Cells Involved In Immune
Responses
• Overview
• Sites occupied by pathogens
- antibody responses
- cell-mediated responses
• Populations of T cells
• Specificity of immune responses
Cells Involved In Immune
Responses (continued)
• Diversity of receptor specificity
• Classes of major histocompatibilty
complex (MHC) molecules
• Cells of the immune system and origin
• Lymphocyte recirculation
• Leukocyte migration and localization
Overview
Sites Occupied By Pathogens
• Extracellular
- site of most bacteria
- elicits antibody (humoral) response
• Intracellular
- site of viruses and some bacteria
- elicits cell-mediated response
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
Neutralization
Bacterial toxins
Host cell
Toxin receptors
Neutralization by antibody
Phagocytosis of
antibody-antigen
complex by
macrophage
Fc receptor
Forming phagosome
Opsonization
Macrophage
Extracellular
bacteria
Opsonization
Ingestion by macrophage
Digestion in lysosome
Complement Activation
C2
C4
C1
Digestion in lysosome
Bacteria in plasma
C1 C4
C2
Complement
activation
Lysis and
ingestion
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
Fate of Antibody-Toxin or
Antibody-Pathogen Complexes
Lysosome
Phagosome fuses with lysosome,
antigen–antibody complex
is digested by lysosomal hydrolases
Phagosome
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
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
Cytotoxic (Tc) T Cells
Virus infects cell
A B
C
Cell expresses
viral antigens
Cytotoxic
T cell
Infected cell is killed by cytotoxic T cell
by activation of nucleases that cleave
host and viral DNA
Helper (Th1) T Cells
Macrophage Macrophage
Th1
cell
lysosome
mycobacteria
antigen
Infected macrophage Activated infected
macrophage
Specificity of Immune Responses
Resides in Receptors
•T cell receptor (TCR) recognizes peptide
associated with major histocompatibility
complex (MHC) and is univalent.
T
cell
•B cell receptor (surface immunoglobulin)
recognizes antigen and is bivalent
B
cell
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
Four Basic Principles of Clonal
Selection
1. Each lymphocyte bears a single type of
receptor of a unique specificity.
2. Interaction between a foreign molecule
and a lymphocyte receptor capable of
binding that molecule with high
affinity leads to lymphocyte activation.
Clonal Selection (continued)
3. 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.
4. Lymphocytes bearing receptors for
self molecules are deleted at an early
stage in lymphoid cell development.
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
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
Cells Expressing Class I and
Class II MHC
Class I MHC
Class II
MHC
All nucleated cells
express class I
MHC
Cells expressing
class II MHC also
express class I
MHC
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
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!
Cells of the Immune System
• All derive from the bone marrow
• Two main lineages derive from the bone
marrow hematopoietic stem cells:
1. Lymphoid lineage
T cells, B cells, Natural Killer (NK) cells
2. Myeloid lineage
Monocytes, Macrophages, Dendritic cells,
Megakaryocytes, Granulocytes
Hematopoiesis
NK
Myeloid
progenitor
Lymphoid
progenitor
Tc
cell
TH
cell
Hematopoietic
Stem cell
B cell
Granulocyte
Platelets Megakaryocyte
Macrophage Monocyte
Dendritic cell AFC
Plasma
cell
Mast cell
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
Lymphocyte Recirculation
Naïve lymphocytes
enter lymph nodes
from the blood circulation
Lymphocytes return
to blood
via the thoracic duct
Antigens from infected area
go to lymph nodes
via the lymphatic system
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
Leukocyte Migration and Localization
T
cell
T
cell
T
cell
B
cell
B
cell
B
cell
APC
T
cell
B
cell
Naive
lymphocytes
Bone marrow
Thymus
Spleen and lymph nodes Tissues
Primed lymphocytes
Dendritic
cell
Macrophage

immune response to pathogen.pdf

  • 1.
    Cells Involved InImmune Responses • Overview • Sites occupied by pathogens - antibody responses - cell-mediated responses • Populations of T cells • Specificity of immune responses
  • 2.
    Cells Involved InImmune Responses (continued) • Diversity of receptor specificity • Classes of major histocompatibilty complex (MHC) molecules • Cells of the immune system and origin • Lymphocyte recirculation • Leukocyte migration and localization
  • 3.
  • 4.
    Sites Occupied ByPathogens • Extracellular - site of most bacteria - elicits antibody (humoral) response • Intracellular - site of viruses and some bacteria - elicits cell-mediated response
  • 5.
    Types of AntibodyEffectiveness • Neutralization: Ab “neutralizes” toxins, binds to attachment molecules • Opsonization: Ab binds to pathogen surface molecules • Complement activation: occurs on antibody bound to pathogens
  • 6.
    Neutralization Bacterial toxins Host cell Toxinreceptors Neutralization by antibody Phagocytosis of antibody-antigen complex by macrophage Fc receptor Forming phagosome
  • 7.
  • 8.
    Complement Activation C2 C4 C1 Digestion inlysosome Bacteria in plasma C1 C4 C2 Complement activation Lysis and ingestion
  • 9.
    Common Fate ofPathogen 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
  • 10.
    Fate of Antibody-Toxinor Antibody-Pathogen Complexes Lysosome Phagosome fuses with lysosome, antigen–antibody complex is digested by lysosomal hydrolases Phagosome
  • 11.
    Cell-Mediated Responses Two intracellularcompartments: • 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
  • 12.
    Location of PathogenDetermines 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
  • 13.
    Cytotoxic (Tc) TCells Virus infects cell A B C Cell expresses viral antigens Cytotoxic T cell Infected cell is killed by cytotoxic T cell by activation of nucleases that cleave host and viral DNA
  • 14.
    Helper (Th1) TCells Macrophage Macrophage Th1 cell lysosome mycobacteria antigen Infected macrophage Activated infected macrophage
  • 15.
    Specificity of ImmuneResponses Resides in Receptors •T cell receptor (TCR) recognizes peptide associated with major histocompatibility complex (MHC) and is univalent. T cell •B cell receptor (surface immunoglobulin) recognizes antigen and is bivalent B cell
  • 16.
    Diversity of ReceptorSpecificity (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
  • 17.
    Four Basic Principlesof Clonal Selection 1. Each lymphocyte bears a single type of receptor of a unique specificity. 2. Interaction between a foreign molecule and a lymphocyte receptor capable of binding that molecule with high affinity leads to lymphocyte activation.
  • 18.
    Clonal Selection (continued) 3.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. 4. Lymphocytes bearing receptors for self molecules are deleted at an early stage in lymphoid cell development.
  • 19.
    Class I MHCMolecules • 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
  • 20.
    Class II MHCMolecules • 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
  • 21.
    Cells Expressing ClassI and Class II MHC Class I MHC Class II MHC All nucleated cells express class I MHC Cells expressing class II MHC also express class I MHC
  • 22.
    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
  • 23.
    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!
  • 24.
    Cells of theImmune System • All derive from the bone marrow • Two main lineages derive from the bone marrow hematopoietic stem cells: 1. Lymphoid lineage T cells, B cells, Natural Killer (NK) cells 2. Myeloid lineage Monocytes, Macrophages, Dendritic cells, Megakaryocytes, Granulocytes
  • 25.
  • 26.
    Lymphocyte Recirculation • Secondarylymphoid 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
  • 27.
    Lymphocyte Recirculation Naïve lymphocytes enterlymph nodes from the blood circulation Lymphocytes return to blood via the thoracic duct Antigens from infected area go to lymph nodes via the lymphatic system
  • 28.
    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
  • 29.
    Leukocyte Migration andLocalization T cell T cell T cell B cell B cell B cell APC T cell B cell Naive lymphocytes Bone marrow Thymus Spleen and lymph nodes Tissues Primed lymphocytes Dendritic cell Macrophage