Introduction to Biology — Cell Biology, Developmental Biology, and Immunology

Cell Signaling

Cell signaling:

Exchanging information between cells and regulating the response to external stimuli
Signaling steps: signal → receptor → intermediary → response

Receptor types:

G-protein-coupled receptors (GPCRs): a protein that spans the membrane seven times GDP → GTP exchange → activates the G protein adrenaline, histamine, and visual and olfactory receptors
Receptor tyrosine kinases (RTKs): ligand binding → dimerization → autophosphorylation the insulin receptor, the EGF receptor, growth-factor receptors
Ionotropic (ion-channel) receptors: neurotransmitter binding → the ion channel opens acetylcholine, GABA receptors
Nuclear receptors: steroid or thyroid hormone binding → directly regulates transcription

Second messengers:

cAMP (cyclic AMP): adenylyl cyclase → ATP → cAMP activates PKA (protein kinase A) broken down by phosphodiesterase
IP3 and DAG (inositol trisphosphate and diacylglycerol): phospholipase C → breaks down PIP2 IP3: releases Ca2+ inside the cell DAG: activates PKC
Ca2+ signaling: binds calmodulin → activates CaM kinase regulates muscle contraction and cell secretion

The MAPK pathway:

RTK → Ras → Raf → MEK → ERK
ERK: phosphorylates nuclear transcription factors → gene expression
Regulates cell proliferation, differentiation, and survival
Ras mutations (KRAS) are common in cancer

The PI3K/Akt pathway:

RTK → PI3K → PIP3 → Akt (PKB)
Activates mTOR → protein synthesis and cell growth
PTEN: breaks down PIP3 → a tumor suppressor
Regulates cell survival, proliferation, and glucose metabolism

The Cell Cycle and Cancer

The cell cycle:

G1 phase (preparing to synthesize): RNA and protein synthesis, cell growth
S phase (DNA synthesis): DNA replication
G2 phase (preparing to divide): spindle-fiber synthesis, DNA-damage checkpoint
M phase (mitosis): prophase → prometaphase → metaphase → anaphase → telophase
G0 phase (quiescent): mature cells (neurons, muscle cells, and the like)

Cyclin-CDK complexes:

Cyclin: its concentration fluctuates periodically
CDK (cyclin-dependent kinase): activated when bound to cyclin
G1 progression: cyclin D-CDK4/6
G1→S: cyclin E-CDK2
S-phase progression: cyclin A-CDK2
M-phase progression: cyclin B-CDK1 (MPF)

Cell-cycle checkpoints:

G1 checkpoint: checks DNA damage, nutrients, and growth factors the Rb protein suppresses the E2F transcription factor
- Rb phosphorylation → E2F activation → S-phase progression
G2 checkpoint: confirms replication is complete and checks for damage
M-phase (spindle-assembly) checkpoint: confirms every chromosome is attached to the spindle
p53: detects DNA damage → induces p21 → inhibits CDK → arrests the cell cycle or triggers Bax expression → induces apoptosis

Cancer:

Accumulated somatic mutations → uncontrolled proliferation
Oncogenes: a proto-oncogene → mutation or overexpression → becomes an oncogene Ras, Myc, HER2, BCR-ABL
Tumor-suppressor genes: p53, Rb, BRCA1/2, APC Knudson’s “two-hit hypothesis”
Metastasis: epithelial-mesenchymal transition (EMT) → vascular invasion → colonizing a distant organ
Angiogenesis: the tumor secretes VEGF → new blood vessels form → the tumor grows

Apoptosis:

Programmed cell death (distinct from necrosis)
Extrinsic pathway: death receptors (Fas, TNFR) → caspase 8
Intrinsic pathway: Bax → mitochondrial cytochrome c → caspase 9
Executioner caspases 3, 6, 7 → DNA fragmentation, cell shrinkage, phagocytic clearance
Bcl-2 overexpression in cancer → suppresses apoptosis

Developmental Biology

Fertilization and early development:

Fertilization: sperm and egg fuse → a zygote
Cleavage: cell division without growth → morula → blastula
Blastula: blastocoel, trophectoderm, inner cell mass
Implantation: the blastocyst implants in the uterine lining (around days 6–7 of pregnancy)

Gastrulation:

The inner cell mass → forms three germ layers
Ectoderm: skin epithelium, the nervous system, sensory organs
Mesoderm: muscle, skeleton, the circulatory system, kidneys
Endoderm: the digestive-tract lining, the respiratory system, endocrine glands
The primitive streak: establishes the vertebrate embryo’s anterior-posterior axis

Neurulation:

The notochord → induces the dorsal ectoderm → forms the neural plate
The neural plate → neural tube (brain and spinal cord) → failed closure → spina bifida
Folate deficiency → raises the risk of a neural-tube defect

Induction:

One tissue induces the differentiation of an adjacent tissue
The notochord induces the neural tube (the Spemann organizer)
Involves the FGF, BMP, Wnt, and Notch signaling pathways

Homeobox genes:

Determine segment identity (along the anterior-posterior axis)
A 180-base-pair homeobox domain: a DNA-binding transcription factor
Four gene clusters in humans (HoxA–D): a distinctive spatial expression pattern
Mutation → homeotic transformation (a fruit-fly antenna becomes a leg)

Stem cells and development:

Totipotent: the 4–8-cell stage after fertilization (can form every cell, including the placenta)
Pluripotent: the inner cell mass → embryonic stem cells (can form every somatic cell type)
Multipotent: adult stem cells (form a limited range of cell types)
Unipotent: form only one specific cell type (e.g., spermatogonial stem cells)

Immunology

Innate immunity:

Nonspecific, rapid response (minutes to hours)
Physical barriers: skin, mucous membranes, cilia, stomach acid
Cellular components: neutrophils: the most abundant white blood cell, phagocytic macrophages: phagocytose, secrete cytokines, function as antigen-presenting cells natural killer (NK) cells: directly kill virus-infected cells and cancer cells dendritic cells: antigen-presenting cells that bridge to adaptive immunity

Pattern-recognition receptors:

Toll-like receptors (TLRs): recognize pathogen-associated molecular patterns (PAMPs) TLR4: recognizes LPS (bacterial-membrane component)
NOD receptors: recognize intracellular PAMPs
The complement system: a serum-protein cascade → lyses bacteria and promotes phagocytosis

Adaptive immunity:

Specific, slower, and generates immune memory
Lymphocytes: B cells (humoral) and T cells (cell-mediated)

B cells and antibodies (humoral immunity):

B-cell development: bone marrow → expression of the BCR (B-cell receptor)
Antigen recognition → helper T-cell assistance → plasma cells and memory B cells
Antibody (immunoglobulin) structure: two heavy chains + two light chains (Y-shaped) Fab region: binds antigen Fc region: effector function (activates complement, promotes phagocytosis)
Antibody classes: IgG: the most abundant, crosses the placenta, dominates the secondary immune response IgM: the early response, a pentamer IgA: found in mucosa and breast milk, a dimer IgE: allergy, parasitic infection IgD: a B-cell receptor

T cells (cell-mediated immunity):

T-cell development: bone marrow → thymus (positive and negative selection)
TCR (T-cell receptor): recognizes an MHC-antigen complex
CD4+ helper T cells: recognize MHC II → activate B cells and cytotoxic T cells Th1: cell-mediated immunity (IFN-γ) / Th2: humoral immunity (IL-4) Th17: inflammation / Treg: immune suppression
CD8+ cytotoxic T cells: recognize MHC I → directly kill infected cells secrete perforin and granzymes

MHC (major histocompatibility complex):

MHC I: on all nucleated cells → presents endogenous peptides
MHC II: on professional APCs (macrophages, dendritic cells, B cells) → presents exogenous peptides
In humans: HLA (human leukocyte antigen)
The underlying cause of organ-transplant rejection

Vaccines:

Pre-forming immune memory → a fast response upon reinfection
Live attenuated vaccines: MMR, chickenpox, rotavirus
Inactivated vaccines: flu, polio (Salk)
Subunit vaccines: hepatitis B, HPV
mRNA vaccines: COVID-19 (Moderna, Pfizer) lipid nanoparticle → mRNA → spike protein → immune response

Autoimmune disease:

A failure of immune tolerance → an attack on self-antigens
Rheumatoid arthritis, type 1 diabetes, lupus, multiple sclerosis
Treatment: immunosuppressants, steroids, biologics (TNF inhibitors)

Frequently Asked Questions

Q. Why is cancer so hard to treat, and why does it recur? A. Several biological factors make cancer difficult to treat. First, there’s tumor heterogeneity: a single tumor mass contains genetically diverse cells, so cells sensitive to a given treatment die while a resistant minority survives and repopulates the tumor — the core cause of recurrence. Second, the cancer stem cell hypothesis holds that a small subset of self-renewing cells within the tumor can regenerate a new tumor even after treatment. Third, there’s immune evasion: cancer cells reduce MHC I expression or raise PD-L1 to escape immune attack. Recent immune checkpoint inhibitors (antibodies blocking PD-1 or CTLA-4) counter this evasion and produce striking results in some cancers. Fourth, there’s metastasis: treating metastatic cancer is far harder than treating the primary tumor.

Q. How does a vaccine create immune memory? A. A vaccine introduces an antigen (or the information to build one) into the body, which triggers an immune response. In the process, some B cells and T cells differentiate into memory cells that persist in the body for decades. Unlike the primary immune response, which takes days, memory cells can produce a large-scale antibody response and activate cytotoxic T cells within hours upon re-exposure to the same antigen. With mRNA vaccines specifically, the mRNA is translated by ribosomes in our own cells to produce the antigen protein, which is then presented to the immune system via MHC. The mRNA does not insert into DNA and degrades within days, so it does not alter the genome.