Anatomy of the Immune Response

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Anatomy of the Immune Response

• Fluid movement in tissues
• Antigen uptake in tissues
• Anatomy of peripheral lymphoid tissues how
  phagocytes connect the innate and adaptive immune
  responses
• Immune system ontogeny

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Arterial circulation
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Venous circulation
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Arterial and venous circulation meet in capillary
beds
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Lung thin walled alveoli
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Vasculature in the thin alveolar walls in the lung
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Small intestine villi have vessels
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Vessels in villi arterioles, capillaries,
venules and lymphatics
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Net pressure drop across capillary forces fluid
out
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Endothelial cells line blood vessels can
separate to let cells and fluid out
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Lymphatics mesh with capillary beds
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Movement of cells and fluid into lymphatics
Pepper and Skobe, JCB 2003
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Vessels in villi arterioles, capillaries,
venules and lymphatics
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Lymphatic circulation
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Where are antigens encountered?(infection,
transplant, autoimmune)

• Skin
• Respiratory tract
• Gastrointestinal tract
• Genitourinary tract
• EPITHELIAL SURFACES!

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Local defenses in tissues the Neighborhood Watch

• Innate immunity complement, defensins,
  neutrophils
• Antigen Presenting Cells macrophages,
  dendritic cells, histiocytes

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The microbes breach the barrier what happens?
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Local infection stimulates innate immunity and
adaptive immunity
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Macrophages and phagocytosis
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Local response to pathogens
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Local infection stimulates innate immunity and
adaptive immunity
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Peripheral lymphoid tissues

• Mucosal associated lymphoid tissue MALT the
  local militia
• Tonsils/adenoids, salivary glands, lung, stomach,
  small intestine
• Lymph nodes the National Guard
• Spleen

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Peripheral lymphoid tissues

• Mucosal associated lymphoid tissue MALT the
  local militia
• Tonsils/adenoids, salivary glands, lung, stomach,
  small intestine
• MALT provides a barrier between the epithelium
  lining the outside world, and the central immune
  system

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Lung a site of mucosal associated lymphoid
tissue (also called BALT)
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Scattered APCs and lymphocytes can respond to
pathogens
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Trafficking of CD8 cells to lung in influenza
infection
Trafficking, retention and survival of
lymphocytes in peripheral tissues essential for
protective immune response Ray et al, Immunity
20167, 2004
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Peripheral lymphoid tissues

• Mucosal associated lymphoid tissue MALT the
  local militia
• Tonsils/adenoids, salivary glands, lung, stomach,
  small intestine
• MALT provides a barrier between the epithelium
  lining the outside world, and the central immune
  system

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MALT in the gut - GALT

• Stomach
• Appendix
• Intestine (small and large) Peyers patches in
  ileum

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GALT lymphoid nodules in small intestine are
Peyers patches
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MALT (GALT) in gut are local defense DCs can
migrate from LP or PP to lymph nodes or spleen
Kraehenbuhl and Corbett, Science 3031624, 2004
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Small intestine lamina propria filled with
immune cells
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Vessels in villi surrounded by lamina propria
cells can traffic out of and into vessels
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MALT (GALT) in gut are local defense DCs can
migrate from LP or PP to lymph nodes or spleen
Kraehenbuhl and Corbett, Science 3031624, 2004
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Peripheral lymphoid tissues

• Mucosal associated lymphoid tissue MALT
• Lymph nodes
• Spleen

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Lymphatic circulation
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Movement of cells and fluid to site of infection
and drainage back into circulation
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Movement of cells and fluid into lymphatics
Pepper and Skobe, JCB 2003
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Local infection stimulates innate immunity and
adaptive immunity
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Bridge between innate and adaptive immunity
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Anatomy of a lymph node
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Lymph node follicles in cortex
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Secondary follicle germinal center and mantle
zone
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Organization of the secondary follicle
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Bridge between innate and adaptive immunity
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T and B cells traffic through lymph nodes,
looking for antigen
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DCs continually scan lymph nodes for random T
cell encounters
12 min image
Miller et al, PNAS 101998, 2004
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Random encounters of lymphocytes and DCs in the
lymph nodeMiller et al, PNAS 101998, 2004
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How do dendritic cellsinteract with lymphocytes?
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Anatomy of a lymph node
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Peripheral lymphoid tissues

• Mucosal associated lymphoid tissue MALT
• Lymph nodes
• Spleen

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Anatomy of the spleen
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Spleen white pulp and red pulp
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Splenic architecture
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Spleen white pulp looks like a follicle!
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Important functions of the spleen

• Lymphocyte exposure to antigens like lymph
  nodes
• Scavenging by macrophages clear old red cells,
  antibody-coated cells and bacteria
• Extramedullary hematopoiesis, if space is needed
  for more blood cell production (looks like bone
  marrow!)

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MALT (GALT) in gut are local defense DCs can
migrate from LP or PP to lymph nodes or spleen
Kraehenbuhl and Corbett, Science 3031624, 2004
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GALT provides protection in absence of GALT,
central lymphoid tissue responds
Bacteria in gut induce local IgA response,
restricts infection and inflammation In absence
of GALT, DCs loaded with bacteria traffic to
spleen to promote immune response
Macpherson and Uhr, Science 3031662, 2004
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Where lymphocytes grow up

• Bone marrow naive B cells and prothymocytes

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Bone marrow cells and fat
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Hematopoiesis in bone marrow
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Whats wrong with this bone marrow?
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Where lymphocytes grow up

• Bone marrow naive B cells and prothymocytes
• Thymus naive T cells

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Location of the thymus
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Thymus cortex and medulla
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Thymic stroma and thymocytes
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Where lymphocytes grow up

• Bone marrow naive B cells and prothymocytes
• Thymus naive T cells
• Lymph nodes
• B cell maturation and differentiation to memory
  B cells or plasma cells

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B cell development in lymph nodes
Memory B Cell
GC B Cell
Y
Y
Naive B Cell
Y
Y
Y
Plasma Cell
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Lymph node follicles in cortex
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Lymphocyte maturation defects
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Hyper IgM Syndrome

• 70 X- linked others have same phenotype from
  different mutations
• Recurrent bacterial infections
• T cell defect prevents B cell maturation
• Only IgM in the serum, no germinal centers in
  lymph nodes, spleen or tonsils

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The bottom line on the anatomy of the immune
response

• Antigen entry and uptake in tissues
• Tissues are bathed in fluid
• Lymphatics drain tissues
• Peripheral lymphoid tissues are sites of antigen
  processing and presentation - MALT, lymph
  nodes, spleen
• B cells arise in the bone marrow, T cells need
  the thymus