Adaptive immunity

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Adaptive immunity
2440 spring lecture 7 5/27/10
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Specific Defenses

• Figure 2214 Forms of Immunity.

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Review Innate immunity
Membranes, surface barriers inflammation fever neu
trophils- macrophages complement NK
cells interferons
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Surface barriers Skin Mucous membranes
Innate defenses
Internal defenses Phagocytes NK cells
Inflammation Antimicrobial proteins Fever
Humoral immunity B cells
Adaptive defenses
Cellular immunity T cells
Figure 21.1
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Specific Defenses

• Four Properties of Immunity
• Specificity
• Each T or B cell responds only to a specific
  antigen and ignores all others
• Versatility
• The body produces many types of lymphocytes
• each fights a different type of antigen
• active lymphocyte clones itself to fight specific
  antigen

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Specific Defenses

• Four Properties of Immunity
• Memory
• Some active lymphocytes (memory cells)
• stay in circulation
• provide immunity against new exposure
• Tolerance
• Immune system ignores normal (self) antigens

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Specific Defenses

• The Immune Response
• Two main divisions
• Cell-mediated immunity (T cells)
• Antibody-mediated immunity (B cells)

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Specific Defenses

• 2215 An Overview of the Immune Response.

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T Cells and Immunity

• Cell-mediated immunity (T cells)
• Cytotoxic T cells (also called TC cells)
• Attack cells infected by viruses
• Responsible for cell-mediated immunity
• Helper T cells (also called TH cells)
• Stimulate function of T cells and B cells
• Suppressor T cells (also called TS cells)
• Inhibit function of T cells and B cells

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T Cells and Immunity

• MHC Proteins Involved in self/nonself recognition
• The membrane glycoproteins that bind to antigens
• Genetically coded in chromosome 6
• The major histocompatibility complex (MHC)
• Differs among individuals

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T Cells and Immunity

• Antigen Recognition
• T cells only recognize antigens that are bound to
  glycoproteins in plasma membranes

Antigens must be presented
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T Cells and Immunity

• Antigen-Presenting Cells (APCs)
• Responsible for activating T cells against
  foreign cells and proteins

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Antigen-Presenting Cells (APCs)

• Engulf antigens
• Present fragments of antigens to be recognized by
  T cells
• Major types
• Dendritic cells in connective tissues and
  epidermis
• Macrophages in connective tissues and lymphoid
  organs
• B cells

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Macrophages and Dendritic Cells

• Present antigens and activate T cells
• Macrophages mostly remain fixed in the lymphoid
  organs
• Dendritic cells internalize pathogens and enter
  lymphatics to present the antigens to T cells in
  lymphoid organs
• Activated T cells release chemicals that
• Prod macrophages to become insatiable phagocytes
  and to secrete bactericidal chemicals

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Figure 21.10
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Self-Antigens MHC Proteins

• Protein molecules (self-antigens) on the surface
  of cells
• Antigenic to others in transfusions or grafts
• Example MHC proteins
• Coded for by genes of the major
  histocompatibility complex (MHC) and are unique
  to an individual

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Diversity of antigen receptors

• Human immune system able to recognize and bind to
  at least a billion different epitopes
• Result of genetic recombination shuffling and
  rearranging of a few hundred versions of several
  small gene segments
• Major Histocompatibility Complex Antigens
• MHC or human leukocyte antigens (HLA)
• Normal function to help T cells recognize foreign
  or self
• Class I MHC (MHC-I) built into all body cells
  except RBCs
• Class II MHC (MHC-II) only on antigen
  presenting cells

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T Cells and Immunity

• Class I MHC Proteins
• Pick up small peptides in cell and carry them to
  the surface
• T cells ignore normal peptides
• Abnormal peptides or viral proteins activate T
  cells to destroy cell

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T Cells and Immunity

• Class II MHC Proteins
• Antigenic fragments
• From antigenic processing of pathogens
• Bind to Class II proteins
• Inserted in plasma membrane to stimulate T cells

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T Cells and Immunity

• CD Markers
• Also called cluster of differentiation markers
• In T cell membranes
• Molecular mechanism of antigen recognition
• More than 70 types
• designated by an identifying number
• CD3 Receptor Complex
• Found in all T cells

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T Cells and Immunity

• CD4 Markers (target for HIV virus)
• Found on cytotoxic T cells and suppressor T cells
• Respond to antigens on Class I MHC proteins
• CD8 Markers
• Found on helper T cells
• Respond to antigens on Class II MHC proteins

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T Cells and Immunity

• CD8 or CD4 Markers
• Bind to CD3 receptor complex
• Prepare cell for activation

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MHC Proteins

• Classes of MHC proteins
• Class I MHC proteins, found on virtually all body
  cells
• Class II MHC proteins, found on certain cells in
  the immune response (APCs)
• MHC proteins display peptides (usually
  self-antigens)
• In infected cells, MHC proteins display fragments
  of foreign antigens, which help mobilize

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Antigen (Ag) intruder
Cell-mediated immunity
Humoral immunity
Inhibits
Inhibits
Triggers
Innate defenses
Adaptive defenses
Surface barriers
Internal defenses
Free Ags may directly activate B cell
Ag-infected body cell engulfed by dendritic cell
Antigen- activated B cells
Becomes
Clone and give rise to
Ag-presenting cell (APC) presents self-Ag complex
Activates
Activates
Memory B cells
Naïve CD8 T cells
Naïve CD4 T cells
Activated to clone and give rise to
Activated to clone and give rise to
Induce co-stimulation
Plasma cells (effector B cells)
Memory helper T cells
Memory cytotoxic T cells
Secrete
Activated helper T cells
Activated cytotoxic T cells
Cytokines stimulate
Antibodies (Igs)
Circulating lgs along with complement mount a
chemical attack on the Ag
Nonspecific killers (macrophages and NK cells of
innate immunity)
Together the nonspecific killers and cytotoxic T
cells mount a physical attack on the Ag
Figure 21.21
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Exogenous and Endogenous Antigens

• Exogenous antigens present in fluid outside
  body cells
• Antigen-presenting cells (APCs) include dendritic
  cells, macrophages and B cells
• Ingest antigen, process, place next to MHC-II
  molecule in plasma membrane, and present to T
  cells
• Endogenous antigens antigens inside body cells
• Infected cell displays antigen next to MHC-I

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Activation and clonal selection of a helper T cell
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Endogenous Antigens
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T Cells and Immunity

• Costimulation
• For T cell to be activated, it must be
  costimulated
• By binding to stimulating cell at second site
• Which confirms the first signal

Without co-stimulation, anergy occurs T
cells Become tolerant to that antigen Are unable
to divide Do not secrete cytokines
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Activation and clonal selection of a cytoxic T
cell
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Immature lymphocyte
Red bone marrow
T cell receptor
T cell receptor
Maturation
Class I MHC protein
Class II MHC protein
CD4 cell
CD8 cell
Thymus
Activation
Activation
APC (dendritic cell)
Memory cells
APC (dendritic cell)
CD4
CD8
Lymphoid tissues and organs
Effector cells
Helper T cells (or regulatory T cells)
Cytotoxic T cells
Blood plasma
Figure 21.16
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B Cells and Immunity

• B Cell Division
• Activated B cell divides into
• Plasma cells
• Memory B cells

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B Cells and Immunity

• Plasma Cells
• Synthesize and secrete antibodies into
  interstitial fluid
• Memory B Cells
• Like memory T cells, remain in reserve to respond
  to next infection

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Five Classes of Antibodies (Immunoglobulins)

1. IgG the main class of antibodies found in the
   blood
2. IgA occurs in small amounts in blood and in
   larger amounts in body secretions (tears, milk,
   saliva and mucus)
3. IgM a huge antibody made up of five monomer
   units and is the first to arrive to neutralize
   antigen
4. IgE has a special affinity for receptors on the
   plasma membranes of basophils in blood or mast
   cells in tissues
5. IgD found mainly on B-cell membranes and is
   rarely secreted

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Immune System Development

• Four Effects of Aging on the Immune Response
• Thymic hormone production is greatly reduced
• T cells become less responsive to antigens
• Fewer T cells reduces responsiveness of B cells
• Immune surveillance against tumor cells declines