Untitled Quiz

Hematopoiesis Overview

• Hematopoiesis is the process of forming blood and immune cells from hematopoietic stem cells (HSCs)
• HSCs are multipotent, meaning they can differentiate into all blood cell types
• HSCs have self-renewal, maintaining their population through replication
• Differentiation pathways lead to common progenitors (MPPs)
• MPPs differentiate into Common Myeloid Progenitors (CMPs) and Common Lymphoid Progenitors (CLPs)
• CMPs create macrophages, neutrophils, and other innate immune cells
• CLPs generate B cells, T cells, and NK cells
• Radiation studies on mice injected with HSCs show their regenerative and multipotent abilities

B Cell Development

• Stages: Pro-B → Pre-B → Immature → Mature B cells
• Heavy chain gene rearrangement begins in Pro-B cells
• Pre-B cells express pre-BCR for antigen recognition
• Immature B cells express IgM on their surfaces
• Mature B cells express both IgM and IgD
• B cells achieve diversity through VDJ recombination
• V (variable), D (diversity), and J (joining) segments rearrange to form the variable region of the Ig heavy chain
• Light chain involves only V and J recombination
• RAG proteins are essential for recombination
• Junctional diversity adds nucleotides, enhancing variability
• Antibody production
• B cells differentiate into plasma cells which secrete antibodies
• B cells differentiate into memory cells for long-term immunity

T Cell Development

• Location: T cells originate in the bone marrow but mature in the thymus
• Stages: Pro-T → Pre-T → Double Negative (DN) → Double Positive (DP) → Single Positive (SP)
• Pro-T cells migrate to the thymus
• Pre-T cells begin beta chain rearrangement
• DN cells lack CD4 and CD8 markers
• DP cells express both CD4 and CD8 markers and TCR alpha chain rearranges
• SP cells commit to either CD4 or CD8 lineage
• TCR diversity is achieved through VDJ recombination (beta chain), and VJ recombination (alpha chain)
• Mechanisms of diversity include random mutations and overlapping segments
• RAG proteins and TDT enzyme are crucial for recombination, adding nucleotides to enhance variability.
• CD4 cells are helper T cells and coordinate immune responses
• CD8 cells are cytotoxic T cells and kill infected cells

Proteins and Factors

• Key transcription factors in immune cell maturation include RAG-1/2, E47, and EZA.
• Their roles involve regulating gene expression and development of immune cells.

Immunological Mechanisms

• Testing for autoimmunity involves checking for self-reactive antibodies in immature B cells.
• Gene silencing and epigenetic regulation prevent B cells from becoming T cells.

Experimental Insights

• Chromatin states (euchromatin and heterochromatin) are important, with euchromatin for actively transcribed genes and heterochromatin for inactive regions
• B and T cell gene clusters are spatially organized to ensure lineage-specific transcription.
• Radiation studies demonstrate the regenerative role of HSCs
• Chromosomes are localized in territories; precise gene regulation.

Chromosome Territories and Enhancers

• Chromosome territories are the distinct regions occupied by individual chromosomes within the nucleus.
• Critical Regulatory Elements like promoters and enhancers are located within these territories
• Euchromatin is active transcriptionally, while heterochromatin is inactive.
• Enhancers activate transcription by serving as binding sites for transcription factors, and contribute to regulation, and gene expression.
• Enhancers can be located far from the promoter regions.

Mutations, Tumorigenesis, and Cellular Behavior

• Contact inhibition is crucial for normal cell growth
• Loss of contact inhibition leads to uncontrolled cell growth
• Oncogenes are normal genes that, upon mutation, drive cancer progression
• Metastasis is the spread of cancer cells throughout the body

Summary of Key Cellular Mechanisms

• Primary cells are directly isolated from organisms and have limited growth potential.
• Immortalized cells are mutated or transformed, dividing indefinitely
• Confluency is when cells cover the whole culture plate, stopping cell division without mutation