CSIR NET Life Sciences Cell communication and cell signaling Syllabus

What is the difference between hydrophilic and lipophilic hormone signaling?

Hydrophilic hormones (peptides, catecholamines) bind cell-surface receptors and use second messengers. Lipophilic hormones (steroids, thyroid hormone) cross the membrane and bind intracellular/nuclear receptors that act as transcription factors.

What is an oncogene and how does it arise?

An oncogene is a mutated/overexpressed gain-of-function version of a proto-oncogene (normal growth-promoting gene) that drives uncontrolled proliferation. Activation occurs via point mutation, gene amplification, or chromosomal translocation (e.g., RAS, MYC, BCR-ABL).

What is a tumor suppressor gene and how is it inactivated?

A gene that restrains cell growth or promotes apoptosis (e.g., p53, RB, APC, BRCA1). It is recessive at the cellular level, requiring loss-of-function in both alleles (Knudson's two-hit hypothesis) to lose its protective function.

What is the role of p53 in the cell cycle?

p53 ('guardian of the genome') senses DNA damage and induces p21, which inhibits cyclin-CDK complexes causing G1 arrest for repair; if damage is irreparable, p53 triggers apoptosis.

How do RB protein and E2F regulate the cell cycle?

Hypophosphorylated RB binds and inhibits E2F transcription factors. Cyclin D-CDK4/6 phosphorylates RB, releasing E2F to drive transcription of S-phase genes, allowing G1-to-S progression.

What is the difference between proto-oncogenes acting dominantly and tumor suppressors acting recessively?

A single activating mutation in one allele of a proto-oncogene (dominant gain-of-function) can promote cancer; tumor suppressors require inactivation of both alleles (recessive loss-of-function) to contribute to cancer.

What is metastasis and its main steps?

The spread of cancer cells from a primary tumor to distant sites: local invasion (loss of E-cadherin, EMT), intravasation into blood/lymph, survival in circulation, extravasation, and colonization/growth at a secondary site.

How do viruses induce cancer (virus-induced transformation)?

Tumor viruses introduce viral oncogenes (e.g., HPV E6/E7 inactivating p53/RB), insert near host proto-oncogenes (insertional mutagenesis), or carry transduced oncogenes (e.g., v-src). Examples: HPV (cervical), HBV/HCV (liver), EBV (Burkitt lymphoma), HTLV-1.

What is apoptosis and how does it differ from necrosis?

Apoptosis is programmed, energy-dependent cell death with cell shrinkage, chromatin condensation, DNA laddering, membrane blebbing, and apoptotic bodies without inflammation. Necrosis is uncontrolled, with cell swelling, lysis, and inflammation.

Compare the intrinsic and extrinsic pathways of apoptosis.

Intrinsic (mitochondrial): internal stress causes cytochrome c release, apoptosome (Apaf-1) formation, activating caspase-9. Extrinsic (death receptor): ligands (FasL/TNF) bind death receptors forming DISC, activating caspase-8. Both converge on executioner caspases (caspase-3).

What is the role of the Bcl-2 family in apoptosis?

It regulates mitochondrial outer membrane permeabilization: anti-apoptotic members (Bcl-2, Bcl-xL) inhibit cytochrome c release, while pro-apoptotic members (Bax, Bak, Bad, Bid) promote it. The balance determines cell fate.

Name therapeutic strategies against uncontrolled cell growth (cancer).

Cytotoxic chemotherapy, radiation, targeted therapies (kinase inhibitors like imatinib, monoclonal antibodies like trastuzumab/rituximab), anti-angiogenesis (bevacizumab), hormone therapy, and immunotherapy (checkpoint inhibitors, CAR-T).

How do pathogens recognize and enter host cells?

Pathogens use surface adhesins/ligands binding host receptors, then enter by receptor-mediated endocytosis, membrane fusion (enveloped viruses), or by injecting effectors (Type III/IV secretion in bacteria) that trigger uptake (e.g., Salmonella 'trigger', Yersinia 'zipper' mechanisms).

How do pathogens alter host cell behavior?

They inject/secrete effector proteins that hijack host signaling—remodeling the cytoskeleton, modulating vesicle trafficking, blocking apoptosis or inducing it, suppressing immune signaling, and reprogramming gene expression to favor survival and replication.

Give examples of pathogen-induced diseases in plants and animals.

Plants: bacterial blight (Xanthomonas), crown gall (Agrobacterium), tobacco mosaic virus, late blight (Phytophthora). Animals: tuberculosis (Mycobacterium), foot-and-mouth disease (virus), trypanosomiasis (Trypanosoma).

What is cell-cell fusion and where does it occur normally vs abnormally?

Fusion of two cells into one multinucleate cell. Normal: fertilization, myoblast fusion (muscle), trophoblast (placenta), osteoclast formation. Abnormal: virus-induced syncytia (e.g., measles, HIV), and tumor cell fusion contributing to malignancy.

What cells and molecules mediate innate immunity?

Cells: macrophages, neutrophils, dendritic cells, NK cells, mast cells. Molecules: pattern recognition receptors (TLRs), complement, cytokines, antimicrobial peptides, acute-phase proteins. It is rapid, non-specific, with no memory.

How does adaptive immunity differ from innate immunity?

Adaptive immunity is antigen-specific, slower, mediated by B and T lymphocytes with diverse receptors generated by gene rearrangement, and produces immunological memory. Innate immunity is fast, germline-encoded, non-specific, and lacks memory.

Define antigen, antigenicity, and immunogenicity.

Antigen: a molecule recognized by antibodies/receptors. Antigenicity: ability to be specifically bound by antibodies/TCR. Immunogenicity: ability to induce an immune response. All immunogens are antigens, but not all antigens (e.g., haptens) are immunogens.

What is the difference between B-cell and T-cell epitopes?

B-cell epitopes are often conformational (3D surface determinants) recognized by antibodies/BCR in native antigen. T-cell epitopes are linear peptides generated by antigen processing and presented on MHC molecules to the TCR.

Describe the basic structure of an antibody (IgG).

A Y-shaped molecule of two identical heavy chains and two identical light chains linked by disulfide bonds; each chain has variable (V) and constant (C) regions. Fab fragments contain antigen-binding sites; Fc mediates effector functions. Hypervariable CDRs form the binding site.

List the five antibody isotypes and a key function of each.

IgG (most abundant, secondary response, crosses placenta), IgM (first produced, pentamer, agglutination/complement), IgA (mucosal/secretory, dimer), IgE (allergy, parasites, mast cells), IgD (mature B-cell surface receptor).

How is antibody diversity generated?

By V(D)J recombination (combinatorial joining of gene segments via RAG1/RAG2), junctional diversity (imprecise joining, TdT-added N-nucleotides), combinatorial heavy/light chain pairing, and somatic hypermutation (affinity maturation, via AID).

What are monoclonal antibodies and how are they classically produced?

Identical antibodies from a single B-cell clone with a single specificity. Produced by the hybridoma technique: fusing antigen-primed B cells with immortal myeloma cells, then HAT selection and screening for the desired clone.

What is antibody engineering (give examples)?

Genetic modification of antibodies to improve clinical use: chimeric (mouse V + human C), humanized (only CDRs from mouse), fully human antibodies, single-chain Fv (scFv) fragments, and bispecific antibodies.

Compare MHC class I and class II molecules.

MHC I (on all nucleated cells) presents endogenous peptides (8-10 aa) to CD8+ T cells; structure: alpha chain + beta2-microglobulin. MHC II (on APCs) presents exogenous peptides (13-25 aa) to CD4+ T cells; structure: alpha + beta chains.

Describe antigen processing for MHC class I vs class II.

Class I: cytosolic proteins degraded by the proteasome, peptides transported by TAP into the ER, loaded onto MHC I. Class II: extracellular proteins endocytosed, degraded in endosomes/lysosomes, loaded onto MHC II after invariant chain (CLIP) removal by HLA-DM.

What signals are required for T-cell activation?

Signal 1: TCR recognition of peptide-MHC (with CD4/CD8 co-receptor). Signal 2: co-stimulation (CD28 on T cell binding B7/CD80-86 on APC). Signal 3: cytokines directing differentiation. Without signal 2, T cells become anergic.

What is the complement system and its three activation pathways?

A cascade of serum proteins enhancing immunity via opsonization, inflammation, and the membrane attack complex (MAC, C5b-9) for lysis. Pathways: classical (antibody-antigen/C1q), lectin (MBL binding mannose), and alternative (spontaneous C3 hydrolysis); all converge at C3 convertase.

What are Toll-like receptors (TLRs) and what do they recognize?

Pattern recognition receptors of innate immunity that detect PAMPs—e.g., TLR4 (LPS), TLR5 (flagellin), TLR3 (dsRNA), TLR9 (CpG DNA). They signal via MyD88/TRIF to activate NF-kB, inducing inflammatory cytokines.

Compare humoral and cell-mediated immune responses.

Humoral immunity: B cells/plasma cells produce antibodies against extracellular pathogens/toxins. Cell-mediated immunity: T cells—CD8+ CTLs kill infected cells, CD4+ Th cells coordinate responses—target intracellular pathogens.

What are the four types of hypersensitivity reactions?

Type I: immediate/IgE-mediated (allergy, anaphylaxis). Type II: antibody-mediated cytotoxic (IgG/IgM vs cell-surface antigens). Type III: immune-complex mediated. Type IV: delayed-type, T-cell mediated (e.g., contact dermatitis, TB skin test).

What is the immune response and immune evasion in HIV infection?

HIV infects CD4+ T cells (via CD4 + CCR5/CXCR4), progressively depleting them and causing AIDS. It evades immunity through high mutation/antigenic variation, latency, and downregulation of MHC I. Responses include neutralizing antibodies and CTLs that ultimately fail to control infection.