Immunology at the Extremes of Life Flashcards
What are the general immune defects seen in children? And the elderly?
Children: Immature immune systems:
- suboptimal antibody responses to bacterial infections and polysaccharide vaccines
- allergic disease
Elderly: Immunosenescence:
- suboptimal antibody responses to infections and vaccines
- low CD8 T cell responses
- cancer
How does the mother pass on antibodies to the child?
- baby exposed to IgG in the placenta
- baby exposed to dimeric IgA in breast milk
What are the key differences in immune cells and antibodies between infants compared to adults?
a) neutrophils – higher blood count, BUT they are less responsive to chemokines
b) dendritic cells – lower stimulation of T cells
c) CD4 T cell helper function – skewed towards Th2 until 12 months old
d) CD8 T cell response – lower until 9-12 months old
e) IgG and IgA antibodies – higher in IgG1 and IgG3, but lower in IgG2, IgG4 and IgA until 13 years old.
Why do children have transient low IgG levels around 6 months?
The passively transferred maternal IgG has been greatly reduced and the baby is not producing much of its own IgG antibodies yet.
Why are babies particularly susceptible to encapsulate bacteria?
They are low in IgG2, which is the dominant IgG antibody response against encapsulate bacteria (polysaccharides). IgG2 and IgG4 reach adult levels slower than IgG3 and igG1.
Why is B cell activation by polysaccharides less efficient in babies? How can we get around this?
B cell activation by polysaccharides is enhanced by T cell activation, however they don’t have many active helper t cells yet.
Antibody responses against bacterial polysaccharides can be enhanced via:
a) protein conjugation of the capsular antigens of bacteria
- pneumococci
- H. influenzae B (Hib)
- meningococci
b) multiple recombinant protein antigens
- meningococci
Why do the elderly also have increased susceptibility to pneumococcal disease?
Lower opsonophagocytic antibody responses to pneumococcal polysaccharide vaccines.
Low opsonophagocytic antibodies is strongly correlated with low IgG antibody avidity.
What causes defects in B cell responses at both extremes of age?
- Naïve B cells
a) Babies:
- decreased expression of cell-surface receptors. They have lots of naïve B cells but they don’t do much yet.
b) elderly:
- decreased production of naïve B cells
- Germinal centers and memory B cells
a) babies:
- impaired germinal center function
- relatively lower numbers of memory B cells compared with naïve T cells
b) elderly:
- impaired germinal center function
- Bone marrow and plasma cells
A) babies – N/A
b) elderly – decreased access to plasma cell niches in bone marrow. Lots of fat deposits. Therefore relatively low number of naïve cells, and accumulation of memory and plasma B cells (but they are not necessarily controlled well, i.e. they could be monoclonal)
What is the difference between the thymus gland in a baby vs an elderly person?
- baby: very large as they are generating lots of naïve cells
- elderly: thymus gland atrophies around the age of 30.
The proportion of circulation CD8 T cells is increased in the elderly. What are they doing?
Reacting to infections such as CMV that have remained in their bodies.
Why is the cellular immune response affected by immunosenescence in the elderly?
- decreased number of naïve T cells and T cell receptor diversity
- increased number of memory CD4+ and CD8+ T cells, BUT…
- decreases T cell receptor diversity
- impaired function - decreased number and function of NK and dendritic cells
What immunizations should be received after the age of 65?
- pneumococcal polysaccharide (PcP) vaccines
- seasonal flu vaccine
- VZV vaccine
What is one immune factor that contributes to increased cancer in the elderly?
Mechanisms of tumour control. In younger people the immune system might recognize and kill tumors. CD4 and CD8 T cells are very important in this. Tumors land up escaping the immune system in the elderly.
