Exam IV Flashcards
Granzymes
- Enzyme that stimulates target cell to go into apoptosis
- Released by NKC
Brain Macrophage
Microglia
Erythema
Redness
Arcuate Artery
- Nephron circulation
- Branch of the renal artery
MHC Class III
- Complement proteins
Epitopes
- Different shapes on the antigen that will have different antibodies stick to them
- String of amino acids that folds in a particular way
- Antibodies can distinguish between epitopes (3rd line)
Celiac Disease
- Immune system attacks gluten
- Leaky intestinal cells
- Gut inflammation
Creatinine Clearance
- Creatinine is the breakdown of creatine (from muscles)
- Look at clearance…. essentially GFR
TCR
T-Cell Receptor
- On helper T
- CD4 is a co-receptor
- Can see antigen in the context of MHC-2 molecule
- MHC-2 Restricted
Aldosterone
- Steroid hormone… acts on distal tubule
Actions
1. Increase Na permeability
2. Run Na/K pump… keep gradient, retain Na
- K builds up in cell and diffiuses down K channel… goes into urine
3. Increase ATP production in mitochondria
V Region
Variable Region
- 500
Kidney Secretion
From peritubular capillaries
Into tubules
Basophils
- 0.1% of WBC
- Produce hisamine and are involved with fighting off parasites
Low Cl and renin
- Slow GFR
- Means filtrate coming through nephron has been too slow… able to take out more Cl
- increase renin
What kind of molecules are antibodies?
glycoproteins
IgE
Monomer
- Mostly involved in allergies
- Promotes the release of histamine
Monocyte –> Macrophage
- Monocyte leaves cirulation at the site of immune battle
- Crawls into battle and becomes a macrophage
- Loses its kidney shaped membrane
ANF Acts On
- Kidney
- Adrenal Cortex
- Hypothalamus
Timing of normal immune response
- IgM peak after a week
- After 2 weeks, IgG enters the scene and IgM fades away
Keeping Penicillin in the body longer
- Penicillin + PAH
- Compete for same transporters on the proximal tubule
- Increase the half life of penicillin in the blood
Urea Loop
- Ascending limb and collecting duct are permeable to urea
- If urea is in the collecting duct, water is reabsorbed… sucked out of the duct
- Urea follows it and accumulates in the medulla –> absorb into ascending loop –> through distal tubule to collect duct
- positive feedback loop that makes filtrate more and more concentrated
Job of the kidney
- Filtration
- Reabsorption
- Secretion
- Excretion
What holds together protein chains on antibody?
disulfide bonds
Alcohol and ADH
- Alcohol inhibits ADH
- Frequent urination
- Diuresis beynd fluid you take in… dehydrated… hungover
-
Germinal Centers
- Collection of immune cells
- Organized to scan everything that enters the mouth
Sends information to the tonsils
Dehydration
- Increase plasma osmolarity
- Decrease blood pressure
Cytokines
- Immune messengers
Cortical Nephrons
Have more of their body in the cortex
Type I Diabetes
Attack beta cells in pancreas
Hemorrhaging and Kidneys
- Mesangial cells
- Decrease blood flow and blood pressure
- Restrict filtration
Neutrophil Attack
- Attack cells that are nonself
- Commit suicide
- Secrete cytokines and free oxygen radicals
- Kill with NETs…. neutrophil extracellular traps
- Accumulate at the site of an infection and turn into pus
Edema
Swelling
How we get a concentrated urine (Henle and collecting duct)
- Filtrate leaves Henle ~100 mosm
- Enters collecting duct… higher osm. in the interstitial space
- Water moves to higher osm
- Osm gradient pulls water out of the collecting duct into the interstitial fluid
- Urine filtrate ~ 1200 mosm
Free Iron
- Microorganisms need free iron to grow
- Stored in the liver and spleen
Fevers reduce free iron
Na is pumped on basolateral membrane
- Na enters the cell (from the tubule lumen) through membrane proteins moving down its chem gradient
- Na is pumped out into the interstitial fluid (basolateral side) by the Na/K ATPase
Energy heavy process. When we get Na moving we can get other stuff to move as well.
Kidney Filtration
From Glomerulus
Into proximal tubule
Angiotensin II
Vasoconstrictor
- Constricts renal arterioles (especially efferent)
- Increases GFR
- Helps increase reabsorption in peritubular bed
Immune Defenses of the Mouth
First Line
- Lymph passages germinal centers
- GCs scan what enters the mouth and sends information to the tonisls
HLA Proteins
3rd Line - Human Leukocyte Antigens
- Human MHC
- First studied on the surface of WBCs
Ascending Limb
Loop of Henle
- Water impermeable
- Ion permeable… ions pumped out in thick limb until filtrate is 100 mOsm
- Lower part is generally passive diffusion
- Concentration of solute goes down as ascend
Monocyte
- Kidney shaped nucleus
- Big
- Live in the blood circulation
- Eat up invaders
Major Role: precursors for macrophages
Red Blood Cell
- Lifespan is 120 days
- Hb
Osmolarity of filtrate in distal tubule
100 mosm
Idiopathic Urticaria
Hives without a cause
MHCs are Polymorphic
- The reason why we have such different tissue types on our surfaces
- Protect from invading pathogens that might try to mimic surface markers on our cells
- Populations with little genetic diversity are susceptible to pathogens
Non-Specific ID Model
- Negative Test
Second line
Angtiotensin I
- Travels through lungs and acted upon by ACE –> angiotensin II (active form)
Innate Immune System
Definition
- Built in
- Already present
- Always on
- Non-specific
Pale with fever
- Vasoconstriction in the periphery
- Conserve heat in the core
- Shivering makes more heat
Plasma Load
mg/min
= plasma concentration (mg/mL) * renal plasma flow (mL/min)
- Overall load into kidneys
-
Stem Cells in the Bone Marrow
- Make all the blood cells
- Start as a hemocytoblast… pluripotent
- Two brances: myeloid and lymphoid progenitors
Cells associated with the distal tubule
Macula Densa Cells
Vasa Recta
“Countercurrent exchanger”
- Readily exchanges Na, Cl, Water
Lysozyme
- In bodily secretions
- Punches holes in bacterial cell walls
Eosinophils
- 1-3% of WBC
- Involved in allergies and defense against parasites
Complement System
Second Line
- 20 or so aseemble into MAC
- Series of protein from the liver that circulate in the blood
- Ability to recogize foreign cells
- See foreign cell –> assemble into membrane attack complex
- Make a hole and kill
- 20 proteins involved…. C3 is at the center of the whole mechanism
ACE Inhibitors
- Inhibits Angiotensin Converting Enzyme
- Blocks Angtiotensin-II
Opsonization
- Complement system and killer cells target things covered in Ab
- Antibody/antigen complex facilitates phagocytosis through….
- Neutralization of function
- Agglutination,
- Precipitation
- All of these enhance inflammatory response
Constrict efferent arteriole
- Renal plasma flow decreases
- GFR increases due to back-up pressure
- Reabsorption in the peritubular bed increases because the fluid is not moving as quickly
Thiazide
- Blood pressure medication
- Block sodium reuptake in the distal tubule
- Diuertic
Organic Ions
Penicillin
PAH (para aminohippuric acid)
Aspirin
Bile Salt
Where does the process of reabsorption begin in the nephron?
Proximal tubule
MIF
Macrophage Inhibitor Factor
- Keeps the macrophage on the scene instead of roaming the body as it usually does
Urushiol
- Oil on the poison ivy plant
- Delayed type hypersensitivity
- Get fluid filled swelling (from leaky vessels)
Percent of reabsorption that occurs in the proximal tubule
75-90%
Exogenous Pyrogen
Components of bacterial cell walls can induce fevers
IBD / Crohn’s
Inflammatory bowel disease
- NOT IBS
Amount of blood to kidneys
- 20% of cardiac output
- 1.2 L/ min
- 600 mL plasma/ min
- Split evenly between the two kidneys
Grave’s and Hashimoto’s
Body makes thyorid agonist/antagonist
Reabsorption in the Proximal Tubule
- Na is reabsorbed by active transport
- Electrochemical gradient drives anion reabsorption
- Water moves by osmosis following solute reabsorption
- Concentrates of other solutes increase as fluid volume in the lumen decreases. Permeable solutes are reabsorbed by diffusion
Secretion
Moving compounds from the blood into the proximal tubule
Cushing’s and Addison’s
Body makes cortisol agonist/antagonist
Lymphatic System Drainage
Second Line
- Dump drainage into the thoacic duct
- Then goes to subclavian veins
- Collect excess fluid from the body and put back into circulation
- Can get blockages in the thoracic duct… lymphodema
- Drainage from the whole body except immunologically privileged sites
T-Helper Cell
Overview
- Work with other cells to improve the immune response
- Some say there are two populations (1 and 2)
- Have CD4 marker on the surface
Transmembrane Domain
- How the antibody is anchored in the membrane
- Ab site is facing out
Effect of Afferent Dilation on GFR
Dilate - increase
Constrct - decrease
ANF and Kidney
- Inhibit renin… stop AT-II cascade
- Decrease AT-II, decrease reabsorption
- Temporary increase GFR
- Decrease Na reabsorb in tubule
Why inhibit ADH in pregancy?
- Increase blood volume
Antigens
- Markers on the ouside of cells that antibodies can bind to
Filtered Load
- How much of a substance is being put into the nephrons
= ([X] in plasma) * (GFR)
mg/min
ADH Secretion vs. Plasma Osmolarity
- Increase plasma osmolarity (dehydration)… increase ADH
Ammonium Ion Trap
- Some H+ secreted by kidney
- Cell removes amine group from glutamine
- Amine binds H+ to make ammonium (pka 9.2)
- 9.2 > 7.4 therefore stays ammonium
- Pee the ammonium out
Collecting Duct
Reabsorb water to make a concentrated urine
Heterologous Transplant
- Someone else’s tissue but with a matching tissue type (MHC match)
- Usually from a relative
Effects of increased ADH
- Increase body water
- Increas blood volume
- Decrease plasma osmolarity
ACE
- Angiotensin converting enzyme
Angiotensin I –> Angiotensin II
Angiotensin II
Hypothalamus
Increases
- Thirst
- Salt hunger
- ADH secretion
- Water volume, BP, GFR
Lymph Capillaries
- Have one way valves
- Only flow away from tissue
Bowman’s Capsule
- Contains the glomerulus
- In the cortex
Antibody
- proteins that ciruclate and have the ability to bind to a specific structure called an antigen
3rd line
Pyrogen
Second Line
- Substances in body that cause a rise in temperature
Positive Test
Third Line
- If you are identified as a pathogen, attack
- Specific ID card model
Angiotensin II
Adrenal Cortex
Inc. Aldosterone and Inc. Sodium Retention
- This increases…..
- Water retention
- BP
- GFR
Inducer T-Cells
- Stimulate the production of more T-Cells when needed
B-Cells
3rd Line - Lymphocyte
- From bone marrow
- When activated become plasma cells
- Activated form has lots of rough ER
What does an antibody actually do?
- Mark for destruction
- When foreign antigens are covered with antibodies, they are attacked more efficiently
- When virus is covered in antibodies, cannot adhere to other cells (be infectious)
Two capillary beds of the nephron
- Glomerulus
- Peritubular
IL-2
- T-cell growth factor
- Sitmulates the growth of more T-cells
- Especially those that have formed an immune synapse
- Clonal selection
What part of the nephron is called the “countercurrent multiplier?”
Loop of Henle
Negative Test
Innate
- Non-specific ID model… second line
- If you do not have the right ID markers on the cell, throw them out
Memory cells
- After two weeks, some specific Tc cells are held in reserve as memory cells
- This is active immunity
ANF and Hypothalamus
Decrease ADH
Hemocytoblast
- Root of all blood cells
- Pluripotent
Lymphedema
- Blockage of the thoracic duct
- Common after breast cancer surgery
Helper T-Cell Activated Release
- MIF
- IL-2
- Stimulate thymus to push out more T cells (might involve Ti cells)
Plasma Clearance
- Ability of kidney to remove solute from blood (mL/min)
- How many mL of plasma are completely cleared of a given substance?
Lymphatic Jobs
Second Line
- Drainage
- Absorb fat in the gut
- Filter fluids it collects through checkpoints called lymph nodes
Buffers in the Body to maintain pH = 7.4
- Proteins
- CO2
- Kidney
Skin Immune Function
First Line
- Immune response when breached
- Glands secrete immune defenses… low pH to inihbit bacterial growth… lysozyme in bodily secretions… antibodies
How do we create an osmotic gradient in the nephron?
- Loop of Henle
- Urea Loop
IgM
- Pentamer
- First antibody secreted during primary immune response
- Promotes agglutination (things sticking together) reactions
Five Classes of Anitbodies
IgM
IgG
IgD
IgA
IgE
T- Cells
Lymphocyte - 3rd Line
- From the bone marrow
- Go to the thymus for education
- Leave thymus and are immunocompetent
MHC Proteins
3rd Line- Major Histocompatibility Complex
- Type of cell surface ID marker
- Three classes
- In humans referred to as HLA proteins
- Polymorphic
Angiotensinogen and Obesity
- High BP and hypertension
- More visceral fat you have, the more angiotensinogen in circulation…
- Increase AT-II, increase sodium/water retention, increase BP
Tc is MHC-1 Restricted
- Can only see antigen in the context of MHC-1
- Clonal selection
- TCR on Tc recognize foreign antibodies on MHC-1
- Only in synapse stimulated by IL-2
Cells associated with the afferent arteriole
Juxtaglomerular Cells
Allergic Response
- Respond to allergen
- B cells ab receptors bind to allergen… convert to plasma cell
- Produce IgE which stick to surface of mast cell
- Mast cells accumulate granules full of histamine
- Later exposure causes histamine release
Osmolarity
particles per liter
Fab Sequence
- Some constant areas
- Variablity towards top (part involved in recognition)
- Especially variable parts are hypervariable regions
Burn Victims
- No skin, lose water, dehydration
- Need urea to maintain osmotic gradient and promote reabsorption
- More reabsorb, less urine, less dehydration
Descending Limb
Loop of Henle
- Permeable to water
- Impermeable to salt
- Suck water out
- Increase concentration of filtrate in tubule
- Do this to set up ascending limb
Autoregulation in the Kidney
- Monitor Na and Cl (mostly Cl) concentrations in the distal tubule by macula densa cells
- MDC talk to JC cells which release renin
- Do not know how the communitcation works
Signals for Renin Release
- NaCl (Cl more important)
- Sympathetic neurons signal JG cells
- Decrease the perfusion pressure in the afferent arteriole
Normal release of antibody
IgM then IgG
D Region
- Diversity region
- 15 of them
Cyclosporin
Immunosuppressant Drug
- Kidney transplants
Tonsils
- 6… three sets of pairs
- Palatine are the ones you can see
- Lingual at the base of the tongue
- Adenoids are behind and above the uvula
Immunologically Privileged Sites
- Do not have normal blood circulation therefore do not have lymph
- Cartilage, cornea
EPO
Erythropoietin
- Increase RBC production
Third Line of Defense
Specific
- Lympocytes (T-Cells)
- B Cells
- Cell surface ID makrers
- Specific ID Card Model
Fever as a defense mechanism
Goals
- Slow growth of microorganisms
- Reduce free iron
- Increase activity of phagocytes
Percent of filtrate that we reabsorb
99%
Humoral Immunity
Phase III
- Free antigen any form
- IL-2 and IL-4
- B cells making the antibody (effector)
NETs
Neutrophil Extracellular Traps
- Throw a bunch of fibers (DNA)
- Ropes up invaders and holes them in place while the immmune system finishes them off
Rheumatoid Arthritis
Attack connective tissue
Newborn Mice Skin Experiment
- Transplant regions of skin from another species of mice onto the skin of young mice
- Will tolerate
- Only young cells… no memory for immune response/ rejection
Plasma Clearance
- Ability of the kidney to remove a solute form blood
Excretion rate = ([x] in plasma) * (plasma clearance)
mg/min
- Can use the plasma clearance of a substance that is only filtered (not reabsorb or secrete) i.e. inulin or creatine
Cimetidine
- Histamine antagonist
- For gastric ulcers
- Competes with cardiac drugs for arrythmia
- Easy to overdose if taking both
MAC
Membrane Attack Complex
- Second line complement system
- Make a hole in foreign cell and kill it
C3 is at the center of the whole mechanism
IgG
- Secreted in secondary response
- Most abundant form of antibody in the blood
- Monomer
Things that are not filtered in the glomureulus
- RBC
- WBC
- Large protein
Skin Secretion Defenses
- Low pH
- Lysozyme
- Antibodies
Thoracic Duct
- Gets drainage from the lymph system
- Dumps it into the subclavian veins
- Can get blocked… called lymphodema
Lung Macrophage
Dust Cell
Autoimmune Mimicry
- T cells presented with an antigen by a virally-infected cell on its MHC-1
- Viral antigen is the same as self-antigen (coincidence)
- T-cells continue to attack self-antigen
Kidney Output
Renin
Vitamin D3 (Calcitriol)
EPO
Histamine
- Allergic reactions
- Cause swelling, leaky vessels, itching
- Release promoted by IgE
Heavy Chain Diversity
V*J*D
37,500
Lupus
Systematic
- Immune system attacks all over the face
Butterfly rash
Functional Unit of the Kidney
Nephron
- Part in cortex, part in medulla
- 1 million nephrons in a kidney
Regulatory T-Cells
- We think they have CD4
- Turn down immune response
- Unclear how they work
Fate of H+ From Kidney
- Make H2CO3
- Combine with phosphoric acid which can be deprotonated as needed
- Ammonium Ion Trap
Cell Mediated Immunity
- MHC-1 proteins display viral antigens
- Tc use CD8 to recognize antigens in MHC-1 groove and form immune synapse (Tc and MHC restricted)
- Tc cells in synapse do nothing until Th cells recognize antigens on macrophage MHC-2 receptors and secrete IL-2… then cytotoxic and replication(clonal selection)
- Takes a week to get peak response
- After 2 weeks, Ts cells turn down the response
Anaphylaxis
- An accute allergic reaction to an antigen to which the body has become hypersensitive
Pathogens Evade Immune Response
- Hide inside a cell
- Knock out Th cells
- Waxy exterior
- Change surface antigens
Worms and Autoimmune Diseases
Inhibit T Cells
- Increase Tr activity/ stimulate release of inihibitory cytokines
- Promoting helpful gut microflora
Increase in blood loss
- Decrease BP
- Sympathetic input for mesangial cell contraction
- Shuts down the glomerulus
- Shuts down areas of kidneys to retain fluid and try to raise BP
Neutrophils
- Lifespan is 8 hours
- Phagocytic
- Multilobed nucleus
- Increase in number during infection
- Can consume invading cells
Major Job: attack cells that are nonself
Cytotoxic T-Cells
- Killing ability for certain infected cells
- Have CD8 marker on their surface
ADH
- Increases the permeability of water in collecting duct
- When ADH is low make a less concentrated urine because the duct is not permeable to water.
Immune Surveillance
Second Line
- Detects invaders (or cancers)
- Eliminated things often before we know they are there!
If there is a defect in immune surveillance, more infections and cancer
Blocking SGLT-2
- Treatment for type II diabetes
- Block glucose uptake so it does not get across
- Glucose stays in lumen, pee it out.
Renal Plasma Flow
- Measures plasma flowing into nephrones through glo.
- GFR varies with RPF
- Flow rate is constant over a wide variety of arterial pressures… only fluctates at extremes
Signals for aldosterone release
- High angiotensin
- High K+
Enlarged Spleen
- Splenomegaly
- Lymphoma, leukemia, mono
- Binds up platelets
- Fewer platelets in circulation and perhaps issues clotting
Dilate afferent arteriole
Increase flow and filtration
IL in Phase III
2 and 4
- Converts activated B cells to plasma cell
- Antibody made in plasma cell is specific to pathogen
- B cells and free antibodies bind to the antigen/invader in any form
Light and Heavy Diversity (numbers)
37,500*1500 = 56 million antibody binding specificities
Constrict afferent arteriole
Decrease flow and filtration
Transport Maximum
- Transporters in nephron are saturated
= (filtered load) - (excretion rate)
+ = reabsorb
- = secreted
T-Cell Activation
- Ciruclate around like regular old lymphocytes
- When activated cell changes….
Get larger
More cytoplasm
Getting ready for battle
Inflammation
Non-specific response
- A call to arms
- There has been a breach of the first line… assemble!
- Makes blood vessels in the area leaky
- Edema and erythema
B-Cell Education
- Do not know where it is happening
- Think it occurs in circulation
Interferon
Second Line
- Proteins that warn of infection
- Cell realizes its been compromised by a pathogen… releases interferons to notify other cells
- Alpha, beta, gamma types
- Local cells alter metabolism to resist viruses (slow their replication processes)… reduce transcription, shorten half-life of RNA
Graft vs. Host Disease
- Try to do an allogeneic transplant with bone marrow
- Body attacks transplanted tissue
Where does the reabsorbed water go?
Vasa recta off the peritubular bed
Deep in the medulla
Things that increase ADH
- Increas plasma osmolarity
- Decrease blood pressure
Filtration forces
- Protein not filtered in GFR
- Blood into efferent arteriole has increase oncotic pressure
- Use oncotic pressure to help with reabsorption
Net filtration pressure is 10 mm Hg
Aplastic Anemia
- Stop making blood cells
- Can occur with no known cause
- Also from exposure to chemicals, pathogens
- Treat with a bone marrow transplant
Three Phases of Immune Response
Phase I:
- Initial, nonspecific
- Antigen presentation
- Th (specific)
Phase IIa: cell mediated immunity
Phase IIb: humoral immunity
Class Switch
- Preserve VDJ
- Change c regaion (Fc)
Inulin
- Polysaccharide from plants
- Filtered, not reabsorbed or secreted
IgA
- Dimer
- Found in bodily secretions (breast milk, tears, saliva, mucus)
Edward Jenner
- Noticed that women who worked with cows never got smallpox (though they got cowpox- less severe, survivable)
- Inject kid with cowpox… first vaccine
4 things that contribute to G.O.D
Somatic Recombination
Combinatorial Diversity
Imprecision around J regions
Somatic Mutation
Things that influence the kidney
Aldosterone
ADH
ANF
Sympathetic Nervous System
PTH
Angiotensin II
Hygiene Hypothesis
- We are too clean
- Not enough enemies for immune system… boredom –> overrations
Evidence: Finland vs. Russia, worse in western world, farmers have less autoimmune diseases
- Worm thing
Self-Tolerance Mechanism in T-Cells
- Prevent T cells from attacking self
- Must receive 2 signals before attack
1. binding of antigen to T-cell receptor
2. Secretion/binding of a protein B7… if T cell is exposed to a self protein that is presented on a nonstimulatory cell, T cell will die or become inactive
APC
Antigen Presenting Cell
- Material presenting derives from thing eaten
Macrophage
Plasma Cell
- Th and B in synapsis
- Th release IL-4 and B cell turns into plasma cell
- Plasma cell works as antibody factory that is pathogen specific
- Release ab into blood and lymph where they can bind pathogens and antigen presenting cells through opsonization
SGLT-2
- Sodium glucose transporter 2
- In proximal tubule cells on the tubule lumen side
MHC-1
Found on all cells
Diplays internally synthesized peptides
J Region
- Joining Region
- Joining the variable parts of the C region
- 5
Ureter
Drains kidney into bladder
Natriuresis
- Excretion of Na in urine
- Caused by ANF
- Increase volume of urine because osmotic forces make water follow Na
Kidney Reabsorption
From tubules
Into peritubular capillaries
TCR is MHC-2 Restricted
- T-cells only detect antigen when it is being presented by MHC-2
Interleukin-1
- Cytokine
- Endogenous pyrogen
- Stimulatesd more T-Cell synthesis (especially helper T cells)
Killer Cell
- Punch holes in cells covered in antibodies
Artery in the kidney
Arcuate artery
C3
- At the center of the MAC
Immune Synapse
- Th cell attached to macrophage’s MHC-2 using TCR
- CD4 on Th acts like co-receptor
- Th cell is activated after synapse forms
- Macrophage secretes IL-1
- Th: secretes MIF and IL-2
Where can pathogens hide?
Phagocytes, in an endosome TB and Plague
RBCs Malaria
Digestive Epithelium Salmonella
Thick Limb
Loop of Henle
- Filled with ion pumps for Na, K, Cl
- Pump out enough salt so the osmolarity inside is ~ 100 mosm at the top
Lymph Nodes
- Checkpoints
- Small organs with same lymphatic arrangement
- Survey what happens in the fluid that passes through
- Send warning signals if something is fishy
- immune surveillance
Fc
- Same for all antibodies in the same class
- Is what signals for destruction
- Signals that antibodies are present and stuck to things
Control of body temperature
hypothalamus
Diapedesis
- Phagocyte mobilization
- Immune cells squeeze through spaces in epithelial cell lining capillaries to get to where they need to be
Kidney Excretion
From collecting duct
Into urine
Lasix
- Drug
- Diuretic
- Inhibits ion pumps in the thick ascending limb
- Na, Cl, K stay in the ascedning limb… go into urine, take water with them
Glucose Absorption
- Use a Na/Glucose cotransporter SGLT-2
- Glucose moves in through GLUT-2
- Use ATP pump that lowers Na to make gtadient
Autologous Transplant
- Get your own tissue
- Happens in some kinds of cancer
- Risky but can work
Immune system “ehancers”
- Science: none of them prevent infection but can minimally shorten duration of symptoms
Zinc, vitamin C, chicken soup (thins mucus, mildly anti-inflammatory)
Second Line of Defesne
Innate
“Cellular mechanisms, specific proteins, other things…”
- Lymphatic
- Bone Marrow
- Non-specific cells
- Other (interferon, temperature, complement)
- Inflammation
- Pattern recognition receptors
- Non-specific ID model
Macula Densa Cells
- Along the outside of the distal tubule
- Monitor [Na] and [Cl] in tubule
ANF
Atrial Natriuretic Factor
- From right atrium of heart
- Stretch RA - release ANF
- Results in natriuresis (increase in urine flow mostly due to Na excretion… temporary)
- Happens when there is too much body fluid
Lymphocytes
- 3rd Line, specific immune cells
- About the size of an RBC
- Large nucleus takes up most of hte cytoplasm
- have surface mounted receptors they use to bind to target antigens
Examples: T-Cells and B-Cells
Delayed Type Hypersensitivity
- Takes 1-3 days
- Classic example is poison ivy
Spleen
- Bag of blood and immune cells
- Pneumonia fighting cells in the spleen
- Many disorders worsen if spleen is not working
- Thin membrane… can rupture/ get injured… removal
Myasthenia Gravis
Affects ACh receptors in the thymus
Immune Repertoire
3rd Line
- All of your receptors and antibodies that can recognize antigens
Natural Killer Cells
- Punch holes in nonself cells
- Secretory granules with perforin protein… dump into target cell
- Perforin assembles into a complex that makes a big round hole
- Also releases ranzymes
- Important for immune surveillance
Juxtamedullary Nephrons
- Longer nephrons
- Will focus on these ones
Nephron Circulation
- Blood intro the glomerulus through an afferent arteriole
- Leaves via the efferent arteriole
- Efferent art. breaks into a cappillary bed that surrounds the proximal and distal tubules called the peritubular capillary bed
Decrease in Cl reaction cascade
Angioteninsogen + Renin
Angiotensin I
ACE
Angiotensin II
Gamma Interferon
- Acts as an immune cytokine
- Has been used for some cancer treatments with some success
Class I MHC
- Glycoprotein
- Have a groove for antigen peptide present for recognition
- Found on all nucleated cells
- Receptors: heavy and beta-2-microglobulin
What happens to the 120 mL/min?
- Some becomes urine
- A LOT is reabsorbed
Perforin
- Protein released by NKC
- Dumps into target cell
- Assembles into a complex that makes a round hole
Opsonization
- If you have a chunk of invading organism with antibodies gets eaten more easily
pH of body
7.4
Things the nephron can reabsorb
- Glucose
- Ions
- Water
Peyer’s Patches
First Line
- Similar to lymphoid areas
- In intestinal tract
- Think they’re monitoring what comes in
How HIV infects cells
- Need CD4 receptor to infect
- Surface marker on virus attacks CD4 on T-Cells
- Needs CCR5 co-receptor
- There are pepople with CCR5 mutation who are immune to HIV
Skin body weight percentage
15%
Reabsorbing from the proximal tubule goes into….
The preitubular capillary bed
What is our protection from high K?
ALDOSTERONE
Net filtration pressure
10 mm Hg
Graft Rejection
Example of cell mediated immunity
- When someone rejects a graft it is usually CMI
Loop of Henle
- Sets up our osmotic gradient
Pattern Recognition Receptors
- Integral proteins in phagocytic cell membranes
- Recognize traditional forms of pathogens (bacteria, virus, fungi, parasites) in a non-specific way
- Sends out signals… warning for the rest of the immune system to say something has been detected
- Worked on by Charles Janeway
Cow Pox
- Difference between cow and small pox is so small that T and B cells involved in immune response cannot tell the difference
- Edward Jenner
Mesangial Cells
- Innervated by the sympathetic nervous system
- Have the ability to contract and close off regions of the capillary bed (stop blood flow)
- If hemorrhaging…. decrease blood volume and pressure, restrict filtration
Pathogen that changes surface antigens
Typanosomes
Appendix
2nd Line
- Unsure what it is doing
- Think it might be a reservoir for immune cells and certain types of gut bacteria
- Think it helps set up a young person’s immune system
Where does urine become concentrated?
Collecting Duct
Angiotensinogen
- Made in liver, circulates blood
- Renin + Angiotensinogen –> Angiotensin I
- Also produced by adipose tissue
Autoimmune Diseases
- Immune education goes awry and lymphocytes attack self antigens
- Some have a genetic component
- Triggered by autoimmune mimicry after a viral infection
Sympathetic Neurons and JG Cells
- Sympathetic resonse if decrease in blood pressure
- Decrease BP … Increase renin
The G.O.D. Search
- Not millions of genes… different regions that can be organized in different ways
C
J
D
V
Anergy
Non-reactive T-Cells
Distal Tubule
- Where filtration occurs (after we have reabsorbed in the proximal tubule and gone through the loop of Henle)
Juxtagolmerular Apparatus
- JG cells + MD cells
MHC Class II
Glycoprotiens
- Found ont he surface of immune cells (macrophages, B-cells, some T-Cells)
- Groove for antigen peptide present for recognition
Somatic Mutation
- Get mutations during transition to plasma cell
Angtiotensin II
Potent Vasoconstrictor
Acts on…
- Adrenal cortex
- Hypothalamus
IgD
- Monomer
- More specialized
- Surface of B cells… serves as a receptor
Two controls of Aldosterone
- Renin
- K+ levels in the blood
J region and diversity
- Deltion in J region is not precise
- also somatic mutation
Four Types of T-Cells
Helper
Inducer
Cytotoxic
Suppressor/Regulatory
Alpha Interpherons
- Stimulate the natural killer cells
Asthma
Attack tissues in airways –> inflammation
What happens in the thymus gland (immune system)?
T-cell education
CD Markers
- Clusters of differentiation
- Surface markers on immune cells
- Important ones are CD4 and CD8
3rd Line
Pathogen that knocks out Th cells
HIV
Concetrated Urine
- To combat dehydration
- 4 times more concentrated than blood
- U/P Ratio
1200 m osmolar / 200 m osm
Scleroderma
Body makes anti-centromere antibodies
- Too much collagen
- alopecia, flare-ups
Decrease Perfusion Pressure in Afferent Arterioles
- Afferent arteriole can monitor pressure
- If there is a decrease in pressure, signals an increase in renin
Protein as a buffer
- Use COOH to donate hydrogens
- Use amino group to accept hydrogen
pK fro proteins = 7.4
Mostly R groups but could be backbone too
Juxtaglomerular Cells
- Associated with the afferent arteriole
- Release renin into afferent arteriole
- Get a series of reactions to stabilize GFR
Water reabsorption without ADH
- Osmotic gradient
- Not permeable to water
- Water goes through collecting duct
Light Chain Diversity
1500
Liver Macrophage
Kupffer’s Cells
Blood Pressure Medications
- Many are diuretics in the class thiazide
- Block sodium reuptake in the distal tubule
- Stop Na reabsorbtion, leaves in urine and water follows
- Decrease blood volume, decrease BP
Antigen Presentation
Phase I
- Macrophage will take what it has eaten abd break it down with digestive enzymes in the lysosome
- Take piece of peptide and put it on MHC molecule
- Present on MHC-2
Immunocompetent
- Lymphocytes shown a bunch of self antigens in thymus
- Any T-cell that sticks toa self antigen gets killed
- The ones that pass the test go into the circulation and we say they are immunocompetent
Standard Glomerular Filtration Rate
(GFR)
- Kidney gets 600 mL of plasma/min
- standard GFR of 120 mLs/min
- The other 480 mL go through the efferent tubule into the peritubular beds
Podocytes
- Specialized cells that surround capillaries
- Control filtration
- In charge of selection based on size
Two types of protein chains on antibody
2 Heavy Chains
2 Light chains
Adaptive Immune System
Definition
Very specific
C Region
- Constant Portion
- Gene
Macrophage as an APC
- Break up virus
- Display peptides from the virus on cell surface
Macrophage saying “invader here this is what it looks like”
- Displayed antigen is seen by the TCR on the helper T cells
Somatic Recombination
- During the maturation of a lymphocyte –> B-Cell… chooses certain genes with four regions through random selection
- DNA splicing
-
Kidney Osmotic Gradient
Cortex: 300 m osm
Medulla: 1200 m osm
Dendritic Cell/ Langerhan’s Cells
- Skin macrophage
- Found in the tissue exposed to the exterior
B7
- Protein that is the second signal in activating a T cell
- If not present and bound, T cell will become inactive or die
Excretion Rate
How much of a substance is being secreted in urine
= ([X] in urine) * (Urine output)
mg/min
TB Test
- Delayed hypersensitivity
- Tuerculin skin test
- If raised or red, have been exposed to TB (do not necessarily hvae it, but need further tests)
How ADH Promotes Water Reabsorption
- ADH binds to membrane receptor
- Receptor activates cAMP second messenger system
- Cell interts AQP2 water pores into apical membrane
- Water is absorbed by osmosis into the blood
Allergy Symptoms
- Leaky vessels
- Swelling
- Runny nose
- Mucus release
- Low BP
- Sneezing
Pathogen with a waxy exterior
Leprosy
First Line of Defense
Physical and biological barrier between body and the outside world
- Skin
- Openings in the skin
- Peyer’s Patches
Charles Janeway
Pattern Regocnition Receptors
- Had a theory that if your innate mechanisms were not working then your immune response would be weak
- Found PRPs
Kidney and Secretion
- Secrete things in proximal tubule
- Organic ion transporters
- Take ions out of the blood put them through tubule
- Antiporter brings in ion from blood… when ion goes to lumen, exchange for a like charge from lumen
Effect of efferent dilation on flow
Constrict - increase flow
Subclavian Veins
- Get fluid form the thoracic duct
- Collect excess fluid from the body and put back into circulation
Burn Victims and Urea
- Dehydration
- Need urea in diet (protein) to get fully functioning osmotic gradient
- Low protein diets made dehydration worse
ANF and adrenal cortex
Decrease aldosterone
Macrophages
Big Eaters
- From monocyte precursors
- Live in tissues
- Different names specific to different tissues
Allogeneic Transplant
- Someone else’s tissue tissue but not a tissue match
- Will not work with bone marrow (because of immune cells)
Clonal Selection
- Going to activate and replicate only those T cells that are specific to this infection and let other T cells rest
Humoral Immunity
- B cells have antibody molecules on membrane
- Recognize pathogen… bind and eat
- After this, work with Th like macrophages do
- In synapsis, Th secrete IL-4… activates B cell and turns into plasma cell
