lecutre 16 immunology: immunological memory

steps in B cell differentiation

1. antigen recognition induces expression of effector molecules by T cell, which activates B cell

2. B cell proliferation

3. differentiation to resting memory cells and antibody secreting plasma cells

germinal centers types:

• Mantle Zone

• Dark Zone (AID, mutation & proliferation)

• Light Zone (Selection and differentiation)

• T-Cell Zone (Paracortex) (Tfh cells, T cell area)

mantle zone

•   Naïve B cells pushed aside by proliferating activated B cells.

dark zone

• Populated by rapidly proliferating B cells.

  • Clonal expansion of activated B cells.

• Somatic hypermutation in immunoglobulin variable region genes.

  • outcome: Generates BCR diversity to improve antigen binding.

light zone

• Contains non-dividing B cells, follicular dendritic cells (FDCs), and Tfh cells.

  • Affinity selection: B cells test their newly mutated BCRs against antigen displayed on FDCs.

  • Competition for Tfh help (CD40L, cytokines).

    • Outcome: High-affinity B cells survive, while low-affinity or autoreactive clones undergo apoptosis.

T-Cell Zone (Paracortex) (Tfh cells, T cell area)

• Adjacent area rich in CD4⁺ T cells (especially Tfh precursors).

• Provides help (CD40L, IL-21, IL-4) to B cells entering or within the germinal center.

Memory B cell responsible for?

responsible for anamnestic (secondary) responses to repeated exposures

plasma cells?

• terminally differentiated  B lymphocyte, able to secrete antibody and bc of that are responsible for antibody-mediated immunity.

Terminally differentiated

• cells that have acquired effector functions, and in the process have lost their plasticity (ability to become something else).

  • E.g.: a memory B cells can be activated, and its daughter cells may become either memory cells or plasma cells.  But a fully differentiated plasma cell cannot revert to being a memory cell. 

memory B cell vs plasma cell

how are B cells dynamic?

what does re-exposure change?

changes in the amount and in the composition of antibodies

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affinity maturation is driven by the?

competition for antigens

T cell activation?

1. naive T cell encounters antigen

2. most activated T cell becomes effector cell, some

   1. short lived by apoptosis

3. activated/effector cells become long lived memory cells

   1. cytokines required for survival

most important phenotypes to characterize T cells

• CD45 receptor (tells u if T cell has seen antigen; RA naive, RO activated)

• CD62L ( helps T cells migrate to lymph nodes)

• CCR7 (guides T cells to lymph nodes and secondary lymph organs)

what can their phenotype (which is a set of expressed markers) reveal about the aspect of T cell role?

• migration

• localization

• differentiation

• activation and function

central localization

• LN

peripheral localization

lymphoid tissue (central localization)

• CD62L and CCR7 are +

• CD45RA + in naive T cell and - in T central memory cell

• CD45RO “ “- and + “ “

peripheral localization

• CD62L and CCR7 are - (NEGATIVE)

• CD45RA - in T effector memory cell and + in T effector cell

• CD45RO ‘ ‘ +, “ “ -

CD45

• transmembrane tyrosine phosphatase with three variable exons (A, B, and C) that encode part of its external domain

Shorter spliced receptor (CD45RO)

• goes toward interactions with TCR and more efficient signal transduction

CD45RO switching to a more efficient signal transduction signifies?

exposure to cognate anigen and priming

memory cell function

poor effector function

Effector cells function

• cytokine production and activation markers (IFN-gamma, Granzyme, CD69, CD25)

Follicular helper T cell

 T (Tfh) cells are specialized providers of T cell help to B cells, and are essential for germinal center formation, affinity maturation, and the development of most high affinity antibodies and memory B cells.

• live in lymph nodes (CCR7 and CD662L +)

• homing to B cell follicles (express CXR5 (downregulate CCR7)

how can we tell apart effector vs memory

• using other activation receptors, but not the same ones we use for other T cells.