The Body’s Defense Against Pathogens -- Memory Dr. Conrad – April 7, 2009

Objectives To understand how memory is important for species survival List the components important in maintaining memory. Define original antigenic sin and what it means to the immune response to a pathogen.

What is memory? A successful adaptive IR also establishes a state of long term protective immunity. Second or subsequent encounter with same pathogen provokes a stronger and faster secondary response. Causes of memory -- Clones of long-lived memory T and B – Constant exposure to low antigen levels.

Protective immunity consist of preformed antibodies and existing effector T cells giving Immunological memory

Advantages of memory Re-exposure to same pathogen results in mild and perhaps unnoticeable disease. Evolutionarily – even with a high mortality pathogen – re-infection mortality low. Survivors can care for sick.

Characteristics of memory With time – decreases Protection requires memory T and B Length of effectiveness varies with pathogen – but can be for life. Mechanism not completely clear Long-lived memory lymphocytes Periodic restimulation

Memory B cells – Isotype switched – produce high affinity Ab. Somatic mutation and affinity maturation has taken place. Means response to lower pathogen levels and quicker response. More efficient in internalizing pathogen. Increased MHC Class II – turns on T faster.

Memory B cells –

Figure shows that the amount, Class and and affinity of antibody Increases with time.

Ab response can be “unhelpful”. Allergy – IgE Serum Sickness – shown at right – antigen antibody complexes cause the problems seen. Foreign protein Drug induced

T Cell Memory Can be difficult to differentiate between long-lived effector T cells and memory T. CTL represent best case for memory in that memory CTL require 1-2 day induction period vs immediate (minutes) for effector T cells. CD4 – examination of surface markers shows differences between memory and effector CD4 T cells.

Cell surface CD4 T cell markers --

Periodic restimulation – importance of FDCs…

Antigens can be retained for long periods on FDCs in the form of immune complexes. FDCs express high levels of Fc and C3 receptors – Bind Ag/Ab complexes Retain for long periods of time. Allows for continual restimulation of B cells. B can restimulate T as well. Which model is correct – probably both --

Memory T… Similar situation to B cell – most naïve T upon activation become short-lived effector cells. A few become memory T – not clear if antigen is required for survival.

Importance of Memory T cells in Secondary Response to Pathogen Naïve lymphocyte activation not usually seen or necessary. Hemolytic disease of newborn example – where anti-Rh is given – prevents primary response from occurring.

Concept of “Original Antigenic Sin” Primary response is prevented when secondary response is available. Can work to disadvantage in situations where pathogen is highly mutatable e.g. influenza virus. New and highly immunogenic epitopes go unused.

Original Antigenic Sin…

Original Antigenic Sin…

Summary