This example specifically address the question asked by Dr. Actor following the "Cells of the Immune System" lecture (How does the lack of a spleen effect B cell function, and what implications does this have towards the immune response to infective agents? In Adults? In Children?). It may also be used as a guide for the format required to complete the Clinical Correlate Assignment.

Case 1. Congential Asplenia

Q1. Define the deficiency/hyperreactivity involved in this case, if one can be identified.

1. The deficiency is a compromise of both the reticuloendothelial (RES) system and adaptive immunity by the congenital absence of a spleen. The major shortcoming is a loss of mononuclear phagocytes to clear opsonized pathogenic organisms from the blood. Secondarily, there is a loss of B and T cell mass which may ultimately be largely compensated at the level of systemic lymphoid tissue. However, it is the lack of the phagocytic function that predisposes the individual to morbidity/mortality from encapsulated organisms like streptococcus pneumoniae, Hemophilus influenzae and/or Neisseria meningitides.

Q2. How does this immune disorder directly or indirectly involve or impact each of the following (answer all): 

· Innate immune system activities

· B cell activities

· T cell activities

2. The innate system component that is primarily affected is the mononuclear phagocytes (splenic macrophages). T cell function is systemically impaired for a time after a therapeutic splenectomy but no role for the spleen in the normal maturation of T cells has ever been established. The loss of B cell mass can and typically does result in a noticeable but clinically insignificant decrease in total immunoglobulin levels. In terms of specific antibody responses to antigen, the route of antigen exposure is critical to the response. Routes that favor lymphatic accumulation of antigen (i.e. percutaneous, enteral, mucosal) produce what is usually adequate antibody titers. However, hematogenous exposure results in suboptimal or absent antibodies against the specific antigens since there is no splenic lymphoid tissue to process the antigen and present for T-B cell interactions.

Q3. Describe the underlying mechanism(s) (e.g. at the organ, cellular or molecular level) in this case (brief paragraph).

3. The missing organ compromises the host’s ability to resist hematogenous dissemination of encapsulated organisms. The lack of T and B cells compromise the host’s ability to mount an antigen-specific immune response to opsonize bacteria for phagocytosis.

Q4. Give a short, succinct summary of the immunologic principle illustrated by this case.

4. Route of antigen exposure as well as cellular/organic integrity of the immune system are both important factors in determining the type of immune response, and therefore in activating an effective host defense against certain pathogenic organisms.

Loss of a spleen would be more detrimental to a child than an adult, primarily due to a pre-established immune response (B cell) to bacterial antigens in the adult. In the adult, pre-existing memory B cells can be activated in other tissues (e.g. lymph nodes, GALT, MALT, BALT), although the overall response in these adults is typically diminished. In the child, there is less likely to be a preexisting memory population. The lack of splenic lymphoid tissue to process antigen greatly decreases the chance of B cell activation and further production of Plasma cells and Memory B cells.