Adaptive Immunology questions

Adaptive Immunology

• Adaptive immunity is a feature of the immune system involving antigen presentation, lymphocyte activation, B cell effector function, T cell effector function, and memory.
• A microbe is initially encountered by the innate immune system (hours).
• B and T lymphocytes (days) specifically recognize and target a pathogen, producing an antibody response.
• Antigen is any molecule recognized specifically by lymphocytes or antibodies.
• Naive lymphocytes: mature T or B cells never encountering foreign antigen.
• T and B cells bind to specific antigens. This leads to their activation, proliferation, and differentiation.
• Adaptive immunity is mediated by T and B cells.

Phases of Adaptive Immunity

• Antigen recognition, lymphocyte activation, antigen elimination, contraction (homeostasis), and memory phases.
• Antigen recognition is followed by differentiation causing clonal expansion of naive T cells and naive B cells.
• Antibody-producing cells and effector T cells eliminate the antigen,
• The immune response contracts (homeostasis)
• Memory cells remain to aid future immune response

Functions of Adaptive Immunity

• B cells: mediate humoral (soluble) immunity by producing antibodies.
• Helper T cells: interact with other immune cells to direct an effective response.
• Cytotoxic T cells: kill infected or malignant host cells.

Memory in the Adaptive Immune System

• After infection resolution, memory cells remain.
• These aid in faster response during future infection and lessen the disease severity.
• Secondary response is much faster and involves less antigen than a primary response.

TCR and BCR

• TCR (T-cell receptor): antigen-binding site, variable regions, constant regions, transmembrane regions, alpha and beta chains.
• BCR (B-cell receptor): antigen-binding site, light chain, heavy chain, transmembrane region.
• BCR directly recognizes antigen.
• TCR does not directly recognize antigen, instead proteins must be processed into peptides and presented in MHC for T cell recognition.

Antigen Presentation

• T cells cannot directly recognize foreign proteins.
• Proteins must be processed into peptides and presented with major histocompatibility complex (MHC) molecules.
• MHC class I pathway occurs in intracellular pathogens where the foreign protein is made inside the host cell.
• MHC class II pathway occurs in extracellular pathogens where the foreign protein is taken up.

MHC Class I Pathway

• Foreign proteins made inside the presenting cell are presented on MHC class I molecules.
• These molecules are recognized by cytotoxic T cells which have the CD8 marker acting as a coreceptor.
• This leads to death of the presenting cell.

MHC Class II Pathway

• Foreign proteins taken up by the presenting cell are presented on MHC class II molecules.
• These molecules are recognized by helper T cells which have the CD4 marker acting as a coreceptor.
• This leads to activation of the helper T cell.

Dendritic Cells

• Play a central role in processing and presenting antigen.
• They're professional antigen-presenting cells (APCs), along with macrophages and B cells.

Diversity of TCR and BCR

• The variable domains are generated via recombination of gene segments.
• This high diversity allows for a large number of different receptors from a limited number of gene segments.

Negative Selection

• Random generation of BCRs/TCRs can result in recognition of self-antigens.
• Immature T cells recognising MHC molecules with self-peptides undergo apoptosis.
• In the bone marrow, B cells may undergo receptor editing or apoptosis.

Activation of Adaptive Cells

• T Helper cell activation: three signals needed (TCR - antigen recognition, co-stimulation by presenting cell, and cytokines). This leads to clonal expansion and differentiation.
• B cell activation: Requires three signals: BCR (antigen recognition), co-stimulation from Helper T cell, and cytokines.

B Cell-T Cell Interactions

• Co-stimulation results from CD40L on activated Helper T cell and CD40 on the B cell.
• Cytokines influence the antibody type produced.

Lymphocyte Trafficking

• Antigens from the tissue are delivered to the lymph nodes via lymphatics.
• Antigens in the blood are delivered to the spleen. Lymphoid tissue is where immune cells are generated and mature, includes bone marrow and thymus, as well as secondary locations like lymph nodes and spleen for antigen interaction.

Lymph Node

• Encapsulated organs throughout the body, transporting antigens from periphery through lymph.
• Antigen presenting cells deliver antigens to lymphoid follicles containing T & B cells.
• Proliferation leads to germinal center formation and maturation to effector T & B cells.

The Spleen

• Filters blood, eliminating blood-borne pathogens.
• Lymphocyte follicles generate germinal centers for antigen activation, leading to effector T & B cell generation.

Effector Functions of Adaptive Lymphocytes

• B cell function: Antigen recognition leads to plasma cells producing antibodies targeting the microbe. Antibody function involves neutralization, phagocytosis, and complement activation.

Antibody Isotypes

• There are five different antibody classes/isotypes (IgG, IgA, IgE, IgM, IgD).
• Differences in constant regions lead to different biological functions like complement fixation.
• IgM is the first antibody produced.

Antibody Isotype Switching

• Depending on the signal, B cells can switch from producing IgM to other isotypes such as IgG, IgE, or IgA.
• The switch depends on cytokine and receptor interactions with Helper T cells.

Antibody Isotype Differences

• Distinct functions (e.g., protection, allergies, etc.)
• Vary in locations in the body (plasma, secretions, mucosa etc.)
• Different molecular forms (monomer, dimer, pentamer, etc.).

Role of Antibodies

• Antibodies aid in microbe neutralization, phagocytosis, complement activation and cytotoxicity in innate immune cells, and other immune system processes.

Antibodies: Neutralisation

• Antibodies block microbe entry, preventing infection.
• They block toxins from binding to their target, neutralizing their effects.

Antibodies: Opsonization

• Antibody binding to microbes enhances phagocytosis by phagocytes.

Antibodies: ADCC

• Antibodies coating a cell target NK cells which then kill the antibody-coated cells.

T cell Function

• Helper T cells (CD4+): Activation, proliferation, differentiation of T and B cells.
• Cytotoxic T cells (CD8+): Killing of infected cells.

Cytotoxic T Cells

• These cells kill infected host cells.
• Their mechanism of cytotoxicity is similar to NK cells.

T Helper Cells

• Different types of T helper cells exist, depending on the environment and cytokines present.
• Treg cells (regulatory T cells) regulate the immune response and are important for maintaining self-tolerance.

T Helper Cell Subsets

• Different T helper subtypes (Th1, Th2, Th17) have specific cytokine profiles and target different cells (e.g., macrophages, eosinophils, neutrophils).

Memory

• Most lymphocytes die after an immune response, however memory cells persist.
• Memory cells reactivate much faster than naive T or B cells.
• Secondary response involves significantly less antigen and is much faster than primary response.

Test your knowledge on adaptive immunity and its mechanisms in the immune system. This quiz covers concepts like antigen presentation, lymphocyte activation, and the phases of adaptive immunity. Challenge yourself to understand how B and T cells contribute to a specific immune response.