Dr' Robert J' McKallip

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Dr. Robert J. McKallip

• Office Building 1, Room C-47
• Phone [phone]
• E-mail rmckallip_at_gw.med.sc.edu

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Cells Involved In Immune Responses

• Overview
• Cells of the immune system and origin
• Innate vs Acquired
• Sites occupied by pathogens
• - antibody responses
• - cell-mediated responses
• Populations of T cells
• Specificity of immune responses

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Cells Involved In Immune Responses (continued)

• Diversity of receptor specificity
• Classes of major histocompatibilty complex (MHC)
  molecules
• Lymphocyte recirculation
• Leukocyte migration and localization

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Overview
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Cells of the Immune System

• All derive from the bone marrow
• Two main lineages derive from the bone marrow
  hematopoietic stem cells
• Lymphoid lineage
• T cells, B cells, Natural Killer (NK) cells
• 2. Myeloid lineage
• Monocytes, Macrophages, Dendritic cells,
  Megakaryocytes, Granulocytes

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Hematopoiesis
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Types of Hematopoietic cells
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Types of Hematopoietic cells continued
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Types of Hematopoietic cells continued
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Proportion of Leukocytes found in the blood
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Non-specific and Specific Immunity Contrasts

• Non-specific (natural, native, innate)
• system in place prior to exposure to antigen
• lacks discrimination among antigens
• can be enhanced after exposure to antigen
  through effects of cytokines

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Non-specific and Specific Immunity Contrasts

• Specific (acquired, adaptive) immunity
• is induced and enhanced by antigen
• shows fine discrimination
• has memory

The non-specific and specific immune systems
interact with each other!
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Sites Occupied By Pathogens

• Extracellular
• - site of most bacteria
• - elicits antibody (humoral) response
• Intracellular
• - site of viruses and some bacteria
• - elicits cell-mediated response

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Types of Antibody Effectiveness

• Neutralization Ab neutralizes toxins, binds to
  attachment molecules
• Opsonization Ab binds to pathogen surface
  molecules
• Complement activation occurs on antibody bound
  to pathogens

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Neutralization
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Opsonization
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Complement Activation
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Common Fate of Pathogen or Toxin After
Neutralization, Opsonization, or Complement
Activation

• Fc or complement receptors on phagocytic cells
  bind pathogen/toxin complexed with antibody
• Endocytosed complex fuses with lysosomes
  containing acid hydrolases
• Complex digested by lysosomal hydrolases

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Fate of Antibody-Toxin or Antibody-Pathogen
Complexes
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Cell-Mediated Responses

• Two intracellular compartments
• Cytosolic cytosol and nucleus connected via
  nuclear pores
• - site of viruses and some bacteria
• Vesicular membrane-bound entities (endoplasmic
  reticulum, endosomes, lysosomes, Golgi apparatus)
• - site of some bacteria, some parasites

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Location of Pathogen Determines Which T Cell
Population Responds

• Cytosolic cytotoxic T cells (Tc) that express
  CD8
• Vesicular subpopulation of helper T cells (Th1)
  that express CD4
• Extracellular subpopulation of helper T cells
  (Th2) that express CD4

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Cytotoxic (Tc) T Cells
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Helper (Th1) T Cells
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Specificity of Immune Responses Resides in
Receptors
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Diversity of Receptor Specificity (Repertoire)

• Historically two different hypotheses to
  explain diversity
• Instructional (template)
• Clonal selection
• Instructional hypothesis, although simpler, does
  not explain how host distinguishes self from
  non-self antigens

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Four Basic Principles of Clonal Selection

• Each lymphocyte bears a single type of receptor
  of a unique specificity.
• Interaction between a foreign molecule and a
  lymphocyte receptor capable of binding that
  molecule with high affinity leads to lymphocyte
  activation.

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Clonal Selection (continued)

• Differentiated effector cells derived from an
  activated lymphocyte will bear receptors of
  identical specificity to those of parental cell
  from which the lymphocyte was derived.
• Lymphocytes bearing receptors for self molecules
  are deleted at an early stage in lymphoid cell
  development.

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Clonal Selection (Continued)
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Generation of lymphocyte antigen receptor
diversity
Variable region encoded by set of gene segments
One member of each set is joined randomly to
member from other sets
Forms unique receptor. It is estimated that
there are at least 108 different specificities in
an individual at any one time
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Class I MHC Molecules

• expressed on surface of all nucleated cells
• recognized by TCR of cytotoxic T cells
• CD8 binds to class I MHC-peptide complex
• source of peptide is cytosolic compartment

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Class II MHC Molecules

• Expressed on surface of some nucleated cells,
  mainly antigen presenting cells (APC)
• Recognized by TCR of helper T cells
• CD4 binds to class II MHC-peptide complex
• Source of peptide is vesicular compartment

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Cells Expressing Class I and Class II MHC
Class I MHC

• All nucleated cells express class I MHC

• Cells expressing class II MHC also express class
  I MHC

Class II MHC
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Lymphocyte Recirculation

• Secondary lymphoid tissues (lymph nodes, spleen)
  main sites where lymphocytes encounter antigen
• Frequency of lymphocytes having a receptor
  specific for a given antigen is low
• Recirculation of lymphocytes through lymphoid
  tissues optimizes productive encounters with
  antigen to initiate response

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Lymphocyte Recirculation
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Leukocyte Migration and Localization

• Bone marrow and thymus (primary lymphoid tissues)
  produce B cells and T cells, respectively
• B cells and T cells recirculate through spleen
  and lymph nodes (secondary lymphoid tissues)
• Antigen presenting cells (APC) pick up antigen
  and migrate to secondary lymphoid tissues and
  interact with T cells and B cells

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Leukocyte Migration and Localization