Download Adaptive Immunity

ADAPTIVE/ACQUIRED HUMORAL IMMUNITY:
Antigen-provoked B Lymphocyte response.
Antibodies are effector molecules of immunity.
TERMS
Antigen (Ag) = sometimes elicits immune response.
Immunogen = always elicits immune response
Allergen = elicits hyper-immune response
Stem cells can become any cell in its lineage.
Pleuripotent Stem Cells can become anything.
Pleuripotent Stem Cell  Differentiation (organize gene expression) 
B Lymphoblast  V / J Gene Reassortment (CLONAL EXPRESSION) 
B Lymphocyte (B cell)  B Cell Receptor
NOTE: There are two separate steps in recombination: 1) selection of VJD
gene. 2) Heavy chain class switching.
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CLASS SWITCHING
Four Gene Groups
Variability genes (V)
Diversity genes (D)
Junction genes (J)
Class genes (C)
V—V—V—V—------D—D—D—--------J—J—J—-------C—C—C—C
a b c d
1 2 3
i ii iii
µ γ δ έ
 Reassortment  Splicing  Product contains one of each VDJ, and the
default is to keep all the C genes:
B cell receptor
V—D—J—C—C—C—C  10 14-16 different B cell
b 2 iii µ γ
δ έ
clones are possible !
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An infinite number of receptors can respond to an infinite number of Ag.
Only the cells that are needed survive and go on to produce antibodies.
Five classes of antibodies : AMGDE (αµγδέ)
* The difference between B cell clone and Plasma cell is Class Switching.
CLONAL SELECTION: Only one antigen will bind and cause a response.
CLONAL EXPANSION: Plasma cells undergo Class Switching, and secrete
antibodies. Also converts subgroup of cells to “Memory Cells” (anamnestic
cells). Plasma cells are short lived, and memory cells are long-lived, can be
life-long.
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ANTIBODY DIAGRAM
Different parts of this molecule affect various aspects of the immune system.
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Both heavy and light chains contain two domains:
1) Constant
2) Variable (Ag-binding)
Therefore, there are four protein types in each antibody:
1) Heavy constant (CH)
2) Heavy variable (VH)
3) Light constant (CL)
4) Light variable (VL)
Heavy Chains are composed of VDJ and C (α, γ, έ, µ, δ)
Light Chains are composed of lambda (λ) and kappa (κ)
Dalton: the mass of one proton
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PEPSIN: An enzyme that cleaves an antibody BELOW the disulfide bridge on
the constant fragment. It leaves three pieces:
Two Fc (constant fragments)
One Fab (antigen-binding fragment)
THREE FUNCTIONS OF ANTIBODIES
1) Neutralization / Agglutination: Pathogens, antigens, venoms, toxins may be
inactivated directly by antibody binding. Neutralization is inactivation by Ab.
When antigens are neutralized by multimeric antibodies (IgM or IgA), large
Ag/Ab complexes form (agglutinate), precipitate, and are cleared from host.
2) Opsonization: Antibody binding helps the phagocyte eat the bacteria.
Occurs at the Fc on the antibody and FcR on the phagocyte.
3) Complement Fixation: Binding of IgM or IgG triggers C’, resulting in
cascade of protein cleavage leading to death of Ag or pathogen, and
modulation of phagocyte responses.
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Property
CH Allele
Subclasses
IgM
Cµ
-
IgD
Cδ
-
IgG
Cγ
IgG 1-4
IgE
Cέ
-
IgA
Cα
IgA 1-2
MW (kDa)
Multimer
% Serum
Mucosal
90
Pentamer
6
-
18
1
-
15
80
-
19
<1
-
30
dimer
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Cross Placenta
Agglutinating
Opsonizing
C’ Fixing
Anaphylaxis
-
-
Yes
Yes
Yes
Yes
-
-
Yes
Yes
-
Yes
Yes
Yes
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PICTURE OF AGGLUTINATION OF IgM
(Agglutination is best done by IgM and IgA, but IgG can do it, too)
The Fc region of IgG has Fc gamma receptors (FcγR) to aid in opsinization.
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NOTE: Complement Proteins are molecular effectors of innate immunity, but
Classical complement is initiated by adaptive immunity.
PICTURE OF IgE ON A MAST CELL
Histamine is released to cause vasoconstriction, but a hyper-allergic response
can lead to anaphylaxis.
AFFINITY MATURATION: Fine tuning of Ab subclass switching
If the best defense is Agglutination: IgG  2, 4
If the best defense is Opsonization: IgG  1, 3
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PRIMARY EXPOSURE TO ANTIGEN OR PATHOGEN:
The IgM is predominant and early; it is greater in speed and quantity than
IgG.
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SECONDARY EXPOSURE (ANAMNESTIC RESPONSE)
IgG is faster than IgM. Reacts in only a couple of days, so there might not
even be any symptoms, and infection can be prevented. This is protective
immunity.
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ACTIVE ANTIBODY RESPONSE
Actual exposure to Ag  Clonal selection  Clonal expansion (generating
plasma and memory cells)  Affinity maturation
ACTIVE ADAPTIVE IMMUNITY
1) Natural: pathogen encountered in the environment (can cause Dz)
2) Artificial: vaccine simulating Ag (saves you from Dz)
PASSIVE ADAPTIVE IMMUNITY (Ab made elsewhere, then you get it)
1) Natural: mother  placenta  in utero fetus
2) Artificial: anti-venom/anti-toxin (usually from horses, can cause
serum sickness from allergy to horse serum)
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ADDITIONAL POINTS TO KNOW:
The effector CELLS of innate immunity are all phagocytes (including Dendritic)
The effector MOLECULES of innate immunity are the antimicrobial peptides, The
effector MOLECULES of humoral immunity are antibodies.
Light and Heavy chains are made out of Globulin Proteins, which in this section of
lecture refers to Immunoglobins.
Class switching is mostly on the heavy chain because VDJ and C are heavy chain
components, and the heavy chain contains the Fc region that dictates class-specific
Ab functions.
LPS, LOS, flagella, capsules, antigens, etc., can trigger both the Classical and the
Alternative mechanisms of C’.
PMN does not return to battle like the Macrophages. They kill then die.
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