Week 4 Essays

Question 1

What are some factors that contribute to diminished immune function in the elderly?

Answer 1

• Immunosenescence → ⇡susceptibility to infection in the elderly
• Immunosenescence is due to:
  
  • Reduced phagocytic properties of neutrophils and macrophages (e.g., ROS & NO)
  • ⇣in # and fxn of cDCs and pDCs (⇣phagocytosis and TLR-induced signaling)
  • Impaired T cell help → impaired AID expression and GC development of B cells

Question 2

What types of vaccines do the elderly receive?

Answer 2

The elderly (>65) receive boosters/TI/polysaccharide only vaccines (e.g., PCV23) because they have trouble making memory cells

Question 3

What are some factors that contribute to diminished immune function in newborns/infants?

Answer 3

• Immune system has yet to develop
  
  • Macrophages and NK cells have not reach full potential until later in childhood
  • T cells biased toward anti-inflammatory Th2 responses and tolerance induction
    
    • Th1 responses (intracellular microbes) delayed until age 1
  • Limited expression of Fc receptors & opsonizing complement proteins → Humoral responses are not fully functional
  • TCR & BCR repertoire constrained by limited antigen exposure of infants

Question 4

What types of vaccines are given to children?

Answer 4

Children receive TD/conjugated vaccines because they are designed to take advantage of a child’s maturing immune system (functional GC response) and help the young expand the memory T and B cell repertoire.

Question 5

What type of vaccine is PCV13 and who is it recommended for?

Answer 5

• Conjugated vaccine ⇒ T cell dependent B cell response (TD vaccine)
  
  • Antigenic polysaccharides on a protein carrier
  • Generates a response that includes B cells that ungergo SHM, affinity maturation, and isotype switching → production of memory B cells and** high-affinity, neutralizing antibodies**
• Given to healthy people that are neither very young nor very old
  
  • Child’s schedule: 2, 4, 6, and 12-15 months old

Question 6

What type of vaccine is the PCV23 vaccine and who is it recommended for?

Answer 6

• Polysaccharide-only vaccine → T cell independent B cell response (TI vaccine)
  
  • Induces B cells to differentiate into plasma cells that produce low affinity IgM antibody
  • Does produce some IgM memory
    
    • Important for early IgM, which can neutralize viruses or blood-borne pathogens like S. pneumo
    • but this memory is by no means as effective as TD IgG and IgA memory for most responses
• Given to:
  
  • Age 65 and over
  • High risk populations younger than 65
  • High risk children age 2 and over (sickle cell, HIV, DM, chronic heart or lung dx)

Question 7

What is herd immunity?

Answer 7

= when a critical number of individuals in a given population are immune to a disease

It breaks the cycle of infection because the infectious agent cannot be transmitted from host to host.

Question 8

How do live attenuated vaccines contribute to herd immunity?

Answer 8

They contained attenuated forms of the organism that causes disease, so the organism replicates in the immunized individual.

The attenuated strain may spread to individuals not immunized, thereby contributing to herd immunity in a population. (Both vaccinated and unvaccinated become immune)

Question 9

How do subunit vaccines contribute to herd immunity?

Answer 9

Since it neither replicates in the host or is transmitted from host to host, a subunit vaccine does not contribute to herd immunity.

Question 10

Hemolytic Disease of the Newborn - Pathogenesis

Answer 10

MCC of HDN is incompatibility of an RhD⊕ infant and an RhD⊖ mother → development of maternal IgG antibodies agains the RhD-Ag on the surface of the fetal RBCs

This requires prior maternal exposure to the RhD antigen (e.g., during a blood transfusion, miscarriage)

Question 11

HUD - Diagnosis

Answer 11

• Blood typing → to check for maternal-fetal incompatibility
• Direct Coomb’s test [aka direct antiglobulin test (DAT)] → to determine if antibody or complement is coating the infant’s RBCs
  
  • Wash infant’s RBCs (to remove proteins not actually bound to the cells)
  • Treat with:
    
    • anti-human IgG (an IgM antibody) directed at the Fc region
    • anti-C3 antibody
  • If infant’s RBCs have mom’s IgG and/or C3 attached, the anti-human IgG/anti-C3 will bind and crosslink the RBCs → agglutination = ⊕direct Coomb’s test
• ​Check peripheral blood for signs of hemolytic anemia:
  
  • Low RBC count
  • Macrocytosis
  • Reticulocytosis
• Determine the total bilirubin level; anticipate that it will be high
• Head/brain ultrasound → to rule out intracranial bleed as a cause of anemia
• CP: hepatosplenomegaly due to extramedullary erythropoiesis

Question 12

HUD - Prevention

Answer 12

• Give Rh⊖ women Rh[D] immunoglobulins at 28 weeks gestation during their first pregnancy and just prior to subsquent births
  
  • Rh[D] Ig = human IgG directed at the RhD antigen
  • Idea is that the Rh[D] Ig will bind all RhD antigen in mom and will then be excreted
  • This will prevent presentation of the RhD antigen to the maternal adaptive immune system → prevention of ab development