What are the 2x conserving processes?
Staying alive
1. Autopoiesis (Self generation) “Auto”= self. “poesis”=to produce.
Whilst living, continue to build components of our body, by all bodily components acting together in a cooperative network to generate what we need in our changing environment.
2. Adaptation (relations with non-self). Live in an ever-changing environment, and need to adapt out relationship with it.
Nervous system and immune system: Maintain Internal-External coherence. Maintain activities occurring inside our body, and our bodies relationship with activities occurring externally. Accomodate body so can stay alive
Functions of Immune system
Needs to know which part of the body needs the immune systems to help
Immune system is a Sensory effector system which detects macromolecular shapes.
Distinguish between self and non-self compartments, in order to:
1. Protect against infections
2. Recover from infection and tissue damage - works with inflammatory systems
3. Maintain adequate relationship with external environment (staying alive)
Responds to Molecular shapes (antigens)
-sense macromolecular shapes and responding with actions in response to those shapes
-antigens/antigenic epitopes
Senses:
1. Unusual shapes(non-normal components)
2. Familiar shapes in unusual/unfamiliar context
-not just about recognising shape, but also recognising the context in which it is occurring
-also influences action
Immune Defences
- Innate immunity: physical, microbial, humoral factors. React first. Born with. Don’t change much throughout lives.
Surface: keeps 99% of potentially harmful factors.
Some get in, and meet Cellular and humoral factors. closely related to inflammatory response.
Adaptive immunity : combination of innate and inflammatory response. Cellular and humoral factors. Recognises shapes, but is more particular and tends to responds later than previous 2x systems
External Surface protection
If compromised, increases posibility for more infections
- Biophysical Defence: Structures physically stop things entering. Mucus(thick, glues, difficult to get through) , Cilia lining Respiratory tract (waves mucus and removes/ moves towards digestive system), Acid in stomach(low Ph to kill organisms), Skin(thick)(enter when cut/abrasion/sebacious glands- inflammatory lesion of pimple/boil) -Harder to cross External surface unless broken, Easier to cross vis internal surfaces (digestion, respiratory and GU system) as need to exchange gases and nutrients
- Biochemical Defence: Lysozyme enzyme in most secretions (v common. breaks peptidoglycan bonds of bacterial cell wall, falls apart and dies) . Sebaceous Gland secretions (tears, saliva, sweat contains secretions, diffidult for bacteria to survive). Commensal organisms in gut and vagina (bacteria that grow with us, and needed for digestion/other functions. Essential for our survival.- More Nonhuman bacteria than human bacteria 1000x) (some secretion help keep bacteria dying or atleast control their multiplication) Spermine in semen
Internal Protection
- Innate Internal barriers. (Non specific). Encountered first. Have specificity/recognise shape. Resistance not improved by repeated infection. Born with, dont change much during life span. Biochemicals: Lysozyme (internal and secretions), *Complement (blood proteins which helps to contain organisms, and activate inflammatory responses), Acute phase proteins (liver, produced in response to inflammatory responses of infection or trauma), Interferon (cells produce and interferes with virus replication and tells other cells about virus)
*Phagocytes, Natural Killer (NK) cells - Adaptive Internal barriers (specific). Relatively more specific. Resistance improved by repeated infection. Adaptive= changes over time.(immune system remembers and changes so responds, (later) quicker, vigorously and is a more sustained response) Immunological memory. gradually diminishes if not revised. Antibodies, complement(works with antibodies), cytokines ( control immune response)
Lymphocytes (main), Monocytes and Antigen-presenting/Dendritic cells (work with lymphocytes)
What are the main 2x features of our body’s innate internal protection?
Complements
Phagocytes
Link the way the innate system works and to inflammatory responses and adaptive responses
Phagocytosis
“phago” = to eat
“Cyto”= cell
e.g. macrophage
Mobile. Sense spores.
Internal Innate factors
Phagocytosis (cell eating)
The complements system (enzymatic cascade in blood) (proteins work together when recognise certain things, form ezyme, then act on/activates other components of complement system products, which help to deal with infection/tissue damage)(amplify initial small signal)
Linked to inflammation and phagocytosis
Local infection: Role of complement
Some blood complement components, get together and read common structures on bacterial cell walls
-bacterial molecules evolved to have characteristic features on cell surface
-Immune system evolved to recognise these
Common cell wall components on Staph Aureus + First complement components. These combine, and then change shape to form an enzyme. Enzyme then acts to activate other complement components. chops some components into 2x pieces, each having different activities. 1x Active component increases Vascular permeability (leaky). BV swells so more blood flows through= swelling, redness, heat of inflammation
2nd forms chemotactic gradient to attract neutrophils out of blood stream “Chemo”= chemicals. “taxis”=movement. Molecules that form an attraction to something else. Produced in high numbers Initially around bacteria where complement is activated. Will gradually diffuse out, to form gradient (high conc. around bacteria, low conc. further out). Neutrophils move towards chemotaxic factors.
3rd complement component is chemically very reactive molecule. Covalently attaches to close by bacterial surface. Neutrophils have a high affinity receptor, and upon binding, triggers them to phagocytose. Opsonisation(enhance phagocytosis by binding to the surface of what the phagocytes need to ingest)
Results: Vessel swelling, leakage of blood/fluids into surrounding tissue, increased blood circulation in local site (heat) (redness), neutrophils move through leakier vessel walls, and crawl towards highest conc. of chemotaxic chemicals, towards what it needs to phagocytose which is surrounded by complement components.
-Complements neutrophils action, to get them to the stage of phagocytosis
How do we remove fluid?
Warm, painful, loss of function, swelling
Lymphatic system
-Non-closed loop. Inverted Tree
Large Thoracic duct in trunk, then branching smaller vessels into all tissues + immune organ lymph nodes
Lymphatic vessels
Thin walls
holes on side
Anchored into tissue
One way leaf valves
-Muscles tense and relax, slightly squeezing and relaxing lymph vessels,
Squeeze: pushing fluid up (one way leaf valves)
Relax: vessels open, sucking in fluid through holes in side from tissue space
-Towards pump (thoracic duct)
-Muscle generated pump system,
Thoracic duct links to blood system via subclavian veins, emptying fluid contents into blood stream
-blood circulation, fluid squeezed into tissue space (enhanced through inflammatory process), lymphatic system collects fluid and brings back into blood system - completing circulation outside of the blood
Collects some of the Infection/tissue damage, drains into and out of lymphatic nodes-packed with lymphocytes. Main organs of 2 secondary lymphoid system. anything travelling through will be filtered out, and lymphocytes from their may gain ability recognise and generate immune response.
1. Collect fluid, and return to blood stream
2. Collect shapes (broken bacteria, virus etc) from body or inflammatory site, and be bought to lymph nodes, to see if system needs to respond
What happens when you sit on a plane for too long or you’ve been lying down without moving for too long?
Your extremities swell up
mostly in our legs
-muscles arent pumping lymphatic system fluid, and not pumping it back into our blood stream
Microfilaria Parasitic Worms
Enters lymphatic system, Latches onto the vessel walls, and Drinking the lymphatic fluid through that lymph
grows fat, and form big long warms which block the vessels
-any tissues downstream wont be able to be drained of its lymph= swollen
-tissue damage and necrosis also, as cells aren’t receiving adequate nutrients and aren’t surviving
What is the scope access that the immune system has?
Immune system has access to virtually all parts of you body
via blood system and lymphatic system
-these pervade everything
-must be able to collect information about both the shapes, information and context of what is occuring
Rash and Neck Lumps
Painful, hot inflammatory lesion + swollen lymph nodes
- Lymphatic system drains into lymph node and was triggering an immune response to grow and divide, therefore lymph nodes enlarged/inflammation. Immune activity or blood problem leading to growth of cells there(more rare)
- Lots off lymph nodes in neck. Axillary Lymph nodes (under arm)
- Lymph node: about the size of a broad bean
- more than one swollen lymph nodes, therefore less likely to be cancer/tumour
- check related to infection via Temperature
- Shingles - viral infection (varicella zoster) involves nerves and immune system
- previously chicken pox. Hides in nerves, integrates DNA into nerve DNA, sometimes with a traumatic injury the virus is reactivated, moves down the nerves (from infected nerve) and infect surrounding tissue
- Latent virus infection (can be reactivated). Herpes class of viruses
- causes resolvable inflammation
Neck Lump
Lumps in neck but feels fine
No temp
Abnormal distribution of blood cells
-highlights that changes in lymphatics can be due to infection or inflammation, but could also be due to other things
-blood abnormality possibly associated with lukemia or lymphoma that was growing in those nodes, causing them to swell
Neutrophil
Main phagocytic cell
-short term phagocytic cells, continually produce, phagocytose, die and then replenished
“Polymorphonuclear nucleocytes”= many funny shapes on the nucleus
-nucleus has funny shapes/lobes on nucleus
Anto-bacteria
Erythrocytes
bionconcave disc
No nucleus
full of Hb carrying O2 and CO2 around body (transport)
Platelets
Clotting factors
Not cells, derived from cytoplasm of bone marrow cells called Megakaryocytes
Packets of clotting factors
Basophil
About same size as neutrophil Also has funny shaped nucleus Multiple purple dots in cytoplasm -stain with basic dye: hence "Basophil" strongly related to phagocytic neutrophils Mucosal Surface Protection
Eosinophil
Similar size and funny shaped nucleus
Orange speckles in cytoplasm stained with Eosin dye : hence “Eosinophils”
related to neutrophils
Anti Parasite immunity
Monocyte
about same size as neutrophil Different shaped and coloured nucleus Longer living phagocytic cells Co-operate with lymphocytes to help them generate adaptive immune responses -Antigen presentation
Lymphocyte
adaptive immunity
Round large nucleus
Where do blood cells originate from?
Bone Marrow of long bones
Haematopoeisis
-Haematopoetic stem cells (give rise to all blood components)
-slowly regenerate, and respond to signals which triggers them to different along one of several pathways, giving rise to all blood components
-1st Myaloid lineage, series of differentiation steps, triggered by various hormones, giving rise to (4) neutrophils, eosinophils, basophils and monocytes
Note:-Monocytes live longer than other 3 blood types, and can move from blood into tissues, differentiating into Macrophages in our tissues
-2nd lineage, under control of different signals, produce RBC/erythrocytes, undergo nucleated stages called Reticulocytes, and eventually lose nucleus and become RBC
-3rd Lineage, megakaryocytes which stay in bone marrow, and pinch off pieces of cytoplasm containing clotting factors, and release these into blood stream (platelets)
-4th Lineage, Lymphoid lineage, adaptive immune system. Influenced by hormones. a) lymphocyte population completely made in bone marrow and then exported into blood system: Bone marrow derived/B-Lymphocytes. b) Some stem cells become partially mature, leave bone marrow –> Thymus (under sternum), undergoing differentiation there, and entering blood stream as Thymus derived/T-Lymphocytes
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Lecture 232
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Lecture 329
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Lecture 532
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Lecture 626
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Lecture 725
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Lecture 848
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Lecture 930
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Lecture 1023
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Lecture 1133
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Lecture 1226
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Lecture 1338
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Lecture 1440
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Lecture 1520
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Lecture 1623
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Lecture 1824
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Lecture 1935
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Lecture 2237
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Lecture 2329
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Genetic Therapies31
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Cystic Fibrosis50
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Principles30
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Genes and Cancer42
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Familial cancer34
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Classification, Grading and Staging49
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Nutrition and Cancer28
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Environmental basis of cancer43
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Non Coding RNAs and Disease38
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Important Ethical and Genetic issues for Maori29
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Cellular basis of Malignancy48
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Review of Basic Genetic and Bioinformatic Technologies in the Context34
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Lecture 2035
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Introduction to Tumour Biology40
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Lecture 21 X-Linked Disorders and Mitochondrial Inheritance35
