LO of Week 3

Name and describe the patterns in which muscles are used, coordinated and controlled in animals.

Animals use muscles as both agonists and antagonists, through coactivation, as synergists (support one another on the same side of the joint), and synergies (neural control mechanism whereby groups of muscles neurally ‘wired together’ to produce patterns of specific movements.

Compare the properties of the main types of skeletal muscle fibre and describe how these are distributed in the healthy and diseased individual.

There are three types of muscle fibre. There is the slow oxidative (Type I) that has a slow contractions and high oxidative capacity. They are usually in smaller diameter and are fatigue resistant. Fast oxidative glycolytic (Type IIa) has a fast contraction and the ability to use both aerobic and anaerobic metabolism. Fast glycolytic (Type IIb) have a fast contraction and has a high glycolytic capacity. They are usually larger in diameter (stronger) and fatigue easily.

Appreciate the concept of a skeletal muscle ‘motor unit’ and how this influences the control of muscle use in the body.

In skeletal muscle, a motor unit is one motor neuron and all the muscle fibres that it innervates. The ratio of nerve to muscle fibres varies depending on function of the muscle. An examp is strength muscles have many fibres by one nerve while those that need control have few fibre per neuron. You can control muscle force by recruiting moe/fewer motor units or by controlling force within a motor unit.

Explain key muscle adaptations and responses which occur due to: exercise, detraining, ageing and injury.

There are two ways a muscle can adapt. There is the change in the area and the length change. The area change is caused by the hypertrophy (getting bigger) of fibres. There is NOT a change in NUMBER of fibres. The length of a fibre can also change through the change in number of sarcomeres (adding to each end), not a change in length of sarcomeres. For exercise, hypertrophy will occur with increased loading/contraction with ‘strength’ training affecting fast fibres twice as much as slow fibres. Exercise can also change the length of the fibre, with stretching lengthening and shortening due to muscle atrophy or detraining. With aging, the number of satellite cells decrease, reducing the proliferative capacity. This can lead to denervation, leading to muscle atrophy, decreased blood supply, and increased fibrous connective tissue. When a muscle is injured, myoblast can turn to myocytes which can either heal to grow or the myocytes can turn to myofibroblasts.

Describe the basic regulatory processes behind skeletal muscle adaptation.

Skeletal muscle adaptation is regulated through satellite cells. They can be found between the basal lamina and the cell membrane. They have stem cell-like properties and are needed for injury repair. They migrate and form myotubes/fuse to myofibers. This is important in hypertrophy. It is stimulated by IGF/other growth factors.

Explain the term proprioception and the sensory receptors involved.

The body's "sixth sense"—the ability to perceive the position, movement, and force of your body parts without looking. Not to be confused with kinaesthesia, the sense of movement of body parts. There are two parts, the conscious and subconscious, both which allow for balance and limb/body posture function. There are also exteroreceptors (detect external influences) and interoceptors (detect internal visceral environment).

It relies on specialized mechanoreceptors to coordinate balance and smooth movement:

• Skeletal muscle: muscle spindles - detect length and stretch in a muscle.

• Tendons: Golgi tendon organ - detect tension and force in a muscles via a tendon.

Describe with the aid of a diagram the general features of muscle spindle receptors.

Muscle Spindles are specialized sensory receptors tucked inside skeletal muscles. They are aligned parallel to regular (extrafusal) muscle fibers. Their function is to detect changes in muscle length (stretch) and the velocity/rate of that change. They are enclosed in a connective tissue capsule. There are two types of muscle spindles the nuclear bag fibers (nuclei clustered in the center; sense dynamic speed and static length) and the nuclear chain fibers (nuclei arranged in a row; sense static length). There are two types of sensory (afferent) innervation: Type Ia (primary): Wrap the center; sense speed and length and Type II (secondary): Flower-spray endings; sense static length only. The motor (efferent) innervation is the Gamma motor neurons which contract the outer ends to adjust spindle sensitivity. This triggers the stretch reflex (e.g., knee-jerk).

Describe the structure and function of a muscle spindle and Golgi tendon organ.

Muscle Spindle

• Location: Located within skeletal muscle, arranged in parallel with extrafusal muscle fibers.

• Function: Acts as a mechanoreceptor monitoring muscle length and the rate/speed of stretch.

• Innervation:

  • Sensory: Type Ia (primary) and Type II (secondary) afferent fibers

  • Motor: Gamma motor neurons.

• Reflex Pathway: Triggers a monosynaptic stretch reflex that excites gamma motor neurons to contract the muscle.

Golgi Tendon Organ (GTO)

• Location: Located at the musculotendinous junction, arranged in series with muscle fibers.

• Function: Acts as a mechanoreceptor monitoring muscle/tendon tension and force.

• Innervation:

  • Sensory: Type Ib afferent fibers.

  • Motor: None (purely sensory).

• Reflex Pathway: Triggers a disynaptic reflex through an inhibitory interneuron in the spinal cord to relax the contracting muscle (autogenic inhibition).

Explain a reflex arc and its function; and distinguish between segmental and long spinal reflexes.

A reflex arc is the functional neural circuit that mediates a reflex action. It is structured as a receptor – nerve/CNS – muscle (effector) complex. The primary function of a reflex arc is to produce rapid motor responses by directly activating motor neurons in the spinal cord, bypassing the delay of routing signals through the brain. Although the reflex action operates automatically at the spinal level, sensory inputs are simultaneously sent up to the brain. This allows higher CNS centers to moderate or voluntarily inhibit/override the reflex response. Reflexes are broadly divided into somatic reflexes (affecting skeletal muscle) and visceral reflexes (affecting internal organ systems). Segmental spinal reflexes are mediated within a single spinal cord segment or tight adjacent segments. Neural connections stay localized to coordinate specific muscle groups (e.g., agonist activation and local antagonist inhibition) and they regulate localized muscular responses, such as muscle tone or rapid limb withdrawal. Long spinal reflexes are mediated across several spinal cord segments. They utilize ascending/descending intersegmental and commissural interneuron fibers to coordinate multiple distant segments, allowing for integrating complex multi-limb movements across distant levels of the body for postural support.

Describe tests and pathways for flexor reflex, reciprocal inhibition and crossed extensor reflex.

Flexor Reflex (Withdrawal Reflex): Elicited by a painful or noxious stimulus (such as pinching a foot or toe). The primary sensory neurons detect the painful stimulus and transmit action potentials into the dorsal horn of the spinal cord. The sensory neurons synapse with ipsilateral interneurons in the spinal cord. These interneurons excite alpha motor neurons supplying the flexor muscles of the stimulated limb, causing them to contract and pull the limb away from the harm.

Reciprocal Inhibition (Reciprocal Innervation): Occurs simultaneously with muscle activation to prevent opposing muscles from contracting against each other. The sensory inputs entering the ventral horn provide direct excitatory impulses to the alpha motor neurons of the agonist muscle (causing contraction through a monosynaptic pathway). Simultaneously, collateral sensory branches synapse with inhibitory interneurons. These inhibitory interneurons suppress the alpha motor neurons of the antagonist muscle, forcing it to relax (a disynaptic pathway). This allows smooth, unimpeded movement or withdrawal by coordinating agonist contraction with antagonist relaxation.

Crossed Extensor Reflex: Activated during a strong flexor withdrawal reflex in a weight-bearing limb to maintain posture and balance. Sensory afferents from the stimulated limb enter the spinal cord and activate both ipsilateral interneurons and commissural interneurons that cross the spinal midline to the contralateral (opposite) side. This produces double reciprocal innervation across both limbs. The Ipsilateral Limb (same side): Flexor muscles contract and extensor muscles relax to withdraw the limb. The Contralateral Limb (opposite side): Extensor muscles contract and flexor muscles relax to extend the opposite leg and support the body's weight.

Describe tests and pathways for the patellar reflex and significance of an abnormal finding.

The Patellar Reflex test is performed by striking the patellar ligament with a reflex hammer. Striking the ligament rapidly stretches the tendon and the attached quadriceps femoris muscle. The patellar reflex operates as a classic monosynaptic stretch reflex, mediated by only a single synaptic junction within the spinal cord. Striking the ligament stretches the muscle spindle apparatus inside the quadriceps femoris, activating its sensory neuron. The sensory neuron transmits impulses to the spinal cord, where it directly synapses with and activates an alpha motor neuron. The activated alpha motor neuron stimulates the extrafusal muscle fibers of the quadriceps femoris to contract, extending the lower leg. Testing the patellar reflex evaluates the structural and functional integrity of the entire reflex arc. An abnormal response (such as an absent, diminished, or exaggerated reflex) indicates potential pathology across one or more components such as muscle damage, nerve or CNS damage (alpha motor neurons or gamma motor neurons), spinal cord (CNS) damage, are conscious control (overriding or suppression of the normal reflex contraction through voluntary inhibition from higher brain centers).

Describe the physical and biochemical barriers to infection.

The body defends its epithelial surfaces against foreign microorganisms through a combination of physical mechanisms, chemical secretions, and symbiotic microflora. Physical barriers include stratified squamous epithelium in the skin and lower urinary tract, forming a durable outer barrier. There is a mucociliary escalator found in the respiratory tract, where cilia sweep mucus and trapped pathogens upward to remove them from the airways. Reflexes such as coughing and sneezing also physically expel foreign particles. Gastrointestinal motility where peristalsis continuously moves contents through the alimentary tract, while vomiting and diarrhoea serve as rapid clearance mechanisms to purge ingested pathogens. There is also mechanical flushing where secretions such as saliva, tears, and mucus continually wash across mucosal surfaces to prevent microbial attachment. There are biochemical barriers as well. Sebaceous glands in the skin secrete sebum containing lactic and fatty acids, creating a chemical environment that inhibits microbial growth. Gastric acid has a low pH which destroys most pathogens that enter the digestive system. Antimicrobial enzymes such as lysozyme are found in saliva, sweat, tears, and mucus secretions, which attacks bacterial cell walls. Antimicrobial/bacterial peptides such as defensins damage bacterial cell membranes directly. Commensal Microflora also help protect the body by inhabiting mucosal surfaces, competing with pathogenic microorganisms for space and producing natural antibiotics to suppress invaders. If these initial outer barriers are breached, tissue-level defenses take over.

Explain how foreign organisms are detected by cells of the innate immune system.

Cells of the innate immune system differentiate foreign pathogens from healthy self-tissue through two primary strategies: recognizing conserved microbial structures and identifying "symptoms" of cellular infection or stress. Innate immune cells express specialized receptors called Pattern-Recognition Receptors (PRRs) that detect intrinsically foreign, invariant structures known as Pathogen-Associated Molecular Patterns (PAMPs). PAMPs include key microbial components that are absent in host tissues such as lipopolysaccharide (LPS) (found in the outer membrane of Gram-negative bacteria), peptidoglycan (found in Gram-positive bacterial cell walls), flagellin (from bacterial flagella), repeating mannose sugars (on prokaryotic carbohydrates), prokaryotic DNA (unmethylated CpG sequences) and double-stranded RNA (dsRNA) or cytoplasmic DNA generated during viral replication. To detect pathogens regardless of where they reside, PRRs are strategically distributed across distinct cellular compartments. Membrane-Bound PRRs: Located on the cell surface of white blood cells like macrophages and neutrophils. Key examples include Toll-like Receptors (TLRs) such as TLR-4 (detects LPS), TLR-2 (detects peptidoglycan), and TLR-5 (detects flagellin). Vesicular PRRs: Located inside endosomal membranes to scan internalized material, such as TLR-3 (detects viral dsRNA) and TLR-9 (detects prokaryotic DNA). Cytoplasmic PRRs: Located within the intracellular fluid to sense cytosolic invaders. Examples include NOD receptors (e.g., NOD2, which recognizes bacterial muramyl dipeptide) and RIG-I (detects viral RNA). Soluble PRRs: Secreted into blood and tissue fluids, including Complement C3 protein, mannose-binding lectin, and C-reactive protein. In addition to detecting structural microbial patterns, innate cells monitor host cells for altered surface expression caused by infection. Healthy host cells continually display Major Histocompatibility Complex (MHC) Class I molecules on their surface. During many viral infections, surface MHC Class I expression declines. Natural Killer (NK) cells recognize this "missing self" signal as a symptom of infection and deliver cytotoxic granules to destroy the compromised cell. Gamma-Delta T Cells react directly to stress proteins upregulated on the surfaces of infected mucosal epithelial cells. Once PRRs engage their targets, intracellular cell signaling triggers vital defensive responses. Macrophages and neutrophils engulf and digest bacteria while secreting pro-inflammatory cytokines to recruit additional immune cells. Detection of viral dsRNA or cytosolic DNA triggers the synthesis of Type I Interferons (alpha, beta, omega), which act in a paracrine manner to inhibit viral replication and degrade viral mRNA in neighboring cells.

Discuss the role of interferon in protecting the hose from viral infection.

Because viruses lack obvious foreign structural components (PAMPs), the innate immune system detects them primarily through intracellular nucleic acids—such as double-stranded RNA (dsRNA) produced during replication or cytoplasmic DNA. Recognition by Pattern-Recognition Receptors (PRRs) like TLR-3 or RIG-I triggers cell signaling to produce Type 1 Interferons (including interferons alpha, beta, and omega. Because viruses can infect any nucleated host cell, all nucleated cells have the ability to synthesize and secrete Type 1 interferons upon viral detection. Once released by an infected cell, interferons act locally in a paracrine manner on neighboring uninfected cells. They bind to surface receptors on adjacent cells to warn them of the threat and induce an "antiviral state". Interferons protect the host through three primary intracellular and immunologic mechanisms. Degradation of viral mRNA stimulates host enzymes that degrade viral messenger RNA, preventing the virus from replicating its genetic material. Inhibition of viral protein synthesis blocks host ribosomal machinery from translating viral proteins, thereby arresting viral assembly. Enhanced antigen presentation increases expression of MHC Class I molecules on host cells, making infected cells more visible for recognition and destruction by the adaptive immune system. Together, these mechanisms slow down viral replication and make surrounding cells far more resistant to infection. Recombinant interferons are used clinically to combat viral infections. For example, feline interferon-omega (Virbagen Omega) is administered to treat persistent viral infections in cats, such as Feline Leukaemia Virus (FeLV), Feline Immunodeficiency Virus (FIV), and Feline Infectious Peritonitis (FIP).

Discuss the role of phagocytosis, complement activation and inflammation in protecting the host against bacterial infection.

When external physical and biochemical barriers fail, the innate immune system defends host tissues against bacterial infection through three tightly integrated mechanisms: phagocytosis, complement activation, and inflammation. Phagocytosis is carried out predominantly by neutrophils and macrophages. Upon detecting bacteria via Pattern-Recognition Receptors (PRRs) such as Toll-like receptors (TLRs) and NOD receptors, these cells engage in a multi-step killing process. Phagocytes extend pseudopodia around the bacterial cell to engulf it, forming an intracellular vesicle termed a phagosome. Then the phagosome can be either digested through radicals or lysosomes. An oxygen-dependent killing mechanism is activated, generating reactive oxygen intermediates (ROIs)—such as superoxide anions, hydroxyl radicals, and hydrogen peroxide —which are pumped into the phagosome. Lysosomes fuse with the phagosome to form a phagolysosome. Antimicrobial factors inside the lysosome complete the destruction include defensins (cationic antimicrobial peptides that damage bacterial cell walls), lactoferrin (chelates free iron required for bacterial growth), acid proteases (active at a low pH to digest microbial debris before detritus is expelled by exocytosis and opsonization). Phagocytosis is significantly enhanced when bacteria are coated with opsonins such as C3b or IgG, because phagocytes express surface receptors that bind directly to these deposited molecules. The complement system consists of soluble blood proteins operating in an enzyme amplification cascade, where a small initial trigger yields a large protective response. The pro-enzyme Complement Protein C3 plays a central role. In the presence of bacteria, C3 cleaves into two biologically active fragments: C3b and C3a. C3b causes opsonin to deposit on bacterial surfaces, marking them for rapid recognition and engulfment by complement receptors on neutrophils and macrophages. It can also act as an enzyme to drive the assembly of the Membrane Attack Complex (MAC). C9 monomers polymerize to form a tube-like C9 polymer structure that punctures holes in the bacterial membrane, leading to fluid influx, cell swelling, and direct bacterial lysis. C3a released into surrounding tissue where it binds to receptors on local mast cells, triggering their degranulation and histamine release to stimulate inflammation. Pro-inflammatory cytokines (such as TNF-alpha, IL-1, and IL-6), lipid mediators (prostaglandins and leukotrienes), histamine, and C3a drive coordinated local and systemic defenses:

• Local Effects:

  • Vasodilation: Increases blood flow to infected tissue, causing localized heat and redness.

  • Increased Vascular Permeability: Allows fluid and plasma proteins to leak into tissues, causing edema/swelling.

  • WBC Recruitment: Recruits circulating neutrophils and monocytes out of blood vessels into the tissue to reinforce phagocytosis.

• Systemic Effects:

  • Hypothalamus: Induces fever to inhibit bacterial replication.

  • Liver: Triggers the acute phase response, producing non-specific opsonins (e.g., C-reactive protein, mannose-binding lectin, serum amyloid protein) that coat bacterial walls and promote complement activation.

  • Bone Marrow: Mobilizes and accelerates the production of new white blood cells.

Discuss the role of T cell-mediated immunity in the host response to infection.

T cell-mediated immunity provides targeted, cell-mediated defense against infections by recognizing digested peptide fragments presented on host cell surfaces. Unlike B cells, which recognize whole extracellular antigens, T cells detect foreign antigens only when displayed alongside Major Histocompatibility Complex (MHC) carrier molecules. The activation and interaction of T cells are governed by strict compartmentalization laws. Cytoplasmic antigens (primarily viral proteins synthesized inside an infected cell) are degraded into peptides and displayed on MHC Class I molecules. Because all nucleated cells express MHC Class I, any infected cell can present intracellular foreign antigens to CD8 T cells. Extracellular antigens in tissue fluids are engulfed by professional Antigen-Presenting Cells (APCs)—dendritic cells, macrophages, and B cells—and digested in endolysosomes. These peptides are loaded onto MHC Class II molecules and presented exclusively to CD4 T cells. Naïve T cells continuously travel through blood and secondary lymphoid organs (entering lymph nodes via high endothelial venules, or HEVs) to examine foreign peptides displayed on dendritic cells. Upon recognizing a specific MHC-peptide complex via its T Cell Receptor (TCR), the naïve T cell stops circulating and undergoes rapid proliferation (clonal expansion). Mature effector T cells alter their surface homing receptors, exit the lymph node via efferent lymphatics into the bloodstream, and migrate directly into inflamed, infected tissues to engage the pathogen. CD8 Cytotoxic (Killer) T Lymphocytes (CTLs) target intracellular pathogens, specifically virus-infected host cells presenting MHC Class I-peptide complexes. CTLs seek out infected cells and force them to undergo apoptosis (programmed cell death) via the caspase cascade before viral replication is complete. They induce cell death through three distinct pathways: secreting perforin (creating membrane pores) and granzymes via degranulation, engaging surface Fas / FAS-ligand receptors, and releasing cytotoxic cytokines, such as Tumor Necrosis Factor (TNF). CD4 Helper T Type 1 cells target vesicular intracellular pathogens that survive inside macrophages. Upon recognizing MHC Class II-peptide complexes on infected macrophages, Th1 cells secrete interferon-gamma. IFN-gamma activates macrophages by triggering the respiratory burst and enhancing lysosomal fusion with endosomes to digest internalized pathogens. CD4 Helper T Type 2 Cells target extracellular pathogens needing humoral defense. Th2 cells bind to MHC Class II complexes on B cells and secrete cytokines such as Interleukin-4 (IL-4). This signals B cells to proliferate and differentiate into antibody-secreting plasma cells and undergo antibody class-switching (transitioning from IgM to specialized isotypes like IgG, IgA, or IgE). CD4 Regulatory T Cells function as the "military police" of the adaptive immune system, suppressing excessive immune activation to prevent immunopathology and autoimmune tissue damage.

Discuss the role of B cells, plasma cells and antibody in the immune response to viruses, bacteria, and parasites.

B cells, plasma cells, and secreted antibodies form the humoral (soluble) branch of adaptive immunity, providing targeted defense against extracellular threats in blood, lymph, and mucosal secretions. Unlike T cells, which require antigen processing and presentation on MHC molecules, B cells recognize whole, unprocessed protein antigens on pathogen surfaces in extracellular fluid using surface immunoglobulins (B cell receptors). Upon recognizing antigen in secondary lymphoid tissues, naïve B cells become activated and proliferate rapidly within germinal centres located in secondary follicles. Activated B cells differentiate into plasma cells, which function as "antibody-secreting factories". These cells either reside locally in the medullary cords of lymph nodes or migrate to the bone marrow to release large quantities of antibody directly into circulation. CD4 Helper T Type 2 cells interact with B cells displaying MHC Class II-peptide complexes. Th2 cells secrete cytokines (such as Interleukin-4) that direct B cells to undergo antibody class-switching, transitioning from initial IgM synthesis to specialized IgG, IgA, or IgE isotypes. IgM is the “First Responder”, secreted as a pentamer during early exposure, IgM neutralizes circulating virions in the blood. Following Th2-mediated class-switching, IgG acts as a potent virus-neutralizing antibody in systemic fluids, binding viral surface antigens to block viral entry into host cells. Produced by plasma cells in Mucosal-Associated Lymphoid Tissue (MALT), dimeric IgA is actively transported across mucosal epithelial linings into saliva, tears, and GI/respiratory mucus to neutralize viral pathogens before they can breach outer mucosal barriers. Antibodies bind directly to bacterial cell walls or secreted bacterial toxins, physically preventing adherence to host epithelial surfaces. Because IgM exists as a pentamer capable of binding 10 antigens simultaneously, it acts as an agglutinin, clumping bacterial cells together for easier clearance. IgG coats bacterial surfaces and binds directly to Fc-gamma receptors on macrophages and neutrophils, drastically enhancing phagocytic uptake and digestion. Both IgM and IgG trigger the classical complement pathway upon binding microbial antigens, driving the assembly of the Membrane Attack Complex (MAC) for direct bacterial lysis. B cells produce IgE specifically during helminth parasite infections in response to specialized cytokine signals. Secreted IgE binds to receptors on the surface of mast cells. When surface-bound IgE encounters and cross-links parasite antigens, it triggers immediate mast cell degranulation and histamine release, driving localized tissue inflammation and enhancing the parasite-killing response.

Describe the ways in which innate and adaptive immune systems work synergistically.

The innate and adaptive immune systems do not operate in isolation; rather, they form an interdependent defense network. Innate immunity provides an immediate, non-specific response that contains pathogens, while adaptive immunity provides antigen-specific clearance and long-term memory. The two systems work synergistically across several key pathways. The adaptive immune system cannot recognize raw pathogens on its own and relies on innate cells for activation. Innate antigen-presenting cells (APCs)—such as dendritic cells and macrophages—engulf extracellular pathogens via endocytosis, digest them into peptide fragments in endolysosomes, and display them on surface MHC Class II molecules. They then migrate to secondary lymphoid tissues to activate naïve CD4 T cells. During viral infection, innate Type 1 interferons (alpha, beta, omega) increase the surface expression of MHC Class I molecules on host cells, enhancing the visibility of viral peptides to CD8 cytotoxic T cells. Once activated, adaptive T cells secrete cytokines that dramatically boost the killing capacity of innate phagocytes. For vesicular intracellular pathogens that survive inside macrophage endosomes, CD4 TH1 cells recognize the displayed MHC Class II-peptide complexes and secrete Interferon-gamma. IFN-gamma activates infected macrophages by triggering a potent respiratory burst and accelerating the fusion of lysosomes with phagosomes to complete bacterial digestion. CD4 TH2 cells secrete cytokines (such as Interleukin-4) that stimulate B cells to differentiate into antibody-secreting plasma cells and undergo class-switching. Secreted antibodies generated by adaptive plasma cells function as precision guidance systems for soluble and cellular innate defenses. While innate Pattern-Recognition Receptors (PRRs) and non-specific acute-phase proteins provide basic pathogen recognition, antigen-specific IgG coats bacterial cell walls. Phagocytic neutrophils and macrophages express surface Fc-gamma receptors that bind the Fc region of IgG, driving rapid and efficient phagocytic engulfment. Bound IgM and IgG antibodies trigger the classical pathway of the complement cascade. This amplifies the deposition of C3b (acting as an additional opsonin), releases C3a to induce tissue inflammation via mast cell degranulation, and drives C9 polymerization to form the Membrane Attack Complex (MAC) for direct bacterial lysis. During helminth parasite infections, adaptive B cells produce IgE, which binds to Fc-varepsilon receptors on innate mast cells. Antigen engagement cross-links these surface IgE molecules, triggering mast cell degranulation and histamine release to eliminate the parasite. The innate immune system serves as the crucial first line of defense during the lag phase (the first 5–7 days before antigen-specific antibodies and expanded T cell clones reach therapeutic levels). By limiting initial microbial replication and recruiting inflammatory cells, innate immunity keeps the host alive long enough for adaptive immunity to develop full protective coverage and immunological memory.