Transcript Slide 1

The Development and Function
of Cells in the Immune Response
“Helpful Secretions”
Ag
Ag
B cell
CD4 T cell
makes antibodies
that target Ag, such
as bacteria
becomes
activated to help
CD8 T cell
becomes
activated to kill
Ag
Ag
Ag
Ag
Ag
Ag
APC
Ag
Ag
Body
Barrier
Immune Locations
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Outside/Inside
Lymph Nodes
Spleen
Thymus
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The Antigen Presenting Cell (APCs)
• Include macrophages, monocytes,
dendritic cells, and B cells
• Detection of Foreign Invasion
(Innate Immune Function)
• Collection Delivery of Antigen to
“Immune Locations”
• Processing of Antigen
APC
Ag
– Cutting up antigen into little segments
that are the right size to be presented
and shuttling them to presenting
molecules
• Presentation of Antigen Via Special
Cell Surface Molecules
– Displaying peptide fragments of antigen
on the cell surface
Ag
Ag
MHC Class II
• A molecule that is expressed only on “professional” APCs such as
macrophages, dendritic cells, and B cells.
– Known as HLA DR, DQ, or DP in human
– Known as MHC I-A and I-E in mice
– These genes are each designated by an allele marker, so I-Ad is a class II
allele
• The molecule contains a groove that allows it to bind processed
peptides
– Each allele has preferred lengths and sequences
• Class II molecules “present” peptides from molecules that are taken up
from outside the cell via processes such as phagocytosis (known as
exogenous processing pathway)
• Together the peptide and MHC form a shape (3-D structure) that may
match (complement) the surface of a T cell receptor
• MHC class II molecules also have a special area that binds CD4;
hence CD4 T cells are “Class II restricted”.
MHC Class I
• A molecule that is expressed on all cells of the human body with few
exceptions
– HLA-A, B, C genes in human
– K, D, and L genes in mice
• The molecule contains a groove that allows it to bind processed peptides
– Each allele has preferred lengths and sequences
• Class I molecules “present” peptides from molecules that are made inside
the cell (endogenous processing pathway). Viral particles, for example,
are made internally.
• Together the peptide and MHC form a shape (3-D structure) that may
match (complement) the surface of a T cell receptor
• MHC Class I molecules also have a special area to bind to CD8; hence
CD8 T cells are “Class I restricted”.
B Lymphocyte
• Produced in the bone marrow
where they undergo most of
their maturation and selectio
• Production of antibody when
bound to its antigen
• Interaction via Antigen with T
Lymphocytes
– Class Switching
– T Cell Differentiation
– Immune interactions are
reciprocal, both cells are
affected
Ag
B cell
Effector Mechanisms 1:
Antibody
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Neutralization
Opsonization
Complement Activation
Antibody Dependent Cellular
Cytotoxicity
T Lymphocyte
• Two Classes: CD4+ and CD8+
– CD4+: “Helper” T Cells
– CD8+: Cytotoxic T Cells
• Activation Results in Proliferation
and Differentiation to Effector Cell
Types
• T cells also originate in the bone
marrow but migrate to the thymus
for their selection and
development
T cell
Cell-Cell Interactions and Activation Requirements
• Surface-Surface Antigen Presentation
– MHC and T Cell Receptor
• Costimulation
– Cell surface proteins
– Secreted Factors
• Cytokines (a.k.a. interleukins)
Ag
T cell
Ag
APC
Effector Mechanisms 2:
Cell Mediated
• Target Cell Lysis (Perforin/granzyme)
• Induced Cell Death
– Cytokines
– Other Secreted Factors
• Activation of Other Immune Cells (help)
Genetic Rearrangement in
Lymphocyte Development
• Enormous diversity in the immune response—
trillions of lymphocytes and possibly no two
recognize the same structure and fewer than
100 recognize even the same organism
• If each receptor were encoded by a separate
gene, these genes might take up more space
than our entire DNA
• The solution is the Nobel winning work of
Susumu Tonegawa….
Genetic Structure and recombination process
for antibody
A similar process is used for the T cell receptor. For each region labeled
above (V-D-J), there are numerous gene segments (i.e., many V gene
segments from which to choose).
Tolerance:
How?
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