1. ADAPTIVE IMMUNITY: B CELLS AND ANTIBODIES
March 31, 2009
10:00-11:00

2. AGE ASSOCIATED CHANGES IN SERUM Ig LEVEL
In utero and at birth maternal Ig protects infants
Infants do not make Ig until approximately 6 months

3. ANATOMICAL LOCATIONS OF ISOTYPES OF Ig
Fc portions of Ig determine anatomical
location and function of isotypes
IgG and IgM predominate in plasma
IgE is associated with epithelial surfaces
IgA predominates in mucosal secretions

4. THE POLY-Ig RECEPTOR MEDIATES TRANSCYTOSIS
Transcytosis is the unidirectional transport of macromolecules
through a cell
IgM can also be transported across epithelial cells

5. THE BRAMBEL RECEPTOR TRANSPORTS IgG INTO
EXTRACELLULAR SPACES

6. NEUTRALIZATION OF TOXINS
IgM, IgG and IgA can neutralize toxins
Many pathogens produce toxins
Immunization with toxoid (inactivated toxin) protects against
tetanus and diptheria

7. NEUTRALIZATION OF VIRUSES
IgM, IgG, and IgA can neutralize viruses

8. NEUTRALIZATION OF BACTERIA
IgM, IgG and IgA can neutralize bacteria

9. CHARACTERISTICS OF FcR
Two broad types: Inhibitory and Activating
Inhibitory FcR have ITIMs on cytoplasmic domains
Activating signal through a “common” g chain containing an ITAM
Most FcR interact the stongest with IgG1
Exceptions: Fce and Fca
FcR have restricted expression
Most types of FcR are on macrophages and neutrophils
Mast cells only have Fce

10. OPSONIZATION FcR ON PHAGOCYTES FACILITATE ELIMINATION OF PATHOGENS
Phagocytes have receptors for IgG
FcR interact with IgG coated pathogens and increase the
efficiency of phagocytosis:
OPSONIZATION

11. IgE BINDS FceR ON MAST CELLS
Crosslinking FceR results in release of inflammatory mediators

12. ADCC IgG1 binds to target cells
Interaction with FcR on NK cell juxtaposes the target and NK
NK gets turned on and kills the target

13. FcR Summary: Part One

14. FcR Summary: Part Two

15. Bill Grignard: An M1 Without Antibodies
Bill was healthy for the first 10 months of his life. At that time he started to
have infections which were treated successfully with antibiotics. He was
bright, active and continued to grow despite repeated ear infections and 2
bouts of pneumonia. At age 2 he was tested for serum Igs: 80mg/dl IgG
normal ( ); no IgA, and 10 mg/dl IgM (normal ). He was treated
with i.m. injections of gamma globulin. At age 9 he was referred to you for
a chronic cough. You observed an absence of tonsils (not removed). His WBC
was normal. A family history revealed that he had a brother with a similar
problem, and two uncles who died of infections when they were young.
Bill was diagnosed with XLA (Btk deficiency). He injects himself daily with
gamma globulins.
Why was Bill healthy until 10 months?
Why doesn’t he have tonsils (he did not have a tonsillectomy)?
If you isolated lymphocyte precursors from his bone marrow and
looked at the Ig gene loci, would you find evidence of Ig gene
rearrangement?
What other genetic defects could lead to arrested B cell development
at the same stage as Btk deficiency?

16. Dennis Fawcett: A Boy Who Can’t Switch
Dennis was referred to you when he was 5, but he had suffered recurrent
infections since he was 1. He was admitted to the hospital with a severe
acute sinus infection. Interestingly, despite the infections his WBC was normal.
Interestingly, antibodies to the infectious agent (Streptococcus) were not present
in his serum 7 days later. Total serum Ig levels were: IgM-210 (normal )
IgA-0; IgG 25 (normal ). Lymph node biopsies revealed poorly
organized structures and no GC. Dennis received a booster shot for diptheria,
tetanus, and pertussis toxoids. 14 days later, no anti-toxoid was detected. He
did have serum antibodies to appropriate blood groups (carbohydrates). FACS
showed he had B cells and T cells. His T cells did not bind CD4O.
Dennis’ B cells expressed IgM and IgD. Why didn’t have difficulty switching
from IgM to IgD?
Why did Dennis make antibodies to blood group antigens, but not toxoids?
Why is IgG more effective at fighting this type of bacterial infection than IgM?
During an infection, would you expect Dennis to have enlarged lymph nodes?