Muscle Structure and Contraction

Muscle Organisation

• Skeletal muscles and cardiac muscles are striated, while smooth muscles are non-striated.

Structure of Skeletal Muscle

• The functional unit of skeletal muscle is the sarcomere, which is replicated down the length of the muscle to form myofibrils.
• Myofibrils are bundled together to form muscle fibers (a cell).
• Muscle fibers are bundled and wrapped in connective tissue to form fascicles.
• Fascicles are in turn bundled to form muscle.

Connective Tissue

• Endomysium: surrounds each individual muscle fiber.
• Perimysium: surrounds each fascicle.
• Epimysium: surrounds the entire muscle.

Sarcomere Structure

• A band: stays the same width during contraction.
• H zone and I band: become shorter during contraction.
• Thick filaments: formed by myosin, consisting of two identical subunits.
• Thin filaments: formed by actin, which interacts with myosin cross-bridge.
• Tropomyosin and troponin are associated with actin.

Myosin Structure

• Myosin head: has an actin binding site and ATPase site.
• Actin (Thin Filament) Structure: forms a helix, with tropomyosin molecules blocking myosin binding sites.

Contraction Mechanism

• Power stroke: bending of myosin heads pulls the actin filament towards the center of the sarcomere.
• Role of calcium: increasing calcium ions bind to troponin complex, causing a conformational change that moves tropomyosin away from myosin's binding site on actin.

Neuromuscular Junction

• Neuromuscular Junction (NMJ): a specialized synapse connecting motor neuron to skeletal muscle fiber.
• Excitation-contraction coupling: action potential at axon terminal opens voltage-gated calcium channels, releasing acetylcholine into the synaptic cleft, which activates nicotinic ACh receptors, triggering muscle contraction.

Sliding Filament Theory

• Myosin heads form a cross-bridge with actin filament.
• Attached heads pull on the actin filament through relaxation.
• ATP attaches to the myosin head, breaking the bond with the actin filament.
• ATP hydrolyses and "cocks" the myosin head back to the starting position, causing the myosin filaments to slide along the actin, resulting in muscle contraction.

Muscle Relaxation

• Relaxation requires breaking the cross-bridge cycle.
• In the absence of motor neuron firing, calcium channels close.
• ATPases in the sarcoplasmic reticulum quickly return calcium to stores or expel it from the cell.
• SERCA (Sarco/Endoplasmic Reticulum Calcium ATPases) causes troponin (TnC) to release calcium, reversing the conformational change in tropomyosin.

Motor Unit

• A motor unit consists of a single motor neuron and muscle fibers.

Smooth Muscle Contraction

• Depolarization opens L-type voltage-gated calcium channels, allowing calcium influx.
• Intracellular calcium binds to calmodulin, activating myosin light chain kinase (MLCK).
• MLCK phosphorylates myosin heads through ATP hydrolysis.
• Phosphorylated myosin heads can attach to actin-binding sites, causing muscle fiber contraction.

Control of Smooth Muscle Contraction

• Smooth muscle contraction is involuntary.
• Varicosities (swellings of axons) filled with neurotransmitters contact the sarcolemma.
• Smooth muscle can be spontaneously active, generating action potentials without external stimuli, often due to pacemaker cells in hollow organ walls.

Innate Immune System vs Adaptive Immune System

• Innate Immune System: present from birth, non-specific defense, rapid response, no memory of previous exposures
• Adaptive Immune System: develops over time, highly specific defense, slower response, memory, involves B cells, T cells, and antibodies

Haematopoiesis

• Definition: development of stem cells and precursor cells into protective cells
• Origin: bone marrow, travel through circulation, and mature throughout the body
• 5 types of stem cells:
  • Totipotent: can generate all cell types needed for a new organism
  • Pluripotent: capable of producing nearly all cell types, in three germ layers
  • Multipotent: able to produce cells within a closely related family
  • Oligopotent: limited to generating a few cell types within the same family
  • Unipotent: can produce only one specific cell type

Waldeyer's Ring

• Located in the upper airway
• Consists of 4 tonsillar structures, containing lymphoid tissue and lymphocytes (T and B cells)

Microfold (M) Cells

• Role: take up antigens expressed by pathogens
• Structure: 'U' shaped, with a pocket toward the basal end, allowing T cells, B cells, and Antigen-Presenting Cells (APCs) to enter
• Function: facilitate interaction with immune cells

Tonsils

• Part of the mucosa-associated lymphoid tissue (MALT)
• Contain lymphocytes (T and B cells)

Peyer's Patches

• Lymphoid cells found in the epithelium of the gut
• Part of the gut-associated lymphoid tissue (GALT)
• Function: supply the gut with B cells

Spleen Functions

• Blood filter
• Recycles old red blood cells
• Stores platelets and other white blood cells
• Facilitates opsonization (coating bacteria with antibodies) for bacterial clearance

Acute Inflammation vs Chronic Inflammation

• Acute Inflammation: occurs in response to injury or infection, immune cells are brought to the site → clear infection or damaged tissue, resolves once threat is eliminated, typically lasts up to 2 weeks
• Chronic Inflammation: (not mentioned)

Monocyte Functions

• M1 Monocytes: fight against infections and foreign invaders
• M2 Monocytes: healing

Phagocytic Cells

• 4 types: Monocytes, Macrophages, Neutrophils, Osteoclasts
• Function: consume invading pathogens
• Attracted by: chemoattractant

MHC (Major Histocompatibility Complex)

• Crucial component for T cell maturation and function
• MHC Class I (MHC I): on all nucleated/infected cells
• MHC Class II (MHC II): only on antigen-presenting cells (APCs)

CD4 Proteins

• Recognize antigens presented by APCs
• CD4 + MHC 2

CD8 Cells

• Recognize antigens on the surface of infected cells
• CD8 + MHC I

B Cell Maturation

• Occurs in lymph nodes

T and B Cell Activation

• T cells await activation in the lymphatic system (lymph vessels or lymphatic vessels)
• After T cell activation by APCs: Th cells (CD4 + MHC 2) are activated, and they, in turn, activate B cells, which mature into plasma cells, and enter the circulation.

Types of Bone Marrow

• Red bone marrow: produces red cells and most white blood cells, typically found at the end of bones (epiphysis) in adults
• Yellow bone marrow: produces some white blood cells, typically found in the canal of long bones in adults, and has a high fat content

Eosinophil Cells

• Involved in fighting parasitic infections and modulating allergic responses

Complement System

• Activates inflammation
• Opsonization (labelling) of pathogens and cells for clearance/destruction
• Direct killing of target cells/microbes by lysis

Myeloid Cells

• Many innate immune cells mature in the bone marrow or shortly after entering circulation
• Maturing cells become myeloid cells

Monocytes and Macrophages

• Monocytes: present in blood circulation (m1 + m2)
• Macrophages: mainly found in tissues, being tissue residents
• M1 Monocytes: fight against infections and foreign invaders
• M2 Monocytes: involved in healing

Phagocytic Cells

• 4 types: monocytes, macrophages, neutrophils, and osteoclasts
• Phagocytic cells consume invading pathogens
• Chemoattractant: attracts phagocytes towards site of infection/injury

MHC 1 and MHC 2

• MHC 1: on all nucleated/infected cells
• MHC 2: only on antigen-presenting cells (APCs)
• MHC is crucial for T cell maturation and function

CD4 Proteins and CD8 Cells

• CD4: recognises antigens presented by APCs
• CD4 + MHC 2
• CD8: recognises antigens on the surface of infected cells
• CD8 + MHC I

B Cell Maturation

• Maturation of B cells occurs in lymph nodes

T Cell Activation

• After T cell activation by APCs, Th cells (CD4 + MHC 2) are activated, and they, in turn, activate B cells
• B cells mature into plasma cells, which enter the circulation

Innate Immune System vs Adaptive Immune System

• Innate Immune System: present from birth, non-specific defence, rapid response, no memory of previous exposures, includes physical barriers, chemicals, and basic cellular components
• Adaptive Immune System: develops over time, highly specific defence, slower response, memory, involves B cells, T cells, and antibodies, communicates with the innate system for a more specific response

Haematopoiesis

• Haematopoiesis: stem cells and precursor cells develop into protective cells
• Originating in the bone marrow, travel through circulation, and mature throughout the body

Types of Stem Cells

• Totipotent: can generate all cell types needed for a new organism
• Pluripotent: capable of producing nearly all cell types in the three germ layers
• Multipotent: able to produce cells within a closely related family
• Oligopotent: limited to generating a few cell types within the same family
• Unipotent: can produce only one specific cell type