Specific Defenses of the Host

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					Specific Defenses of the Host
      The Immune response
           The Immune System
Innate (Nonspecific) Immunity        Acquired
First line of defense Second line    Third line of
(barriers at the body defense        defense
•Skin                •Inflammation   •T cell
•Mucous              •Phagocytes     lymphocytes
membranes            •Fever          •B cell
•Secretions          •Complement     lymphocytes
•Reflexes            system          •Antibodies
•Normal microbiota   •Interferon
   Acquired (specific) immunity
• The Acquired immune system recognizes
  foreign substances and develops a specific
  immune response against them.

• Substances that provoke an immune response
  are called Antigens (Ag).
  – Bacteria, viruses, fungi, protozoa, helminthes, and
    cancerous cells are examples.

• The main type of cells of the Acquired immune
  system are lymphocytes.
  Acquired (specific) immunity

• Humoral immunity             • Cell mediated
  – B-cells (B- lymphocytes)     – T-cells (T-lymphocytes)
  – Carried out by               – Carried out by Perforin
    Antibodies                   – Effective against
  – Effective against              Intracellular antigens
    Extracellular antigens         (antigens inside cells
    (antigens outside our          i.e.… viruses)
    cells like bacteria)         – Cancer
  – MHC independant              – Tissue transplant
                                 – MHC dependant
Cell Mediated Response

    T cytotoxic (Tc ) cells
                         T- cells
• Thymocyte (immature T-
  cells) are produced by the
  bone marrow.
   – Thymocytes are immature
     and are unable to react
     with antigen
   – They travel to the thymus
     where they are screened
     and mature into T-cells.
• Mature T cells must be
  able to distinguish
  between self and non-
Distinguishing self from non-self
• How do T-cells recognize self cells (The
  cells that make up your body) from foreign

• Answer: They bind to and analyze a
  protein marker found on all of your cells
  called the Major Histocompatability
  complex (MHC).
 Major Histocompatability complex
The MHC is a marker found
  on all of your cells.
   – It identifies your cells as
     “self” to your immune
   – The MHC also randomly
     picks up proteins from
     inside your cell and
     displays them on the
     outside to your immune

• T-cells must be able to
  differentiate your MHC
  markers from others
Positive selection of Thymocytes in
            the thymus.
• Thymocytes that enter the thymus are self
  programed to die.

• The thymoctyes that are able to recognize
  the MHC and bind to it receive a signal
  that allows them to live.

• All thymocytes that are unable to bind to
  your MHC die.
• How do your T-cells recognize unhealthy
  body cells harboring intercellular parasites
  from your normal healthy cells?
• The bone marrow generates T- cells that collectively are
  able to recognize any possible protein in the context of
  your MHCs.

• The T-cells that bind to healthy normal self-proteins in
  the context of an MHC die in the thymus.

• Only T-cells that are able to bind to an MHC coupled
  with a foreign protein are released out to the body.

• This is called Negative selection
• The MHC constantly
  samples proteins in the

• The MHC displays these
  proteins to the immune
  system outside the cell.

• If the protein displayed is
  normal and are regularly
  found in the cell, the T-
  cells will not attack.

• If the protein in the MHC
  is foreign, (ie…viral
  protein) the T-cells will
  attack the cell.
          Screening of T-cells
• In the thymus, Thymocytes undergo a double
  screening process.
  – Positive selection: Selects for thymoctes that have
    receptors capable of binding self-MHC. These cells
    are given a positive stimulus which allow them to live.
     • Thymocytes that fail positive selection die.

  – Negative selection: selects against thymocytes that
    are able to bind self proteins presented by self-MHC.
     • Thymocytes that have high affinity receptors for self proteins
       receive a negative stimulus that causes them to die.
  Results of Positve and Negative
• The T-cell repertoire in the body consists
  of T-cells which are only able to recognize
  foreign proteins in the context of self MHC.

• The Cell mediated response is MHC
Turning on the Specific
  Immune Response
A job left to the Innate Immune
       Overview of Cell Mediated
• Antigen presenting cells (APC) ingest microbes
  and present the Antigens to a type of T-cell
  called a T-Helper cell (TH-cell).
• The TH-cell becomes activated and secretes a
  cytokine called interleukin 2.
• Interleukin 2 from the TH-cell, binds to T Tc-cell
  and has 2 effects.
   – 1. Activates Tc-cells causing them to produce
        perforin molecules. These cells are now able to kill
        infected host cells.
   – 2. Causes activated Tc-cells to proliferated and go
        through clonal expansion.
The non-specific or innate immune response
  turns on the specific immune response.

• APC (macrophages,
                                         MHC II /AG complex
  dendritic cells and B cells)
  ingests a microbe.
• The microbe is processed
  into short antigenic
• These fragments are
  combined with a MHC
  molecule inside the APC.
• The MHC /Ag complex is
  presented on the surface       Antigen Presenting Cell (APC)

  of the APC
                        T Helper cells
• The APC travels to the lymph
  node where it meets T-helper
  cells (TH-cells)

• A TH-cell with an appropriate
  receptor binds to the MHC II
  /Ag complex.                                                     V
    – This is called the primary
• The Primary signal causes
  receptors for interleukin 2 to be
  expressed on the surface of
  the TH-cell.

                                      Interleukin 2 receptors (IL-2)
            Co-stimulatory signal

• B7 protein on the APC
  binds to a CD28 receptor
  on the TH-cell.
   – This is called the
     Costimulatory signal

• The costimulatroy signal
  induces the TH-cell to
  produce and secrete IL-2.
                Interleukin 2
• The costimulatroy
  signal induces the TH-
  cell to produce and
  secrete IL-2.

• The IL-2 binds to IL-2
  receptors on the TH-
            Clonal Expansion
• IL-2 causes the TH-
  cell to clone itself over
  and over.

• The TH-cell is now
  ready to activate a T-
  cytotoxic cell.
              Activating Tc-cells
• T cytotoxic cells (Tc-cells)
  migrate into an area of
  infection by chemotaxis.
                                         Infected Cell
• A Tc-cell with an
  appropriate T-cell receptor
  binds to an MHC I /Ag
  complex.                                      MHC I /Ag
• This binding stimulates the    IL-2R             C
  Tc-cell to produce
  receptors for IL-2
      Differentiation of Tc-cells
• After the IL-2Rs are expressed on the
  outside of the Tc-cell the Tc-cell lets go of
  the infected body cell and migrates into
  lymph-nodes or other lymphatic tissues.

• If the Tc-cells in the lymphatic tissue finds
  an activated TH-cell and receives IL-2 it
  will proliferate into active T cytotoxic
  lymphocytes and memory cells.
Cell Mediated Cytolysis
         The MHC Question
• Why doesn’t activated Tc-cells bind to the
  APCs and kill them?
     Answer to MHC Problem
• There are two different types or classes of
  MHCs: MHC I and MHC II
                    MHC I.
• This class is found on every nucleated cell
  of the body.
• Proteins and antigens bound to MHC I are
  always taken up from the pool of free
  floating proteins in the cytoplasm.
• Only T-cytotoxic cells are able to bind to
  this class of MHC.
  – Tc cells can only kill cells with MHC I.
                          MHC II
• This class is only found on the surface of APCs.
• Antigens that are bound to this class of MHC are
  always taken from phagolysomes.
  – This means that the cell is healthy

• Only T-Helper cells can bind to this class of MHC
  – TH-cells activate Tc- cells but never kill cells that they
    interact with. Thus APCs are perserved.

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