Adaptive Immunity Overview

Adaptive Immunity

• Ability of the body to defend itself against specific invading agents
• Antigens (Ags) are substances recognized as foreign, triggering an immune response.
• Distinguished from innate immunity by specificity and memory.

Maturation of T cells and B cells

• Both develop from pluripotent stem cells originating in red bone marrow.
• B cells complete development in red bone marrow.
• T cells develop from pre-T cells, migrating from red bone marrow to the thymus.
• Helper T cells (CD4 T cells) and cytotoxic T cells (CD8 T cells) are components.
• Immunocompetence is the ability to carry out adaptive immune responses due to antigen receptors (proteins inserted into plasma membranes), identifying specific antigens.

Types of Adaptive Immunity

Cell-mediated

• Cytotoxic T cells directly attack invading antigens.
• Particularly effective against intracellular pathogens (viruses, bacteria, fungi), some cancer cells, and foreign tissue transplants.
• Involve cells attacking cells.

Antibody-mediated

• B cells transform into plasma cells, producing antibodies (Abs) or immunoglobulins.
• Works against extracellular pathogens found in fluids outside cells.
• Helper T cells assist in both types.
• Cell-mediated (CM) and antibody-mediated (AM) immunity often function together to eliminate large numbers of specific antigens.

Clonal Selection

• Process where a lymphocyte proliferates and differentiates (becoming highly specialized) in response to a specific antigen.
• A clone is a population of identical cells recognizing the same antigen as the original cell.
• This process occurs in secondary lymphatic organs and tissues, evidenced by swollen lymph nodes and tonsils during illness.
• Lymphocytes undergo clonal selection to produce effector cells (inactivation of antigens) such as active helper T cells, active cytotoxic T cells, and plasma cells (which die after the immune response).
• Memory cells do not participate in the initial response but react to subsequent invasions, differentiating into effector and memory cells with long lifespans.
• These cells rapidly eliminate antigens before any signs or symptoms appear.

Antigens

• Antigens have two key characteristics:
  • Immunogenicity: ability to provoke an immune response.
  • Reactivity: ability to react specifically with antibodies it provoked.
• Entire microbes can act as antigens, but typically only specific parts (small components called epitopes or antigenic determinants) trigger an immune response.

Diversity of Antigen Receptors

• The human immune system can recognize and bind to at least a billion different epitopes.
• An epitope, also known as an antigenic determinant, is the part of an antigen recognized, specifically by antibodies, B cells, or T cells.
• Major Histocompatibility Complex Antigens (MHC) are proteins (self-antigens) located at the plasma membrane surface of most body cells (MHC or human leukocyte antigens (HLA).
• MHC helps T cells recognize foreign or self molecules.

Pathways of Antigen Processing

• B cells can recognize and bind to antigens in lymph, interstitial fluid, or blood plasma.
• T cells only recognize processed antigen fragments presented by antigen-presenting cells (APCs) in a specific way.
• Antigenic proteins are broken down into peptides and associated with MHC molecules for antigen presentation.
• The antigen-MHC complex is inserted into the plasma membrane.
• Antigen processing pathway depends on whether the antigen is outside or inside body cells.

Antigen-Presenting Cells (APCs)

• Process and present antigens.
• APCs include dendritic cells, macrophages, and B cells.
• Locations where antigens may penetrate, such as skin (Langerhans cells), mucous membranes of respiratory, gastrointestinal, urinary, and reproductive tracts, lymph nodes.
• APCs migrate from tissues to lymph nodes via lymphatic vessels.

Exogenous and Endogenous Antigens

Exogenous

• Antigens present in fluids outside body cells.
• APCs (dendritic cells, macrophages, B cells) engulf, process, attach antigens to MHC-II molecules and present them to T cells.
• This process migrates the APC to lymphatic tissue where it can present processed antigens to T cells, triggering a cell-mediated or antibody-mediated immune response.

Endogenous

• Antigens located inside body cells (e.g., infected cells).
• The infected cell displays endogenous antigens bound to MHC-I molecules to T cells, subsequently activating immune responses.

Cell-Mediated Immunity

• Activation of T cells involves a first signal (T-cell receptors (TCRs) binding to specific foreign antigen fragments presented on antigen-MHC complexes) and a second signal (costimulation through membrane molecules like cytokines and interleukin-2). This allows targeted responses and prevents accidental immune reactions.
• Different T cell types like helper T cells (CD4 T cells) and cytotoxic T cells (CD8 T cells) have distinct roles in combating intruders and eliminating infected cells.

Activation and Clonal Selection of Cytotoxic T cells

• Cytotoxic T cells (CD8 T cells) recognize antigens combined with MHC-I molecules.
• Activation requires antigen presentation with MHC-II and IL-2 production by helper T cells.
• Activated cytotoxic T cells attack and destroy infected body cells.
• Memory cytotoxic T cells do not attack immediately. Instead, they remain in the body to provide a faster response if the same antigen appears again.

Elimination of Invaders

• Cytotoxic T cells seek out and destroy infected target cells with mechanisms similar to natural killer cells (NK cells), but targeting is antigen-specific. Cytotoxic T cells use granzymes to induce apoptosis or perforin and granzymes to directly destroy infected cells.
• Immunological surveillance identifies and destroys abnormal cells like cancerous cells.

Activity of Cytotoxic T Cells

• Activated cytotoxic T cells release granzymes and perforins to destroy infected body cells.
• Granzymes induce apoptosis, while perforins cause cytolysis (cell bursting).