyes)
c. muscle spasms (some cases)
Anaphylaxis or anaphylactic shock:
This is the sudden and severe allergic reaction to a substance that
can cause death.
Treatments for Allergies
1.Avoidance of material – especially food.
2.Epinephrine – “epi – pen”
3.Antihistamines -- benadryl
Dr. Mohamed Farouk Elshal