Dr.William E.

Bowers
Office: Building #1, Room C-26
Phone: 733-3275
E-mail: wbowers@gw.med.sc.edu
 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
Toxin receptors

Host cell
Bacterial toxins
Neutralization by antibody

Phagocytosis of
antibody-antigen
complex by
macrophage
Forming phagosome Fc receptor
 Opsonization
Extracellular
Opsonization
bacteria

Macrophage

Ingestion by macrophage

Digestion in lysosome
 Complement Activation
Bacteria in plasma

Lysis and
ingestion

C1
C1 C2 C4

C2 Complement
C4
activation
Digestion in lysosome
 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

Phagosome

Phagosome fuses with lysosome,

antigenantibody complex
is digested by lysosomal hydrolases
Lysosome
 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
A B

Cell expresses
viral antigens

Cytotoxic
C T cell

Virus infects cell

Infected cell is killed by cytotoxic T cell

by activation of nucleases that cleave
host and viral DNA
 Helper (Th1) T Cells
lysosome

Th1
Macrophage Macrophage cell

antigen
mycobacteria

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.
B cell receptor (surface immunoglobulin)
recognizes antigen and is bivalent

T B
cell 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

All nucleated cells

express class I
MHC
Class I MHC
Cells expressing
Class II class II MHC also
MHC
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
Platelets Megakaryocyte

Tc
cell
Hematopoietic
Stem cell
Granulocyte TH
cell

Myeloid Lymphoid
progenitor progenitor
B cell
Mast cell

NK AFC
Dendritic cell
Plasma
Macrophage Monocyte 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
Nave 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
Bone marrow

Macrophage
Thymus
Dendritic
cell
T T B B
cell cell cell cell
Naive
T lymphocytes B
cell cell

Spleen and lymph nodes APC Tissues

Primed lymphocytes
T B
cell cell