-
4 stages of estrous cycle or 2 stages of estrous cycle
- proestrus
- estrus
- diestrus
- anestrus
- OR
- follicular stage (influence of estrogen produced by maturing follicle)
- luteal phase (progesterone produced by corpus luteum)
-
behavior of estrus vs proestrus
estrus is when a female will stand for a male. Any other behavior is proestrus
-
GnRH
gonadotropin releasing hormone from hypothalamus, stimulates pituitary to release FSH and LH
-
FSH
- Follicle stimulating hormone, released from anterior pituitary
- controls growth and maturation of follcile in ovary (releases estrogen, enough causes ovulation/LH release)
- Proestrus and estrus
-
-
LH
luteinizing hormone, causes ovulation (diestrus)
-
corpus luteum
what's left of follicle after ovulation, relases progesterone which readies uterus for pregancy and maintains environment for fetus if pregnancy occurs.
-
progesterone
released from corpus luteum, readies uterus for pregnancy and maintains environment to allow fetus to grow
-
Fetus hormones
at end of pregnacy/diestrus, fetus releases ACTH, cortisol increases, uterus releases prostaglandins and estrogen, which sensitize uterus to oxytocin
-
oxytocin
starts uterine contractions, stimulated by prostaglandins and estrogen
-
Prostaglandin F2a
causes breakdown of corpus luteum, causing end of diestrus. Otherwise, persistent anestrus and animal can't cycle again.
-
Luteolysis
- caused by prostaglandin F2a, signals end of diestrus.
- Otherwise persistent anestrus and animal won't cycle again, so CL MUST be broken down.
-
Gonadotropins
- actions like endogenous GnRH, FSH or LH.
- Gonadorelin (GnRH)
- Chorionic Gonadotropin (hCG)
-
Gonadorelin (Cystorelin)
- gonadotropin, normally endogenous from hypothalamus (from slaughtered animals)
- causes release of FSH and LH
- used in cattle and guinea pigs for cystic ovaries
- horses and cats to induce estrus (limited success)
-
Chorionic gonadotropin (hCG) (Follutein)
- gonadotropin, endogenously secreted by uterus. Obtained from urine of pregnant women.
- Mimics LH activity with limited FSH
- Used in cattle and guinea pigs for cystic ovaries
- in males, cryptorchidism and infertility (also makes testosterone)
- causes abortion in mare early (pre-35 days) pregnancy. Some hypersensitivity reactions
-
Estrogens
- synthesized by ovaries, adrenal cortex, placenta and testicles from cholesterol
- development of female gonads and secondary female sex charateristics (birth control pills)
- inhibits ovulation, increase uterine tone, cause endometrium proliferation
- Estradiol, diethylstilbestrol (DES)
-
Estradiol, DES (diethylstilbestrol) uses
- Cattle for persistent CL, expel purulent material, retained placenta or mummified fetus, promote weight gain
- dogs to induce abortion, incontinence (low estrogen causes urethral sphincter problem)
- horses for estrus induction
- DES banned in food animals due to cervical cancer in humans
-
Progestins
- compounds similar to progesterone, some secreted by CL
- anti-insulin effect and adrenal suppression
- increase endometrium secretions, decrease uterine motility, increase mammary gland secretion, inhibits release of gonadotropins from pituitary to prevent ovulation (during pregnancy)
- Megestrol acetate
-
Megesterol acetate (megace, ovaban), uses
- Progestins
- Dogs, as appetite stimulant, control estrus, treate false pregancy, male behavior issues, male galactorrhea (milk glands in male)
- Cats for dermatitis, behavior (urination and territorial), suppress heat cycle instead of spay
- Adverse: hyperglycemia, Addisons (GI, bradycardia, electrolytes), endometrial hyperplasia, increased appetite
-
Prostaglandins
- Group of long-chain fatty acids called icosenoids
- Regulates and treats conditions of female reproductive tract IF there is a luteum to lyse
- Lutalyse
-
Lutalyse (Dinoprost tromethamine)
- salt of endogenous prostaglandin F2a.
- lyses luteum, uterine contractions, cervix relaxation
- Cattle, sheep goats: estrus sync, pyometra, silent heat, abortion
- swine: parturition induction
- horses: control of estrus cycle timing, anestrus mares with CL
- dogs/cats (off-label): pyoetra, endometrial hyperplasia, abortion
-
adverse effects of dinoprost tromethamine (Lutalyse)
- bronchoconstriction
- increses smooth muscle contraction (early labor)
- sweating (horses)
- abdominal pain/cramps (h/d/c/p)
- urination/defecation(d/c/p)
- dyspnea, panting (d/c)
- tachycardia (d)
- increased vocalization (c/p)
-
Oxytocin
- uterine contractility (neurohormonal). Comes from posterior pituitary, increases contractility.
- Uterus must be primed first for a time by progesterone and estrogen
- dystocia (makes contractions stronger), retained placenta, uterine prolapse, induce milk letdown, agalactia in pigs
- NO birth canal obstruction! Can rupture uterus
-
Hygiene hypothesis
Kids get allergies because they grow up in a sterile environment
-
Three lines of defense of the body
- physical barrier
- innate
- acquired
-
immune system
- defends body against invasion by pathogens and minimize damage caused by them
- includes primary (thymus, bone marrow, Peyer's Patches, Bursa of Fabricus) and secondary (WBC, lymph nodes, lymphatic vessels, spleen, tonsils, other tissues).
-
Physical barrier (3) in immunity
- intact skin, first defense
- self-cleaning of other surfaces (sneeze, cough, v/d, UTI, etc)
- COmmensal bacteria (synergistic effect) (skin and GI), out-compete poorly adapted bad guys
-
Innate immunity
- general, non-specific immune mechanisms that defend body against first and subsequent exposures to pathogens.
- LACK MEMORY. Every response is the same.
- Activated immediatly, rapid elimination. Lasts minutes to hours.
- Reacts against common carb component most microbes have (different from "self" tissues)
-
two parts of innate immunity
- cells: detect, eat, kill pathogens and virus-invaded cells
- Molecules: bind and kill, coat so other cells can kill, block growth, prevent spread, mobilize defenses
-
Cellular innate immunity
- Natural killers, macrophages, dendritic cells
- Sentinel Cells: recognize and respond to invading pathogen/microbe, recruit WBC to phagocytize. Usually mast or dendritic
- Compliment: set of enzymatic paths that activate proteins that kill invaders
-
Compliment
set of enzymatic paths in innate immunity that activate proteins that kill invaders
-
molecular innate immunity
kill invaders directly or promote destruction by defense (bind to pathogen and increase chances/ease of phagocytosis).
-
Inflammation as (innate) immune response
- Protective, localized response of tissue to damage.
- Begins immediatly at site of damage.
- dilutes, destroys or walls off agent and damaged tissue, lets blood components into damaged site. induces phagocytosis and cleans damaged tissue
- acute is protective, chronic becomes damaging/disease
-
acute inflammatory response
- 1. increases vascular caliber (diameter of vessels), allows more blood to site. Vascular structure changes, allows plasma proteins and cells to get into tissue and form exudate
- 2. exudate: accumulation of plasma/protein rich fluid at site, causing swelling
- 3. WBCs are chemically attracted, emerge from blood to get tissue, eat and produce chemicals to clean tissue and attract other things
-
Chemical mediators in inflammation
- inflammation is triggered by chemical mediators released by injured tissues and migrating WBCs.
- Cause vasodilation, increased blood flow, vasopermeability. Plasma dilutes and fibrin tries to immobilize, WBC are phagocytic for tissues and microbes
- Prostaglandins (PGs)
- leukotrienes (LTs)
- Histamine
- Serotonin (5-HT)
- Bardykinin
-
Eicosinoids
- diverse family of fatty acids collectively, effecting everything
- Come from cell membranes. Phospholipases release arachadonic acids (essential) after damage (trauma or immune)
-
Things arachadonic acid can turn into
- with cyclooxygenase 1 or 2, prostaglandins
- with lipoxygenase, leukotrienes
- Platelet-activating factor
-
Constituitive prostaglandins
- present in normal healthy animals
- made by arachadonic acid and COX 1
-
inducible prostaglandins
- not detectible without injury and inflammation
- made by arachadonic acid and COX2
- abundant in macrophanges activated by inflammation
-
Leukotrienes
- increase vascular permeability
- increases smooth muscle contraction
- attract neutrophils
-
Mast cells in immunity
- huge with blue granules and big round nucleus
- Found especially in skin, respiratory, GI (where they'll find invaders), close to blood vessels
- Regulate blood flow and influence cellular migration.
- Histamine, seratonin
-
Pavementing
when WBC, attracted to damage in a tissue, line endothelium. Endo cells contract, WCB migrate, release chemical mediators, phagocytize
-
Histamine
- comes from mast cells, basophils and platelets
- Increases vascular permeability and causes pain (increases nocioceptor sensitivity) in acute inflammation
-
Serotonin
- comes from mast cells, basophils, platelets
- increases vascular permeability in acute inflammation
-
Mast cell primary degranulation process
- B cell covered in receptors binds to antigen (can be allergen), processes, presents to T-helper cell.
- T produces lymphokines (cytokines specific to lymphocytes) that differentiate B cell into memory cell or plasma cell (produce antigen-specific antibody = IgE)
- IgE binds to FC receptor on mast cell (irreversible), causes "sensitized" mast cell
- Cross link, bind to 2 IgE, degranulates to release histamine and seratonin, cause effect.
- Can include increased secretions, constriction, sensitized nerves, attract eosinophils.
-
When does hypersensitivity reaction happen
mast cell degranulation, caused by cross link of 2 IgE, so must happen twice
-
4 cardinal signs of inflammation
- redness (vasodilation)
- swelling (permeability)
- heat (vasodilation)
- pain (pressure from swelling, histamine release)
-
Complement system
- Protect against infection, regulate inflammation, remove damaged cells, send danger signals, regulate acquired
- 2 pathways, classical and pattern recognition
- innate defense, network of inactive serum proteins and cell surface receptors
-
Pattern recognition pathway
activation of compliment by molecules in microbes (usually carbs), activated innate immunity
-
classical pathway
- evolutionarily recent
- associated with acquired immunity
- compliment becomes activated when antibodies bind to surface, work with acquired to destroy microbe
-
function of complement system
- alter cell membranes or induce inflammation
- hastens elimination of invader
- induces bacterial lysis, opsimization (makes pathogen more susceptible to phagocytosis)
-
opsimization
- makes pathogen more susceptible to phagocytosis
- microscopic molecule can bind to surface of large pathogen so other cells can more easily eat invader
-
Compliment funtions
- alter membranes (bacterial lysis, opsimization)
- inflammation (mast cell degranulation, neutrophil chemotaxis to attract phagocytes)
- other (immune regulation, angiogenesis, removal of apoptotic cells
- blood coagulation
-
acquired or adaptive immunity
- antigen-SPECIFIC immune response to a particular substance that the body IDs as "non-self"
- directed against specific pathogen
- Slower, but LEARNS, long-lasting
- does not fully develop unless body has been previously exposed to that specific pathogen
- 2 types: Cell-mediated (T and B cells) and Humoral (antibody-mediated)
-
auto-immune disease is a mistake in the
acquired immune system
-
cells of innate vs adaptive
- innate: macrophages, dendritic, neutrophils, natural killers (sentinel and phagocytic)
- adaptive: T and B cells
-
antigen
- any substance that can induce a specific immune response
- usually a large protein molecule recognized by cells of acquired
-
Antigen presenting cell
- usually macrophage, dendritic cell, some B cells
- Traps and processes antigen
- presents antigen to immune system cells who take care of it.
- Process antigen, present it on surface, T-helper recognizes, B cell coated in receptors binds to same antigen, tell B to become memory or plasma, plasma cell produces antibodies specific to antigen, make antibody-antigen complex.
-
Why do we need 2 types of acquired immunity?
- exogenous antigens openly proliferate, can be found by antibodies (humoral)
- intracellular pathogens proliferate in cell and are taken care of by cell-mediated immunity (not accessible to antibodies)
-
B-cells proliferate in
lymph nodes, sometimes in secondary lymph organs like spleen
-
immunoglobulins
- glycoproteins. Antibodies.
- Antigen-specific, usually not seen for at least a week after exposure (can't test right away)
- Bind to antigen they are specific to, cause antigen/antibody complex
-
Serum protein electrophoresis
- test. Apply electric field to sample, molecules separate by size and charge. Run when see hyperproteinemia characterized by hyperglobulinemia.
- Albumin most negative, rest separate into alpha, beta and gamma.
- Gamma is immunoglobulins.
- Look for spike--is it one Ig or several? Monoclonal vs polyclonal gammopathy
-
list immunoglobulins
GMADE
-
IgG
- highest concentration in serum, longest half life (in circulation longest), smallest molecule (escapes vaso in inflamm)
- defense of tissues, can bind to pathogens and specific antigens, causes bacteria to clump and activates opsimization (more susceptible to phagocytes) in classical compliment pathway
- Produced in spleen, lymph, bone marrow (1 and 2 lymph tissue)
- Predominant transferred from mom to offspring in colostrum
-
IgM
- 2nd highest concentration in serum, largest molecule so stays in circulation
- antibody produced on initial exposure to antigen
- primary immune response (also 2 but less)
- More efficient than IgG in activation of opsimization, activation of compliment and neutralizing viruses
- produced by plasma cells in 2 lymph organs (NOT bone marrow)
- Shaped like a polygon, not linear like other Igs
-
IgA
- third highest concentration in serum, predominate Ig found in body secretions of nonruminents
- produced in body surfaces (guard at the gate), makes pathogens and viruses clump to each other and body surfaces "not sticky", major in preventing pathogen invasion.
- Bord IN (airborne pathogens)
- NOT increase opsimization or activate compliment
- produced in respiratory, skin, urogenital, GI, cornea, mammary glands
-
IgD
- B-cell receptor, very little in blood
- Not yet found in rabbits, chicken, cats
- not sure what does.
- Found attached to B cells only
-
4 types of Hypersensitivity reaction
- 1. immediate allergic reaction, red, swollen, itchy, sneezy
- 2. antibodies attack self (auto-immune)
- 3. deposition of antibody/antigen complex in tissue creates inflammation (glomerulonephritis, for example)
- 4. delayed, very slowly developing, mediated by T cells and natural killer cells. Takes 24-96 hours to develop.
-
IgE
- low concentration in serum (shortest half life)
- mediate allergic reactions, especially type I. Causes degranulation of mast cells if cross-linked, more than 1 IgE on surface
- enhances local defenses, triggers acute inflammation (FC on mast and basophils) and compliment in PARASITIC WORM IMMUNITY
- produced by plasma cells beneath body surfaces (respiratory, skin, urogenital, GI, cornea, mammary)
-
monoclonal vs polyclonal gammopathy
- LOTS of Igs.
- monoclonal could be cancer
- polyclonal suggests infection (FIP?)
-
FC stands for
- fragment receptor crystallized.
- Steadier part on stem of antibody, antigen binding sites can change, FC is more constant
-
Acquired passive immunity, artificial and natural
- Administer pre-formed antibodies from another immune animal (inject Ig)
- Immediate but not long-lasting
- artificial: antiserum, antitoxin
- natural: colostrum/placenta, from mom
-
acquired active immunity, artificial and natural
- IV organism (killed or modified live if artificial), animal fights.
- Takes longer to develop, lasts longer
- artificial: vaccination
- natural: infection
- Repeated exposure makes immunity stronger, booster vaccines
-
Vaccination
- administration of antigen to stimulate immune so individual can develop immunity
- 1st: development of effector T and B cells (helper, killer, suppressor), temporary protection
- 2nd: development of memory T and/or B cells, re-exposure (3rd), recognition, clonal expansion and differentiation into effector T and B cells, kill invader.
-
suppressor cell
T or B cell that stops allergic response from going on, spares "self".
-
Types of vaccinations
- Inactivated vaccine: virus or bacteria grown in culture then killed (formaldehyde or heat). Proteins remain intact enough to be recognized by immune (exogenous antigen) and stimulate mostly T helper cells (CD4)
- Modified live vaccine: attenuation (goldilocks) to reduce virulence, stimulates response of mostly cytotoxic T cells (CD8), act as endogenous, cell-mediated immunity.
- viral purified subunit: inject into another species
- viral recombinant product: inject into another species
- viral DNA vaccine: most recent, protein off capsid, purified
-
viral DNA vaccine
DNA that encodes antigen is injected into the individual
-
viral recombinant product
take gene responsible for coding of antigen, inject into another species or virus (cat rabies = canary pox)
-
viral purified subunit
most recent, take protein off capsid, purify and make vaccine from that
-
modified live vaccine
- attenuated, strong enough to stimulate, too weak to replicate.
- Response primarily cytotoxic T cells (cell-mediated, get into cells and replicate, endogenous)
- fewer smaller doses required, more effective, adjuvents unnecessary, less chance of hypersensitivity, cheaper, given with natural route, stimulate humoral and cell mediated response, lover-lasting (3 year)
-
Killed vaccine
- killed with formaldehyde or heat, mostly T helper cell response (acts as exogenous)
- Stable on storage, safer, unlikely to cause disease, do not replicate, will not spread, safe in immunodeficient patients, easier to store, no risk of reversion
-
attenuation
process that reduces virulence of virus in vaccine (goldilocks).
-
Adjuvants
additives to enhance effectiveness so you need less. Often causes reactions.
-
bacterin
vaccine for bacteria, almost always killed
-
vaccines began in
1940s, with smallpox
-
Cell-mediated immune response
- defense inside cells where antibody can't reach.
- Eliminate abnormal cells and intracellular organisms (endogenous)
- cytoxic T cells (CD8) cause forced apoptosis
- Cells leave lymph organs and seek abnormal cells. Don't wait to be presented.
- Cancer
-
immunodiagnostic technique, ELISA
- most common primary binding test
- Detect and measure antibodies.
- Well is pre-coated with antigen, serum goes in well, makes a/a complex if present. Add anti-globulin (protein that binds to Ig, which is bound to a/a complex, sandwich), causes color change.
-
immunodiagnostic technique, immunofluorescence assays
- Fluoresce when irradiated with blue or UV light
- tests serum for antibodies
- Direct and indirect
- Direct: label antibody specific for antigen, antibody fluoresces
- indirect: fluoresce on anti-globulin
-
immunodiagnostic techniques serology
- indirect. Tests infection based on post-exposure (not definitive, or straightforward. current? May not be active)
- false + can be post-clinical, exposure without disease, vaccination, colostrum.
- 2 samples (acute and convalescent later)
- Lyme, toxoplasmosis (problematic)
- Most common in alive animal
-
seroconversion
fourfold increase in antibody titer (between acute and convalescent sample) consistent with recent antigenic stimulation
-
Serology immunogloblins (help with diagnosis)
- IgM indicates recent exposure, usually seen first in immunoresponse
- IgG is produced later in response, indicates exposure several weeks to months previously
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