Responding to Antigens

Three lines of immune defence: overview

  • The immune system is organized into three lines of defence: 1.1. 1st line (external barriers), 2.2. 2nd line (innate immune system), 3.3. 3rd line (adaptive immune system).
  • Innate vs adaptive immunity:
    • Innate = Non-specific, no memory
    • Adaptive = Specific, with memory
  • Key goal: prevent pathogen entry, recognize non-self, and mount appropriate responses across lines of defence.

The innate immune system: overview and mnemonic

  • The innate system constitutes the 2nd line of defence and is non-specific and immediate.
  • Key features (ICFIP): IInterferons, CComplement system, FFever, IInnate inflammatory cells, PPhagocytosis.
  • Characteristics of the innate immune system:
    • Non-specific (broadly targets pathogen classes)
    • Effective at sites of infection
    • No immunological memory
    • Present from birth
    • Short-lasting defence
    • Not focused on a single antigen
    • Produces inflammation
  • Innate inflammatory cells include: Neutrophils, Macrophages, Eosinophils, NK cells, Mast cells, Dendritic cells.
  • Phagocytosis: core process linking innate and adaptive immunity, involving:
    • Recognition and engulfment
    • Formation of the phagosome
    • Formation of the phagolysosome
    • Digestion and recycling
  • Pathogen recognition in the innate system relies on PRRs (pattern recognition receptors) that detect PAMPs (pathogen-associated molecular patterns) and, in some cases, DAMPs (damage-associated molecular patterns).
  • Important note: An innate immune response can be initiated without antigens, via PAMPs/DAMPs, triggering cytokine release and inflammation; however, at VCE 3/4 Biology level, antigens trigger inflammation via APCs.
  • Antigen presentation begins linking innate to adaptive immunity; phagocytes can display antigenic fragments on their surface to inform the adaptive system.

1st Line of Defence: external barriers in animals and plants

  • In animals: physical barriers, chemical barriers, and microbiota barriers.
    • Physical barriers: intact skin, hair in openings, mucous
    • Chemical barriers: Lysozymes in tears, stomach acid, saliva
    • Microbiological barriers: commensal microbes on the skin and in the gut help protect against invaders
  • In plants: physical barriers and chemical barriers
    • Physical barriers: thick cellulose cell walls, bark, cuticle on leaves
    • Chemical barriers: phytoalexins (antimicrobial plant substances)
  • Phytoalexins: toxins produced by plants to protect against pathogens.
    • Key features:
    • Antimicrobial activity
    • Mostly lipophilic (cross membranes easily)
    • Produced in response to pathogens
    • Mechanisms include puncturing cell walls, delaying maturation, disrupting metabolism, or preventing pathogen reproduction
  • Plant strategies to reduce pathogen attachment and entry:
    • Leaves oriented vertically to hinder pathogen attachment
    • Modified leaves/branches with spikes or thorns
  • Role of the plant cell wall and cuticle: cellulose-based walls and waxy cuticle reduce water accumulation and pathogen entry; thick bark acts like an external barrier.
  • Note: Plants release phytoalexins in response to invading pathogens; these toxins disrupt cell walls, delay maturation, or interfere with metabolism.
  • Quick plant examples of antimicrobial plant substances used in medicine: Cinnamon, Caffeine, Turmeric, Matcha
    • Source references provided in slides

The Innate Immune System: components and early responses

  • The innate immune system is the non-specific defence that activates immediately when a pathogen is detected.
  • It serves as the body’s 2nd line of defence and includes dissolved plasma proteins and white blood cells.
  • Features of the innate system (ICFIP mnemonic re-stated): Interferons, Complement system, Fever, Innate inflammatory cells, Phagocytosis.
  • Interferons:
    • Group of cytokines produced by host cells in response to viral pathogens.
    • Function: interfere with viral replication and signal nearby cells to prepare for possible infection (autocrine and paracrine actions).
    • Antiviral state: neighbouring cells upregulate defence mechanisms to blunt viral spread.
    • Antiviral actions can include signaling to prepare to destroy viral RNA and to hinder viral entry (e.g., reducing membrane fluidity at the plasma membrane).
  • Complement system:
    • A large group of proteases in plasma that enhance antibodies and phagocytes in clearing microbes and damaged cells.
    • Major functions:
    • Opsonisation (tag pathogens for phagocytosis)
    • Chemotaxis (recruit WBCs to the infection site)
    • Lysis via the Membrane Attack Complex (MAC)
    • Three main outcomes when activation occurs:
    • Opsonisation
    • Phagocytosis (enhanced uptake)
    • MAC formation (membrane perforation leading to lysis)
  • Fever:
    • Fever arises during infection or tissue damage and is part of the inflammatory response.
    • Effects:
    • Stimulates WBCs to kill pathogens
    • Higher body temperature inhibits pathogen growth and spread
  • Innate inflammatory cells (summary):
    • Neutrophils, Macrophages, Dendritic cells, Eosinophils, Natural killer (NK) cells, Mast cells
    • Basophils are also involved in inflammatory responses (mentioned in related figures)
    • NK cells contribute via cytotoxic mechanisms and degranulation
  • Degranulation: release of antimicrobial and toxic granules from innate immune cells (mast cells, eosinophils, basophils, NK cells, etc.)
    • Key molecules found in granules include: Histamine, Cytokines/Interleukins, Prostaglandins, Chemokines, Granzyme B, Perforin
  • Probiotics and innate immunity: Some probiotic strains can enhance NK cell activity and immune factor secretion (example foods include yogurt and fermented milk)
  • Pathogen recognition in phagocytes:
    • Phagocytes express PRRs that recognize PAMPs on pathogens, providing broad non-specific recognition
    • Distinction: PAMP recognition supports broad innate responses; specific adaptive responses depend on antigen-specific markers
  • PAMPs versus antigens:
    • PAMPs: generic patterns used by innate immunity to recognize “foreign-ness”
    • Antigens: contain specific information about pathogen identity used to trigger adaptive responses
  • Note on linking innate and adaptive immunity: phagocytes can present antigens via MHC molecules, acting as a bridge to adaptive immunity

Phagocytosis: process and players

  • Phagocytosis is performed by phagocytes such as neutrophils, macrophages, and dendritic cells.
  • Steps of phagocytosis:
    • 1)1) Recognition and engulfment
    • 2)2) Formation of phagosome
    • 3)3) Formation of phagolysosome
    • 4)4) Digestion and recycling
  • Pattern recognition and antigen presentation:
    • Phagocytes recognize pathogen-derived molecules via PRRs (linking innate to adaptive)
    • Phagocytes can present antigen fragments on MHC molecules to activate adaptive responses
  • Special note: Phagocytes live only a few days; millions are produced continuously; when they die they contribute to pus at sites of infection
  • Antigen-presenting cells (APCs) include: dendritic cells, macrophages, B cells

Inflammation: the vascular, cellular, and resolution stages

  • Inflammation is the localized response to infection, injury, or tissue damage, aiming to remove harmful stimuli and initiate healing.
  • Key symptoms of inflammation: redness, heat, swelling, pain; pus can form from dead phagocytes and debris
  • Important notes:
    • Inflammation can be triggered by non-infectious damage (e.g., burns, chemicals)
    • Acute inflammation is protective; chronic inflammation is a risk factor for diseases such as arthritis and diabetes
  • The three main stages of the inflammatory response:
    • 1)1) Vascular stage: release of chemical signals (e.g., histamine from mast cells) and capillary vasodilation; increased blood flow; phagocyte attraction
    • 2)2) Cellular stage: phagocyte migration to site; engulfment of bacteria and debris; ongoing inflammatory signaling
    • 3)3) Resolution stage: clearance of debris; release of anti-inflammatory molecules to terminate inflammation and promote healing
  • Exam tips: visualise inflammation like a three-step meal analogy – open passage (vascular), chew/absorb nutrients (cellular), swallow/resolve (resolution)

Initiating an adaptive immune response: APCs, antigens, and MHC

  • Innate responses (like inflammation) can occur without antigens, via PAMPS/DAMPS, but antigens are pivotal for triggering a full adaptive response.
  • Antigen-presenting cells (APCs): dendritic cells, macrophages, B cells
    • APCs enable antigen recognition and activate T and B cells in the adaptive immune system
  • The role of MHC molecules in antigen presentation:
    • MHC I: present on almost all nucleated cells; presents endogenous antigens to cytotoxic T cells (CD8+)
    • MHC II: expressed mainly by APCs; presents exogenous antigens to helper T cells (CD4+)
  • Notes from the slides:
    • MHC II presentation is essential for activation of T cells
    • APCs express MHC II, whereas all cells express MHC I
    • The adaptive response involves two major steps: phagocytosis of antigen by an APC, followed by presentation of antigen on MHC molecules to T cells
  • Antigen recognition and the clonal response:
    • The module notes that clonal selection and expansion will be covered in a future booklet (#18) with the humoral response model answer
  • Antigen presentation sequence (summary):
    • Innate APC recognizes antigen (which may be free-floating or bound on MHC I) and engulfs it
    • APC migrates to a lymphoid organ (e.g., lymph node) to recruit more immune cells
    • APC presents antigen as a peptide on MHC II to activate helper T cells; MHC I interactions activate cytotoxic T cells
  • Quick recap: Antigen presentation is a two-step process – phagocytosis by APCs, followed by antigen presentation on MHC molecules to T cells
  • Important reminder: Innate responses can be triggered by PAMPS/DAMPS even in the absence of antigen, but antigens are key to engaging the adaptive response via APCs

Antigen presentation and MHC: ordering and roles

  • Refresh on MHC molecules:
    • MHC I: present on all nucleated cells; presents endogenous peptides to CD8+ T cells
    • MHC II: present on APCs; presents exogenous peptides to CD4+ T cells
  • General order of events (as depicted in the slides):
    • Step 1: Agent with antigen enters the body
    • Step 2: APC recognizes and engulfs the antigen
    • Step 3: APC travels to a lymphoid organ (lymph node) to interact with adaptive immune cells
    • Step 4: APC presents processed antigen on MHC II (to helper T cells); MHC I interactions can occur with cytotoxic T cells to recognize endogenous antigens
  • Note on innate APCs and antigen uptake:
    • Innate APCs can recognize antigens free-floating or bound on MHC I
    • The presentation on MHC II is essential for activation of helper T cells
    • Some slides emphasize the distinction: APCs are the primary expressers of MHC II; other cells primarily express MHC I
  • Reminder on PAMPS/DAMPS in innate triggering of inflammation without antigens; the antigen-based adaptive response adds specificity and memory

Quick reference: Divisions of immunity and exam framing

  • Three divisions of immunity (as per the slides):
    • 1st Line of Defence = external physical barriers (animals) or physical/chemical barriers (plants)
    • 2nd Line of Defence = innate immune system (non-specific; immediate)
    • 3rd Line of Deference = adaptive immune system (specific; memory)
  • Analogy used in the slides: a castle with multiple layers of defence to illustrate layers of immunity
  • Relevance to VCAA study design:
    • Innate immune response
    • Roles of components of the adaptive immune response
  • Exam tips included in the slides:
    • Visualise the three divisions of immunity as castle defences to aid understanding of their roles
    • Remember the criteria distinguishing the lines of immunity: specificity, memory, and activation time

Glossary and key terms (selected)

  • APC: Antigen-presenting cell
  • MHC I: Major Histocompatibility Complex class I
  • MHC II: Major Histocompatibility Complex class II
  • PAMP: Pathogen-associated molecular pattern
  • DAMP: Damage-associated molecular pattern
  • PRR: Pattern recognition receptor
  • Phagosome: vesicle formed around ingested material
  • Phagolysosome: phagosome fused with a lysosome for digestion
  • MAC: Membrane attack complex
  • Opsonisation: tagging for enhanced phagocytosis
  • Chemotaxis: recruitment of immune cells to the site of infection
  • Degranulation: release of granule contents (e.g., histamines, cytokines) by immune cells
  • Phytoalexin: antimicrobial compound produced by plants in response to infection
  • Pus: accumulation of dead neutrophils and cellular debris at infection sites

References and notes

  • Plant phytoalexins and antimicrobial substances example sources cited in slides:
    • Phytoalexin antimicrobial activity and modes of action
    • Leaves oriented vertically to hinder pathogen attachment
    • Bark and cuticle roles in providing barriers
    • Specific plant substances: Cinnamon, Caffeine, Turmeric, Matcha
    • Source links provided in the original booklet
  • Additional notes on exam framing and perceived mechanisms were included to support understanding of the innate-adaptive bridge, particularly antigen presentation and the role of MHC II in APCs.