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Transcript
Host Defenses
Immune System Terminology
Immunity
Antigen (Ag)
Specific antibody and lymphocyte response to an antigen
A substances that causes the body to produce specific
antibodies or sensitized T cells
Antibody (Ab)
Proteins made in response to an antigen
Humoral immunity
Involves Ab produced by B cells
Cell-mediated immunity Involves T cells
Acquired immunity
Developed during an individual's lifetime
•Naturally acquired active immunity (Resulting from infection)
•Naturally acquired passive immunity (Transplacental or via colostrum)
•Artificially acquired active immunity (Injection of Ag (vaccination))
•Artificially acquired passive immunity (Injection of Ab)
White Blood Cells
Antigenic Determinants
•
•
•
•
•
Neutrophils:
Basophils:
Eosinophils:
Monocytes:
Phagocytic
Produce histamine
Toxic to parasites, some phagocytosis
Phagocytic as mature macrophages
60-70% of WBCs
0.5-1% of WBCs
2-4% of WBCs
3-8% of WBCs
– Fixed macrophages in lungs, liver, bronchi
– Wandering macrophages roam tissues
•
Lymphocytes:
Involved in specific immunity
20-25% of WBCs
Antibodies recognize and react with antigenic determinants or epitopes.
Immunoglobulins (classes of antibodies)
Antibody Structure
IgG
IgM
IgA
IgD
IgE
Structure
% of
serum
antibody
80%
5-10%
10-15%
Location
Blood,
lymph,
intestine
B cell surface, Secretion B cell
blood, lymph s (tears,
surface
saliva,
milk)
Mast cell
and
basophil
surfaces
Half-life
in serum
23 days
5 days
3 days
2 days
Functions
See next slide First Ig
Protects
produced.
mucosal
Binds large
surfaces
microbes;
aggulutination
Unknown
Release of
histamines,
lysis of
parasitic
worms
6 days
0.2%
0.002%
Antibody Genetics
Results of AG-AB Binding
VH1
VH2
VL1
VL2
VL3
Chromosome 2
300 Variable
genes
VH199
VH200
VL299
DH1
VL300
DH2
Chromosome 14
JL1
JL2
JL3
5 Joiner
genes
DH12
JH2
JH3
4 Joiner
genes
JH4
1 Constant
gene
CH
Light chain genes
12 Diversity
genes
JH1
JL4
JL5
CL
200 Variable
genes
Heavy chain genes
8 Constant
gene
Clonal Selection
Antibody Titer
Random deletion and recombination of antibody genes results in one set of
VLC Light chain genes and one set of VDJC Heavy chain genes in each B cell.
Bone Marrow
Stem Cell
VL212-J4-C
VH189-D1-J3-C
VL57-J4-C
VL34-J1-C
VH198-D17-J3-C VH69-D8-J4-C
V188-J5-C
VH41-D12-J2-C
VL2-J1-C
VH99-D10-J3-C
300VL * 5JL = 1500
Light Chains
VL256-J5-C
VH111-D11-J1-C
X
200VH * 12DH * 4 JH =
9600 Heavy chains
B cells are genetically
identical to all other
body cells except they
have fewer antibody
genes
= 14 Million Different B
Cells (each produce
unique antibody)
Provide long-term
protection in case body is
ever re-infected with
same pathogen. The
more memory cells, the
longer the immunity lasts.
Active
antibody
production
during
infection
T cell-dependent immune response
1.
2a. Macrophage phagocytizes microbe.
2b. B cell with SPECIFIC ANTIBODY binds to free microbial
antigen (AG-AB complex).
3a. Macrophage digests microbe (using lysosomes).
4a. Macrophage displays microbial antigen (AG) along with
MHC-II protein (AG-MHC complex). Macrophage is now
an Antigen Presenting Cell (APC).
5a. Helper T cell with SPECIFIC T CELL RECEPTOR
(TCR) binds to specific AG-MHC complex. Macrophage is
stimulated to secrete Interleukin-1.
6.
Major Histocompatibility Complex
Pathogenic microbes infect human body.
3b. B cell ingests AG-AB complex by endocytosis.
4b. B Cell displays microbial antigen (AG) along with MHC-II
protein (AG-MHC complex). B Cell is now an Antigen
Presenting Cell (APC).
Interleukin-1 stimulates T Cell to reproduce many times.
7. T Cell clones differentiate into:
• Helper T Cells which have the identical TCR to the T Cell
in step 5a (in other words, they recognize and bind to the
specific AG-MHC of the infecting microbe).
• Memory T Cells which recognize the same AG-MHC but
are not active. They circulate and reproduce but die off
faster. So eventually, they become depleted.
• Cytotoxic T cells which recognize the same antigen.
8a. Cytotoxic T cells bind to infected body cells and release
perforins which kill the body cells. This is an especially
important defense against viruses.
8b. Helper T cell, which recognizes specific AG-MHC, binds to B
cell (from step 4B) which displays the correct AG-MHC.
Helper T cell secretes cytokines which stimulate the B cell to
reproduce and differentiate.
Mom
Dad
A3
B6
C1
Dp7
Dr8
Dq3
A2
B8
C7
Dp2
Dr15
Dq13
A6
B2
C13
Dp11
Dr10
Dq21
A8
A6
B4
B2
C10
C13
Dp11
Dp1
Dr10
Dr3
Dq16
Dq21
MHC Genotypes of Children
A3
B6
C1
Dp7
Dr8
Dq3
A2
B8
C7
Dp2
Dr15
Dq13
A3
B6
C1
Dp7
Dr8
Dq3
A8
A6
B4
B2
C10
C13
Dp11
Dp1
Dr10
Dr3
Dq16
Dq21
A6
B2
C13
Dp11
Dr10
Dq21
A2
B8
C7
Dp2
Dr15
Dq13
A6
B2
C13
Dp11
Dr10
Dq21
A8
A6
B4
B2
C10
C13
Dp11
Dp1
Dr10
Dr3
Dq16
Dq21
9. B Cell clones differentiate into:
• Plasma Cells which circulate and secrete large quantities of
the specific antibody from step 2b.
• Memory B Cells which have the genes to produce the same
antibody, but are immunologically inactive. They circulate
and reproduce but die off faster. So eventually, they
become depleted.