immune response to pathogen.

1. Cells Involved In Immune
Responses
• Overview
• Sites occupied by pathogens
- antibody responses
- cell-mediated responses
• Populations of T cells
• Specificity of immune responses

2. 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

3. Overview

4. Sites Occupied By Pathogens
• Extracellular
- site of most bacteria
- elicits antibody (humoral) response
• Intracellular
- site of viruses and some bacteria
- elicits cell-mediated response

5. 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

6. Neutralization
Bacterial toxins
Host cell
Toxin receptors
Neutralization by antibody
Phagocytosis of
antibody-antigen
complex by
macrophage
Fc receptor
Forming phagosome

7. Opsonization
Macrophage
Extracellular
bacteria
Opsonization
Ingestion by macrophage
Digestion in lysosome

8. Complement Activation
C2
C4
C1
Digestion in lysosome
Bacteria in plasma
C1 C4
C2
Complement
activation
Lysis and
ingestion

9. 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

10. Fate of Antibody-Toxin or
Antibody-Pathogen Complexes
Lysosome
Phagosome fuses with lysosome,
antigen–antibody complex
is digested by lysosomal hydrolases
Phagosome

11. 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

12. 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

13. 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

14. Helper (Th1) T Cells
Macrophage Macrophage
Th1
cell
lysosome
mycobacteria
antigen
Infected macrophage Activated infected
macrophage

15. 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

16. 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

17. 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.

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 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

20. 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

21. 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

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 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

25. 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

26. 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

27. 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

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 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