Adaptive immunity Comprehensive Study Guide on Adaptive Immunity and Lymphocyte Biology

The Adaptive Immune Process and Antibody Production

• The transformation of a B cell into a plasma cell marks the point at which the immune system begins producing antibodies.

• These antibodies are highly specific for the particular antigen that has been presented to the cell.

• The output of an antigen presentation to a B cell is the creation of antibodies, which serve as the byproduct produced by the plasma cell.

• This activity represents the beginning of the adaptive immune process.

• The adaptive process takes a longer time to develop compared to the innate system. It typically requires at least a second exposure to an invader to be fully effective because it takes time for specific antibodies to develop.

• In contrast, the innate immune system provides an immediate, nonspecific attack. It includes mechanisms such as mucus, the throat, and skin edges (where cuts or injuries occur). Key cells in the innate system include NK cells and phagocytes.

• Acquired or adaptive immunity enters the picture only when the natural resistance of the first and second lines of defense is overcome by an invader.

Characteristics of the Adaptive Immune System

• Specificity: The adaptive system is highly specific. For example, an antibody formed against the chicken pox virus will have no effect on the mumps virus. These cells are described as being like CIA agents or target-specific cells that focus on one thing and nothing else.

• Scope: The response is large in scope, meaning it can hit many epitopes of an antigen. Epitopes are the specific sites where the antigen and antibody hook together.

• Discrimination: The system has a critical ability to discriminate between self and nonself. This prevents immune responses against one's own body, which would otherwise result in autoimmunity or autoimmune disorders.

• Memory: Lymphocytes, including T cells and B cells, can live for years in the body. They retain a memory of the virus, so the body does not have to "go back to the drawing board" to reprocess an antigen upon second exposure. They can quickly replicate the genetic code of the required antibody.

• In patients with AIDS, these memory cells are lost, rendering them unable to fight off mundane infections that a healthy immune system would handle without the person even noticing.

Development and Migration of Lymphocytes

• All lymphocytes arise from hematopoietic stem cells, which are "mother cells" located in the bone marrow.

• The stem cell acts like a pinball machine; chemical messengers like chemokines and cytokines tell the stem cell which cell line to produce. It might go down the lymphocyte category, the megakaryocyte column to produce platelets, or columns for red cells.

• If the bone marrow is nonfunctional, such as in aplastic anemia, the individual will lack white cells, red cells (hemoglobin for oxygen), and platelets, necessitating a stem cell transplant.

• While all cells originate in the bone marrow, they differentiate and mature in primary lymphoid organs:

  • B cells: They originate in the bone marrow and stay in the bone marrow to mature (B for Bone marrow).

  • T cells: They originate in the bone marrow but migrate to the thymus to mature (T for Thymus). The thymus is a small organ located behind the thyroid.

Anatomy and Function of Lymphoid Organs

• Primary Lymphoid Organs: These are the sites where lymphocytes arise and mature (Bone marrow and Thymus).

• Secondary Lymphoid Organs: Once mature, lymphocytes proceed to these areas to "hang out" and wait for infections. These organs are interconnected by the lymph system.

• The lymph system runs adjacent or perpendicular to the circulatory system, containing lymph fluid that acts as a highway for cell transport.

• Secondary lymphoid structures include:

  • Lymph nodes: Found in pockets throughout the system, such as in the throat, under the arms, and in the groin. Swollen or sore knots in these areas during illness indicate the nodes are fighting an infection.

  • Spleen: Highly prolific in lymph nodes.

  • Tonsils: Essentially large lymph nodes.

  • Appendix: A huge lymph node that acts as a "patch basin." It can become infected but is not strictly necessary for survival.

  • Mucosal-associated lymphoid tissue: Found throughout the GI tract and respiratory tract, which are common entry and exit points for invaders.

Cellular and Humoral Arms of the Acquired Immune System

• The acquired system is divided into cellular and humoral components:

  • Cellular Arm: Mediated by T cells. T cells recognize antigens through specific T cell receptor (TCR) sites on their surface. They receive processed antigen information from macrophages or Antigen Presenting Cells (APCs).

  • Humoral Arm: Influenced by the liquid portion of the blood. It involves B cells that produce antibodies in response to an antigen binding to surface immunoglobulins. These B cells convert to plasma cells to secrete antibodies.

• Antigen Presenting Cells (APCs) include dendritic cells, macrophages, and mast cells. These cells phagocytize invaders and present the processed information to T lymphocytes, which then hand off the information to B cells.

• Proliferation: After meeting an antigen, cells undergo mitosis (division) to multiply. Juvenile cells continue to split until they reach adulthood/maturity, at which point they perform their specific function without further division.

Immunoglobulin Structure and Categories

• There are five types of antibodies, remembered by the acronym GAMED:

  1. IgG (can cross the placenta)

  2. IgA

  3. IgM

  4. IgE

  5. IgD

• Basic Structure of an Antibody Molecule:

  • It consists of two heavy chains and two light chains.

  • Binding Sites: It has two binding sites called paritopes, formed by the combination of one heavy and one light chain.

  • Constant Portion: Shown in blue in diagrams, this part does not change and determines the identity of the antibody (e.g., whether it is IgG or IgA).

  • Variable Portion: This part changes depending on the specific antigen it was formed to bind with. It matches the antigen's epitopes.

The Major Histocompatibility Complex (MHC)

• T cells respond to antigens presented in the Major Histocompatibility Complex (MHC).

• MHCs are markers on cells (like macrophages) that act as identifiers. While they are "self" markers in one individual, they would be "non-self" (antigens) if introduced to another person.

• The quality of a person's MHC complex is determined by genetics. A "good" MHC complex leads to a better immune response against non-self entities.

• It is vital to identify where the antigen is and where the antibody is in any laboratory procedure (e.g., antigen typing in microbiology vs. red blood cells) to understand the test's principle.

Flow Cytometry and Cell Identification

• Different types of T cells include Helper T cells ($CD4$), Cytotoxic T cells ($CD8$), and Regulator T cells ($CD4$).

• All immature T cells carry the $CD3$ marker before they differentiate in the thymus.

• Flow Cytometry: A laboratory methodology used to count and bucket these cells based on their CD markers. It uses a fluorescence tag that attaches to the cell. The specimen is run through a laser, and the emission of light allows the count of specific cells like $CD4$ and $CD8$.

Types of Acquired Immunity and Vaccinations

• There are four categories of acquired immunity:

  • Natural Active Immunity: Antibody production following a natural infection (e.g., producing antibodies after having COVID without a vaccine).

  • Artificial Active Immunity: Antibody production in response to a vaccine. The body produces long-term protection without having the actual disease (e.g., the chickenpox vaccine available since the late 1980s).

  • Natural Passive Immunity: The transfer of antibodies from one person to another naturally. This provides short-term protection. Examples include antibodies passing through the placenta (IgG) or through breast milk to a nursing baby.

  • Artificial Passive Immunity: The injection of antibodies (immunoglobulins) into an individual for immediate but temporary protection. Examples include:

  • Immunoglobulin shots after Hepatitis exposure.

  • RhoGAM shots for Rh-negative mothers to prevent the formation of anti-D antibodies that could harm future Rh-positive fetuses.

  • Convalescent plasma infusions for COVID patients.

• "Passive" always indicates that an antibody was involved and passed on, rather than being produced by the recipient's own immune system.

Questions & Discussion

• Question: How do we tell the difference between Natural and Artificial Active immunity?

• Answer: Natural comes from being born with the capacity or catching the infection naturally. Artificial comes from receiving a vaccine.

• Question: What does the word passive always refer to?

• Answer: It is always associated with the word antibody; it means an antibody is being passed to the individual.

• Question: Who are the antigen presenting cells?

• Answer: Dendritic cells, macrophages, and mast cells.

• Question: Which cells are phagocytic?

• Answer: Neutrophils, eosinophils, and monocytes (which become macrophages).