Immunity Overview: Innate and Adaptive Immunity (Chapter 1-9 Notes)

Innate vs Adaptive Immunity and Barriers

• Overview

  • Innate immunity is the nonspecific part of the immune system and forms the first and second lines of defense. It responds quickly but has no memory. It is present at birth and is something everyone is born with.
  • Adaptive immunity is more specific and involves learning antigens. It is slower to respond initially (about 1 week to 14 days to become fully functional) but develops memory for faster responses on re-exposure.
  • The innate and adaptive systems are interconnected: antigen exposure can activate the innate system (e.g., via complement) and shape the adaptive response; the adaptive system can enhance innate processes via antibodies and memory.

• Key timelines

  • Innate immunity: immediate, fast, no memory.
  • Adaptive immunity: slower start, typically
    t \in [7,14] \text{ days}
    to become fully functional, but memory allows faster responses upon subsequent exposures.

• Major components of innate immunity

  • Barriers (first line of defense): physical/structural, chemical, and mechanical protections that prevent entry of pathogens.
  • Inflammation: localized response to injury or infection.
  • Fever: systemic response to infection.
  • Complement system: a cascade of blood proteins that enhances (complements) the ability of antibodies and phagocytic cells to clear microbes.

• Innate barriers and barriers-plus-defense concepts

  • Mechanical barriers (previously introduced): urine flushing, tears, etc., that physically remove invaders.
  • Chemical barriers: components associated with the skin and mucous membranes that deter microbial growth.
  • Inflammation vs fever
  • Inflammation: localized response at the site of injury or infection.
  • Fever: systemic rise in body temperature.
  • Complement proteins: circulate as inactive proteins and become activated in response to pathogens or antigen-antibody interactions.

• Adaptive immunity: two arms and key features

  • Recognition and learning: T cells and B cells recognize foreign antigens and learn to respond.
  • Slower onset: initial response takes about a week to two weeks to become fully functional.
  • Memory: after initial exposure, memory cells ensure faster and stronger responses upon re-exposure.
  • Humoral immunity (antibody-mediated): B cells and antibodies
  • Cellular immunity (cell-mediated): T cells
  • Functional distinction
  • Humoral: antibodies can act systemically and target extracellular pathogens.
  • Cellular: T cells can directly target specific intracellular antigens.

• Examples and practical implications

  • A first exposure to a pathogen (e.g., chickenpox): slow adaptive response, potential symptoms until the response is mounted.
  • Upon re-exposure to the same pathogen: memory mediates a much quicker and more robust response.
  • The concept of memory underpins vaccination strategies.

• Epidermis and skin defenses

  • Epidermis is composed of stratified squamous epithelium and is keratinized.
  • Keratin provides dryness and waterproofing, helping prevent entry into deeper layers.
  • The epidermis is salty; high salt concentrations can inhibit bacterial growth.
  • Sebaceous glands
  • Secrete sebum, a oily substance that coats hair follicles and helps seal the follicle, hindering pathogen access.
  • Sweat glands
  • Secrete dermaciide (dermaciide) in sweat, which helps inhibit bacterial and fungal growth.

• Mucous membranes and mucous-based barriers

  • Line open orifices and tracts (eyes, nasal passages, respiratory tract, digestive tract, urinary and genital systems).
  • Goblet cells secrete mucus, which traps viruses and bacteria.
  • Cilia move mucus out of the body (coughing, sneezing) to expel pathogens.

• Normal microbiota as a physical barrier

  • Coat host cells and compete for attachment sites, making it harder for pathogens to establish themselves.
  • Secrete chemicals such as bacteriocins that inhibit potential pathogens.

• Endothelium and tight junctions

  • Simple squamous epithelial cells line locations like the urogenital tract, blood vessels, and lymphatic vessels; this lining is called endothelium.
  • Tight junctions between endothelial cells create a highly selective barrier that impedes pathogen entry.
  • Example: the blood–brain barrier is a highly selective endothelial barrier that protects the CNS.

• Acute phase proteins and iron sequestration

  • C-reactive protein (CRP): an acute phase protein that indicates inflammation; can help inhibit bacterial growth and aid in trapping bacteria.
  • Ferritin and transferrin: bind iron to limit its availability to bacteria, thereby inhibiting bacterial growth.
  • Fibrinogen: a plasma protein that initiates clotting; fibrin formation can wall off bacteria and limit spread.

• Complement system (detailed, from the second video)

  • Role and nature
  • Part of the innate immune system proper, circulating as a cascade of blood proteins that are mostly inactive until activated.
  • Activation can occur via two routes: antigen–antibody reaction or presence of a pathogen.
  • Regardless of trigger, the downstream effects are the same once activation occurs.
  • Major effects/effects when activated
  • Opsonization: coating of the target with complement proteins (e.g., C3b) to enhance phagocytosis; antibodies can also mediate opsonization.
  • Membrane Attack Complex (MAC): assembly of proteins (C5b, C6, C7, C8, C9) inserted into the target cell’s plasma membrane, forming a pore and causing cell lysis.
    • General idea: a hole in the plasma membrane disrupts osmotic balance, leading to cell death.
  • Inflammation: complement components (e.g., C3a, C5a) promote inflammatory responses, drawing in immune cells.
  • Chemotaxis: complement fragments attract immune cells to the site of infection.
  • Activation pathways (illustrative, not exhaustive)
  • Antigen–antibody binding can activate the cascade.
  • Pathogen presence alone can activate the cascade (innate route).
  • Practical notes
  • The C3 protein activation splits into different downstream paths: C3b for opsonization, C3a for inflammation, and further downstream C5b–C9 forming the MAC.
  • The exact protein numbers (e.g., C3, C3b, C3a, C5, C6, C7, C8, C9) are shown in diagrams; memorizing all numbers is not required.
  • The Tor Tor microbiology book visuals are often used to illustrate these cascades.

• Summary and connections

  • Innate and adaptive immunity work together for protection: innate provides immediate defense and shapes adaptive responses; adaptive memory provides long-term protection.
  • Barrier defenses (skin, mucous membranes, microbiota) are the first line, reducing the chance of infection and buying time for adaptive responses.
  • Complement links innate and adaptive immunity by enhancing opsonization and promoting inflammation and cell lysis.

• Notation and key formulas/equations (LaTeX)

  • Adaptive timing
  • Initial adaptive response: t \in [7,14] \text{ days} to become fully functional.
  • Iron sequestration and bacterial growth inhibition
  • 
    \,\text{Ferritin},\; \text{Transferrin} \,\text{bind Fe}^{3+} \rightarrow \downarrow \text{available iron} \Rightarrow \downarrow \text{bacterial growth}
    
  • Fibrinogen and clotting wall-off
  • \text{Fibrinogen} \xrightarrow{\text{activation}} \text{Fibrin} \rightarrow \text{clot formation} \rightarrow \text{wall off bacteria}
  • Complement activation and outcomes
  • Activation: \text{Activation} = f(\text{antigen- antibody binding}) \cup f(\text{pathogen presence})}
  • Opsonization: \text{C3b} \rightarrow \text{opsonization of target}
  • Inflammation: \text{C3a}, \text{C5a} \rightarrow \text{inflammatory mediator release}
  • MAC: \text{MAC} = \text{C5b} + \text{C6} + \text{C7} + \text{C8} + \text{C9} \rightarrow \text{membrane perforation} \rightarrow \text{cytolysis}

• Connections to prior lectures and real-world relevance

  • Barrier function is foundational to preventing infections; understanding keratin, salt content, and sebum gives insight into everyday protection (skin care, wound care).
  • The concept of memory in adaptive immunity underpins vaccines and booster strategies.
  • Complement’s dual activation routes illustrate the synergy between innate and adaptive responses and how antibodies can enhance innate pathways.
  • Practical implications include recognizing how disruptions in barrier function (e.g., skin damage, poor mucous clearance) or deficiencies in complement components can increase infection risk.