Basic Immunology

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Basic Immunology
University of Tabuk Faculty of Applied Medical
Science Department of Medical Laboratory
Technology
Mr.AYMAN.S.YOUSIF MSc.Medical Microbiology
Immunology
Academic Year 1433-1434 (2012-2013)
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Acquired Immunity

• Mr.AYMAN.S.YOUSIF 10- 11/03/2013

Lecture 5
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Objectives

• At the end of this lecture, you should be able
  to
• To compare and contrast antigens recognized by
  the TCR and BCR.
• To describe the pathways involved in processing
  endogenous and exogenous antigens.
• To discuss self MHC restriction in antigen
  presentation to T cells.
• To describe the major antigen presenting cells.

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Comparison of BCR and TCR

• B cells and T cells recognize different
  substances as antigens and in a different form.
• The B cell uses cell surface-bound immunoglobulin
  as a receptor and the specificity of that
  receptor is the same as the immunoglobulin that
  it is able to secrete after activation.
• B cells recognize the following antigens in
  soluble form
• Proteins.
• Nucleic acids.
• Polysaccharides.
• Some lipids.
• Small chemicals (haptens).

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Comparison of BCR and TCR

• In contrast, the overwhelming majority of
  antigens for T cells are proteins, and these must
  be fragmented and recognized in association with
  MHC products expressed on the surface of
  nucleated cells, not in soluble form.
• T cells are grouped functionally according to the
  class of MHC molecules that associate with the
  peptide fragments of protein
• Helper T cells recognize only those peptides
  associated with class II MHC molecules, and
• cytotoxic T cells recognize only those peptides
  associated with class I MHC molecules.

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Antigen Processing and Presentation

• Antigen processing refers to the. ability of APCs
  to break down antigen into peptides and to
  associate those peptides with MHC molecules
• Antigen presentation is he process of displaying
  peptide antigens associated with MHC molecules to
  a T cell.
• MHC class I molecules present degradation
  products derived from intracellular (endogenous)
  proteins in the cytosol.
• MHC class II molecules present fragments derived
  from extracellular (exogenous) proteins that are
  located in an intracellular compartment.

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I. Class I MHC Pathway.

• All nucleated cells express class I MHC.
• Proteins are fragmented in the cytosol by
  proteosomes or by other proteases.
• The fragments are then transported across the
  membrane of the endoplasmic reticulum by
  transporter proteins (TAP).
• Synthesis and assembly of class I Within the
  endoplasmic reticulum .
• The partial folded MHC class I complex binds to
  the TAP complex, and, after binding of peptide .
  The peptide/MHC complex is  transported through
  the Golgi apparatus to the cell surface.

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I. Antigen Processing and Presentation - Class I
MHC Pathway.
(Transporter Antigen Processing (TAP) in the
endoplasmic reticulum)
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I. Antigen Processing and Presentation - Class I
MHC Pathway.
proteosomes (complex of proteins having
proteolytic activity)
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Activation of naïve CTL cell (CD8)
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II. Class II MHC pathway

• Whereas all nucleated cells express class I MHC,
  only a limited group of cells express class II
  MHC, which includes the professional Antigen
  Presenting Cells (APC).
• The principal APC are Macrophages, Dendritic
  cells (Langerhans cells) ,and B cells.
• The expression of class II MHC molecules is
  either constitutive or inducible ( especially by
  interferon-gamma (INF) in the case of macrophages
  ).

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II. Antigen Processing and Presentation - Class
II MHC Pathway.

• Exogenous proteins taken in by endocytosis are
  fragmented by proteases in an endosome.
• The alpha and beta chains of MHC class II, along
  with an invariant chain, are synthesized and
  assembled in the endoplasmic reticulum.
• The invariant chain prevents endogenous peptides
  from the cytosol from associating with class II
  MHC molecules.
• The class II MHC molecules with the associated
  invariant chain are transported through the Golgi
  and trans-Golgi apparatus to reach the endosome
• where the invariant chain is digested, and the
  peptide fragments from the exogenous protein are
  able to associate with the class II MHC
  molecules, which are finally transported to the
  cell surface.

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Invariant chain
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II. Antigen Processing and Presentation - Class
II MHC Pathway.
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Activation of naïve T helper cell (CD4)
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III. Self MHC Restriction

• In order for a T cell to recognize and respond to
  a foreign protein antigen, it must-
• Recognize the MHC on the presenting cell as self
  MHC. This is termed self MHC restriction.
• Helper T cells recognize antigen in context of
  class II self MHC.
• Cytotoxic T cells recognize antigen in context of
  class I self MHC.

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Antigen Presenting Cells (APCs)

• The three main types of antigen presenting cells
  are -
• Dendritic cells.
• Macrophages.
• B cells.
• although other cells, that express class II MHC
  molecules, (e.g., thymic epithelial cells) can
  act as antigen presenting cells in some cases.

Dendritic Cell
B cell
Macrophage
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I. Dendritic cells

• Are found in skin and other tissues.
• Ingest antigens by pinocytosis and transport
  antigens to the lymph nodes and spleen.
• Are the most effective antigen presenting cells
  and can present antigens to naïve (virgin) T
  cells.
• They can present internalized antigens in
  association with either class I or class II MHC
  molecules (cross presentation).
• The predominant pathway for internalized antigen
  is the class II pathway.

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I. Dendritic cells

• Constitutively express MHC I and MHC II (can
  stimulate both CD4 and CD8 T cells) as well as
  B7 (the co-stimulatory signal)
• Antigen presentation appears to be the sole
  purpose of dendritic cells, and these cells can
  be infected by a wide variety of viruses.
• They can present some viral peptides on their MHC
  II, and contribute to the induction of antibody
  against viruses.
• Very efficient at stimulation of cytotoxic
  responses.

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II. Macrophages

• Are not as effective in presenting antigen to
  naïve T cells but they are very good in
  activating memory T cells.
• Express little MHC II or B7, but have receptors
  for bacterial cell wall components which, upon
  binding, activate the macrophage to express high
  levels of B7 and MHC II.
• Once activated, macrophages are efficient at
  stimulating CD4 T cells, both for inflammatory
  responses and helper (antibody) responses.

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III. B cell

• B cells express high levels of MHC II, but not B7
• These cells bind antigen via their surface Ig and
  ingest antigens by pinocytosis. Like macrophages
• These cells are Not as effective as dendrite
  cells in presenting antigen to naïve T cells.
• B cells are very effective in presenting antigen
  to memory T cells, especially when the antigen
  concentration is low because surface Ig on the B
  cells binds antigen with a high affinity.

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Capture of circulating T cells in lymph nodes
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Thank You