Download Slide 1

Genes and Immunity
Immune response system is remarkably adaptive
defense system
a. protects against pathogens and cancer
b. immune recognition or specificity is the hallmark of
IRS
c. distinguishes between self versus non-self
d. effect or response-calls in a variety of cells and
proteins (B cells, T cells etc)
e. exhibits memory--protection against second
invasion
eg polio vaccine
Problems with immune system
Type I diabetes (B cells and insulin cells are killed by the
immune system)
Pioneers:
Discipline of immunology has its roots in the early observations and
experiments by Edward Jenner and Louis Pasteur (human medicine and
veterinary medicine)
Edward Jenner, 1898---viral etiology
country physician
smallpox--40-50% fatality
observations for almost 20 years--milk maids no pock marks on their
body from small pox
cowpox--blisters on their hands, did not get small pox
fluid from cowpox blister--inoculated 8 year old boy, waited and inoculated
with smallpox--did not get small pox
established procedure for preventing smallpox throughout Europe
Louis Pasteur--chance observation--1880,
experimenting with chicken cholera--major disease of chickens
left preparation of cholera bacteria on shelf 2 weeks
injected chickens--did not die--re-injected with live bacteria-did not die
1881--injected sheep with attenuated anthrax--gave live anthrax-did not die
Duality of the IRS:
Elie Metchnikoff, 1883 cellular immunity (T cells)
Emil von Behring, 1890--humoral immunity (Ab's)
Today's thinking is that IRS is combination of cellular and
humoral
Thymus-----------------------T cells (cellular)
(T helper/killer)
Bone Marrow ----Bursa Equiv-------------------B cells (humoral)
T cells are present in all areas of the body and ask the
question: self or non-self?
Without T helper cells there would be not B cell response.
Take home lesson
These two systems are not independent of each other, but are in
constant communication..
Where do our immune cells come
from?
Formation and development of RBC’s
and WBC’s (leukocytes)
All blood cells arise from one type of
cell called the hematopoietic stem
cell
Stem cells have the ability to
differentiate into a number of different
cell types.
They are self renewing and maintain
their populations via division.
The Major Players
B cells (Humoral)

produce antibodies
which bind to pathogens
and disable them or flag
them for destruction
T cells (Cellular)
 kill infected cells
 coordinate entire
adaptive response
Humoral Branch
Antibodies are immune system-related
proteins called immunoglobulins.
Antibody consists of four polypeptides– two
heavy chains and two light chains joined to
form a "Y" shaped molecule.
The amino acid sequence in the tips of the
"Y“ varies greatly among different
antibodies.
•This variable region, give the antibody its specificity for binding antigen.
The variable region includes the ends of the light and heavy chains.
•The constant region (Fc) determines the mechanism used to destroy
antigen (secondary biological function)
five major classes, IgM, IgG, Iga, IgD and IgE
IgA about 15% of total antibody count. Found in mucous secretions and
mother’s milk
IgD less than 1%
Appears to have a role in activating and suppressing lymphocyte activity
Found in large quantities in the cell walls of many B-cells. IgD has a single
binding site.
IgE less than 1%
Mediator in allergic responses. Most importantly activates histamine
secreting cells. Also appears to play a role in parasitic infection.
IgG- composes 75% of our immunoglobulin pool. IgG stimulates
high immune response. Most importantly, it is the only antibody that
can cross the placenta and confer immunity on the fetus.
IgM - makes up 10% of our total antibodies. This is the predominant
early antibody; the one that first activates in an initial attack of
antigen.
Because of its high number of antigen binding sites (5), it is an
effective agglutinator of antigen . This is important in the initial
activation of B-cells, macrophages, and the complement system.
Explaining Ab specificity.
ImmunoGlobulin (Ig) molecules

Thousands on surface of each B cell

Ig are essentially just bound antibodies
What do Antibodies bind to?
An antigen is defined as "anything that can be
bound by an antibody". This can be an enormous
range of substances from simple chemicals, sugars,
small peptides to complex protein complexes such
as viruses.
In fact antibodies interact specifically with relatively
small parts of molecules. These are known as
antigenic determinants or epitopes.
Antibody diversity
How is this astonishing diversity
generated?
This problem has been resolved over
the past 20 years by the
demonstration that Ig genes
rearrange during B cell
development.
light chains- two types k or λ


contain V J C gene segments
Rearranged V J segments encode the
variable region of the light chain.
heavy chain family contains V D J C
genes segments

Rearranged V D J segments encode the
variable region of the heavy chain.
Pairing of different combinations
of Ig heavy and light chains.
Recombination of V, D and J
segments (VJ for light chains)
Together these potentially
generate some 5x106 different
antibodies.
Cellular Branch
T cells
T lymphocytes constitute the "cellular" arm of immunity.
There are two major subsets of T lymphocytes that differ
in function
Specificity of T cells
Each T cell has a unique
surface molecule called a T
cell receptor (TCR)
Specificity through similar
process of DNA splicing...
Like Ig’s, each cell’s TCRs
recognizes a unique pattern
(10^7 TCR types)
TH cells are activated and proliferate only
when presented with the antigen via self
MHC.



MHC genes are organized into regions that
encode 3 classes of molecules
Class I – present on the surface of nearly all
nucleated cells.
Major function is to present antigens to Tc cells
Class II – present on APC’s
Major function to present antigens to TH cells
APC –Dendritic Cells (can present with
either class I or class II). They are the major APC
in our body
 Macrophages
Establishing Self Tolerance
T cells originate in the bone marrow then migrate to the
Thymus where they mature
Selection of T cells through binding to common MHC-self
peptides in thymus



strong binders are killed (clonal deletion)
weak binders die from lack of stimulation (clonal selection)
They then go on to make either Tc or TH cells, but 95% of all
cells entering the thymus undergo apoptosis.
Remaining T cells are not self-reactive
Bringing it all together
Typical Immune
Response
Ex. Polio
Initial response started
out by IgM
IgG activated later
Low Response
IgM response.
T cell independent
Taking a closer look at
cell involvement.
Clonal Expansion
High Response
T cell dependent
IgG now becomes
involved
How do T cells get
involved in the IRS?
In order for a T cell to get involved in the IRS, it needs to be
presented the antigen in a very specific manner.
This is made possible via presentation of the antigen by an
Antigen Presenting Cell (APC)
•Macrophages
•B cells
•Dendritic cells
Sequence of Events
Ag recognized by Ab on B cell
Ingested by (APC), immunogen
broken down
Select peptides of immunogen
presented on surface of APC via
MHC
Peptide is presented to T helper cell
via TCR.
Cytokine release (chemical signals)
Cytokine release from T helper cell
telling B cell to continue making
Ab's that are specific to the
immunogen.