Download B cells and T cells Immunoglobulins

Immune system
B cells and T cells
- many different types of cells mediate
the immune response to destroy
bacteria and viruses as well as
pre-cancerous cells
stem cell
myeloid
progenitor
lymphoid
progenitor
Y
T
- all cells in the immune system,
as well as all the red blood cells,
arise from totipotent stem cells
in the bone marrow
B
Y
Y
Y
r.b.c
Y
Immunoglobulins (antibodies)
B cells and T cells
IgA, IgE, IgG
Y
Memory
T cell Effector
Y
Y
Y
Plasma
B cells
T cells
Memory
T cell
Effector
T cells
Class [IgX]/ml
IgG
12 mg
IgA
1 mg
Y
Plasma
B cells
IgA, IgE, IgG, IgM
Y
Immunoglobulins
Y
Y
Memory
B cell
Y
Memory
B cell Y
pre
B cell
Y
Y
Y
pre
T cell
Y
Y
stem cell
Y
lymphoid
progenitors
Immunoglobulins
structure function
K2 2
bind antigens
which invade
body
Class
IgM
[IgX]/ml structure function
1 mg
K2 2
immature Ab
IgD
1 mg
K2
2
K2
IgE
* 0.001
K2
2
2
in tears, saliva,
mucus; resp.,
intestinal tracts
* IgE levels are elevated
during allergic response
unknown
-stimulates
mast cells
to release
histamine
Immunoglobulins
Antibody structure
(antibodies)
N
N
N
- antibody molecules (Ab) are large
globular proteins located on
surfaces of B lymphocytes
N
L
L
light chain
heavy chain
- oligo saccharide chains of specific seq.
of sugars is attached to some a.a.,
generally asn, ser and thr residues
constant
region
carbohydrate
C
Light chains
N
1
constant
a.a. seq.
C
Heavy chains
N
C
variable 109
a.a. seq.
variable
region
214
- variable a.a. sequence is different
in each antibody
- constant a.a. sequence is same
in each antibody
Functions of different regions
1. variable region = site of antigen binding
- hypervariable segments of both chains
are extremely variable in a.a. sequences
antigen binding
site
1
CHO chains
109
variable
a.a. seq.
C
446
constant
a.a. seq.
- variable a.a. sequence is different
in each antibody
- constant a.a. sequence is same in each
antibody
Functions of different regions
2. constant regions
- recognize cell membrane
glycoproteins of host cells
recognizes
host cell
membranes
antigen binding
site
oligosaccharide
chains
Immunogenetics
Healthy adults have about 500,000 different
antibody molecules circulating in blood.
Does a new antigen (foreign protein)
cause a new antibody to be
formed specifically against it?
- each antibody has a unique H chain
and L chain
NO!
Is there one gene for each unique H protein
and L protein in the human body?
NO!
Heavy chain formation in B cell
Different regions of the different
V,D,J and C genes in the DNA
of B lymphocytes are selected
AT RANDOM to form the mRNA.
DNA
V genes
D
J
genes genes
10 families 12
4
“gene” for
antibody
DNA
RNA
polymerase
DNA
“new gene”
for antibody
Modifications are made to
nascent protein
(pre-pro IgG Heavy chain)
N
1. N-terminal seq. is
removed at membrane
immature
m RNA
removal of
intervening
sequences
8 genes
joining randomly selected
V, D, J and C regions
This mRNA is modified and
translated into an immature
antibody protein (Ab).
Formation of heavy chain mRNA
C genes
2. 2 H chains and
2 L chains associate
m RNA
V DJ
C
3. sugars are added
C
Clonal selection theory of
immune response
1. RANDOM selection of specific V,
D, J, and C genes to produce
“recombinant gene’ for
antibody
Clonal selection theory of
immune response
3. Mature B cells die unless activated
by an antigen binding to V region
Y Y
Y
B cell
Y
Clonal selection theory of
immune response
2. Each mature B lymphocyte
produces only ONE specific
antibody protein.
Clonal selection theory
- each Ab protein recognizes a specific
chemical grouping on antigen surface
- if antigen binds Ab, then B cell divides
rapidly producing millions of B cell clones
Y
- V region of antibody projects out of
cell membrane
Immune repertoire
Many different antibodies are formed
against one virus coat or one
bacterial cell wall.
Antigens such as virus coat proteins
and bacterial cell walls may be
bound by different antibodies .
New viruses and bacteria are usually
bound by one or more old antibodies.
Y Y
Y
Y
Y
Y
Y
Y
B cells
B cells
Immune system
Bone marrow
Totipotent stem cells are dividing
continuously and the daughter cells are
differentiating into red and white blood
cells.
bone
marrow B
lymph tissue
bone
marrow
B
lymph tissue
B
T
B
B
B
B
B
virus
T
B
B
B
B
Antigen
independent
bone
marrow
Antigen dependent
lymph tissue
B
Antigen independent
Antigen dependent
Typical pattern of immune dysfunction
after HIV infection
1000
B
B
T
AIDS virus kills
helper T cells
B
concen.
T cells
250
B
0
B
Antigen
independent
Antigen dependent
Nutrition and
the Immune system
- folate, vitamins C, E, B-6 and B-12
are essential for optimal
functioning of immune system
- also a moderate to high protein
diet increases immune efficiency
12
24
36
48
60
months after infection
Deficiencies and decreased
immune response
• deficiency of vitamin B-6 causes
reduced stimulation of lymphocytes
by antigens
• Cu++ and Zn++ deficiencies lead to
decreased number of B lymphocytes
• deficiency of vitamins A, C and E
result in impaired T-cell mediated
immunity
Cancer and immune
surveillance
- pre-cancerous cells arise in all humans
every day
- most pre-cancerous cells are identified
by T cells of the immune system
and are destroyed before dividing
Cancer risks for Americans
Risk factors
for cancer
Deaths / yr. per
million Amer.
1. diet quality (anti-oxidants)
2. tobacco use
3. sexual behavior
4. alcohol
5. pollution
6. industrial waste
7. occupational
8. food additives
714
612
143
82
61
41
< 20
< 20
Cancer risks for Americans
Risk factors
for cancer
alcohol abuse
food additives
diet quality
industrial waste
occupational hazards
pollution
sexual behavior
tobacco use
Deaths / yr. per
million Amer.
714
612
143
82
61
41
< 20
< 20