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inmunohematología

    Jul 20, 2012
The Immune System - includes all parts of
 the body that help in the recognition and
 destruction of foreign materials. White
 blood cells, phagocytes and lymphocytes,
 bone marrow, lymph nodes, tonsils,
 thymus, and your spleen are all part of the
 immune system.
• First-Line Defenses /Innate Immune System-
  The body's first line of defense against
  pathogens uses mostly physical and chemical
  barriers such as
• Skin – acts as a barrier to invasion
• Sweat – has chemicals which can kill different
  pathogens.
• Tears - have lysozyme which has powerful
  digestive abilities that render antigens harmless.
• Saliva – also has lysozyme.
• Mucus - can trap pathogens, which are then
  sneezed, coughed, washed away, or destroyed
  by chemicals.
• Stomach Acid – destroys pathogens
• Second-Line Defenses - If a pathogen is
  able to get past the body's first line of
  defense, and an infection starts, the body
  can rely on it's second line of defense. This
  will result in what is called an……….
• Inflammatory response causes
• Redness - due to capillary dilation
  resulting in increased blood flow

• Heat - due to capillary dilation resulting in
  increased blood flow

• Swelling – due to passage of plasma from
  the blood stream into the damaged tissue

• Pain – due mainly to tissue destruction
  and, to a lesser extent, swelling.
• Third-Line Defenses - Sometimes the second line
  of defense is still not enough and the pathogen is
  then heading for the body's last line of defense, the
  immune system.

• The immune system recognizes, attacks, destroys,
  and remembers each pathogen that enters the
  body. It does this by making specialized cells
  and antibodies that render the pathogens harmless.

• Unlike the first line and second line defense the
  immune system differentiates among pathogens.

• For each type of pathogen, the immune system
  produces cells that are specific for that particular
  pathogen.
• An antibody is a protein produced in
  response to an antigen.
• Antigens are macromolecules that elicit an
  immune response in the body. The most
  common antigens are proteins and
  polysaccharides.
• Antigens can enter the body from the environment.
  These include

• inhaled macromolecules (e.g., proteins on cat hairs
  that can trigger an attack of asthma in susceptible
  people)

• ingested macromolecules (e.g., shellfish proteins that
  trigger an allergic response in susceptible people)

• molecules that are introduced beneath the skin (e.g.,
  on a splinter or in an injected vaccine)
• antigens can be generated within the cells
  of the body. These include

• proteins encoded by the genes of viruses
  that have infected a cell

• aberrant proteins that are encoded by
  mutant genes; such as mutated genes in
  cancer cells
• Lymph is a milky body fluid that contains
  a type of white blood cells, called
  lymphocytes, along with proteins and fats.




• Lymph seeps outside the blood vessels in
  spaces of body tissues and is stored in the
  lymphatic system to flow back into the
  bloodstream.
• Through the flow of blood in and out of
  arteries, and into the veins, and through the
  lymph nodes and into the lymph, the body is
  able to eliminate the products of cellular
  breakdown and bacterial invasion.
• There are more than 100 tiny, oval
  structures called lymph nodes. These are
  mainly in the neck, groin and armpits, but
  are scattered all along the lymph vessels.

• They act as barriers to infection by filtering
  out and destroying toxins and germs. The
  largest body of lymphoid tissue in the
  human body is the spleen.
• As the lymph flows through lymph vessels,
  it passes through lymph nodes.

• White blood cells called macrophages
  trap and engulf cell debris and pathogens.
  Other white blood cells, called

• Lymphocytes - are a type of white blood
  cell capable of producing a
  specific immune response to unique
  antigens. They produce antibodies which
  are chemicals that mark pathogens for
  destruction.
The scanning electron micrograph above, shows a human
macrophage (gray) approaching a chain of Streptococcus
pyogenes (yellow). Riding atop the macrophage is a spherical
lymphocyte. Both macrophages and lymphocytes can be
found near an infection, and the interaction between these
cells is important in eliminating infection.
• Once a white cell has left the blood vessel and
  migrated to the enemy, the next job is to EAT the
  microbe.

• The macrophage is a large phagocyte. A
  phagocyte is an eating cell (phago = "eating",
  cyte = "cell") which engulfs invaders.
• Immunity is the result of the action of two types lymphocytes,
  the B lymphocytes and the T lymphocytes.

• B cells produce antibodies that are secreted into the blood
  and lymph.

• T cells attack the cells that have antigens that they
  recognize.
 Killer T Cells (lymphocytes) recognize surface
markers on other cells labeled for destruction. They,
Killer T Cells, help to keep virus-infected or malignant
cells in check.

 Here, a smaller Killer T Cell (arrow) is attacking and
killing a much larger flu virus-infected target. The
sequence represents 30 minutes elapsed time.
• It has been estimated that during our lifetime, we
  will encounter a million foreign antigens capable of
  causing disease, and our bodies need the same
  amount of lymphocytes to defend against them.

• There will always be a different type of lymphocyte
  for each possible antigen.
•Active Immunity occurs when when
one makes his/her own antibodies. This
type of immunity is long term.

•Getting the disease : If you get an
infectious disease (like Chicken
Pox), often times, that stimulates the
production of MEMORY cells which
are then stored to prevent the
infection in the future.
Vaccination: A vaccination is an injection
of a weakened form of the actual antigen
that causes the disease. The injection is
too weak to make you sick, but your B
lymphocytes will recognize the antigen
and react as if it were the "real thing".
Thus, you produce MEMORY cells for
long term immunity.
Passive Immunity occurs when the
antibodies come from some other source.
This type of immunity is short term.

Breastmilk : Milk
from a mother's
breast contains
antibodies. The
baby is acquiring
passive
immunity. These
antibodies will
only last several
weeks.
Gamma Globulin: A Gamma Globulin shot is
 purely an injection of antibodies to provide
 temporary immunity. You might receive an
 Gamma Globulin shot if you travel outside
 of the country.
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.
Duality of Immune System
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.
Antibodies are Produced by B
        Lymphocytes
Antibodies are Proteins that Recognize Specific
                   Antigens
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
Cell Mediated Immunity is Carried Out by T
               Lymphocytes
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.
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.
Epitopes: Antigen Regions that
    Interact with Antibodies
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.
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.
Antibody Structure
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.
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.
Clonal Selection of B Cells is
Caused by Antigenic Stimulation
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.
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.
Consequences of Antibody
        Binding
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.
Consequences of Antibody
        Binding
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.
Antibody Response After Exposure to
             Antigen
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.
T Cells and Cell Mediated Immunity
Cellular Components of Immunity:
– 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.
T Cells Only Recognize Antigen
Associated with MHC Molecules on
          Cell Surfaces
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.
Central Role of Helper T Cells
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.
Cytotoxic T Cells Lyse Infected
             Cells
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:
  – 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
Humoral Response to T Dependent
           Antigens
Humoral Response to 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
Destruction of Large Parasites by
             ADCC
Overview of the Immune
       Response

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Inmuno 1

  • 1. inmunohematología Jul 20, 2012
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  • 23. The Immune System - includes all parts of the body that help in the recognition and destruction of foreign materials. White blood cells, phagocytes and lymphocytes, bone marrow, lymph nodes, tonsils, thymus, and your spleen are all part of the immune system.
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  • 25. • First-Line Defenses /Innate Immune System- The body's first line of defense against pathogens uses mostly physical and chemical barriers such as • Skin – acts as a barrier to invasion • Sweat – has chemicals which can kill different pathogens. • Tears - have lysozyme which has powerful digestive abilities that render antigens harmless. • Saliva – also has lysozyme. • Mucus - can trap pathogens, which are then sneezed, coughed, washed away, or destroyed by chemicals. • Stomach Acid – destroys pathogens
  • 26.
  • 27. • Second-Line Defenses - If a pathogen is able to get past the body's first line of defense, and an infection starts, the body can rely on it's second line of defense. This will result in what is called an……….
  • 28. • Inflammatory response causes • Redness - due to capillary dilation resulting in increased blood flow • Heat - due to capillary dilation resulting in increased blood flow • Swelling – due to passage of plasma from the blood stream into the damaged tissue • Pain – due mainly to tissue destruction and, to a lesser extent, swelling.
  • 29.
  • 30. • Third-Line Defenses - Sometimes the second line of defense is still not enough and the pathogen is then heading for the body's last line of defense, the immune system. • The immune system recognizes, attacks, destroys, and remembers each pathogen that enters the body. It does this by making specialized cells and antibodies that render the pathogens harmless. • Unlike the first line and second line defense the immune system differentiates among pathogens. • For each type of pathogen, the immune system produces cells that are specific for that particular pathogen.
  • 31. • An antibody is a protein produced in response to an antigen. • Antigens are macromolecules that elicit an immune response in the body. The most common antigens are proteins and polysaccharides.
  • 32. • Antigens can enter the body from the environment. These include • inhaled macromolecules (e.g., proteins on cat hairs that can trigger an attack of asthma in susceptible people) • ingested macromolecules (e.g., shellfish proteins that trigger an allergic response in susceptible people) • molecules that are introduced beneath the skin (e.g., on a splinter or in an injected vaccine)
  • 33. • antigens can be generated within the cells of the body. These include • proteins encoded by the genes of viruses that have infected a cell • aberrant proteins that are encoded by mutant genes; such as mutated genes in cancer cells
  • 34. • Lymph is a milky body fluid that contains a type of white blood cells, called lymphocytes, along with proteins and fats. • Lymph seeps outside the blood vessels in spaces of body tissues and is stored in the lymphatic system to flow back into the bloodstream.
  • 35. • Through the flow of blood in and out of arteries, and into the veins, and through the lymph nodes and into the lymph, the body is able to eliminate the products of cellular breakdown and bacterial invasion.
  • 36. • There are more than 100 tiny, oval structures called lymph nodes. These are mainly in the neck, groin and armpits, but are scattered all along the lymph vessels. • They act as barriers to infection by filtering out and destroying toxins and germs. The largest body of lymphoid tissue in the human body is the spleen.
  • 37.
  • 38. • As the lymph flows through lymph vessels, it passes through lymph nodes. • White blood cells called macrophages trap and engulf cell debris and pathogens. Other white blood cells, called • Lymphocytes - are a type of white blood cell capable of producing a specific immune response to unique antigens. They produce antibodies which are chemicals that mark pathogens for destruction.
  • 39. The scanning electron micrograph above, shows a human macrophage (gray) approaching a chain of Streptococcus pyogenes (yellow). Riding atop the macrophage is a spherical lymphocyte. Both macrophages and lymphocytes can be found near an infection, and the interaction between these cells is important in eliminating infection.
  • 40. • Once a white cell has left the blood vessel and migrated to the enemy, the next job is to EAT the microbe. • The macrophage is a large phagocyte. A phagocyte is an eating cell (phago = "eating", cyte = "cell") which engulfs invaders.
  • 41. • Immunity is the result of the action of two types lymphocytes, the B lymphocytes and the T lymphocytes. • B cells produce antibodies that are secreted into the blood and lymph. • T cells attack the cells that have antigens that they recognize.
  • 42.  Killer T Cells (lymphocytes) recognize surface markers on other cells labeled for destruction. They, Killer T Cells, help to keep virus-infected or malignant cells in check.  Here, a smaller Killer T Cell (arrow) is attacking and killing a much larger flu virus-infected target. The sequence represents 30 minutes elapsed time.
  • 43. • It has been estimated that during our lifetime, we will encounter a million foreign antigens capable of causing disease, and our bodies need the same amount of lymphocytes to defend against them. • There will always be a different type of lymphocyte for each possible antigen.
  • 44. •Active Immunity occurs when when one makes his/her own antibodies. This type of immunity is long term. •Getting the disease : If you get an infectious disease (like Chicken Pox), often times, that stimulates the production of MEMORY cells which are then stored to prevent the infection in the future.
  • 45. Vaccination: A vaccination is an injection of a weakened form of the actual antigen that causes the disease. The injection is too weak to make you sick, but your B lymphocytes will recognize the antigen and react as if it were the "real thing". Thus, you produce MEMORY cells for long term immunity.
  • 46. Passive Immunity occurs when the antibodies come from some other source. This type of immunity is short term. Breastmilk : Milk from a mother's breast contains antibodies. The baby is acquiring passive immunity. These antibodies will only last several weeks.
  • 47. Gamma Globulin: A Gamma Globulin shot is purely an injection of antibodies to provide temporary immunity. You might receive an Gamma Globulin shot if you travel outside of the country.
  • 48. 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.
  • 49. 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.
  • 50. Duality of Immune System 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.
  • 51. Antibodies are Produced by B Lymphocytes
  • 52. Antibodies are Proteins that Recognize Specific Antigens
  • 53. 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
  • 54. Cell Mediated Immunity is Carried Out by T Lymphocytes
  • 55. 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.
  • 56. 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.
  • 57. Epitopes: Antigen Regions that Interact with Antibodies
  • 58. 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.
  • 59. 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.
  • 61. 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.
  • 62. 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.
  • 63. 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.
  • 64. 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.
  • 65. 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.
  • 66. 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.
  • 67. Clonal Selection of B Cells is Caused by Antigenic Stimulation
  • 68. 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.
  • 69. 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.
  • 70. 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.
  • 72. 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.
  • 74. 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.
  • 75. 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.
  • 76. Antibody Response After Exposure to Antigen
  • 77. 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.
  • 78. T Cells and Cell Mediated Immunity Cellular Components of Immunity: – 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.
  • 79. T Cells Only Recognize Antigen Associated with MHC Molecules on Cell Surfaces
  • 80. 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.
  • 81. Central Role of Helper T Cells
  • 82. 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.
  • 83. Cytotoxic T Cells Lyse Infected Cells
  • 84. 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.
  • 85. 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.
  • 86. 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
  • 87. Humoral Response to T Dependent Antigens
  • 88. Humoral Response to T Dependent Antigens
  • 89. 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
  • 90. Destruction of Large Parasites by ADCC
  • 91. Overview of the Immune Response