Session 2 - Immune System + Pathogen detection

What are the three primary transcription factors (TFs) activated by Toll-like Receptor (TLR) stimulation, and what do they produce?

1. NF-κB: Drives the production of pro-inflammatory cytokines (IL-1, IL-6, IL-8, TNF-α). 2. AP-1: Involved in cellular differentiation and apoptosis.

3. IRFs (Interferon Regulatory Factors): Explicitly drives the production of Type 1 Interferons (IFN-α/β).

Match the following Pattern Recognition Receptors (PRRs) with their specific structural Pathogen-Associated Molecular Pattern (PAMP) ligands: TLR4, NOD1/NOD2, CLRs, RLRs.

TLR4 → Bacterial Lipopolysaccharide (LPS / Lipid A).

• NOD1/NOD2 → Bacterial Peptidoglycan fragments (intracellular).

• CLRs (C-type Lectin Receptors) → Fungal glycans (mannan/glucans).

• RLRs (RIG-I-like Receptors) → Viral cytoplasmic RNA.

How do Type 1 Interferons (IFN-α and IFN-β) mechanically induce the "anti-viral state" in neighboring uninfected cells?

They bind to neighboring cell receptors to trigger a step-by-step intracellular block:

1. Activating RNase enzymes to rapidly degrade foreign viral RNA.

2. Inhibiting host and viral protein synthesis.

3. Shutting down viral gene expression and structural assembly.

What are the three main clinical/physiological functions of the complement system, and which specific protein fragments orchestrate them?

Opsonisation: C3b coats the surface of the microbe, marking it for high-affinity phagocytosis. 2. Inflammation: C3a and C5a act as potent chemoattractants (anaphylatoxins) to recruit and activate leukocytes. 3. Cell Lysis: C5b recruits C6, C7, C8, and multiple C9 molecules to assemble the Membrane Attack Complex (MAC), punching a transmembrane pore to cause osmotic lysis.

What are the exact structural components found within the cytoplasmic granules of Neutrophils used to destroy engulfed bacteria inside the phagolysosome?

Defensins (disrupt microbial membranes), Myeloperoxidase (generates toxic hypochlorous acid), Catalase, Elastase, and Metalloproteinases.

Map the sequential, step-by-step molecular cascade of Extravasation during acute tissue inflammation.

• 1. PAMPs/DAMPs bind to tissue resident mast cells/macrophages → 2. Triggers rapid degranulation and release of Histamine → 3. Histamine binds endothelial cells to dramatically increase vascular permeability (causing fluid leak/edema) → 4. Nitric Oxide (NO) is synthesized, driving profound capillary vasodilation (increasing local blood flow).

Explain the exact molecular and neurological mechanism behind the induction of Fever.

Pro-inflammatory cytokines (IL-1, TNF, IL-6) stimulate the production of Prostaglandin E2 (PGE2) → PGE2 travels to the brain and binds explicitly to the EP3 receptor subtype in the preoptic area of the hypothalamus → This triggers systemic thermogenesis (fever generation). Note: This is why NSAIDs work—they block the COX enzyme, stopping PGE2 synthesis.

Describe the structural anatomy of an Antibody (Immunoglobulin) molecule, detailing the functions of its specific regions.

Y-shaped glycoprotein consisting of 2 heavy chains and 2 light chains linked by disulfide bonds.

• Variable (Fab) Region: The tips of the Y; acts as the antigen-binding site (highly specific).

• Constant (Fc) Region: The stem of the Y; binds to host immune cell Fc receptors (e.g., on macrophages) or fixes complement.

Differentiate between MHC Class I (MHCI) and MHC Class II (MHCII) regarding which cells express them and which T-cells recognize them.

MHC Class I: Expressed on all nucleated host cells. It presents endogenous antigens (like viral proteins) directly to CD8+ Cytotoxic T-cells to induce target cell apoptosis via perforin/granzyme B.

• MHC Class II: Expressed exclusively on professional Antigen-Presenting Cells (APCs) (Macrophages, Dendritic cells, B-cells). It presents exogenous processed antigens directly to CD4+ T-helper cells to drive cytokine release and B-cell clonal expansion.