KS

Infection Science & Immunology – Fungal / Parasitic Infections, Immunisation & Diagnostics

Lecture & Module Road-Map

  • Four major thematic blocks covered across the sessions

    • Fungal infections (intro → host defence → pathogen evasion; NETosis emphasis)

    • Parasitic infections (focused case studies: malaria, schistosomiasis, lymphatic filariasis)

    • Immunisation (definitions, history, herd immunity, old vs. new-generation vaccines)

    • Diagnostics in Infection Science (serology, un-/labelled immunoassays, result interpretation)

  • Supporting skills sessions on:

    • Revision techniques (expand-topic lists, mind-maps, connection grids)

    • Scientific answer planning, composition, editing

    • MCQ practice with Vevox (ID 141\text{–}745\text{–}205)

Fungal Infections

  • Pathogen forms: hyphae vs. yeast

  • Key host PRR–PAMP pairs (β-glucan–Dectin-1, mannans–TLR4, etc.)

  • Innate immunity: neutrophils, macrophages, complement, NETosis

  • Adaptive immunity: Th1 (IFN-γ), Th17 (IL-17) responses critical

  • Pathogen evasion

    • Shielding of β-glucan, secretion of proteases, complement inhibition

  • NETosis highlighted as an anti-hyphal mechanism; also appears in bacterial & parasitic contexts (cf. filariasis notes below).

Parasitic Infections

Malaria (Plasmodium spp.)

  • Vector: Anopheles mosquito; erythrocytic & hepatic stages (sexual in mosquito, asexual in human).

  • Immune response:

    • Early IFN-γ, NK-cell activation

    • Antibody-mediated inhibition of merozoite invasion

    • Pathology partly due to excessive inflammatory cytokines.

Schistosomiasis (Schistosoma mansoni, S. japonicum, S. haematobium)

  • Transmission: skin penetration by water-borne cercariae while bathing/swimming.

  • Dual-host life-cycle:

    • Human: cercariae → schistosomulae → portal veins (liver) → paired adults → eggs in mesenteric/vesical venules.

    • Snail: eggs → miracidia → snail tissue (sporocysts) → release of L3 cercariae (infective for 24\text{–}48 h).

  • Innate defence: PRR recognition of Lewis^X antigen; early IL-4/IL-10 bias.

  • Adaptive defence: Th2 dominated; high IgE → FcεR-mediated eosinophil degranulation (MBP, EPO) & mast-cell activation; ADCC.

  • Complement, IgG opsonisation assist macrophage phagocytosis.

  • Diagnostic: ova detection in stool/urine; serology.

Lymphatic Filariasis (Wuchereria bancrofti, Brugia malayi, B. timori)

  • Global burden ≈ \big( 30\text{–}100 \big) million cases

  • Life-cycle key points (CDC diagram reference):

    1. Mosquito ingests microfilariae (L1) during blood meal.

    2. Mid-gut penetration → thoracic muscles → develop to L3 (infective).

    3. Next bite: L3 exit proboscis, enter human skin → lymphatics → adults.

    4. Adults release sheathed microfilariae into bloodstream (diagnostic stage).

    5. Cycle duration: 6\text{–}12 months to patent infection.

  • Chemotherapy: diethylcarbamazine + albendazole.

  • Early immune cell actors: eosinophils (poll 66.67\%) capable of

    • Degranulation (MBP, EPO, EDN, ROS)

    • Granuloma formation

    • Cytokine release (IL-4, IL-13, eotaxins \text{CCL}11).

  • Cytokine milieu schema (Makepeace et al. 2012):

    • Th1 (IFN-γ, TNF, IL-2): intracellular killing

    • Th2 (IL-4/5/9/13): granulocyte recruitment, tissue repair/damage

    • Th17 (IL-17/22): neutrophil-rich inflammation

    • Treg (IL-10, TGF-β): modulation

    • ILC2/nuocytes amplify Th2.

  • NETosis: Wolbachia (endosymbiotic Gram-negative bacteria in filariae) trigger neutrophil extracellular traps; parallels with fungal hyphae & bacterial infections (poll Q: bacterial 66.67\%, hyphal 33.33\%).

    • Wolbachia skew host immunity toward Th1 (poll 100\%) → potential immune evasion by distracting away from anti-helminth Th2.

  • DC migration experiment (FITC skin painting → dLN CD11c^+ tracking) illustrates: “DC capacity to migrate to draining lymph nodes to trigger Th response” (poll 75\%).

Host Defence Architecture

Innate Components

  • Physical barriers, complement, phagocytes (neutrophils, macrophages, dendritic cells), NK cells, eosinophils, basophils, mast cells.

  • NETosis definition: chromatin + granular protein scaffold extruded to trap/kill pathogens; prominent in anti-hyphal, bacterial, filarial contexts.

Adaptive Components

  • B cells → plasma cells → Ab classes (IgM → IgG/IgA/IgE)

  • T cells

    • Th (CD4^+) subsets: Th1, Th2, Th17, Treg, Tfh

    • Tc (CD8^+) cytotoxic killing (perforin, granzymes)

  • Antigen recognition: BCR (native) vs. TCR (MHC-restricted).

  • MHC-I cross-presentation by DCs (“licensing” cytotoxic responses).

Haematopoiesis Quick-Chart

  • HSC → myeloid vs. lymphoid lineages.

  • Myeloid: \big[ RBCs, platelets, basophils, neutrophils, eosinophils, monocytes → macrophages/DCs \big].

  • Lymphoid: \big[ B cells, T cells, NK cells \big].

Pathogen Immune-Evasion Tactics (selected examples)

  • Fungi: cell-wall masking, complement regulators.

  • Helminths: molecular mimicry, anti-oxidant enzymes, induction of Treg, Wolbachia-driven Th1 diversion.

  • Protozoa (e.g., malaria): antigenic variation (PfEMP1), cytoadherence.

Immunisation Block

  • Definitions: active vs. passive, herd immunity threshold > \approx 75\text{–}95\% depending on R_0.

  • Historical milestones: Jenner’s smallpox 1796, Pasteur, Salk/Sabin polio, mRNA COVID-19.

  • Vaccine generations

    • Live-attenuated (e.g., MMR)

    • Inactivated/killed (e.g., IPV)

    • Toxoids (e.g., tetanus)

    • Subunit (recombinant HBsAg)

    • Recombinant-vector (ChAdOx1-S)

    • DNA/RNA platforms.

  • Monitoring: seroconversion (ELISA titres), breakthrough infection rates.

Diagnostic Immunoassays

  • Unlabelled

    • Radial immunodiffusion (Mancini)

    • Agglutination (latex, haemagglutination).

  • Labelled

    • Radioimmunoassay (RIA)

    • ELISA variants: direct, indirect, direct-sandwich, indirect-sandwich, competitive; poll identified protocol as “direct sandwich ELISA” (83.33\%).

    • Western blot

    • Flow cytometry (fluorochrome-labelled Abs; poll 40\%).

    • Luminex (multiplex bead-based, “multiplex ELISA”).

  • Interpretation: sensitivity/specificity, predictive values, paired acute-convalescent sera, cut-off OD.

Revision & Answer-Writing Techniques

Expand-Topic List (vertical)

  • Left column = keywords; right = incremental notes; iterative recall.

Mind-Map

  • Central bubble (topic) → spokes (concepts) → links/colour-coding advantages, disadvantages, comparisons; e.g., DC tissue vs. lymph-node roles.

Connection Grid

  • Select \approx 10 key terms (macrophage, cytokine, PAMP, opsonisation, TLR1\text{–}9…) and write relational sentences.

Answer Workflow

  1. Plan (outline points, allocate marks/time).

  2. Compose (scientific tone, past tense, third person; full species naming rules).

  3. Revise (structure, coverage, avoid repetition, add insight).

  • Example Q1 (Life-cycle) illustrated incremental improvement; Q2 (immune defence) requires balanced innate/adaptive, cellular/humoral coverage.

Research Focus Snippet

  • Lecturer driving towards tumour control & anti-microbial immunity via “lymphocyte” research; likely interest: NK cells (poll evenly split 25\% each among B, T, NK, eosinophils).

  • Core technique: flow cytometry (fluorescent Ab panels, TruCount absolute quantitation).

Quick Reference Global Infection Numbers (endemic millions)

  • Schistosoma spp. \approx 207

  • Ascaris lumbricoides \approx 1450

  • Trichuris trichiura \approx 1050

  • Hookworms (Ankylostoma spp.) \approx 1300

  • Strongyloides spp. \approx 30–100

  • Filariases \approx 200

  • Plasmodium spp. \approx 250

  • Leishmania spp. \approx 12

  • Trypanosoma spp. \approx 16–18

  • Giardia intestinalis \approx 50

  • Entamoeba histolytica \approx 280

These bullet-point notes synthesise all major & minor details, key examples, immune mechanisms, numerical data, experimental highlights and study-skill strategies from the transcript. They form a self-contained revision resource capable of replacing the original slides/tutorial material.