Altered Phys. Notes
Lecture 1: (September 17, 2015)
What does physiology mean? * Normal function of a living thing, human cell, tissue, organ , system
What is Pathophysiology? * Abnormal function caused by an adverse event/stimulus * The event can be mechanical/chemical/radiation/etc. * It has a negative impact on function
How relevant is A&P to Patho? * Pretty relevant * You know when something is wrong with the human body if you know how it functions when its healthy * You need to know what’s normal to appreciate what’s different
Cell and tissue biology * If you can understand what is happening in a cell, you can see what is happening in a tissue, (tissue is group of cells performing a similar function) * Injuries can be caused by chemical, intentional or unintentional, etc.
Sub-lethal (reversible), or lethal (irreversible) * Cellular aging is a normal part of cell life
Structural and functional changes leading to cell death or decreased capacity to heal * Different cells age at different rates * Skin cells get replaced every day, red blood cells get replaced every 4 months * There are 5 million blood cells travelling in the human body at a time
Adaptation: how a cell responds to stimulus (ex. Pregnancy), to escape and protect themselves from injury
Normal cells meet injury it could do one of two things * It could say, I’m going to change myself so I can stay healthy adaptation * If the adaptation doesn’t work or unsuccessful, then the cell becomes injured * When cell goes from normal to adapted, what happens is that these states are reversible
Atrophy
* Once a cell reached a certain age, the cell will die * Once a cell decreases in size the organ will also decrease (muscle, heart, brain) * Your uterus lining has atrophied so that’s the reason why women have menstruation, normal cycle of life.

Difference b/w Physiologic and Pathologic Atrophy: * Phys: occurs with early development, normal part of life cycle * Path: due to decrease in workload, pressure, use, blood supply * Cause is different, effect is same * Uncontrolled Diabetes, your circulation gets slowed down, so a person with too much glucose has capillaries that are glycosylated which means there’s a thick barrier, so amount of nutrient reaching the tissue is decreased leads to loss in organs
Hypertrophy
* Increase in cell size leads to increase in organ size eg. Working out gives you bigger muscles * Different causes: * Mechanical signals: lifting heavy weight increases muscle size (increased workload, stretch) * Trophic signals: due to signal factors, hormones, vasoactive agents, (uterus in pregnancy)
Number of cells stay the same, some organs can’t increase in cell number, so cell’s volume increase * Cardiac hypotrophy: * Working a lot harder to get the same result * Heart becomes tired, needs more energy to do the work since cell is larger * When the aortic valve is narrowed * Heart becomes bigger * Cells in a hypertrophic heart are much bigger than normal heart, because heart needs to exert more force thus making it (stronger) = more blood needed to function = less blood inside the heart
Hyperplasia
* Increase in number of cells, due to increase rate of cellular division * Hyperplasia usually occurs with hypertrophy
Cells that cannot enlarge, multiply to do the work * Compensatory * For adaption * Eg. Callous formation in skin due to excessive guitar playing * Hormonal * In response to estrogen * Hyperplasia in prostate, enlarges prostate, which presses on the urethra, which causes increase urinary pressure = bladder increases in size due to hyperplasia/trophy * Toxic waste products can accumulate and cause different problems
Metaplasia
* Reversible replacement of 1 type of mature cell with often a less differentiated cell * In metaplasia, the replacement cell is less functional than the original cells * They’re not cancer cells, just different * Eg. Smokers, normal stratified columnar cell gets replaced with * Goblet cells produce mucus * Epithelial cells move things around
Dysplasia
* Uncontrollable abnormal growth * No cleanup service, even cells that are half made are kept * Nucleus are different sizes and cells are different shape no function due to irregular shape * Atypical hyperplasia: results in uncontrolled growth of non-functional cells
Linked to neoplastic growth, and is found next to cancer cells
Free Radicals and ROS (reactive oxygen species) * Electrically uncharged atom or group of atoms having an unpaired electron which can damage cell
DAMAGE MECHANISM by FREE RADICALS and ROS * Lipid peroxidation – destruction of polyunsaturated lipids, causing membrane damage * Alteration of proteins – stop protein pumps & transport pump * Alternation of DNA – decrease protein synthesis * Mitochondria – release Ca2+ in the cytosol
Hypoxemia = reduced oxygen content in blood
Lecture 2: Online Chapter 3
Cellular Accumulations (infiltrations)
4 reasons substances can accumulate in cell: 1. Increased rate of production of normal endogenous product
More stuff because more stuff being made

2. Normal endogenous products in cell don’t get broken down as quickly (catabolized)
Defective or decreased enzyme level

3. Mutated gene (degradation)
Abnormal product formed, protein not made properly, abnormal folding or protein (loses shape, can’t function optimally, transport inhibited)

4. Harmful exogenous including heavy metals, microbes
Inhalation, ingestion, or infection

4 common forces of cellular infiltrations/accumulations:
Water:
Cell swelling: most common
Cause: production of ATP decreases (needed for Na/K ATPase to work)
Kicks sodium back out of the cell, if no ATP or less, pump doesn’t work, NEEDS ATP
Sodium stays in cell if it doesn’t get kicked (water follows where Na+)
Lipids and Carbs:
Location: primarily in the spleen, liver and CNS
Effect: In CNS neurological dysfunction, severe mental retardation in developing people
Glycogen:
Glycogen accumulation results in excessive vacuolation of the cytoplasm
Most common cause: Diabetes Mellitus, lack of insulin, excess glucose in blood, gets stored at glycogen
Proteins:
Protein metabolites can damage cellular organelles
Excessive protein push against organelles, causing loss of functions, as well as disrupt intracellular communication

Process of ONCOSIS 1. Injury occurs 2. Hypoxemia (decrease in O2 levels) 3. Decreased mitochondrial function 4. Decreased ATP production 5. Decreased activity in Na+/K+ ATP pump 6. More Na+/water staying inside cell 7. Increased osmotic pressure (due to H20 increase) 8. Vacuolation – water is isolated from the cytoplasm 9. Oncosis (swelling) 10. Cell, and organelle swell, leads to loss of function
Lipid Accumulation:
Increase in fatty acids in liver cells
Decreased breakdown of fatty acids
Decreased production of apoproteins and lipoproteins
Decreased transport of lipoproteins out of cell
Precursor to serosis, mainly throught the loss of liver function
Tay Sachs – early childhood, slow accumulation of lipids in brain
Development of the child has decreased
Other Cellular Accumulations:
Pigments:
* Melanin: moles, freckles, nevi melanoma * Hemoproteins: excess iron due to increase intestinal uptake, release of tissue storages, overactive macrophages which destroy RBC * Bilirubin accumulates in liver: jaundice * Bruising – increased breakdown of RBCs
Calcium:
* Influx of extracellular Ca+ into mitochondria * Ca+ ions can accumulate, precipitate, clump together and harden, interfering with normal cell processes * Calcification accumulating in the aortic valve * Psammoma bodies – accumulation of calcium in tumors
Decrease O2 supply * Stenosis – narrowing * Aortic stenosis is common

Urate: * Increase in sodium urate levels (end metabolic product) leading to crystallization * Uric acid can crystallize, can cause kidney stones or lead to gout

Gout & Uric Acid 1. Hyperuricemia (increased uric acid in blood) 2. Deposition of sodium (big toe/kidney stones) males 40+ years old 3. Cell injury 4. Inflammation 5. Painful disorders (gout) 6. Urate crystals persist in dead cells
Cell Death:
Apoptosis - occurs in single cells, characterized by apoptotic bodies, cell fragments formed as part of process
Necrosis – due to sudden or severe injury, loss of plasma membrane structure, organelle swelling, mitochondrial dysfunction oncosis
New term programmed necrosis or necroptosis
-Apoptosis processing leading to necrosis due to activation of enzymes called death proteases (breakdown proteins)
Necrosis:
* At the start it is reversible before progression (sudden or severe) doesn’t always lead to necrosis * Water accumulated in E.R, mitochondria, causes sodium potassium pump to stop working * Breakdown of cell membrane * Causes blebs, cell membrane pushes out, expands * Leakage of contents * Causes inflammation progressive cell injury to neighboring cells
Apoptosis:
* No inflammation * Programmed organized cell death * Single isolated cells * Not external injury (within DNA) * Apoptotic bodies are parts of cells that break off when cells separate in different pieces * Phagocytes are vacuums and clean any apoptotic bodies
Necrosis Process: 1. Cell death occurs – due to irreversible injury 2. Pyknosis – nucleus shrinks to a small dense mass 3. Karyorrhexis – fragmentation of the nucleus into smaller particles 4. Karyolyis – nuclear dissolution & lysis of chromatin 5. Leads to cellular self-digestion (autolysis) implodes on itself
Types of Necrosis:
Coagulative Necrosis: * Common sites: kidneys, heart, adrenal glands * Common cause: hypoxia due to severe ischemia or caused by chemical injury, eg mercuric Cl * Pathway: protein denaturation causing albumin to change from a gelatinous, transparent state to a firm, opaque state
Liquefactive Necrosis: * Common sites: neurons & glial cells * Common cause: ischemic injury to neurons due to bacterial infection * Pathway: digestive hydrolytic enzymes cause auto-digestion, so the tissue becomes soft, liquefies, and is walled off from healthy tissue, forming cysts
Caseous Necrosis: prevalent in tuberculosis * Common cause: tuberculous pulmonary infection, especially by Mycobacterium tuberculosis * combination of coagulative and liquefactive necroses * Pathway: dead cells disintegrate, but the debris is not completely digested by the hydrolases. Tissues resemble clumped cheese in that they are soft and granular. A granulomatous inflammatory wall encloses areas of caseous necrosis.
Fat Necrosis: * Common sites: breast, pancreas, and other abdominal structures * Pathway: Lipases break down triglycerides, releasing free fatty acids, which then combine with calcium, magnesium, and sodium ions, creating soaps (saponification). The necrotic tissue appears opaque and chalk-white
Apoptosis
* Programmed cell death to ensure normal turnover of cells (need new cells) * Activation of “suicide gene” stops life-sustaining genes and promotes killer genes * Affects single scattered cells
Types
* Physiologic apoptosis: important in the development of body tissue, eg local deletion of cells during tissue turnover and normal embryonic development. * Pathologic apoptosis: due to intracellular events or adverse exogenous stimuli, eg Viral hep C
Aging vs. Disease
Aging – normal progression of growth development, maintenance and death of cells
Normal physiological process
Disease – caused by a pathological stimuli
Theories and Mechanisms of Aging:
Theories:
1. Accumulation of injurious events (wear and tear) 2. Genetically controlled program (limited lifespan genetically determined)
Mechanisms:
1. Genetic and environmental lifestyle factors: Programmed aging combined with exposure to damaging factors throughout lifespan 2. Alterations of cellular control mechanisms 3. Degenerative extracellular and vascular changes
#2 Neuroendocrine theory: * increased hormonal degradation (less hormone produced) * decreased rate of hormonal synthesis and secretion * decreased target-organ sensitivity (type 2 diabetes) related to the number of cellular receptors for hormonal ligands, ligand-receptor binding, or ligand internalization
Immune theories: * immune function declines with age * decline in immune function is related to certain diseases, eg cancer * number of autoantibodies (attack own tissue) increases with age

#3 Degenerative extracellular and vascular changes * Cross-linking of collagen so that collagen becomes insoluble, more rigid which decreases cell permeability * increase in free radicals’ effects on cells: lead to changes in cell function (wear and tear) * structural alterations of fascia, tendons, ligaments, bones, and joints; and peripheral vascular disease, particularly arteriosclerosis * Deposition of lipid, calcium, and plasma proteins in blood vessel walls cause serious basement membrane thickening and alterations in smooth muscle functioning, resulting in arteriosclerosis
Aging:
* Cellular aging * Atrophy, decreased function, and loss of cells leads to tissue and organ aging * Tissue and systemic aging * Progressive stiffness and rigidity * Sarcopenia (shrinkage of muscle cells) * Frailty * Changes in mobility, balance, muscle strength, motor activity, cognition, nutrition, endurance, falls, fractures, and bone density
Lecture 4: Online Chapter 2
Questions:
* Catabolism breaking down * More going in that’s being used = accumulation of substance * Anabolism synthesize
DNA: Watson and Crick
Polynucleotide
* Pentose sugar * Phosphate * Nitrogen base * These 3 are considered NUCLEOTIDES
DNA directs synthesis of all proteins * Codes for proteins with codons for specific amino acids * 3 base pairs per codon

From DNA to protein:

* Nucleus mRNA leaves nucleus and enters cytoplasm for translation * DNA polymerase autocorrects the DNA strand when errors are present
Transcription
* From DNA to mRNA * To create mRNA strand from DNA * Single stranded * RNA Polymerase used – enzyme used to produce mRNA starts at promoter site ends at termination sequence
Translation
* Functional mRNA: edited RNA that is going be used for protein * Spliced mRNA exists nuclear pore into cytoplasm, attaches to ribosome * Protein synthesis begins at initiation sequence, ends at termination signal * In ribosomes, tRNA with anticodon bind to mRNA codon amino acid initiation * Ribosomal enzymes form peptide bonds between amino acids * When termination signal reaches, translation stops, mRNA, ribosome, polypeptide separate, causing polypeptide to be released into cytoplasm
INTRONS PART THAT’S DISCARDED tRNA * Translate mRNA to aa sequence * Attaches to ribosomes (protein synthesis site) * Has anticodons, complement codons of mRNA
Mutation
* An inherited alteration of genetic material * Some can be lethal, others unlethal * Most of the time they are clinically undetectable * A lot of times people do function with mutation * Types are chromosomal aberrations, base pair substitutions and insertions
Missense mutations * One codon is affected * Missense mutation causes a different amino acid being inserted into chain

Nonsense mutation * One codon is affected * Inserts a stop codon instead of the required amino acid * Chain could be 50 amino acids instead of 200
Frameshift deletion * More than one codon is affected * Base pair taken out * Whole amino acid sequence will shift and will code for a different codon than the original sequence
Frameshift Insertion * More than one codon affected * Base pair inserted * Polypeptide made after insertion or deletion is very different than normal one needed * Some mutations cause the same amino acid to be attached due to more than one codon are coded for an amino acid
Mutagen
* Agents known to increase mutation rates * Intercalating agents (flat planar molecules, intercalate b/w base pairdisrupt DNA synthesis) * UV light (photodimers = linking of adjacent thymine base pairs in same strand)
Double helix structure perturbed
Spontaneous mutation * Rare * Oxidative damage to bases base pairing properties are altered by superoxide/peroxide radicals * Eg. Trinucleotide Repeats * X chromosome is fragile – it breaks * Associated with retardation
DNA Repair mechanisms * Direct reversal of damage * Photodimer repair: by photolyase * Photolyase binds to photodimer
Homology dependent repair systems * Use complementary nature of DNA molecule * Excision repair, repairs damage before replication * Post replication repair: repairs during or after S phase
NEITHER SYSTEM COMPLETELY EFFECITVE HOWEVER

Summary of Mutagenic events * Wild type gene – normal phenotype * Pre-mutational – some damage, however doesn’t affect DNA quite yet * Repair system – chops out damaged DNA, replaces with DNA made on template * Gene mutation – kicks in only when repair system is affected and makes an error
Lecture 4: Online Chapter 2
Mitosis:
* Occurs in body cells * Constantly occurring * Diploid to diploid cells
Meiosis:
* Formation of haploid cells from diploid cells * Starts at puberty * Ends at menopause for females
Chromosomes:
Somatic cells * Contain 23 pairs of chromosomes (euploid number good) * Diploid cells * Aneuploidy not 23 pairs
Gametes (sperms/oocytes) * Contain 23 chromosomes * Haploid cells: one member of each chromosome pair
Autosomes: non-sec chromosome * First 22 of 23 pairs in males and females * Two members are virtually identical homologous
Sex chromosomes: * Last remaining * In females it is homologous (XX) * In males it is non-homologous (XY) – heterogeneous
Ploidy (# of chromosomes)
Euploid (good number) * Haploid (gametes = 23 chromosomes) * Diploid (somatic = 46 chromosomes, 23 pairs) * Aneuploidy = aberrant euploid: more or less than normal #
Chromosome 21 3 copies cause Down syndrome
Disjunction: normal separation of chromosomes during cell division
Nondisjunction: failure of homologous chromosomes or sister chromatids to separate normally during meiosis or mitosis
USUALLY CAUSE OF ANEUPLOIDY
Autosomal (non-sex chromosome involved) Aneuploidy
Down syndrome (Trisomy 21) * Best known example of aneuploidy * 1:800 live births * Mentally retarded, protruding tongue, poor muscle tone * Risk increases with maternal age > 35 * Risk does not increase with paternal age (sperm are always being made)
Sex Chromosome Aneuploidy
Trisomy X * Female with 3x amount of chromosomes * Symptoms are variable: sterility, menstrual irregularity, mental retardation * Symptoms worsen with each additional X
Turner Syndrome * Female affected * 1 copy of X chromosome
Abnormalities in Chromosome Structure
Deletion: breakage or loss of DNA * Deletion of short arm of chromosome 5 low birthweight, mental retardation, microcephaly
Duplication: presence of repeated gene or gene sequence * Less serious consequence because better to have more genetic vs. less or missing material
Inversion: two breaks on a chromosome * Reversal of gene order which can lead to duplication and deletion in offspring * Effect change of gene expression
Translocation: interchange of material between non-homologous chromosomes * Reciprocal translocation 2 chromosomes break and segments are rejoined in an abnormal arrangement
Robertsonian Translocation * Occurs at chromosomes 13,14,15,21,22 short arms are very short contains no essential genetic material (if it’s lose, doesn’t matter) * Long arm of 2 non-homologous chromosomes fuse at centromeres, forming 1 chromosome parents have 45 chromosomes (normal, no loss of essential genetic material) offspring can have trisomy or monosomy copies
DOWN SYDROME RESULT OF ROBERTSONIAN TRANSLOCATION AT CHROMOSOME 21
Genotype:
* what genes you have * genetic makeup of organism
Phenotype
* what you show visibly * observable characteristics/appearance of the genetic makeup of organism
Locus
* Position of gene along chromosome
Allele
* Different form of a particular gene at a given locus * Polymorphism locus that has 2+ alleles that occur often (eye color)
Homozygous
* Loci have same type of gene
Heterozygous
* Loci has different types of genes
Allele that is observable is dominant, allele that isn’t showing is recessive * Alleles can be codominant * Recurrence risk: Parents with a child with a genetic disease will have another child with the disease
Pedigrees
* Autosomal dominant disease * If you have an affected child, then one of the parents has it also * If all children are normal, high chance neither parents have condition * Autosomal recessive disease (dd for disease to be present) * A person with this condition has to be homozygous (dd) * Trait usually appears in children and not parents * MALE AND FEMALES ARE EQUALLY AFFECTED * Consanguinity – marriage between related individuals * Increases risk for rare recessive diseases * Avg. of 1/4 of carrier offspring will be affected
Penetrance genotype vs. phenotype * Higher degree of penetrance = higher % of ppl expressing genotype * Individual can have a gene for an illness but it doesn’t show in the phenotype incomplete penetrance
Expressivity
* Degree that genotype is expressed * Spectrum disorder * Similar to emotions a group of ten ppl are all happy but one person will be jumping for joy while the other is just smiling calmly * Sex linked disorders * X gene: always carries disease linked gene (recessive, females usually carriers) * Y gene: never carries disease linked gene * Affected is male, can transmit gene to daughters, not sons
Multifactorial traits * Variation in traits caused by genetic and environmental factors * IQ can be increased by exposing children to enriched learning opportunities
Polygenic traits * Variation in traits caused by more than 2 genes acting together
Threshold of liability * The point in between all the factors where the disease/condition is expressed

Lecture 5: (October 1st 2015)
First line of defense is * physical and mechanical barriers * Skin * Lining in gastro and respiratory tract * Biochemical barriers * Antimicrobial enzymes in mouth
Second line of defense: inflammation * Fast * Nonspecific * No memory of past events * Humoral (needs vascular supply) * Protects body against further injury, prevents infection, and promotes healing

Third line of defense: Adaptive * Relatively slow * More specific * Memory of past events are present, more rapid response with every exposure to same microbe * Humoral and cellular * Eradicate particular invading microorganisms
Inflammation
* Neutrophils and macrophages are inactive in our blood * If there is an injury then the chemokines act as a distress signals that attracts neutrophils to affected area to help * If you have a splinter you want the tissue damage to be limited (limit inflammation)
Vascular response of inflammation * Blood vessel dilation: slower blood flow & increased blood flow * Increased RBCs cause erythema & increase warmth * Increased vascular permeability: leakage of WBC * WBC cell adherence to the inner walls of the vessels and migration through the vessels
Goals of Inflammatory response 1. Limits and controls tissue damage: clotting system and WBC prevent the inflammatory response from spreading to areas of healthy tissue 2. Prevents infection by contaminating microorganisms: by diluting bacterial toxins with fluid, containing and destroying bacteria 3. Initiates adaptive immune response: microbes drained to the lymph nodes, where they activate lymphocytes and macrophages 4. Initiates healing: bacterial products, dead cells, and other products of inflammation are removed (through the epithelium or drainage by lymphatic vessels) and mechanisms of repair are activated
Characteristics of plasma proteins systems * Important for inflammation
Needs to be efficient to ensure survival * Activated by cascade reaction * 3 plasma protein systems in our body; activation in one leads to activation in the other two * If clots form all around the body , it is very dangerous * Complement system: * Can destroy pathogens directly using the MAC * MAC Membrane Attack Complex * Kinin system: * Has bradykinin which is released which causes pain, permeability, vasodilation * Coagulation system: * Traps microbes and foreign bodies; prevents spread
Cytokines: proteins secreted by cells to coordinate inflammatory process (pro or anti) | Interleukin | Interferon | Tumor Necrosis | Secreted by | Macrophages and lymphocytes | Virally infected host cells | Macrophages and mast cells | Trigger | Pathogen or stim. By other inflam. products | Presence of viral double-stranded RNA | Activation of macrophages and mast cells | Examples | Pro-infl, anti-infl | Protects against viral infections | Induces fever, cachexia, thrombosis |

* Pyrogens can be exogenous or endogenous * Cellular components of inflammation: * Mast cells eg. Benedryl; releases histamine which increases inflammatory response * Most important cellular activator of inflammatory response * Located: skin, digestive lining, resp. tract * Dendritic cells communication b/w innate and acquired immune systems * Leukocytes * Granulocytes most common * Monocytes develop into macrophages * Lymphocytes involved in innate and acquired immune systems * Phagocytosis process by which cell ingests and disposes foreign material * Neutrophils: neutrophils keep ingesting bacteria (short-lived)
Predominate in early inflammatory responses * Monocytes are secondary to neutrophils they become macrophages that also ingest and dispose foreign material * Monocytes produced in bone marrow, develop into macrophages at inflammatory site * Macrophages – arrive 24 hours after neutrophils * How do phagocytes leave blood vessels? * Neutrophils develop and accumulate at an injury site * Increase adhesion to walls (margination/pavementing) * Undergo chemotaxis where they migrate toward chemotactic factor (CTF) * In tissues, neutrophil detects CF through receptors migrates to high CF concentration, where CF immobilizes neutrophil * What happens when the macrophages cannot protect the host cell? * Giant cell forms * Surrounded by lymphocytes * Isolate the infected cell * Can become cartilaginous or calcified * Steps in Phagocytosis: 1. Recognition and adherence (binding) 2. Engulfment and formation of phagosome 3. Fusion with lysosome to form phagolysosome 4. Destruction (killing) and digestion
Acute Inflammations:
Fever – caused by exogenous and endogenous pyrogens direct action on hypothalamus (temp.)
Leukocytosis – increased #’s of circulating WBCs immature cells being released increases
Increased PPS – leads to increased erythrocytes sed. rate * 2 types of healing: * Resolution: * Returned injured tissue to its original form * Repair * Replaced with scarred tissue * Cannot carry same functions as before * Both types start with debridement * Cleans up dissolved clots, dead cells, etc. * Healing Process: * Phase 1: Inflammation (Day 0-2) * Phase 2: Proliferation and new tissue formation (Day 3-14) * Phase 3: Remodeling and Maturation (week 2-year2) * Intention of wound healing * Primary intention * Wounds that heal to minimize tissue loss * Secondary intention wounds that require more than tissue replacement * Ex: open wound * Dysfunctional Wound Healing * Hemorrhage: increase space for granulation tissue to fill * Fibrous adhesion: detrimental to healing. Must be reabsorbed first * Infection: debridement of necrotic tissue and foreign bodies * Excess scar formation– keloid or hypertrophic scar

Lecture 6 – Online Chapter 6
Third line of defense is adaptive immunity * Purpose is to provide long term protection * To neutralize microbes * Very specific * They have memory; defense is faster in 2nd exposure * Needs to recognize self * Its relatively slower
Relationship between inflammation and adaptive immunity * The antigen of the microbe can bind to antibodies and they can lead to the release of factors which will trigger acute inflammation * The antigen can bind to tcell that causes the release of lymphokines which activates macrophages which trigger inflammation
Components of adaptive immunity * T cells * Attack antigens directly * Very specific for one single antigen * B cells * Produce antibodies * Very specific for 1 single antigen * Antibodies * React with antigens * Very specific for 1 single antigen
Two different phases of adaptive immunity * Before birth (generation of clonal diversity) * Generates B and T cells * Clonal selection * Exposure to specific antigen * When the t cells are exposed to a specific antigen * B cells produce antibodies * T cells differentiate into becoming t effector cells * These two work to eradicate the antigen * Bone marrow produces a thymus that produces a immunocompetent T cells and B cells
First phase of adaptive immunity Humans produce large t & b cells that have a capacity to recognize any foreign antigen found in the environment
Thymus/bone marrow produce lymphocytes
Lymphocytes mature into T or B cells
Immunocompetent cells released into blood (can recognize antigen)
Cells migrate into secondary tissue to wait for antigen
Phase two * When both lines develop into memory cells that can respond even faster to the same antigen * APCs interact with t helper cells
Antigen – foreign cells (eg. Bacteria, virus, fungi, food, pollen, bee venom)
Epitope – part of antigen that can bind to antibodies or antigen receptors on b and t cells
See slide 14 * Antibodies = immunoglobulins * Know the different types of antibodies
Types of t cells * Produce cytokines to activate microphages * Memory t cells: key to 2ndary response * Cytotoxic: kill virus infected cancer * Regulatory: control the immune response to manage cell destruction
T cell activation * T cells are produces by the thymus released into blood * Reside in secondary peripheral as mature immunocompetent cells * Once antigen is presented by APC * Direct killing of antigen * Indirect killing through t helper cells
B cell activation * Produced by bone marrow released into blood * Antigen presented by APC to specific BCr * B cells to proliferated into plasma cells/memory cells * Produce antibodies
Antibodies
Direct action * Check slides
Passive acquired antibodies * When maternal igG transferred into baby fetus blood * The moms igGs bind to the FcR, which transfers it into the fetal blood circulation
Immune response * Primary * Encounter foreign antigen * 5-7 days * B cells differentiate into plasma cells which produce antibodies * IgM gets produces first * IgG gets produced later * Secondary * Same foreign antigen second time * Memory cells produces antibodies much quicker * IgM same time * IgG gets produced faster
(Watch video in last three mins of chapter 6 online lec)
(Still go through slides for info missed in notes)

Lecture 8: Online Chapter 8
Stress
* A person experiences stress when a demand exceeds a person’s coping abilities, resulting in reactions such as disturbances of cognition, emotion, and behavior that can adversely affect well-being * Stress can be different for different people and the same for the different people at different times. * Some of us say we feel stressed when we enter a new situation, but after a while, your stress levels start to cope with the situation * It’s a balance between demand (increase in the demand that is placed on you) and coping ability (some of us cope normal but when you don’t get enough sleep or you have family troubles or anything than it affects your coping ability)

Stressors * things that trigger the alarm response, not all events are equally stressful, or equally stressful all the time (you learn to adapt) * Physiological there are physiological stressors to climbing mount Everest because it has such low oxygen content and it is very high * Psychogenic internally driven, what is stressful for one person is not stressful for the other, (driving on the 401 being scary)
GAS (General Adaption Syndrome) - nonspecific response to stressors, and there are 3 stages to gas 1) Fight or flight- where your sympathetic nervous system kicks in
2) Resistance or adaptation- whether or not u resist or cope with the stress
3) Exhaustion - if there is resistance, it can lead to exhaustion and that’s when your body gives out and fall sick or get chronic conditions
- Stressors- trigger stress (not all events are equally stressful to everyone)
- Stress induction- trigger stress response
- Alarm stage- endocrine system (this takes a while) and fight or fight (fast acting) response
- Resistance/ adaptation- cope with the new normal (homeostasis)
- Exhaustion- other defenses being mobilized, where u still have the increased flight or fight response there and the increased sympathetic nervous system activation
- This can lead to either recovery (with or without the removal of the stressor) or it can lead to exhaustion, your different organs have to adapt or change and cope with the continued stress that u feel
- Compensatory mechanisms lead to immune compromise (impaired immune system) and you open yourself to opportunistic infections (heart, kidney failure) and if prolonged it can also lead to death
3 different scenarios 1) A – healthy - stressful event in life if they cope with it, is called transient effect (return back to homeostasis [ different homeostasis level or same])…..or u can have resistance (ineffective coping) and can lead to exhaustion and can lead to stress and illness and can be pathogenic in nature where it can affect different organs 2) B - symptomatic - stressful life event, u have affective coping if someone already has a base line stress level…. Ineffective or the stressful life event can lead to their illness being worse 3) C - medical intervention - with these affective or symptomatic individuals, if they receive treatment then it can decrease the symptoms, but if the treatment is perceived as a stressor it can be made worse, which is why medical intervention can be a good thing if done for the right reason
Integrated response to stress * Immediate response to anything is mediated by the nervous system- ANS (auto) = sympathetic nervous system * Endocrine- involved in released catecholamine's and cortisol, and it is shown that stress has a negative impact on the immune system long term, this might lower the immune response if the stressor event is around for a long time * So the bottom right diagram shows that the stressor affects the nervous system in the fist instance then it affects the endocrine system and immune system and one can cause the others activation
Alarm stage in response to stressor * The alarm response to stress where you have epinephrine released from the (and activation by) sympathetic nervous system through the adrenal medulla- this occurs in seconds * If the stressor is around for a prolonged period of time(hours-min or whatever), this causes the release by the cortisol from the adrenal cortex * Adrenaline increases heart rate, breathing rate, blood sugar, ect because it’s in the flight or fight. * It increases blood sugar because the skeletal muscle is getting ready to run away or fight and so in the long term when the blood sugar is used up, then the liver released glucose from the glycogen source and this causes an increase in blood sugar which is used to continue the fight or flight response
Immediate response to stress: Sympathetic response
In the sympathetic nervous system you have epinephrine and norepinephrine being released Leads to affects * Increased cardiac output, increased blood glucose, sweaty gland action (sweaty palms, armpits) * BP goes up, bronchioles dilate to let more oxygen come in and more co2 to leave * Increased glyocogenolysis (increased blood glucose level) * ALL OF THIS IS VERY IMMEDIATE (kicks in within seconds of trigger of alarm response)