A rough guide to the immune system

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A rough guide to the immune system

• Dr Adrian Palfreeman
• Senior Clinical Scientist MRC CTU

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Stem cells

• Stem cells why they matter

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Neutrophil (polymorph)

• Multi-lobed nucleus.
• Commonest leucocyte (2500-7500/mm3 of blood).
• A short-lived phagocytic cell whose granules
  contain numerous bactericidal substances.
• leave the blood to go to tissues where infection
  or inflammation is developing

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Eosinophil

• A leucocyte whose large refractile granules
  contain a number of highly basic or cationic
  proteins,
• possibly important in killing larger parasites
  including worms.
• Bind avidly to IgE-coated particles (i.e.
  Helminthic parasites) .
• Abundant at sites of allergic reactions.

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Components of the immune system
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• Monocyte
• The largest nucleated cell of the blood (16-20µm
• diameter), developing into a macrophage when it
• migrates into the tissues.
• Macrophage (A professional antigen presenting
  cell)
• The principal resident phagocyte of the tissues.
• Strongly phagocytic of particles and microbes.
• Has receptors for Ig and complement.
• CNS microglia
• Liver Kupffer cells
• Lungs alveolar macrophages
• Bone osteoclasts

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T lymphocyte (T cell)

• A thymus-derived (or processed) lymphocyte.
• 1500 - 4000/mm3 blood
• 6-15µm diameter (red blood cell 7.2µm diam.)
• 2 main subdivisions
• CD8 (cytotoxic T cells)
• - CD4 (helper T cells)

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• B lymphocyte
• A bone marrow- (or in birds, bursa-) derived
  lymphocyte, the precursor of antibody-forming
  cells. In foetal life, the liver may play the
  role of bursa.
• NK (Natural Killer) cells
• do not have to recognise a specific antigen
  before acting against it
• are effective against a wide range of infectious
  microbes.

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The 2 arms of the adaptiveimmune response

• 1. Humoral immunity (antibodies)
• 2. Cellular immunity (T-cells)
• Sub-divided into T helper cells (CD4) and
• Cytotoxic T cells (CD8)

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CD4 Lymphocytes (T helper cells)

• coordinate much of the immune response to
  micro-organisms
• help B-cells respond to foreign proteins
• secrete substances that enable CD8 T-cells to
  proliferate
• activate macrophages so that they can kill
  certain organisms, including some organisms
  associated HIV infection.

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CD8 Lymphocytes (Cytotoxic T cells)

• kill cells in the body identified as abnormal or
  foreign
• tumour cells
• cells that have been infected by viruses.

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How does HIV reduce CD4 Cells?

• Increased turnover of cells in response to
  infection
• Trapping of HIV in lymph nodes
• Shortened survival of CD4 cells
• Reduced production of new cells
• Reduction of T cell progenitor production from
  bone marrow

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Sites of theprincipallymphoid tissueswithin
the humanbody.Primary lymphoidorgansSec
ondary lymphoidorgans
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Human lymphoid organsPrimary lymphoidorgansSe
condary lymphoidorgans
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• Lymphoid tissues
• Immune system compartmentalised into
  organs/tissues.
• Funtionally unified via blood and lymph systems.
• Lymphocytes recirculate.
• In total, equivalent in weight to brain or liver.
• Primary lymphoid organs
• Bone marrow where T and B lymphocytes are made.
• Thymus where T lymphocytes mature/are selected.
• Secondary lymphoid organs
• e.g. spleen, lymph nodes and Peyers patches.
• Contain T cells, B cells, antigen presenting
  cells (APCs)

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T cell precursors(thymocytes) migratefrom the
bone marrowto the thymus to mature.

• Mature T cells leave the
• thymus and migrate to
• secondary lymphoid tissues
• where they may encounter
• foreign antigen.

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Thymus

• Lobules show - a lymphocyte-dense outer cortex
• - an inner lighter-staining medulla.
• Stromal framework with specialised epithelial
  cells, DCs
• and macrophages (APCs).
• T cell precursors arrive from the bone marrow.
• Cortex and medulla educate thymocytes into
  mature,
• competent T cells (1 to 3 of T cells survive
  education).
• Mature T cells are released into the peripheral
• circulation.

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THYMUSDevelopingthymocytesoccupy
theinterstices ofan extensivenetwork
ofepithelial cells
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Clusters of Differentiation (CD)

• CD3 T cells
• CD4 Helper T cells
• CD8 Cytotoxic T cells
• CD16 Macrophages
• CD19 B cells

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Maturation of T lymphocytes in the thymus
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Circulatinglymphocytesmeetlymph-bornepathogens
in draininglymph nodes.
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Lymph node
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Cytokines

• Il2 stimulates division of B and T cells and
  killing of HIV infected cells by NK cells
• IL2 levels reduced in HIV infection

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IL2

• Does administration of IL2 help?
• Raises CD4 numbers
• Significant side effects
• Injectable
• Short term benefit in clinical trials
• Does it reduce mortality and morbidity in the
  long term?

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Summary

• B cells recognise antigens (antigenic epitopes)
  via their monomeric IgM receptor
• T cells recognise antigens (small peptides)via
  the T cell receptor (TCR) which is always
  associated at the cell surface with CD3 11
• The monomeric B cell receptor (and, in fact,
  all antibodies) recognise antigens in solution
  in their native (folded) state
• The TCR does not recognise soluble antigens but
  only small antigenic peptides associated with the
  Major Histocompatibility (MHC) molecules I II
• For a T cell or B cell to be activated 2
  appropriate signals are always required
• T cells need binding of the TCR to peptide/MHC
  plus specific cytokines from the APC (notably IL-
  1 and IL-2) and interaction between B7 and CD28
• B cells need binding of mIgM surface receptor
  plus signals from TH cells (notably IL-4 and IL-
  10) and interaction of CD40/CD40L.
• This process has evolved to prevent unwanted
  activation of immune cells which can lead to
  harmful responses such as allergies and
  autoimmunity