Pathophysiology Exam #3 Flashcards
The precursor to fibrin is?
fibrinogen
Hemocytoblast Stem Cell become Myeloid Stem Cells which become Megakaryoblast which form Megakaryocytes……each Megakaryocytes can fragment into how many platelets?
2000 - 5000
The precursor cell for platelets is?
Megakarycote—>platelets are formed from the fragments of them
Platelets are anuclear…what does this mean?
- they cannot multiply and divide(they have no nucleus)
- Bone marrow (BM) has to be constantly producing and moving those platelets from the BM into the circulation to maintain an adequate circulating level of platelets
What is the normal circulating concentration and the lifespan of platelets?
• Normal circulating concentration:
150,000 – 450,000/μL (could also use mm3)
• Half-life: 8 – 12 days
What are six things that are found in the cytoplasm of platelets?
- Contractile proteins
- ER and Golgi apparatus
- Mitochondria
- PGs and TXA2 synthesis
- Fibrin-stabilizing factor synthesis
- Growth factors
What are three contractile proteins found in the cytoplasm of platelets?
- actin
- myosin
- thrombosthenin
What is the function of the ER and Golgi apparatus that is found in the cytoplasm of platelets?
-Ca++ storage and enzyme synthesis
§ Ca is very important in the coagulation cascade (both intrinsic and extrinsic pathways of the coag cascade)
§ ER ribosomes will produce enzymes that are needed for coag
§ Golgi apparatus will further process the enzymes needed
What is the function of the mitochondria found in the cytoplasm of platelets?
ADP and ATP synthesis
§ ADP itself actually aids in the aggregation of platelets, as well as recruitment of other platelets
What is the function of the Fibrin-stabilizing factor?
§ Once you get to the final clot, the final fibrin fibers, the fibrin−stabilizing factor enhance the bonds between the fibrin fibers and create a stronger clot
What is the function of the Growth factors found in the cytoplasm of platelets?
cause vascular endothelial cells, vascular smooth muscle cells, and fibroblasts to grow and divide for repair of damaged blood vessels.
§ When you have an injury and platelets respond, those growth factors are released from the platelets which helps aid in the healing of that damaged tissue
What makes up the cell membrane of platelets?
- Glycoprotein coating
- Phospholipids
- Receptors
What is the characteristics of the Glycoprotein coating of the platelet cell membrane?
o Glycoprotein coating that prevents adherence to normal vascular endothelium, but causes adherence to
injured endothelium.
§ Very important because this prevents the platelets from adhering to normal vascular endothelium; platelets will not adhere to NORMAL vasc endothelial cells.
§ Anything that’s causes injury to the vasc endothelium, will activate the platelets and they will respond to the damaged vasc endothelium
What is the role of the phospholipids found in the platelet cell membrane?
Plays important role in the clotting cascade
What is important about the receptors found in the platelet cell membrane?
o Numerous receptors involved in platelet plug formation and coagulation
o When individuals have clotting disorders, that are r/t platelets; it’s the receptors themselves that are dysfunctional or deficient which leads to the coagulopathy
What is the definition of hemostasis?
prevention of blood loss
How is hemostasis achieved and in what order does it occur(5)?
- Vascular constriction
- Platelet plug formation
- Blood coagulation/blood clot
- Fibrin formation and repair of injured vessel
- Clot lysis
What are four ways in which Vascular Constriction achieves hemostasis?
• TRAUMA CAUSES VASCULAR CONSTRICTION, WHICH DECREASES BLOOD LOSS
• VASCULAR SMOOTH MUSCLE SPASM
o The greater the trauma to the blood vessel (BV), the greater the spasm
o EX: Nick yourself shaving in the bathroom; you think your going to bleed to death while a crushing injury or severed limb: because of the greater degree of injury, the greater degree of vasospasm
• PAIN AND SNS REFLEXES: VASOCONSTRICTION
o NE is released from the postganglionic symp fibers
o EPI/NE released from the adrenal medulla
o causing activation of alpha1 receptors of the vasc smooth muscle; causing vasoconstriction
• PLATELETS → TXA2 → VASOCONSTRICTION
§ When platelets become activated they release thromboxane A2 (TxA2)
§ TxA2 is also a very very potent vasoconstrictor
Platelet plug is the second way in which Hemostasis occurs…what are the characteristics of Platelet plug?
• PLATELETS CONTACT DAMAGED VASCULAR ENDOTHELIUM AND COLLAGEN IN BLOOD VESSEL WALL
o Swell, exude pseudopods
§ pseudo = false; pod = foot
o Actin, myosin, thrombosthenin contract: release active clotting factors
o Platelets then become sticky and aggregate; adhere to collagen and von Willebrand factor (vWF) in blood vessel wall
§ vWF has to be present for the platelets to stick to the collagen in the BV wall
§ vWF is a protein secreted by the BV endothelial cells; it mediates platelet adhesion to the BVs by
forming a bridge between the collagen and the platelets
§ von Willebrand factor binds to both platelet membrane receptors and collagen in the vascular wall to
form the bridges
o ADP and TxA2 secretion: activation of other platelets
v ADP and TxA2 actually combine with receptors on other platelets and recruit them to come play along
o More and more platelets aggregate and are activated and form the platelet plug in the vasc wall
o Eventually the platelets will Express fibrinogen receptors; and the fibrinogen receptors will bind with
the fibrinogen
v the fibrinogen forms bridges between the fibrinogen receptors of the platelets to form platelet plug
o Fibrin threads form in platelet plug
o Platelet plug may seal small blood vessels injury
o However, Large injury also requires blood
coagulation/blood clot
Some people are born with a deficit or a complete absence of vWF; and they will need surgery.
Q: What will you do to correct that problem?
Administer vWF; they have vWF concentrate that you can admin; can also admin cryo
The third stage of hemostasis is Blood coagulation/Blood clot….what are its characteristics?
• BEGINS: 1-2 MIN. FOR MINOR TRAUMA AND 15 – 20 SEC. FOR MAJOR TRAUMA
• 3 – 6 MIN. TEAR IN VESSEL FILLED WITH CLOT
• CLOT RETRACTS IN 20 – 60 MIN.: CLOSES TEAR(APPROXIMATES) MORE AND AIDS IN HEALING
• NORMALLY THERE’S A BALANCE BETWEEN PROCOAGULANTS AND ANTICOAGULANTS
o Normal conditions: anticoagulants predominate
o After injury: procoagulants predominate
o However, procoagulants predominance should be
localized to the area of the injury; you do not
want systemic procoagulant predominance
There are three steps of coagulation in relation to hemostasis…what is the the first step?
- Activation of blood coagulation factors and formation of PROTHROMBINASE (PROTHROMBIN ACTIVATOR)
There are three steps of coagulation in relation to hemostasis…what is the the second step?
- Prothrombinase converts PROTHROMBIN TO THROMBIN
There are three steps of coagulation in relation to hemostasis…what is the the third step?
- Thrombin converts FIBRINOGEN TO FIBRIN FIBERS = Enmesh platelets, blood cells, and plasma to form the clot
What is the final outcome of step 1 of coagulation?
Prothrombinase is the final outcome of step 1 of coagulation
There are two pathways for prothrombinase formation in step one…what are they?
- Extrinsic (tissue factor) pathway
- Intrinsic (contact activation) pathway
What are the characteristics of the Extrinsic pathway
v Its called extrinsic because the damage is EXTERNAL to the BV
v Once tissue is damaged, that causes the release of thromboplastin; released from the traumatized tissue
v Thromboplastin along with Factor VII and Ca ions activate Factor X
v Activated Factor X, Factor V, platelet phospholipids, and Ca ions activate prothrombinase (the final outcome of step 1 of the coagulation pathway.
In step one of coagulation, what initiates the action of the extrinsic clotting pathway, and what is the final outcome of it?
- tissue damage(trauma)
- Prothrombinase
In step one of coagulation, what initiates the action of the intrinsic clotting pathway, and what is the final outcome of it?
- contact w/ collagen of damage bv activates factor xii
- Prothrombinase
Do both the intrinsic and the extrinsic pathways lead to the same result?
yes; Note that beginning with activation of Factor X, both become a common pathway
What ion plays an important role in both the intrinsic as well as the extrinsic pathway?
§ You can see here that Ca plays an important role in both the intrinsic and extrinsic coag pathways
v If you have low levels of extracellular Ca, that is going to affect your ability to clot
§ The extrinsic pathway actually feeds into the intrinsic pathway
§ Extrinsic pathway can become out of control—EXPLOSIVE; intrinsic pathway has a much more
controlled and slower response
§ If blood vessel ruptures, both pathways are activated simultaneously
In step two of coagulation, what initiates the action of the clotting pathway and what is the final outcome?
• Prothrombinase converts prothrombin to thrombin
-The final outcome of step 2 is THROMBIN
o Requires sufficient Ca++
o Prothrombin
§ An alpha-2 globulin (plasma protein) an unstable
protein that can split easily.
§ Synthesized in liver
§ Vit K dependent coagulation factor
§ Vitamin K required for normal activation of
prothrombin (also required for liver synthesis of
Factors VII, IX, X)
v Sources of vitamin K: diet and synthesis by E. coli
in colon
Q: SO, consider your pt is on an antibiotic that is
decreasing the amount of E. coli within their GI tract or they have a colon cleansing (GoLYTELY) before the procedure; what kind of implications will that have?
A: Decreased synthesis of prothrombin of the liver.
v Vitamin K is a fat soluble vitamin, so adequate bile in the GI tract is necessary for vitamin K absorption
In step three of coagulation, what initiates the action of the clotting pathway and what is the final outcome?
• THROMBIN, ALONG WITH CALCIUM IONS, converts FIBRINOGEN into FIBRIN FIBERS, which, in
combination with platelets, blood cells, and plasma, FORM A CLOT.
o Requires Ca++
• NOW WE HAVE THE FINAL CLOT: meshwork of fibrin fibers entrapping platelets, blood cells, plasma
Clot retraction is a part of step three of hemostasis ….what are its characteristics?
• The clot retracts and Expresses most fluid (serum) from clot within about 20−60 minutes
o Actin, myosin, thrombosthenin, and Ca++ in platelets
o What happens is actually the actin, myosin and thrombosthenin, those contractile proteins actually
causes the platelets to contract which causes total clot retraction
• Pulls edges of blood vessel closer together: aids in hemostasis and healing
What is the name of the fluid expressed from the clot that has all of the clotting factors removed from it?
serum
The fourth step of hemostasis is fibrin/ fibroblasts formation and repair of injured blood vessel…what is the characteristics of this step?
• Following formation of fibrin fibers (see above), clot becomes invaded by fibroblasts, which form connective tissue throughout clot
• If the entire Clot is changed to fibrous tissue and repair is complete in about 1 to 2 weeks
o Now depending on the extent of injury, this depends on if this new tissue is similar to function and form to the original tissue
o Think about a myocardial infarction, tissue becomes damaged, it gets repaired; does it function the same
as it did before
o EX: burn victim’s skin forming contractures, etc
o So depending on the extent of the injury, if the injury is small that tissue can be similar in function and form; if it is large, the new tissue will be scar tissue and will not heal or function like it used to
• Platelet growth factors enhance repair
Describe the 5th step of hemostasis…clot lysis.
• When blood has leaked into tissues and clot is formed, it must be dissolved.
• Very essential step; do not want clot hanging around in your body
• Plasminogen (inactive plasma protein) trapped in clot
o Plasminogen is usually in the inactive state
• Injured tissue and vascular endothelial cells release tissue plasminogen activator (t-PA)
• In 1−2 days after clot has stopped the bleeding, t-PA will convert plasminogen to plasmin
• Plasmin
o Proteolytic enzyme
§ Breaks down proteins, digest the fibrin fibers and the clot is lysed
o Digests fibrin fibers and procoagulants
How does the vascular endothelium help prevent coagulation in normal blood vessels?
• VASCULAR ENDOTHELIUM
o Smooth (under normal conditions) prevents activation of intrinsic pathway
§ when it is smooth that is a good thing; that does not activate the coag cascade
o There’s also a Mucopolysaccharide glycocalyx on the vasc endothelium that repels platelets and clotting
factors
o Thrombomodulin is a protein that is bound with the vasc endothelium; it binds thrombin and removes it
from the blood
o When Endothelial tissue/ cells is damaged: that activates the INtrinsic pathways, with the activation of
Factor XII and platelets
How do fibrin fibers help prevent coagulation in normal BV?
• Fibrin fibers (after a clot has been formed) will absorb thrombin and remove it from blood to prevent spread
of clot.
o Remember that thrombin feed back into the INtrinsic pathway; if that kept happening, then the clot would just continue to grow and spread
o So the fibrin fibers will absorb the excess thrombin to prevent the spread of the clot and keep it localized
just to the damaged tissue
How does Antithrombin III help prevent coagulation in normal BV?
• Antithrombin III: an endogenous substance that combines with and inactivates thrombin
o It also removes Factors VII, IX, X, XI, XII (with the endogenous heparin)
How does endogenous heparin help prevent coagulation in normal BV?
• Endogenous heparin
o Synthesized and secreted by mast cells and basophils
§ Mast cells are responsible for secreting heparin in the tissue spaces
§ Basophils secrete the heparin into the blood; basophils are located within BVs
o Neg. charged polysaccharide, which combines with Antithrombin III and increases effect by
100 – 1000 X to inactivate thrombin
o Removes Factors VII, IX, X, XI, XII
Endogenous heparin is synthesized and secreted by what kind of cells?
mast cells and basophils
Q: If I give to much heparin or I want to reverse the heparin at the end of a case; what do I use to reverse
heparin?
A: PROTAMINE:
§ It neutralizes it; heparin is a strong acid, protamine a base
§ Must give protamine on a weight−by−weight basis according to how much heparin you gave;
protamine alone is an anticoagulant
Q: What if someone has a warfarin overdose; what do you give to reverse?
A: Vitamin K; there is a formula that will tell you how much Vit K to give based on the warfarin levels
When we think of HEPARIN we want to associate it with the _____ pathway; and warfarin with the
_____ pathway.
- Intrinsic
- Extrinsic
What clotting factors are inhibited by Heparin?
ACTIVATED FACTOR VII ACTIVATED FACTOR IX ACTIVATED FACTOR X (ALSO INHIBITED BY LOVENOX) FACTOR XI FACTOR XII THROMBIN
• As you can see, heparin acts on the ACTIVATED factors whereas warfarin acts on the factors BEFORE
they become activated
• Heparin also works on Factors XI and XII
What clotting factors are inhibited by Warfarin?
FACTOR VII
FACTOR IX
FACTOR X
PROTHROMBIN
• As you can see, heparin acts on the ACTIVATED factors whereas warfarin acts on the factors BEFORE
they become activated
• Heparin also works on Factors XI and XII
Platelet count?
-measures platelet concentration in blood
-150,000 – 450,000/μL
o Just because someone has an adequate number of platelets doesn’t mean that person has adequate
platelet function
o there are many people who have adequate platelets but they have a deficiency of a certain receptor or a
dysfunction of a certain receptor on the platelets which causes those platelets to be dysfunctional
o Even though they have an adequate number, they are not going to work properly
o EX: When I patient’s lab values are WNL and the competent surgeon says, “this patient is oozing”.
Prothrombin time?
o Assesses the extrinsic and the common pathway
-11 – 16 sec. (compared with International Normalized Ratio [INR])
What drug did I say affects the EXtrinsic pathway?
WARFARIN
o WARFARIN = PT
INR?
§ If a patient’s INR is 1; that patient’s PT is equal to the INR for NORMAL
§ 2 = 2x the standard for normal; and so on
§ Used to standardize PT levels from one lab to another
§ Different goals for INR levels based on patient’s reason for being on warfarin; a−fib, prosthetic
valve, etc
• Activated partial thromboplastin time?
o Used to assess heparin
o Measures the INtrinsic and common pathway
D-dimer test
o Measure of fibrin breakdown; degradation products
o After a clot has been formed, it then gets lysed; this measure those degradation products
What does a positive D-dimer test mean?
o If the D−dimer is POSITIVE, that is suggestive of an increase or excessive fibrinolysis and/ or
coagulopathy
Q: What do we use a D−dimer test to look for?
A: PEs; DIC
ACTIVATED PARTIAL THROMBOPLASTIN TIME (APTT)?
- measures intrinsic and common pathway
- 26 – 42 sec
PLASMA FIBRINOGEN?
-assesses plasma level of the precursor of fibrin.
adequate level needed for normal clot formation.
-200 – 400 mg/dl
What is DISSEMINATED INTRAVASCULAR COAGULATION(DIC)?
o Initially, procoagulants predominate until they are consumed faster than they are synthesized, then
anticoagulants predominate
§ Hence, the paradox of widespread, extensive blood clotting and then widespread, extensive bleeding
o An acquired clinical syndrome with manifestations the result of increased protease activity in the blood
caused by unregulated release of thrombin with subsequent fibrin formation and accelerated fibrinolysis
o May be localized to one organ or may be generalized
There are many predisposing conditions that may cause DIC…what is the most common one?
o Infection (most common cause, especially
gram-negative septicemia, but also grampositive
septicemia, fungal infections, protozoal infections, and viral infections)
§ Gram neg bacteria septicemia causes DIC from the endotoxins
§ When the bacteria is lysed, the endotoxins is released into the body fluid
§ Those endotoxins increase all the inflammatory immune response
o Cardiopulmonary arrest
§ The longer the arrest is, the greater the chance the pt will develop DIC
How is DIC managed in the OR setting?
o Remove/treat underlying causes
o Talk to the surgeon and discuss importance of the surgery
o Restore balance between coagulation and fibrinolysis
§ Heparin (use in DIC is very controversial, and currently not usually done)
v If you prevent the initial clotting you can prevent the using up of clotting factors that lead to the
sequence of events that lead to DIC
§ Platelet transfusions
§ Fresh frozen plasma, cryoprecipitate, packed RBCs to replace clotting factors
§ Antithrombin III
v Same as heparin above…
o Maintain organ viability
LABORATORY RESULTS TYPICAL OF DIC
• Bleeding time?
-increased
o All of their coagulation factors have been used up
LABORATORY RESULTS TYPICAL OF DIC
• Platelet count?
-decreased
o All the platelets are being used up
LABORATORY RESULTS TYPICAL OF DIC
• Plasma fibrinogen?
-decreased
LABORATORY RESULTS TYPICAL OF DIC
• Fibrin degradation products?
-increased
o Because of widespread clotting and widespread lysis of those clots
LABORATORY RESULTS TYPICAL OF DIC
• D-dimer test?
-increased
LABORATORY RESULTS TYPICAL OF DIC
• Prothrombin time/INR?
-increased
LABORATORY RESULTS TYPICAL OF DIC
• APTT?
-increased
LABORATORY RESULTS TYPICAL OF DIC
• Clotting factors II, V, VII, X?
-decreased
o These factors are being consumed faster than the liver can produce them
ANESTHESIA IMPLICATIONS
• Platelets?
o Does not have to be ABO compatible
o Never slam platelets in a patient or put in a cooler
o Transfusion depends on both quantitative and qualitative measures.
§ Stable patients w/o evidence of bleeding
v 1 blood volume)
v
ANESTHESIA IMPLICATIONS
• Fresh Frozen Plasma?
o Contains all the factors involved in coagulation
o Must be ABO compatible because of the antibodies
o Indications include:
§ Correction of inherited factor deficiencies when there is no specific factor concentrate (e.g., factor V) and when the PT or aPTT is >1.5 times normal
§ Correction of acquired factor deficiencies w/ clinical evidence of bleeding or in anticipation of major surgery
v Liver disease
v DIC
v Massive transfusion
o Reversal of vitamin K antagonists (warfarin)
ANESTHESIA IMPLICATIONS
§ Cryoprecipitate?
• Contains fibrinogen, vWF, factor VIII, and factor XIII
• Indications include:
§ DIC w/ fibrinogen
What is an Antigen?
- ANY substance that can elicit an immune response
- Can be an exogenous substance that enters the body
- Can be an endogenous substance
- Usually a protein
- Can also be polysaccharides or lipids or toxins secreted by microorganisms
- ANYTHING WHATSOEVER THAT INDUCES AN IMMUNE RESPONSE IN THE HOST
- All living cells express antigens on their cell membranes (antigenic)
All living cells express antigens on their _____ _____.
- cell membranes; so all living cells are antigenic.
Projections coming off of that are antigenic
determinants aka _____?
-epitopes.
o Don’t confuse epitopes with idiotypes (will be
talked about later)!
o Epitopes deal with antigens. Idiotypes deal with
antibodies.
• Each antigen has many different epitopes on the
surface. Each epitope on the surface of the antigen
can elicit a different effect on the immune system. So
each antigen has multiple implications for the
immune system based on which epitopes are on the surface.
What is an Epitope?
-AKA Antigenic Determinants
-Part of an antigen that is recognized by the immune system
-Specifically by:
*Antibodies
*B Cells
*T Cells
-Specific piece of the antigen that the antibody binds to
-Usually Non-self proteins (except in autoimmune disorders)
-Each antigen usually has many different epitopes on cell surface
-Each epitope can elicit a different arm of the immune system
What are the purposes of Antigens?
- Genetically determined through gene (DNA) inheritance
- Used as Cell markers
- Differentiation of self from non-self
- Normally, self antigens do not activate the person’s immune system (except autoimmune disease: DM type I, Lupus, Hashimato’s thyroiditis, etc.)
- Non-self (foreign) antigens can activate the immune system in an attempt to destroy the antigen:
- Microorganisms (bacteria, fungi, viruses)
- RBC antigens
- Transplant antigens (transplant tissue from one individual to another, need to make sure match)
What’s the significance of a person’s RBC ABO antigen?
o Each person inherits genes from each parent to determine that person’s ABO antigen profile or blood
type
What’s the significance of a person’s RBC Rh antigen?
o Also inherited from parents
o No naturally occurring antibodies for Rh antigen
o Antibodies only developed when Rh – individual is exposed to Rh +
§ Example: Pregnancy; not with first baby, see it with the 2nd baby. When mom is Rh - & fetus is Rh +
à mother develops antibodies that aren’t a problem for the 1st baby, but with the 2nd baby those
antibodies attack the fetus.
o Rh + : About ___ of people inherit the Rh gene and express this antigen on their RBCs
85%
o Rh - : About ___ of people do not inherit the Rh gene and do not express the antigen on their RBCs
15%
Where are the antibodies found in blood?
-plasma
Type A blood type.
- Antigen A on RBC
- Anti-B antibody in plasma
- Can receive Type A and O
Type B blood type.
- Antigen B on RBC
- Anti-A antibody in plasma
- Can receive Type B and O
Type AB blood type.
- Antigens A and B on RBC
- Neither Anti-A nor Anti-B antibodies found in plasma
- Can receive Type A, B, AB, or O
**AB+: universal recipient…can receive any blood
o Pt with type AB blood don’t have the anti-A or anti-B antibodies in their blood à so don’t have antibodies in plasma portion of blood to amount an immune response against any blood cell type.
Type O blood type.
- Neither antigen A nor B on RBC
- Anti-A and Anti-B antibodies found in plasma
- Can receive Type O only
**O-: Universal donor…any blood type can receive it
• Blood type O can only receive O, bc have both anti-A & anti-B antibodies in their plasma à so will have an immune response against A, B or AB type blood.
Describe Plasma Donor-Recipient Compatibility
- Type O recipient is the universal recipient: can receive FFP from each blood type
- Type A can receive from A and AB
- Type B can receive from B and AB
- Type AB can only receive from AB
- Type AB is the universal donor of FFP
**Plasma contains ANTIBODIES
• These are opposite of what you can receive of RBCs.
• So in this instance O is universal recipient & AB is universal donor that bc the plasma contains the
antibodies.
• Think carefully about this bc now transfusing antibodies into someone. We’re transfusing antibodies, not
antigens! If we’re transfusing plasma that has antibodies in it, we don’t want to transfuse antibodies into
someone that would amount an immune response against that persons own RBC antigens. If giving RBCs,
I’m giving antigenic material to someone, where their own antibodies may amount an immune response
against the RBC antigens that are being transfused.
Describe MHC’s.
- Major Histocompatibility Complex (MHC) Antigens
- AKA: Human Leukocyte Antigens (HLA’a)
- Each person inherits 6 MHCs from each parent = total 12 MHCs in each person
- The MHCs are divided into class I and II
- MHCs are expressed on all nucleated body cells
- Allows immune system to differentiate self from non-self antigens
- Self antigens normally do not activate immune response while non-self antigens do activate an immune response
Class I MHC’s.
- Designated MHC-A, B, or C (based on chromosomal location)
- Expressed on all nucleated body cells
- Combine w/ intracellular antigens (once the antigen is ALREADY IN THE CELL, THE CELL IS ALREADY INFECTED) to form a complex that is displayed on the cell’s surface
- Class I MHC/foreign antigen complex prompts the immune system to destroy the displaying cell
- Mainly interact with cytotoxic (CD8+) T cells
- Endogenous pathway
Class II MHC’s.
- Designated MHC-DP, DQ, or DR (based on chromosomal location)
- Expressed on antigen-presenting cells (B cells, macrophages, monocytes, dendritic cells)
- Antigen-presenting cells > endocytosis of foreign antigens> antigens broken down and combine with class II MHCs> class II MHC/antigen complex presented to other immune cells
- Mainly interact with helper (CD4+) T cells
- Exogenous pathway
§ different from class I which respond to cells that are already infected and have antigens on the inside
Describe Antibodies.
- AKA Immunoglobulins (Ig)
- Proteins with MW 150,000-900,000 daltons
- Produced by PLASMA CELLS (plasma cells originate as B-lymphocytes) in response to antigens
- Produced in response to foreign antigens
- Each antibody is antigen specific
B-lymphocytes DO NOT produce antibodies…they differentiate into plasma cells, and the PLASMA cells produce antibodies
- Composed of 2 heavy chains and 2 light chains
- Constant regions of light and heavy chains (that part of the antibody is the same on EACH antibody…its constant!)
- Variable regions of light and heavy chains (different on each antibody, depending on specific antigen that it was made for)
- Antigen binding sites located in variable region (specific for certain antigen)
Five classes of Antibodies (Immunoglobulins Ig).
- IgG
- IgM
- IgA
- IgE
- IgD
Describe antibody IgG.
- Gamma globulin
- 75% of all antibodies
- Activate complement system and promotes phagocytosis
- SECOND antibody to respond to antigens
- Respond to bacteria, viruses, parasites, fungi, and toxins
- Can give as infusion to immune compromised patients
Describe antibody IgM.
- Largest size antibodies
- FIRST antibody to respond to antigens
- Function similar to IgG
- Responsible for blood transfusion reactions
Describe antibody IgA.
- Second most abundant antibodies
- Activates complement system
- Present in body secretions (saliva, nasal secretions, vaginal, urethral…)
Describe antibody IgE.
-Major antibodies in allergic and inflammatory responses
Describe antibody IgD.
-Function as antigen-binding receptors on B cells
Organs of the Immune System: Lymphatic System(what organs are included and their 3 functions)
- Includes: lymph, lymphatic vessels, lymphatic tissue, lymphatic nodules, tonsils, spleen, and thymus
- 3 main function:
1. Fluid balance
2. Lipid absorption
3. Defense
Lymph Node.
- Afferent lymphatic vessel carrying lymph to the lymph node (originates: terminal lymphatic vessels that constantly suck fluid (3 mm/Hg) from interstitial space)
- Efferent lymphatic vessel carrying lymph away from the lymph node > another lymph node > another lymph node, etc. > eventually lymph empties back into the subclavian veins
- Lymph nodes are in sequence, providing great filtering
- Major storage sites for WBC’s
Where is the most extensive area of lymph nodes located in the body?
abdomen
Thymus.
- Where T lymphocytes are processed and mature
- Functional until about age 20, then atrophies and loses function over time
Spleen.
- Site for WBC storage
- When the body undergoes acute infection/inflammatory process, the spleen contracts and expresses the WBC’s out into the circulation
Cells of the Inflammatory-Immune systems: WBC’s (Leukocytes)…Polymorphonuclear Granulocytes
- Neutrophils:
- Majority of leukocytes (50-75% WBC’s)
- Produced in bone marrow
- Very good PHAGOCYTOSIS of foreign microorganisms, cellular debris, antibody primed foreign matter
- Release chemotactants which attract other WBC’s
- Release pyrogens which induce fever - Eosinophils:
- Primarily allergic reactions and parasitic invasion - Basophils:
- Found in blood stream
- Similar function of mast cell found in tissues
- Secrete histamine and heparin
Cells of the Inflammatory-Immune systems: WBC’s (Leukocytes)…Lymphocytes
- B-Lymphocytes
- Produced in the bone marrow
- Transform into plasma cells, and its PLASMA cells which secrete antibody
- Responsible for humoral immunity (antibody-mediated immunity)
- Memory B lymphocytes are stored in lymphoid tissue and respond rapidly to subsequent exposure to the same previous antigen - T-Lymphocytes
- Initially produced in bone marrow, then mature in thymus and other lymphoid tissue
- Responsible for cell mediated immunity
- Secrete cytokines (biochemical mediators that are involved in inflammation and immunity)
a. Helper (T4/CD4) cells initiate B lymphocyte response
b. Cytotoxic (T8/CD8) cells destroy foreign antigens directly
c. Memory T cells are stored in lymphoid tissue and respond rapidly to subsequent exposure to the same antigen
d. Suppressor T cells (regulator T cells) slow down or stop immune response
- Monocytes:
- Produced in the bone marrow
- Tiny antigen-presenting cells, squeeze through capillaries and pores
- After leaving the vascular system, transformed into tissue macrophages
Cells of the Inflammatory-Immune systems: Derivatives of WBC’s…Macrophages.
Macrophages:
- Transformed from monocytes
- PHAGOCYTOSIS of foreign microorganisms and cellular debris
- Compose the tissue macrophage system (macrophages placed in strategic areas of the body, such as liver kupffer cells, or in the alveoli, or microglia cells in nervous system)
- Antigen-presenting cells (present processed antigens to T lymphocytes)
Cells of the Inflammatory-Immune systems: Derivatives of WBC’s…Mast Cells
- Possibly derived from basophils
- Found in tissues surrounding blood vessels
- Functionally similar to basophils
- Secrete HISTAMINE and HEPARIN in response to interactions with complement proteins and IgE
Cells of the Inflammatory-Immune systems: Derivatives of WBC’s…Natural Killer Cells.
- Function is similar to cytotoxic T cells
- Respond to tumor formation and virally infected cells
Cells of the Inflammatory-Immune systems: Derivatives of WBC’s…Plasma Cells.
- Derived from B-lymphocytes
- Secrete antigen-specific antibody
What is the stem cell that all blood cells originate?
Pluripotential Hematopoietic Stem Cell (PHSC)
What is created from the PHSC with the Myeloid precursor pathway?
- RBCs
- Platelets
- Granulocytes (Neutrophils, Eosinophils, Basophils, and Mast cells)
- Monocytes > Macrophages
What is created from the PHSC with the Lymphoid stem cell pathway > Thymus?
-Activated T lymphocytes (Helper T4 cells, Cytotoxic T8 cells, Memory cells, and Suppressor cells)
T or F: During fetal development, T lymphocytes are processed in the Thymus. Billions of T lymphocyte clones are laid down in lymphatic tissue.
- True
- Theoretically, there is a clone of T lymphocyte for any antigen that you might come into contact with
- Called T lymphocytes, because they are processed in Thymus
What is a clone of T lymphocyte?
- Group of cells that are antigen specific
- That clone will then recognize the antigen and further activate the subtypes of T lymphocytes (helper, cytotoxic, memory, and suppressor)
What is created from the PHSC with the Lymphoid stem cell pathway > Human Bursa Equivalent?
- B lymphocytes
- Processed in human bursa equivalent (probably liver and some lymphatic tissue in fetus)
- Clones of B lymphocytes are stored in lymphatic tissue
- When foreign antigen enters, and activates a clone of B lymphocyte, it initiates the formation of plasma cells and then the antibody response (specific for antigen)
Describe Biochemical Mediators.
- Promote inflammation by causing:
- vasodilation
- vascular permeability
- attracting WBCs
- stimulating phagocytosis
- Histamine
- Bradykinin
- Eicosanoids
Histamine pathway.
- Cellular destruction/inflammation
- Activation of Mast cells/Basophils
- Mast cells produce histamine in tissue spaces/basophils intracellular
- Histamine acts on histamine receptors (histamine-1, and 2)…Histamine-1: vascular smooth muscle
- Histamine-1 causes local vasodilation, increased vascular permeability
**Think nose: because of histamine activation, nasal vasculature is dilated, more permeable, fluid serum escapes, RUNNY NOSE
Bradykinin pathway.
- Cellular destruction/inflammation
- Activates clotting factor XII
- Activates the inactivated enzyme (Kallikrein)
- Active Kallikrein activates Kininogen (protein)
- Active Kininogen turns into Kinins (ex. Bradykinin…most popular)
- Bradykinin responsible for local vasodilation, increased vascular permeability, and chemotaxis (attraction of WBCs)
- Bradykinin also plays a major role in stimulation of pain receptors in the area of injury
Eicosanoid pathway.
-A group of biochemical mediators
- Stimuli (physical, chemical, hormonal, neuronal) activates the enzyme Phospholipase A2 (inhibited by glucocorticoids)
- Phospholipase A2 converts fatty acid in cell phospholipid bilayer into arachidonic acid
- Arachidonic acid can take two different pathways: lipoxygenase and cyclooxygenase
a. Lipoxygenase:
- lipoxygenase converts arachidonic acid into leukotrienes
- leukotrienes are secreted from following sites: leukocytes, mast cells, platelets, lung and heart vascular tissue)
- leukotrienes promote inflammation, cause smooth muscle contraction, chemotactants, and increase vascular permeability
b. Cyclooxygenase:
- Cyclooxygenase (inhibited by ASA and NSAIDs) converts arachidonic acid into various prostaglandins and thromboxanes
- Prostaglandins, multiple effects: ex. vasodilation
- PGI2 (prostacycline): promotes platelet anti-aggregation
- Thromboxane A2 (TxA2): promotes platelet aggregation and VERY POTENT vasoconstriction
What drug given would have the most widespread anti-inflammatory effects? Inhibition of phospholipase A2, cyclooxygenase, or lipoxygenase?
- Phospholipase A2
- Decadron, prednisone, etc.
Examples of other Cytokines: Interferons.
- Enhance Natural killer (NK) cell activity
- Induce Human leukocyte antigen (HLA) expression
Examples of other Cytokines: Tumor necrosis factor.
- Enhances coagulation
- Extremely pro-inflammatory and pro-catabolic
Examples of other Cytokines: Macrophage-migration inhibition factor
-Inhibits migration of macrophages away from antigen site
Examples of other Cytokines: Colony stimulating factors.
- Promote growth of pluripotential hematopoetic stem cells (PHSCs) and Colony forming units (CFUs) for various leukocyte lines
- Speeds up process of formation of WBCs
Examples of other Cytokines: Interleukins-1, 2, 3, 4, 5, 6, etc…
-Promote development and differentiation of T and B lymphocytes.
Complement System.
- Composed of about 20 proteins
- Normally inactive
- What activates them determines which pathway they take
- Classical pathway: begins when antibody binds w/ antigen
- Alternative pathway: begins when protein C3 becomes active (C3 becomes active by either classical pathway becoming active, or foreign substances, or couple endogenous factors)
- All the complement proteins in the complement cascade promote:
- phagocytosis
- inflammation
- chemotaxis
- They also all form a membrane attack complex: will drill holes in membrane of foreign material, allowing water to rush into cell and lysis the foreign cell body
Complement system: Classical pathway.
- Initiated when Antigen binds with Antibody > forms complex
- That complex activates protein C1 > activates protein C4 > activates protein C2 > activates protein C3
- Then C5, 6, 7, 8, 9
Complement system: Alternative pathway.
- Initiated by foreign substances and endogenous proteins: factors B, D, and P
- Stabilization of activated C3
- Then C5, 6, 7, 8, 9
Inflammatory Response.
- NONSPECIFIC response to cell damage
- May or may not involve foreign antigens
- if you have a heart attack, there is an inflammatory response, no antigens need to be present
T or F: You can have an inflammatory response without an immune response, but you can’t have an immune response without an inflammatory response.
-True
Sequence of events in Acute Inflammatory Response.
Cellular damage > release of biochemical mediators (histamine, kinins, eicosanoids, complement (alternative b/c no antigen/antibody)) > tissue macrophages migrate to area of injury (1st line of defense) > Phagocytosis of microorganisms and cell debris
release of biochemical mediators > migration and diapedesis of neutrophils into interstitial/tissue space > cause chemotaxis and ameboid motion (then neutrophils become primary defense…good at phagocytosis) > phagocytosis of microorganisms and cell debris > also after chemotaxis, monocytes are attracted and migrate from capillaries > once moved from vascular to tissue, they differentiate/become macrophages > they phagocytose microorganisms and cell debris
release of biochemical mediators > vasodilation and increased vascular permeability > fluid and proteins (fibrinogen) leak into tissues > cellular edema and fibrin mesh formation > walling off effect > decreased spread of microorganisms and toxins
What is diapedesis?
-When WBC will move from vascular compartment through the capillary space and forced into the interstitial compartment
Immune response.
- SPECIFIC response to exogenous or endogenous antigens
- Involves T- and B-lymphocytes
- B lymphocytes > plasma cells > antibodies respond to antigens in the body fluids
- Cytotoxic T-lymphocytes respond to antigens inside body cells
- Once activated, the T and B lymphocytes produce memory cells (laid down in lymphatic tissues) and that provides long-lasting immunity against the specific antigen
How does a macrophage recognize, process, and present foreign antigens to helper T-lymphocytes?
-They phagocytose foreign antigen > processes and combines with class II MHC > MHC class II/foreign antigen complex presented on cell surface of macrophage > stimulates other immune cells (they identify the foreign antigen), specifically the helper T-cell (CD4) > T-cell attaches to the above complex >
Macrophage will secrete cytokines, specifically interleukin-1 > interleukin-1 will costimulate the helper t-cell via cytokine receptor located on helper t-cell
Helper t-cells also secrete interleukin, specifically interleukin-2 > actually binds to receptors on the helper t-cell that secreted it (auto-receptors) > causes helper t-cell to multiply and divide
Helper t-cells can be stimulated to divide again or can stimulate B cells or differentiate into effector/memory T cells > memory t-cells laid down in lymphatic tissue for future
Activation and proliferation of Cytotoxic T-Lymphocytes, recognition, and response to infected body cells.
Non-macrophage cell is infected (antigen is already within the cell) > antigen is processed > processed antigen combines with MHC class I > cell presents this complex on outside of cell membrane > stimulates cellular destruction (normally only foreign antigen/MHC class I complex, not self-antigen/MHC class I complex)
MHC class I/processed antigen complex presented on cell membrane > initiates cytotoxic t-cell (CD8) response > helper t-cells already have secreted interleukin-2 that caused t-cells to divide > interleukin-2 also causes cytotoxic t-cells to divide, creating daughter t-cells so they can respond to more infected cells and also create memory t-cells > memory t-cells lay down in lymphatic tissue for future response
Activation of a cytotoxic T-cell by antigens on the surface of a cell > divides and forms more cytotoxic t cells and memory t cells > cytotoxic t-cells will release cytokines > cytokines will promote inflammation, phagocytosis, and activate more t-cells > the t-cells themselves cause active lysis of the infected cells when bound to infected cell
B-Lymphocyte recognition and processing of antigens, proliferation, antibody production, and response to antigens.
*B-cells are antigen-presenting cells
Unprocessed antigen > b-cell processes it and presents it along with MHC class II > stimulates the helper T-cells > helper t-cell secretes interleukins 4,5,6 > interleukins 4,5,6 stimulate B-cell reproduction > b-cells multiply and divide > are able to respond to more antigens > then either become memory B-cells (laid down in lymphatic tissue for future) or they differentiate into plasma cells > plasma cells produce the antibodies specific to the antigen that started the process
Outcomes of when an Antigen binds with an Antibody.
Antigen binds with antibody > inactivates antigen > then agglutination/clumping of antigens > makes it easier for macrophages and other phagocytes to phagocytose those antigen/antibody complexes
Antigen binds with antibody > activates the complement cascade (classical pathway) > activates inflammation, chemotaxis, and lysis of cells
Antigen binds with antibody > enhances almost all inflammatory processes, esp. mast cells and basophils > causes them to release histamine > promotes more inflammation
Primary response to a specific antigen
- First response of the body’s exposure to the antigen
- Longer response time (3-14 days) for initial response
- Weak magnitude of response due to:
- fewer B-cells
- fewer plasma cells
- fewer antibodies
Secondary response to a specific antigen: role of memory B-lymphocytes.
- Second exposure to body of antigen
- Memory B-cells lie latent in lymphatic tissue
- Response is MUCH shorter (hours to a few days)
- Magnitude of response is MUCH greater
- Antibody titers higher due to increased B-cells > plasma cells > antibodies
Summary of interactions between T-Lymphocytes and B-lymphocyte/antibody responses to an antigen.
Foreign antigen > processed by macrophage > macrophage presents processed antigen to helper T cells > helper T cells proliferate and secretes cytokines > cytokines enhance inflammation and phagocytosis
Helper T cells also divide into other helper t-cells > they can activate a B-cell or a cytotoxic T-cell
Cytotoxic T-cell will proliferate further > differentiates into either more cytotoxic t-cells or memory t-cells > cytotoxic t-cells cause lysis of cells expressing antigen
B-cells activated by helper t-cells > proliferate and differentiate into either plasma cells producing antibodies or into memory B-cells
**Memory B-cells and T-cells are responsible for long-term Adaptive immunity
Types of Immunity: Innate (natural)
- Species specific
- Intact skin
- IgA and enzymes in saliva, tears, perspiration
- Acid of stomach
- GI tract enzymes and IgA
- Neutrophils and macrophages phagocytosis
- Complement alternative pathway
- Interferons
- Natural antibodies
- Natural Killer Cells (NKCs)
- Various cytokines
Types of Immunity: Acquired
- Requires exposure to antigen
- Immunity develops SPECIFIC to each antigen
- Memory T-lymphocytes
- Memory B-lymphocytes/Antibodies
- Two-types:
- Passive (the person becoming immune did not form the antibodies on their own, such as mother to fetus, transfusion of antibodies)…short-term, maybe a few weeks
- Active (individual develops antibodies on their own)
- -Natural: antigen enters naturally, body responds by producing antibodies
- -Artificial: immunizations
Halting the immune response.
- Elimination of foreign antigen
- Suppressor/regulatory T-lymphocytes
- Feedback inhibition
- Idiotypes-antiidiotypes-antiantiidiotypes-antiantiantiidiotypes, etc. (when plasma cell produces an antibody, a part of the antibody is an idiotype…idiotype is viewed as a foreign antigen…body produces antiidiotype inresponse…antiidiotype is also viewed as foreign antigen so the body produces an antiantiidiotype…
Anesthesia implications: Hypersensitivity reactions…TYPE I (ALLERGY)
- IgE mediated
- ANAPHYLAXIS, asthma
- MOST FREQUENTLY ENCOUNTERED DURING ANESTHESIA
Anesthesia implications: Hypersensitivity reactions…TYPE II (CYTOTOXIC)
- IgG, IgM, Complement mediated
- ABO incompatibility
Anesthesia implications: Hypersensitivity reactions…TYPE III (IMMUNE COMPLEX)
- IgG, Complement, Neutrophil mediated
- Rheumatoid arthritis, systemic lupus erythematosus AUTOIMMUNE TYPE REACTIONS
Anesthesia implications: Hypersensitivity reactions…TYPE I (ALLERGY)
- IgE mediated
- ANAPHYLAXIS, asthma
- MOST FREQUENTLY ENCOUNTERED DURING ANESTHESIA -Most common offending drug class: Non-depolarizer paralytics
Anesthesia implications: Hypersensitivity reactions…TYPE IV (CELL-MEDIATED)
- T-cell mediated
- Multiple sclerosis
Anesthesia implications…Hypersensitivity reactions
- Allergic reactions occur once every 5000-25000 anesthetics
- Mortality: 3.4%
- 3 minute time frame for intervention
- Most common life-threatening manifestation: CV collapse, hypotension
- Most common offending drug class: Non-depolarizer paralytics
Anesthesia implications: Identification of anaphylaxis
Respiratory: wheezing, increase peak airway pressures, decrease pulmonary compliance
CV: hypotension, tachycardia, decrease SVR, arrhythmias
Cutaneous: urticaria, generalized edema
Anesthesia implications: Management of anaphylaxis
-Plan must be established before the event occurs
Primary treatment:
- Stop administration of offending agent
- Maintain airway and administer 100% O2
- Discontinue anesthetic agents
- Intravascular volume expansion
- Epinephrine
Secondary treatment:
- Diphenhydramine
- Bronchodilator
- Corticosteroids
What is the difference between the intrinsic and the extrinsic clotting pathways?
v Its called extrinsic because the damage is EXTERNAL to the BV
v Once tissue is damaged, that causes the release of thromboplastin; released from the traumatized tissue
v Thromboplastin along with Factor VII and Ca ions activate Factor X
v Activated Factor X, Factor V, platelet phospholipids, and Ca ions activate prothrombinase (the final outcome of step 1 of the coagulation pathway.
o WARFARIN = PT
§ INtrinsic (contact activation) pathway
v Damage is within the BV
v When the BV is injured that activates Factor XII; Activated Factor XII then will activate Factor
XI
v Activated Factor XI along with Ca ions activates Factor IX
v Activated Factor IX along with factor VIII, platelet phospholipids and Ca will activate Factor X
v Activated Factor X along with Factor 5, platelet phospholipids and Ca will activate
prothrombinase
What initiates extrinsic as opposed to what initiates the intrinsic clotting pathway?
Extrinsic:
v Its called extrinsic because the damage is EXTERNAL to the BV
v Once tissue is damaged, that causes the release of thromboplastin; released from the traumatized
tissue
Intrinsic:
v Damage is within the BV
v When the BV is injured that activates Factor XII; Activated Factor XII then will activate Factor
XI
How might hypocalcemia affect the clotting cascade?
§ You can see here that Ca plays an important role in both the intrinsic and extrinsic coag pathways
v If you have low levels of extracellular Ca, that is going to affect your ability to clot
EXTRINSIC: Thromboplastin along with Factor VII and Ca ions activate Factor X
v Activated Factor X, Factor V, platelet phospholipids, and Ca ions activate prothrombinase (the
final outcome of step 1 of the coagulation pathway.
INTRINSIC:v Activated Factor XI along with Ca ions activates Factor IX
v Activated Factor IX along with factor VIII, platelet phospholipids and Ca will activate Factor X
v Activated Factor X along with Factor 5, platelet phospholipids and Ca will activate
prothrombinase
If a patient has a bowel prep preoperatively which significantly reduces the bacteria in their GI system(specifically ecoli), what kind of implications can that have on the clotting cascade?
§ Vit K dependent coagulation factor
§ Vitamin K required for normal activation of
prothrombin (also required for liver synthesis of
Factors VII, IX, X)
v Sources of vitamin K: diet and synthesis by E. coli
in colon
Which lab monitors heparin?
activated PTT
Which labs monitor warfarin?
PT/INR
What alterations in lab values would you see for DIC?
• BLEEDING TIME: INCREASED
o All of their coagulation factors have been used up
• PLATELET COUNT: DECREASED
o All the platelets are being used up
• PLASMA FIBRINOGEN: DECREASED
• FIBRIN DEGRADATION PRODUCTS: INCREASED
o Because of widespread clotting and widespread lysis of those clots
• D-DIMER TEST: INCREASED
• PROTHROMBIN TIME/INR: INCREASED
• APTT: INCREASED
• CLOTTING FACTORS II, V, VII, X: DECREASED
o These factors are being consumed faster than the liver can produce them
What are some clinical signs of DIC?
o Hemorrhage from venipuncture sites, vascular lines, and surgical incisions
o Ecchymoses and hematomas
o Bleeding into and from eyes, nose, bums
o Microvascular and macrovascular occlusions and organ system dysfunction: cardiovascular, pulmonary,
central nervous system, renal, hepatic
Is an MI an immune response or an inflammatory response?
Inflammatory…..no antibodies produced
What types of cells produce antibodies?
plasma cells
If someone has a major anaphalxis reaction is that a primary or a secondary immune response?
Usually secondary that person has laid down memory B and memory T lymphocytes and on secondary exposure the WBC mount the response
What determines antigen antibody specificity?
Antibody biding site is antigen specific
What type of WBC is responsible for long term immunity?
Memory B cells and Memory T cells
Is Thromboxane A2 a potent vasodilator or a potent vasoconstrictor?
§ Thromboxane A2 promotes plt aggregation &
vasoconstriction
If I wanted to give one drug that had the most widespread anti-inflammatory effects would I give something
that inhibited lipoxygenase, cyclooxygenase or phospholipase A2?
Phospholipase A2; decadron &
prednisone are such great anti-inflammatory drugs à they are more powerful than an NSAID bc they can
stop inflammatory process from the beginning.
What is the difference between natural(innate) immunity and acquired immunity?
AQUIRED:
• Requires exposure to antigen
• Immunity develops specific to each antigen
àinnate is more generalized; acquired is more
specific to each antigen
• Memory T-lymphocytes à memory T & B
lymphocytes are laid down in lymphatic tissues &
respond to those antigens
• Memory B-lymphocytes/Antibodies
• Two-types
o Passive à person that’s becoming immune didn’t form the antibodies on their own; ex: mother to fetus; admin of IgG to pt. Short term process; lasts couple wks-months
o Active à person develops antibodies on their own; this type of immunity lasts longer
§ Natural à an antigen enters body & respond by producing antibodies
§ Artificial à ex: immunization; artificially inject an antigen to initiate an immune response, producing memory cells that can respond to antigen if exposed to it again.
INNATE:
• Species specific à why humans can get infection
that isn’t transmittable to dogs
• Intact skin à prevent microorganisms from
entering the body
• IgA and enzymes in saliva, tears, perspiration
• Acid of stomach à most microorganisms cant
survive in stomach bc of low pH
• GI tract enzymes and IgA
• Neutrophils & macrophages phagocytosis
• Complement alternative pathway
• Interferons
• Natural antibodies
• NKCs
• Various cytokines
• Requires exposure to antigen
• Immunity develops specific to each antigen à
innate is more generalized; acquired is more
specific to each antigen
• Memory T-lymphocytes à memory T & B
lymphocytes are laid down in lymphatic tissues &
respond to those antigens
• Memory B-lymphocytes/Antibodies
• Two-types
o Passive à person that’s becoming immune didn’t form the antibodies on their own; ex: mother to fetus; admin of IgG to pt. Short term process; lasts couple wks-months
o Active à person develops antibodies on their
own; this type of immunity lasts longer
§ Natural à an antigen enters body & respond by producing antibodies
§
What are the different types of acquired immunity?
• Two-types
o Passive à person that’s becoming immune didn’t form the antibodies on their own; ex: mother to fetus; admin of IgG to pt. Short term process; lasts couple wks-months
o Active à person develops antibodies on their own; this type of immunity lasts longer
§ Natural à an antigen enters body & respond by producing antibodies
§ Artificial à ex: immunization; artificially inject an antigen to initiate an immune response, producing memory cells that can respond to antigen if exposed to it again
