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Principles of immunity
Requirements for protective immune
                   response


• be able to detect foreign object
• prevent host from being killed by foreign
  object
• limit replication of foreign object in host
• limit damage to host by foreign object and
  immune system
Types of Infectious Agents


• 5 groups
     1. Viruses
     2. Bacteria
     3. Fungi
     4. Protozoans
     5. Helminths
Anatomic Barriers

• External/First line of defenses
• Epithelial Barrier
   – Skin
   – Mucous membranes
   – Conjunctivae, GI, resp, urogenital
     tracts
• secretions (saliva, tears, urine,
   mucus)
   – wash/trap/inhibit growth
• Cilia
   – (Mucociliary clearance)
Physiological Barriers

• Defecation and Vomiting-expel microbes
• pH‐Stomach, vagina, and skin
• Normal microflora of GI tract, skin
• Chemical Mediators
  – Hydrolytic enzymes of Saliva
  – Lysozyme in tears
• Inflammatory Barriers
•   injured cells release a protein called HISTAMINE, which starts
    the a series of changes called the Inflammatory Response
    Histamine increases blood flow to the injured area and
    increases the permeability of the surrounding capillaries, as a
    result, Fluid and White Blood Cells (WBC) leak from blood
    vessels into nearby tissue.
• fever
– Fever is an abnormally high body temperature. It
  occurs during infection and inflammation. Elevated
  temp. intensifies effects of interferons, inhibits growth
  of microbes and speeds up body reactions that aid
  repair.
organism

use preformed      produce specific
components to      components
non-specifically   directed against
clear the agent    the agent
Components of the Immune
         Components of the Immune
                System
                 System



              Nonspecific           Specific
                innate              adaptive

      Humorall       Cellular   Humoral       Cellular


                macrophages,
                                                 T cells; other
interferon,      neutrophils     antibodies
                                                 effectors cells
                   NK cell
Characteristics of Innate and Adaptive
       Characteristics of Innate and Adaptive
                      Immunity
                       Immunity

Innate Immunity             Adaptive Immunity

Antigen independent           Antigen dependent

No time lag                  A lag period

Not antigen specific          Antigen specific

 No Immunologic               Development
  memory
                              of memory
Innate or Nonspecific Immunity

    Cellular
                       Humoral
  Neutrophiles
 Macrophages           (interferon)
Natural killer cells
Non specific cellular
• Macrophages
• Neutrophiles
• Natural killer cells
NEUTROPHIL
• The most common
  Phagocyte, 50 to 70
  percent of the White
  Blood Cells in the body.
• circulate freely through
  blood vessels.
• They then engulf and
  destroy any pathogens
  they encounter
MACROPHAGE (big eaters)




•   they consume and destroy any pathogens they
    encounter,
•   Macrophages present pathogen antigen to cells
NATURAL KILLER CELLS
•   are large white blood cells
•   attack cells that have been
    infected by pathogens, Not the
    Pathogen Themselves.
•   They are particularly effective in
    killing Cancer Cells and Cells
    Infected with Viruses.
•   A Natural Killer Cell punctures
    the cell membrane of its target
    cell, allowing water to rush into
    the cell, causing the cell to burst
•   NK cells are Activated by IFN-
    alpha/beta
Immunity1
Non specific humoral immunity
IFN
• Interferons are proteins produced by cells infected
  with viruses,
• protect other cells against virus infection or
  decrease drastically the virus yield from such
  cells.
• Interferon itself is not directly the anti-viral agent,
  but it is the inducer of one or many anti-viral
  mechanisms
Activities of interferon
                      Antiviral actions
Interferon initiate an antiviral state in cells
Interferons block viral protein synthesis
Inferons inhibit cell growth
               Immunomodulatory actions
Interferons-alpha and IFN-beta activate NK cells
Interferon activates macrophages
Interferon regulate the activities of T cells
                        Other actions
Interferons regulate inflammatory processes
Interferon regulate tumor growth
Mechanism of action
• Release from an initial infected cell occurs
• IFN binds to a specific cell surface receptor on an
  other cell
• IFN induces the “antiviral state” :
• Inhibition of viral and cellular protein synthesis
  occurs
Interferon “priming” Interferons are produced in response to
a viral infection and spread to the nearby cells where they activate
interferon-stimulated genes (ISGs), which are responsible for the
establishment of an “antiviral state” by preventing viral replication and
also alert the immune system.
Immunity1
Immunity1
The Complement System
       heat-labile antibacterial substance in immune serum

                            kills bacteria
non immune (normal) serum……………no
immune serum……………………….….. Yes
heated* immune serum…………………. no
heated immune serum plus
non-immune serum………………….…. yes
     560C for 30 minutes or 600C for 5 minutes
complements

• Conclusion: Two components are needed for
  bacterial inactivation: a heat-stable immune
  component (antibody)
• and a heat-labile non immune component
  (complement).
But if all that is not enough …
IF A PATHOGEN IS ABLE TO GET PAST THE
   BODY'S NONSPECIFIC DEFENSES, THE IMMUNE
   SYSTEM REACTS WITH A SERIES OF SPECIFIC
   DEFENSES THAT ATTACK THE DISEASE
   CAUSING AGENT.


This is called the IMMUNE RESPONSE
A SUBSTANCE THAT TRIGGERS THE SPECIFIC DEFENSES
   OF THE IMMUNE SYSTEM IS KNOWN AS AN ANTIGEN.

AN ANTIGEN IS A SUBSTANCE THAT A MACROPHAGE (WBC)
  IDENTIFIES AS NOT BELONGING TO THE BODY.
Specific (adaptive) immunity
  Antigen Specific: Immune response specific to
            component of pathogen




Humoral        Active/passive Cellular
antibodies                      T cells
Sites Occupied By Pathogens

• Extracellular
   - site of most bacteria
   - elicits antibody (humoral) response

• Intracellular
    - site of viruses, ,some bacteria,
      fungi, rickettsiae and protozoa
    - elicits cell-mediated response
HUMORAL IMMUNITY

• The production of antibody molecules in
  response to an antigen; mediated by B-
  lymphocytes.
Humoral specific immunity
Immunity1
Immunity1
Immunity1
This message activates T-helper cells and triggers the
immune response. Once the T cell has read the antigens, it
will send out messages to activate other cells, known as B
cells
Immunity1
The activated B cell will then produce millions of antibodies
The antibody is a protein that will bind to an antigen. Each
antibody is unique and specific; for example, a measles
antibody will only bind to a measles virus. We produce
antibodies because, given the high concentration of infectious
agent that is needed to cause disease, our macrophages could
not go after the invaders alone. However, antibodies can
outnumber the invaders and help us get rid of them.
How do the antibodies bind to the infectious agent? The
antibody resembles the mirror image of the antigen (like a key
and a lock), usually providing such a close fit that, if they bump
into each other, the antibody will grab the antigen and hang on
Once an antibody has "caught" an invader, it will broadcast a
signal that says "eat me and
A macrophage will in turn get the
message and will devour the
antibody-antigen complex and rid
the body of the infectious agent
Eventually, as this process continues,
the number of infectious agents will
decrease and the body will need to stop
the battle. However, all the cells are
still activated and the immune system
needs to put them to rest. Another kind
of T cell, the T-suppressor cell (or T8
cell), will send out messages to the
other cells and "de-activate" them).
Without the T-suppressor cells, the
body would continue trying to fight off
a disease that no longer exists (and
eventually would end up fighting its
own cells).
Immunity1
Antibodies
• also called immunoglobulins or Igs
• constitute the gamma globulin part of the blood
  proteins.
• They are soluble proteins secreted by the plasma
  offspring (clones) of primed B cells.
• The antibodies inactivate antigens by,
   – (a) complement fixation (proteins attach to antigen surface
     and cause holes to form, i.e., cell lysis),
   – (b) neutralization (binding to specific sites to prevent
     attachment—this is the same as taking their parking space),
   – (c) agglutination (clumping),
   – (d) precipitation (forcing insolubility and settling out of
     solution),
Cell mediated immunity


• Mediated by T lymphocytes.
• An immune response against intracellular
  microbes,such as viruses and some bacteria, survive
  and proliferate inside phagocytes and other host
  cells, where they are inaccessible to circulating
  antibodies.
• Promotes destruction of microbes within phagocytes
  or killing of infected cells.
CELL-MEDIATED IMMUNITY

• The production of cytotoxic T-lymphocytes
  and cytokines in response to an antigen;
  mediated by T-lymphocytes.
T cell
• Cytotoxic or killer T cells (CD8+)
   – do their work by releasing lymphotoxins, which cause cell
     lysis.
• Helper T cells (CD4+)
   – serve as managers, directing the immune response. They
     secrete chemicals called lymphokines that stimulate
     cytotoxic T cells and B cells to grow and divide, attract
     neutrophils, and enhance the ability of macrophages to
     engulf and destroy microbes.
• Suppressor T cells
   – inhibit the production of cytotoxic T cells once they are
     unneeded, lest they cause more damage than necessary.
• Memory T cells
   – are programmed to recognize and respond to a pathogen
     once it has invaded and been repelled.
CYTOKINES
• A wide variety of intercellular regulatory
  proteins produced by many different cells in
  the body which ultimately control every
  aspect of body defense.
• Cytokines activate and deactivate phagocytes
  and immune defense cells,
• increase or decrease the functions of the
  different immune defense cells, and promote
  or inhibit a variety of nonspecific body
  defenses.
Cellular Immunity
                                        Infected cells
            Pathogen
            engulfed by                          Perforin
                                 Foreign
                                 antigen                        Infected cell lyses

          Macrophage                         Cytotoxic T cell
Displays antigens
on surface and                              Attacks infected
                                            cell
stimulates T cell



                               Stimulates
               Helper T cell
                                      Cytotoxic T cell
Immunity1
Immunity1

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Immunity1

  • 2. Requirements for protective immune response • be able to detect foreign object • prevent host from being killed by foreign object • limit replication of foreign object in host • limit damage to host by foreign object and immune system
  • 3. Types of Infectious Agents • 5 groups 1. Viruses 2. Bacteria 3. Fungi 4. Protozoans 5. Helminths
  • 4. Anatomic Barriers • External/First line of defenses • Epithelial Barrier – Skin – Mucous membranes – Conjunctivae, GI, resp, urogenital tracts • secretions (saliva, tears, urine, mucus) – wash/trap/inhibit growth • Cilia – (Mucociliary clearance)
  • 5. Physiological Barriers • Defecation and Vomiting-expel microbes • pH‐Stomach, vagina, and skin • Normal microflora of GI tract, skin • Chemical Mediators – Hydrolytic enzymes of Saliva – Lysozyme in tears
  • 6. • Inflammatory Barriers • injured cells release a protein called HISTAMINE, which starts the a series of changes called the Inflammatory Response Histamine increases blood flow to the injured area and increases the permeability of the surrounding capillaries, as a result, Fluid and White Blood Cells (WBC) leak from blood vessels into nearby tissue. • fever – Fever is an abnormally high body temperature. It occurs during infection and inflammation. Elevated temp. intensifies effects of interferons, inhibits growth of microbes and speeds up body reactions that aid repair.
  • 7. organism use preformed produce specific components to components non-specifically directed against clear the agent the agent
  • 8. Components of the Immune Components of the Immune System System Nonspecific Specific innate adaptive Humorall Cellular Humoral Cellular macrophages, T cells; other interferon, neutrophils antibodies effectors cells NK cell
  • 9. Characteristics of Innate and Adaptive Characteristics of Innate and Adaptive Immunity Immunity Innate Immunity Adaptive Immunity Antigen independent Antigen dependent No time lag A lag period Not antigen specific Antigen specific No Immunologic Development memory of memory
  • 10. Innate or Nonspecific Immunity Cellular Humoral Neutrophiles Macrophages (interferon) Natural killer cells
  • 11. Non specific cellular • Macrophages • Neutrophiles • Natural killer cells
  • 12. NEUTROPHIL • The most common Phagocyte, 50 to 70 percent of the White Blood Cells in the body. • circulate freely through blood vessels. • They then engulf and destroy any pathogens they encounter
  • 13. MACROPHAGE (big eaters) • they consume and destroy any pathogens they encounter, • Macrophages present pathogen antigen to cells
  • 14. NATURAL KILLER CELLS • are large white blood cells • attack cells that have been infected by pathogens, Not the Pathogen Themselves. • They are particularly effective in killing Cancer Cells and Cells Infected with Viruses. • A Natural Killer Cell punctures the cell membrane of its target cell, allowing water to rush into the cell, causing the cell to burst • NK cells are Activated by IFN- alpha/beta
  • 17. IFN • Interferons are proteins produced by cells infected with viruses, • protect other cells against virus infection or decrease drastically the virus yield from such cells. • Interferon itself is not directly the anti-viral agent, but it is the inducer of one or many anti-viral mechanisms
  • 18. Activities of interferon Antiviral actions Interferon initiate an antiviral state in cells Interferons block viral protein synthesis Inferons inhibit cell growth Immunomodulatory actions Interferons-alpha and IFN-beta activate NK cells Interferon activates macrophages Interferon regulate the activities of T cells Other actions Interferons regulate inflammatory processes Interferon regulate tumor growth
  • 19. Mechanism of action • Release from an initial infected cell occurs • IFN binds to a specific cell surface receptor on an other cell • IFN induces the “antiviral state” : • Inhibition of viral and cellular protein synthesis occurs
  • 20. Interferon “priming” Interferons are produced in response to a viral infection and spread to the nearby cells where they activate interferon-stimulated genes (ISGs), which are responsible for the establishment of an “antiviral state” by preventing viral replication and also alert the immune system.
  • 23. The Complement System heat-labile antibacterial substance in immune serum kills bacteria non immune (normal) serum……………no immune serum……………………….….. Yes heated* immune serum…………………. no heated immune serum plus non-immune serum………………….…. yes 560C for 30 minutes or 600C for 5 minutes
  • 24. complements • Conclusion: Two components are needed for bacterial inactivation: a heat-stable immune component (antibody) • and a heat-labile non immune component (complement).
  • 25. But if all that is not enough … IF A PATHOGEN IS ABLE TO GET PAST THE BODY'S NONSPECIFIC DEFENSES, THE IMMUNE SYSTEM REACTS WITH A SERIES OF SPECIFIC DEFENSES THAT ATTACK THE DISEASE CAUSING AGENT. This is called the IMMUNE RESPONSE A SUBSTANCE THAT TRIGGERS THE SPECIFIC DEFENSES OF THE IMMUNE SYSTEM IS KNOWN AS AN ANTIGEN. AN ANTIGEN IS A SUBSTANCE THAT A MACROPHAGE (WBC) IDENTIFIES AS NOT BELONGING TO THE BODY.
  • 26. Specific (adaptive) immunity Antigen Specific: Immune response specific to component of pathogen Humoral Active/passive Cellular antibodies T cells
  • 27. Sites Occupied By Pathogens • Extracellular - site of most bacteria - elicits antibody (humoral) response • Intracellular - site of viruses, ,some bacteria, fungi, rickettsiae and protozoa - elicits cell-mediated response
  • 28. HUMORAL IMMUNITY • The production of antibody molecules in response to an antigen; mediated by B- lymphocytes.
  • 33. This message activates T-helper cells and triggers the immune response. Once the T cell has read the antigens, it will send out messages to activate other cells, known as B cells
  • 35. The activated B cell will then produce millions of antibodies The antibody is a protein that will bind to an antigen. Each antibody is unique and specific; for example, a measles antibody will only bind to a measles virus. We produce antibodies because, given the high concentration of infectious agent that is needed to cause disease, our macrophages could not go after the invaders alone. However, antibodies can outnumber the invaders and help us get rid of them.
  • 36. How do the antibodies bind to the infectious agent? The antibody resembles the mirror image of the antigen (like a key and a lock), usually providing such a close fit that, if they bump into each other, the antibody will grab the antigen and hang on Once an antibody has "caught" an invader, it will broadcast a signal that says "eat me and
  • 37. A macrophage will in turn get the message and will devour the antibody-antigen complex and rid the body of the infectious agent
  • 38. Eventually, as this process continues, the number of infectious agents will decrease and the body will need to stop the battle. However, all the cells are still activated and the immune system needs to put them to rest. Another kind of T cell, the T-suppressor cell (or T8 cell), will send out messages to the other cells and "de-activate" them). Without the T-suppressor cells, the body would continue trying to fight off a disease that no longer exists (and eventually would end up fighting its own cells).
  • 40. Antibodies • also called immunoglobulins or Igs • constitute the gamma globulin part of the blood proteins. • They are soluble proteins secreted by the plasma offspring (clones) of primed B cells. • The antibodies inactivate antigens by, – (a) complement fixation (proteins attach to antigen surface and cause holes to form, i.e., cell lysis), – (b) neutralization (binding to specific sites to prevent attachment—this is the same as taking their parking space), – (c) agglutination (clumping), – (d) precipitation (forcing insolubility and settling out of solution),
  • 41. Cell mediated immunity • Mediated by T lymphocytes. • An immune response against intracellular microbes,such as viruses and some bacteria, survive and proliferate inside phagocytes and other host cells, where they are inaccessible to circulating antibodies. • Promotes destruction of microbes within phagocytes or killing of infected cells.
  • 42. CELL-MEDIATED IMMUNITY • The production of cytotoxic T-lymphocytes and cytokines in response to an antigen; mediated by T-lymphocytes.
  • 43. T cell • Cytotoxic or killer T cells (CD8+) – do their work by releasing lymphotoxins, which cause cell lysis. • Helper T cells (CD4+) – serve as managers, directing the immune response. They secrete chemicals called lymphokines that stimulate cytotoxic T cells and B cells to grow and divide, attract neutrophils, and enhance the ability of macrophages to engulf and destroy microbes. • Suppressor T cells – inhibit the production of cytotoxic T cells once they are unneeded, lest they cause more damage than necessary. • Memory T cells – are programmed to recognize and respond to a pathogen once it has invaded and been repelled.
  • 44. CYTOKINES • A wide variety of intercellular regulatory proteins produced by many different cells in the body which ultimately control every aspect of body defense. • Cytokines activate and deactivate phagocytes and immune defense cells, • increase or decrease the functions of the different immune defense cells, and promote or inhibit a variety of nonspecific body defenses.
  • 45. Cellular Immunity Infected cells Pathogen engulfed by Perforin Foreign antigen Infected cell lyses Macrophage Cytotoxic T cell Displays antigens on surface and Attacks infected cell stimulates T cell Stimulates Helper T cell Cytotoxic T cell