Introduction to the Immune System, Pathogens, and Lymphatic Organs

H. G. Wells – Microbial Foresight

• Opening quotation (The War of the Worlds, 1898) underscores two key ideas:

  • Co-evolution: humanity’s “birth-right” was purchased by 10^{9} deaths through natural selection against microbes.

  • Microorganisms as silent allies: Earth bacteria destroyed the Martians, illustrating innate resistance the host acquires over evolutionary time.

  • Ethical/Philosophical link: underscores why immunology matters— our survival and dominion rely on unseen microbial interactions.

Course / Unit Learning Outcomes

• Students should be able to

  • Describe immune-microbe interactions, host disease effects, and principles of vaccination & immunotherapy.

  • Perform, troubleshoot, and interpret pathogen-isolation laboratory procedures.

• These map onto broader programme outcomes of diagnostic reasoning, clinical decision-making, and research literacy.

"Simplicity does not precede complexity, but follows it" – Alan Perlis

• Pedagogical reminder: master complex immune phenomena first; elegant therapeutic “simplicity” (e.g., vaccines) arises only after deep mechanistic understanding.

Lecture Scope & Learning Objectives

• Pathogens: classes, structure, immunologically relevant features.

• Functions, organs, and tissues of the immune system.

• After the session you should be able to

  • Recognise pathogen features crucial for infection/immune response.

  • Identify immune organs/tissues and explain their roles.

Core Function of the Immune System

• Protection against harmful

  • External threats: pathogens (viruses, bacteria, fungi, parasites, etc.).

  • Internal threats: malignant/cancerous cells.

• Tripartite activities

  • Recognition: distinguish \text{Foreign} vs \text{Self}.

  • Response: effector mechanisms tailored to threat type/site.

  • Regulation: avoid

  • Autoimmunity (failure of self-tolerance).

  • Hypersensitivity (over-reaction causing tissue damage).

Pathogen Taxonomy

• Microbes → disease-causing (“pathos” = suffering, “gene” = to give birth).

  • Viruses

  • Bacteria

  • Fungi

  • Parasites

  • Protozoa

  • Helminths (worms)

Viruses – Fundamental Traits

• Inert regarding energy generation; metabolic parasitism.

• Replication strictly inside host cells (prokaryotic or eukaryotic).

• Minimal virion structure

  • Nucleic-acid genome: ss/ds DNA or RNA.

  • Protein capsid (nucleocapsid).

  • Optional lipid envelope acquired by budding; contains virally-encoded glycoproteins → receptor binding, membrane fusion.

Virus Envelope – Significance

• Derived from modified host membrane: lipid bilayer + embedded viral proteins.

• Immune implications

  • Envelope glycoproteins = major antigenic targets (e.g., HIV gp120, SARS-CoV-2 spike).

  • Budding permits persistent infection without immediate host-cell lysis.

Viral Genome Diversity (selected families)

• \text{dsDNA (enveloped)} → Herpesviridae, Poxviridae.

• \text{dsDNA (non-enveloped)} → Adenoviridae, Papovaviridae.

• \text{ssDNA} (non-enveloped) → Parvoviridae.

• \text{gapped ds/ssDNA} (enveloped) → Hepadnaviridae (e.g., Hepatitis B).

• \text{dsRNA (segmented)} → Reoviridae.

• +\text{ssRNA (enveloped)} → Coronaviridae.

• +\text{ssRNA (non-enveloped)} → Picornaviridae.

• Reverse-transcribing \text{RNA} → Retroviridae (HIV).

• -\text{ssRNA (segmented)} → Orthomyxoviridae (Influenza).

• -\text{ssRNA (nonsegmented)} → Filoviridae (Ebola).

• \pm\text{ssRNA (ambisense)} → Arenaviridae.

Bacteria – Key Immunological Aspects

• Prokaryotic cell organisation.

• Gram Classification (wall structure)

  • Gram-positive: thick peptidoglycan retains crystal violet.

  • Gram-negative: thin peptidoglycan + outer membrane containing lipopolysaccharide (LPS) → endotoxin.

• Morphology: bacilli (rods), cocci (spheres), etc.— influences phagocytosis efficiency and dissemination.

Bacterial Toxins: Endo vs Exo

• Endotoxin = LPS (≈ 10\,\text{kDa})

  • Integral to outer membrane; not inactivated by boiling.

  • Immunogenic; induces strong innate cytokine release (IL-1, IL-6, TNF) → fever, septic shock.

• Exotoxins = secreted proteins (≈ 50{-}1000\,\text{kDa})

  • Often enzymes targeting vital host pathways (e.g., cholera toxin on \text{G_{s}} protein → cAMP ↑).

  • Denatured by heat; can be detoxified to form toxoids for vaccines (e.g., diphtheria, tetanus).

• Comparative summary

  • Potency: 1\,\mu g exotoxin vs >100\,\mu g LPS for similar lethality.

  • Specificity: exotoxins highly specific; endotoxin broad inflammatory trigger.

Fungi – Structural & Clinical Points

• Eukaryotic; ~10^{6} species, ~400 pathogenic.

• Morphologies

  • Yeasts: unicellular, asexual budding.

  • Hyphae/mycelia: multicellular filaments, spores.

  • Dimorphic: switch between forms (e.g., Candida albicans) depending on temperature/host milieu → immune evasion.

• Cell wall architecture

  • Mannoproteins, \beta(1,6)- & \beta(1,3)-glucans, chitin; absent in mammals → PAMPs for innate receptors (Dectin-1, TLRs).

  • Drug target: \beta(1,3)-glucan synthase (e.g., echinocandins).

Parasites

Protozoa (Unicellular Eukaryotes < 50\,\mu m)

• Classified by locomotion

  • Sporozoa: non-motile adults (Plasmodium spp., Cryptosporidium).

  • Amoeboids: pseudopod movement (Entamoeba histolytica).

  • Flagellates: flagellar propulsion (Giardia, Leishmania).

  • Ciliates: ciliary motion (Balantidium coli).

• Immune notes: complex antigenic variation (e.g., Plasmodium falciparum PfEMP1) challenges vaccine design.

Helminths (Multicellular Worms)

• Trematodes (flukes): leaf-shaped, e.g., Fasciola hepatica.

• Cestodes (tapeworms): segmented hermaphrodites, e.g., Taenia spp.

• Nematodes (roundworms): bisexual, e.g., Ascaris lumbricoides infecting 8.07{-}12.21\times10^{8} people.

• Th2-skewed immunity: IgE, eosinophils, mast cells.

Pathogen Location vs Immune Strategy (Janeway Fig 2.3)

• Extracellular – interstitial/blood/lymph

  • Examples: Neisseria gonorrhoeae, Streptococcus pneumoniae, Vibrio cholerae.

  • Effectors: complement, antimicrobial peptides, IgG/IgM-mediated opsonisation & lysis.

• Extracellular – epithelial surfaces

  • Helicobacter pylori, Candida albicans, worms.

  • Effectors: secretory IgA, antimicrobial peptides.

• Intracellular – cytoplasmic

  • Viruses, Chlamydia, Rickettsia.

  • Effectors: cytotoxic T lymphocytes (CTLs), NK cells.

• Intracellular – vesicular

  • Mycobacterium, Salmonella, Leishmania.

  • Effectors: Th1 cells → IFN-γ → macrophage activation.

Lymphatic System – Architecture & Flow

• Lymphatic vessels collect fluid (lymph) from interstitium → return to bloodstream; one-way valves.

• Lymph = plasma ultrafiltrate + leukocytes, antigens, lipids.

• Functions

  • \text{Fluid balance}: drain excess interstitial fluid.

  • \text{Lipid transport}: chylomicrons with vitamins A, D, E, K from GIT.

  • \text{Immune traffic}: ferry APCs & lymphocytes to secondary organs.

Primary Lymphoid Organs

Bone Marrow

• Hematopoietic stem cells (HSCs) generate all blood lineages.

• B-cell maturation & central tolerance: self-reactive clones deleted (clonal deletion/anergy).

Thymus

• T-cell maturation + selection

  • Positive selection: recognise self \text{MHC} (MHC restriction).

  • Negative selection: high-affinity self-reactive TCRs eliminated (self-tolerance).

• Age-related involution decreases output of naïve T cells → implications for elderly immunity.

Secondary Lymphoid Organs & Tissues

Spleen

• Red pulp: fetal hematopoiesis; macrophage clearance of senescent erythrocytes; platelet reservoir (≈ \frac{1}{3} body supply).

• White pulp: periarteriolar lymphoid sheaths (T cells) & follicles (B cells) orchestrate responses to blood-borne antigens.

• Asplenia → susceptibility to encapsulated bacteria (e.g., Streptococcus pneumoniae).

Lymph Nodes

• Cortex: primary/secondary follicles (B cells, germinal centers), macrophages, dendritic cells.

• Paracortex: T cells + interdigitating dendritic cells.

• Medulla: plasma cells secreting antibody + macrophages.

• Function: filter lymph, present antigens, activate naïve lymphocytes; regulate magnitude/quality of adaptive response.

Mucosa-Associated Lymphoid Tissue (MALT)

• Adenoids, tonsils, Peyer’s patches, appendix, bronchus- and reproductive-associated sites.

• Major IgA production locale; first line against mucosal pathogens.

Reading & Resources

• Kuby Immunology (8th ed.) – Ch 1, 2 (overview), Ch 7 (lymphoid organs).

• Janeway’s Immunobiology – Ch 1 (conceptual), Ch 6 (MHC function).

• Roitt’s Essential Immunology; Parham’s The Immune System 3rd ed.

• Medical Microbiology texts for pathogen-specific chapters.

Integrative Take-Home Messages

• Immune defence is anatomically compartmentalised and pathogen-tailored.

• Structural quirks of microbes (e.g., LPS, glucans, viral envelopes) dictate immune recognition and clinical outcome.

• Vaccines/toxoids exploit antigenicity while minimising toxicity – echoing Perlis’s “simplicity after complexity”.

• Understanding laboratory isolation/diagnosis feeds directly into selecting immunotherapeutic or antimicrobial strategies.

• Evolutionary arms race underlies both Wells’s fictional narrative and real-world challenges like HIV mutability and antibiotic resistance.