AIRWAY MUCOSA SKIN TEAR GLANDS • Formed of thick layers as formidable barrier • Tears act as FLUSHING AGENT • Airways secrete mucous that trap bacteria and viruses to prevent their BUT ONLY when unbroken • Contain LYSOZYME enzyme that can destroy • attachment to the underlying cells Cuts and scrapes allow invaders inside bacteria SWEAT GLANDS GUT MUCOSA GUT ACIDITY NORMAL GUT FLORA • Sweat & Sebaceous • Gastrointestinal tract secrete mucous which • Gastric juices • Gut is colonized by commensal glands produce fatty trap bacteria and viruses to prevent their are very acidic bacteria who can out-compete any acids that stop bacterial attachment to underlying cells which kill lots foreign invading bacteria for essential growth on skin of different nutrients and docking sites bacteria
URINATION UROGENITAL MUCOSA
• Peeing gets rid of waste fluid which makes difficult for bacteria that • Urogenital tract secretes mucous which trap bacteria and have invaded from the outside via urethra to attach to the bladder wall viruses to prevent their attachment to the underlying cells
Innate Immune System Adaptive Immune System
VARIOUS SPECIALISED T-CELLS • Cells are always patrolling: Natural killer (NK) cells, Eosinophils, CELLS • Lymphocyte produced in thymus Basophils, Mast cells • Help in immune regulation • Destroy infected and inappropriate cells VARIOUS SPECIALISED •PROTEINS Complement, Interferons, Acute phase proteins B-CELLS • Lymphocyte produced by bone marrow INFLAMMATORY • Produce antibodies • Collection of physiological changes triggered by trauma (injury, RESPONSE infection) – “triple-response” INNATE / NATIVE / NATURAL IMMUNITY Always present even when there is no infection Circulating Cells NEUTROPHIL MACROPHAGE MAST CELL • Most common white cell with 2 types of granules • Born in bone marrow • Contain granules, which its release is triggered by • Granules contain a number of different agents = • Matured in various tissues injury or signals from other parts of the immune system Released to fight, kill and digest invaders • Engulf and destroy bacteria • Granules contain histamines = Increase blood flow • All-rounders & First line of defence via phagocytosis during inflammation • Granules contain proteases = Destroy invaders
NATURAL KILLER (NK)
•CELL Secrete perforin and granzyme proteases = Kill cells that have been infected by virus EOSINOPHIL • Secrete perforins and peroxidases and other substances = Fight invaders (helminth worms, other classes of parasites) BASOPHIL • Similar to eosinophils and mast cells • Make up the smallest numbers of circulating cells of innate immune system INFLAMMATION 1 Process Of Inflammation PHAGOCYTOSIS DEGRANULATION – chemical • Few different cells can recognize, •weapons Most innate cells carry pre-made packages of granules that they can engulf and digest invaders empty (degranulate) onto invaders • Macrophages & Neutrophils • Substances – digestive enzymes, reactive oxygen intermediates, toxins, … Inflammation SIGNS OF (ACUTE)PROCESS BEHIND INFLAMMATION • Vasodilatation – blood vessels widen so many things can flow through more for help • Redness • Oedema – swelling, liquid infiltrate tissues • Pain • Flare – skin flushing due to lots of blood in the infected area • Swelling • Acute cellular phase – white blood cells infiltrate the area, tissues to go to where needed • Heat • Resolution – area healed IF CAN’T HEAL – Innate immunity system seal it off away from the body as GRANULOMA INFLAMMATION 2 Triggers Of Inflammation • Powerful response • COMPLEMENT PROTEIN = Collection of small liver-derived proteins patrolling blood in an inactive state Activation (detection of plasma leaking into the spaces between cells in tissue) triggers a chain reaction of protein cleavage Culmination in the release of cytokines (Factors secreted by immune cells that activate other cells) Massive amplification of distress signal & Activation of MEMBRANE ATTACK COMPLEX Destroy bacteria • Complement system activation unleashes lots of action against invaders: Inflammation; Cytolysis (= formation of a lethal channel in bacteria – Membrane Attack Complex); Opsinization (= coating that makes bacteria ‘tastier’ to phagocytes) 1. Patrolling complement protein C3b coats bacteria in the blood 2. Chain reaction of complement cleavages and activations 3. Nearby mast cells release their granules into interstitial spaces 4. Attract circulating neutrophils in blood & Facilitate their infiltration into the tissues = DIAPEDESIS / EXTRAVASATION 5. NEUTROPHIL = Cells which patrol the bloodstream are attracted to an area of tissue distress by signals (interleukin-1 cytokine released by mast cells) & ENDOTHELIAL CELL = Line the blood vessels and become dilatated and retract in response to distress signals (basement membrane underneath) 6. ROLLING: Neutrophils can’t attach to endothelial cells normally due to fast blood flow = Mast cells express a protein, P-SELECTIN on their surfaces which bind neutrophils = Slow neutrophils down 7. FIRM ATTACHMENT: Neutrophil encounters a CYTOKINE RECEPTOR on the endothelial cell surface which can activate the neutrophil 8. MIGRATION: Neutrophil squeeze between 2 cells to enter tissues to attack bacteria ADAPTIVE / ACQUIRED IMMUNITY Requires initial exposure to stimulate future responses Is exquisitely specific to a particular invader Immune Cells & Proteins T CELL B CELL ANTIBODY • Various types exist • Produce & • Proteins produced by B-cells that • Helper T-Cells = Help Secrete recognize 1 unique shape activate B-cells antibodies (ANTIGEN) Bind to that • Cytotoxic T-cells = with help shape to immobilize the invader Recognize infected or from bearing that shape OR to target it cancerous cells and kill helper T- for phagocytosis by another cell them in close proximity cells • 5 kinds of antibodies – IgA, IgG, by releasing toxic agents IgD, IgE, IgM Self & Non-Self Recognition • All cells in body express integral membrane proteins – MHC (MAJOR HISTOCOMPATABILITY COMPLEX) / HLA (HUMAN LEUKOCYTE ANTIGEN) = Function as “self” flag and anything without these are recognized as invaders • MHC-I = General self-flag on all cells from virus – if a cell is infected and displays foreign markers in parallel to it, MHC-I & PEPTIDE cytotoxic T-cells can recognize and kill it • MHC-II = Specialised self-flag on certain immune cells (B-cells, macrophages) helper T- cells see this and know to offer help in activation • MHC-III = Specialised class • Difference in the similar structure of MHC-I and MHC-II: class-I – has only 1 membrane- spanning protein subunit in association with a small protein, BETA-2 MICROGLOBULIN & class-II – comprised of 2 similar proteins with 2 subunits each ANTIBODY ANTIGEN = Any agents that can induce an adaptive immune response (proteins make great antigens but sugars aren’t); All B- cells with capacity to produce antibodies against self-antigens are deleted EPITOPE = Shape on an antigen that is recognised by antibody ANTIBODY = Proteins comprised of 2 heavy chains and 2 light chains; Variations of tips of Y shape are where antibody can recognize and bind a unique antigen ANTIGEN-BINDING DOMAIN = Diversity in binding pocket is generated by massive genetic recombination during B-cell development LIGHT CHAIN = Smallest of the 2 subunits of an antibody • ANTIBODY HEAVY CHAIN BINDING – Antibodies = Biggest can immobilise of the 2 subunits – insertedtheir into targets & flag them the membrane up for&destruction of B-cells via complement and phagocytes act like receptor • VACCINATION – Vaccines are a mixture of antigens derived from a pathogen (a piece of its protein coat, killed or weakened version of entire pathogen) which stimulate antibody response • VIRUS ATTACK = Virus or other pathogen’s native antigens elicit immune response Antibody Binding 1. Antigen presented to B-cell by other cells, ANTIGEN –PRESENTING CELLS 2. Antigen only bind to the matching antibody receptor on 1 specific B-cell onto B-CELL RECEPTOR (= MEMBRANE BOUND ANTIBODY) [B-cells display a receptor born of massive genetic variation] 3. B-cell engulfs, internalises, entire receptor/antigen complex, process it, display it in the context of MHC-II on its surface 4. This flag attracts helper T-cell which activated B-cell B-cell proliferates and grow many clones & Stimulate T-cell to make more helper clones 5. B-cell clones develop and differentiate into 2 types of cells: Plasma cells (= bigger and more specialised) & Memory cells (looks like original) 6. Plasma cell secretes, releases lots of antibodies exactly same as original receptor that its progenitor cell was expressing when encountered antigen & A small subset of memory cells produced Memory • Repetition of process More T-cells More memory cells • Faster response & More antibodies made T-CELL Helper T-Cells – B-Cells Helper T-Cells – Cytotoxic / Killer T-Cells 1. B cell presents antigen in terms of MHC-II 1. Virus-infected cells loaded with viral antigens, displayed on the cell surface 2. T cell attracted to physically dock and bind with T cell receptor, in the context of MHC-I CD4 (2 different docking protein) 2. This flag attracts cytotoxic T-cells (CTL – cytotoxic T-lymphocyte) 3. MHC-II/antigen complex can co-bind T cell receptor 3. Cell-to-cell binding occurs via T-cell receptor in the context of CD8 protein 4. Physically touching to activate – 4 proteins come together as T 4. Binding stimulates T-cell to degranulate = Release PERFORIN protein cell act very locally (makes holes in virally infected cell) 5. Growth factor, activating cytokines (chemoattractant), secreted 5. Infected cell bursts open due to full of holes = LYSIS in immediate environment 6. Cytotoxic T-cells contacted by helper T-cells = Clonal expansion of 6. Cytokines trigger B cell to proliferate cytotoxic killer T-cells
Helper T-Cells – Macrophages
1. SAME AS BEFORE (MHC-II/antigen presentation, T-cell receptor/CD4 interaction) 2. Phagocytes ingest and destroy invaders • RESOLUTION = How virus infects a person via being sneezed on by infected person through clearance of virus • Immune cell proper: tissue resident innate immune cells – macrophage • Dendritic cell – relate ___ to innate cells • Cd4&8 help t cells to correctly identify mhc • B cell chop it up then absorb then present via mhc ii so it attracts t helper to release more antibodies • Virus – dendrite cells – mhc ii – t helper