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Transcript
General Microbiology (Micr300)
Lecture 15
Adaptive Immunity
(Text Chapter: 22.5-22.11)
Lymphocytes: The Cellular Arms
of Adaptive Immunity

T-lymphocytes



Mature in thymus
Interact with other defense cells (T helper cells,
TH) or kill abnormal cells (cytotoxic T cells, Tc)
B-lymphocytes


Mature in bone marrow
Produce antibodies
The Adaptive Immune Response


In adaptive immunity, phagocytes present
antigen to specific T cells, triggering the
proliferation of effector T cells and
subsequently the production of antibodies.
Immune T cells and antibodies attack directly or
indirectly the antigen.
The adaptive immune response is characterized
by specificity for the antigen, the ability to
respond more vigorously when reexposed to
the same antigen (memory), and the ability to
discriminate self antigens from nonself antigens
(tolerance) (Figure 22.8).
Specific Interactions
Memory
Tolerance
Immunogens


Immunogens are foreign macromolecules that
induce an immune response. Molecular size,
complexity, and physical form are intrinsic
properties of immunogens.
Molecular size is an important component of
immunogenicity. For example, low-molecularweight compounds called haptens cannot
induce an immune response but can bind to
antibodies. Because haptens are bound by
antibodies, they are antigens even though they
are not immunogenic.
Structure of the T-cell
Receptor (TCR)
Antigenic Determinants
Epitope

The antibody or TCR does not interact
with the antigenic macromolecule as a
whole but only against a distinct portion
of the molecule called an antigenic
determinant or epitope.
Presentation of Antigen to T
Lymphocytes



T cells recognize digested antigens presented
by antigen-presenting cells (APCs) or by
pathogen-infected cells.
At the molecular level, TCRs bind peptide
antigens presented by major
histocompatibility complex (MHC) proteins.
Class I MHC proteins are found on the
surfaces of all nucleated cells.
Class II MHC proteins are found only on the
surface of B lymphocytes, macrophages,
and dendritic cells, all of which are APCs
(Figure 22.11).
Class I
MHC
Class II
MHC
T-Cytotoxic Cells and Natural
Killer Cells


T-cytotoxic (TC) cells recognize antigens
presented via MHC I on virus-infected
host cells and tumor cells through
antigen-specific TCRs. Antigen-specific
recognition triggers killing via perforin
and granzymes (Figure 22.13).
TC use a special molecule called CD8 to
dock onto MHC I.
T-Cytotoxic Cells
T-Helper Cells


T helper cells secrete cytokines to direct
the function of other immune cells.
Depending on the cytokine profile T
helper cells are dived into subgroups


TH1 cells enhance phagocyte function in
destroying pathogens and promote
inflammation
TH2 cells stimulate B cells to proliferate,
augment antibody production and develop
into plasma cells (Figure 22.14).
T-Helper Cells
Pro-inflammatory
cytokines
Antibody
inducing
cytokines
T cell – B cell
Interaction
Antibodies (Immunoglobulins)




Immunoglobulin (Ig) (antibody) proteins consist of
four chains, two heavy and two light (Figure 22.15).
Each chain consists of different domains.
The amino-terminal region is a variable domain,
meaning that the amino acid sequence in this structural
region differs in each different antibody. The antigenbinding site is formed by the interaction of variable
regions of heavy and light chains.
The constant regions are very uniform among groups
of antibodies
There are 5 major groups of antibodies (isotypes) that
differ in the make up of their constant region of the
heavy chain (IgG, IgM, IgA, IgD, IgE)
Immunoglobulin G Structure
Fab
(antigen-binding
fragment)
Fc
(constant
fragment)
L: light chain
H: heavy chain
The Antigen Binding Groove:
Lock-Key Principle
Antibody Isotypes
Isotype IgG
IgM
g
m
Phagocytosis
Agglutination
Complement
activation
Placentatransfer
Neutralization
Agglutination
Complement
activation
Neutralization
Heavy chain
type
Main function
IgA
IgD
IgE
a
d
e
Mucosal
protection
Neutralization
?
B cell
maturation
marker
Allergies
Effector Functions of Antibodies



Neutralization
(blocking)
Opsonization
(enhancing
phagocytosis)
Complement
Activation (direct
killing, enhancing
phagocytosis)
Antibody Production


Antibody production is initiated by antigen
contact with an antigen-specific B cell and is
always IgM (Primary antibody response)
B cells require support from T helper cells for
full production of antibodies including other
isotypes

B cells take up and process antigen, present it to T
helper cells, which in turn secrete cytokines to
signal large scale production and isotype switch
Antibody Production



Some activated B cells develop into plasma
cells and produce and secrete large amounts
of antibody of isotypes other than IgM
Some activated B cells develop into long living
memory cells and can rapidly produce large
quantities (high titers) of antibodies upon
reexposure to antigen (secondary antibody
response, Figure 22.21).
Memory B cells do not need T cell activation
Primary &
Secondary
Antibody
Responses
Antibodies As Tool




Inject antigen into
rabbit (with immune
stimulator = adjuvant)
Re-inject for 2 or 3
times
Rabbit will make
antibodies against the
antigen
Draw blood, prepare
serum = polyclonal
antibodies
Antibodies in Immunoassays: ELISA