HTHS Mod 15

• one component of cardio system (along w heart and vessels)
• Considered a connective tissue because:
• it has cells - WBC, RBC, platelets
• and an extracellular matrix - plasma
• *to be considered connective tissue: has cells & matrix (ground substance= plasma)& has fibers
• *the fibers aren't in the blood UNTIL the clotting mechanism is activated, then the proteins for clotting become fibers

• Very important part of maintaining homeostasis
• Transportation: oxygen, carbon dioxide, hormones and nutrients
• Regulation: body temp and pH
• Protection: resistance to diseases

• Viscosity
• Temp - (100.4°)
• pH
• Color - variable shades of red depending on O₂
• Volume - 4-6 L depending on person (gender and body mass)

it's thicker than water due to solutes, colloids, and suspended formed elements

• 45% - Cells, or more specifically formed elements = WBC, RBC, platelets
• 55% - Plasma - typically clear, yellow liquid

*called formed elements cause of platelets: they aren't cells, they are fragments of cells

• they are actually the remnants of cells
• *we have great big cells in bone marrow (megakaryocytes) which are too big to leave bone marrow. Therefore, when they implode and the cytoplasm breaks apart, it's the  cytoplasm fragments that become the platelets
• Thats why they are classified as formed elements

• 92% water, 8% solutes
• * 7 of the 8% are plasma proteins. The other 1% are misc solutes

• Many types that have individual functions, frequently as carrier molecules
• Collectively they contribute to osmotic balance
• Majority produced by hepatocytes, so liver problems can lead to plasma protein problems

• 54% albumins
• 38% globulins - named from "globe" like appearance
• 7% fibrinogen (clotting protein)
• 1% misc solutes: electrolytes, nutrients, gases, hormones, and waste products

• important type of globulins
• also called immunoglobulins or antibodies
• produced in response to organic molecules the body see's a foreign
• Serve as flags for immune system, so it knows what needs to be destroyed

• Platelets = 150-400 K
• WBC = 5 - 10 K
• RBC = 4.8 - 5.4 million
• *PER CUBIC millimeter (μL = microliter- is same thing)

-making

• general term for the development of the 3 types of formed elements of the blood:
• Leuko-poiesis = making WBC
• Erythro - poiesis = making RBC
• Thrombo - poiesis = making platelets (thrombo- meaning clots, so platelets make clots)

• happens in red bone marrow
• Formed from pluripotent stem cells and mature as either a myeloid or lymphoid stem cell, which is decided under the influence of various cytokines

• "pluri-" = many; "potent" = potential
• what all blood cells begin as, in the red bone marrow
• can be influenced by body to become any of the mature blood cells
• *In infants, all bones contain red bone marrow & are actively making formed elements. As person matured, red bone marrow in long bones is replace w yellow bone marrow (mostly adipose tissue)

• chemical signals from one cell that influences another
• act as small protein hormones to control cell growth and differentiation
• proliferation and maturation of blood cells depends on specific cytokines ~ cells differentiate into either myeloid group or lymphoid group

• EPO
• TPO
• Interleukins
• Interferon
• TNF
• CSF

• erythropoietin ~ type of cytokines
• increases # of early red blood cells in the bone marrow

• Thrombopoietin ~ specific type of cytokines
• increases the formation of platelets

• type of cytokines
• colony-stimulating factors
• increases production

• Cytokines btwn white blood cells
• *"inter" - "leukins"

• Cytokines which have anti-viral properties and stimulators of the immune system
• **Ferron battling viruses

• Tumor-necrosis factor
• type of cytokines
• Produced by macrophages to encourage inflammation
• **Think of the tumor as a zit...After you eat a big Mac,  You're going to squeeze the hell out of the zit cause its got inflammation n ready to pop

The group in which the immature myeloid (bone marrow) cells differentiate and become red blood cells, platelets, and many types of white blood cells

• The group in which immature lymphoid cells mature in the lymphatic system 
• give rise to a specific group of white blood cells called lymphocytes

• Are bi-concave discs (like donut but middle doesn't go all the way through) - gives high surface to volume ration
• Demonstrate reversible-deformity - able to squeeze through small spaces (capillaries) and snap back into shape
• Live 120 days
• *the bi-concave shape results through the loss of it's nucleus

• Loses it's nucleus and organelles - this provides max cytoplasmic space to carry O₂
• hemoglobin increases
• decreased cellular size
• *cause they lack mitochondria, they don't use any of the oxygen they carry. They utilize glycolysis to stay alive

• Carry oxygen
• If damaged, they are removed from circulation by phagocytic white blood cells, the spleen, and the liver

• the oxygen & CO₂  carrying molecule of red blood cell
• Makes blood red
• approx 280 million in each RBC
• Each consist of 2 main components: heme and globin
• each hemoglobin has 4 globin and 4 hemes
• Therefore, one red cell can carry 1.1 billion oxygen atoms

• a protein comprised in hemoglobin
• made up of 4 polypeptide chains; two alpha chains and two beta chains
• Each polypeptide chain has a heme molecule bound to it

• a ringed molecule with one iron (Fe²⁺) atom at the center
• Is the binding site for oxygen on hemoglobin
• Each Fe²⁺ can pick up one oxygen molecule at the lungs

• In the lungs, has a high affinity for oxygen; wants to pick it up and hold it
• At tissue level, has lower affinity for oxygen; so it wants to let go. That's when it can pick up CO₂ to transport it to lungs for exhale

• part of hematopoiesis, specifically production and maturation of RBC
• produced continuously

• means "in the blood"
• or emic

• by a reticulocyte (retic) count
• measured as they are coming out of the bone marrow

• results when the number of red blood cells lost exceeds the number made
• Therefore, too little oxygen in the blood
• *this lack of oxygen isn't from breathing problems, there just isn't enough red cells to transport the available oxygen around the body
• The decreased amount of oxygen stimulates the kidneys to secrete EPO

• erythropoietin = cytokine
• a hormone secreted by the kidneys when oxygen levels in blood become low
• circulates to red marrow and speeds up maturation and release of immature red cells

• an almost mature RBC
• still contains some mitochondria, ribosomes, and endoplasmic reticulum
• released into blood stream and will mature over next 1-2 days
• Normally, 0.5 - 1.5% of circulating red blood cells are reticulocytes

• hematocrit
• the % of a pt's whole blood that is occupied by red blood cells
• average is 45%, with men being a little higher and women being a little lower

• the presence of too many red blood cells
• can manifest as a primary or secondary disease
• Increases the blood viscosity

• also called primary polycythemia
• an abnormality of the bone marrow causing overproduction of red blood cells
• may also result in increase of white cells and platelets (so increase in formed elements)
• Biggest problem is it increases the viscosity of blood which can make the heart work harder and increase likelihood of clotting

• an increase in red cell numbers due to another condition
• *any stimulus that causes hypoxemia can cause the bone marrow to increase the production of red cells
• Ex: smoking, sleep apnea, prolonged exposure to low atmospheric oxygen, or heart disease

• type of secondary polycythemia which involves dehydration
• **When I go visit my "RELATIVE" in AZ I get dehydrated

• an insufficient amount of RBC's or hemoglobin
• most common cause is iron deficiency
• 2 ways to classify: Etiology or Appearance

• etiology = the cause of the disease
• Ex: hemorrhagic, iron deficiency, etc

• Size: Macrocytic, normocytic, and microcytic
• Hemoglobin (color) content: Hypochromic and normochromic
• *"-chromic" = color

• Size of RBC: Normocytic
• Amt. of Hemoglobin: Normochromic
• Cause: Bleeding

• Size of RBC: Microcytic
• Amt of Hemoglobin: Hypochromic
• Cause: lack of iron
• **Small ironing board and small iron...

• Size of RBC: Macrocytic
• Amt of hemoglobin: Normochromic
• Cause: Vitamin B₁₂ deficiency
• **Imagine turning the P in Pernicious into a B, as in Bern... but linking to Burns at Rockin R. He was a big guy, but normal in color

• Size of RBC: normocytic
• Amt of Hemoglobin: Normochromic
• Cause: destruction of RBC's

• Size of RBC: Normocytic
• Amt of Hemoglobin: Normochromic
• Cause: bone marrow failure

• a white blood cell
• Larger then red cells
• Have nuclei
• Don't have hemoglobin
• normal WBC count is 5.0 - 10.0 x 10³
• Two groups, divided by presence of cytoplasmic granules:
• Granulocytes and Agranulocytes
• *the granules are visible under microscope when stained

• also called granular leukocytes
• 3 specific groups:
• Neutrophils
• Eosinophils
• Basophils
• *names come from staining characteristics

• type of granulocyte
• Makes up 60-70% of total WBC's in blood stream
• Function: Powerful phagocyte, increased in bacterial infections and inflammation
• In an eosin stain, stains somewhere btwn red and dark purple
• Self destructs after attack, in pus
• *Think of "Neut" protecting me much of the time, fighting bacteria bad guys

• Type of granulocyte
• Makes up 2-4% of total WBC's in blood stream
• Function: Allergic reactions, parasitic infections
• *full of histamine 
• Has large red granules when stained
• **Remember allergies are "sin"-ful, E stains red like Erythro = red blood cells

• Type of granulocyte
• makes up .5-1% of total WBC's in blood stream
• Function: is poorly understood, chronic inflammation
• has traces of anticoagulant and histamine
• Has large dark blue granules (when stained)
• **B = Blue

• one of 2 types of WBC
• do contain some cytoplasmic granules, but they are much less prominent and don't stain as well as their granulocytic counterparts
• Include Lymphocytes and Monocytes

• type of agranular leukocytes
• Makes up 20-25% of total WBC's in bloodstream
• provide long term immunity
• Function: Major role in viral infections and cancer prevention
• include T Lymphocytes, B lymphocytes, and NK (Natural killer) cells

• type of agranular leukocytes
• makes up 3-8% of total WBC's in bloodstream
• Function: differentiate into macrophages (phagocyte), present in chronic inflammation and infections
• Enlarge and mature into macrophages in various tissues of the body
• Have various names depending on where it's at
• Comes into play if infection sticks around longer after neutrophils attack

• an increase in the number of white blood cells
• WBC count is greater than 10.0 x 10³ WBC/mm³
• Is a normal physiologic response, up to a point - any disruptions in homeostasis can cause increase in WBC
• Common causes are bacterial infections, viruses, parasites, stress, temp extremes, etc.

cancer of blood-forming cells, most often white cells

• a decrease in white cell numbers
• WBC count is less than 5.0 x 10³   WBC/mm³
• Never a normal response
• There isn't a normal physiological reason for a persons WBC count to go down
• Causes include: AIDS, chemotherapy, bone marrow failure (aplastic anemia)
• **Think of small "penis" ( -penia )

• way to figure out the percentage of each type of WBC in the blood
• provides info relating to pt condition

• Physicians use % of WBC in blood to aid in diagnosis of specific diseases
• WBC work together to provide a powerful immune response, but each type has unique role:
• Increased granulocytes in bacterial infections
• Increased lymphocytes in viral infections

• also called platelets
• cytoplasmic fragments of megakaryocytes
• 2-5 k platelets develop from one megakaryocyte
• very active in clot formation by:
• forming plug
• releasing chemicals to encourage vasoconstriction and activate coagulation
• *live 5-9 days

large cells in the bone marrow which are too big to leave, so they emplode and form blood platelets

formed by platelets to help limit blood loss

• the overall process by which bleeding is stopped
• Three mechanisms:
• Vascular spasm
• Platelet plug formation
• coagulation

• the constriction of damaged blood vessels
• One of 3 mechanisms involved with hemostasis
• limits the amount of blood lost
• due to chemicals released from platelets, damage to the smooth muscle, and pain receptor reflexes
• *Only vessels with smooth muscle can do this, capillaries can't

• Platelets are very active in hemostatic process - like little bags of procoagulant chemicals
• Three step process:
• 1st ~ platelets adhere to wall of blood vessel
• 2nd ~ platelets release their chemical contents (which encourages further vasoconstriction and recruitment of other platelets) 
• 3rd ~ due to chemical release, the newly activated platelets become sticky (platelet aggregation)
• W activation of enough platelets, a loose platelet plug is formed

the clumping of platelets during hemostasis

• taking plasma and making a clot
• Series of complex enzymatic reactions designed to activate specific coagulation proteins; most are plasma proteins
• Activated in step-wise/cascading fashion (such as knocking down domino's... said domino's referred to as clotting or coagulation factors)
• The coagulation proteins are enumerated with Roman numerals
• Most clotting factors synthesized by liver

• Two separate pathways to activate coagulation, which merge to form a common pathway:  (could consider it as 3 pathways)
• Extrinsic pathway
• intrinsic pathway
• *each pathway activated in a slightly different fashion, name gives hint to their activator
• *typically activated at same time

• One of two clotting pathway activation's
• activated by damage outside of vessel, specifically tissue
• TF is released from damaged tissue into the blood
• Has fewer steps and occurs rapidly

• tissue factor
• also called tissue thromboplastin
• A tissue protein (is a fluid) released from damaged tissue, used to activate clotting
• involved in extrinsic pathway for clotting
• activation
• *Tips over the first domino for extrinsic (if begins w intrinsic injury)

• one of two clotting pathway activation's
• activated by damage to vessels
• Exposed vascular collagen, damaged endothelium, or activated platelets are all potent coagulation activators

• Merge at the common pathway
• Activate the enzyme prothrombinase
• Prothrobinase acts on prothrombin (factor II) to become thrombin
• Newly formed thrombin activates fibrinogen (factor I) to become fibrin
• *Fibrin proteins are threads that form the clot and strengthen the platelet plug

• exogenous is outside of body cells
• endogenous is inside body cells

• Vitamin K - in the synthesis of clotting factors 2, 7, 9, 10
• Calcium - required for almost every step of coagulation process
• *therefore, a person deficient in these would have a hard time clotting

• Plasma is the liquid portion of unclotted blood, where the clotting process is inhibited and clotting factors remain inactive and soluble
• *Still have "domino's" within the blood so it will clot
• Serum is the liquid portion of clotted blood, which forms a clot by activating the soluble clotting factors
• *The "domino's" have already been tipped over. Can't clot

a clot that is stationary

• a circulating particle, often a clot that may obstruct a blood vessel
• Can be fat, air, cholesterol plaque, blood, clump of platelets, etc.

a stationary clot that dislodged from it's primary site and traveled to another location

clot dissolution

• the "un-clotting" system
• As coagulation occurs, substances from both tissue and blood activate the enzyme plasminogen to become plasmin

• a very potent proteolytic enzyme (proteolytic enzyme meaning digesting/breaking down protein)
• dissolves the clot:
• fibrinolysis (digesting fibrin)
• interferes w new clot formation by inactivating fibrinogen, prothrombin, and other clotting factors

• Although they are commonly referred to as "blood thinners", they do not thin the blood
• it interferes w the coagulation process
• are a # of different ones; some used for therapeutic reasons and others for specimen collection
• common goal is to inhibit coagulation process

• Anticoagulant
• Administered intravenously to a stroke or heart attack victim
• also used in surgery and dialysis
• Discourages the common pathway: Inactivates thrombin and factor X

• Also called Coumadin
• Anticoagulant
• Oral medication used to inhibit clotting in high-risk pts
• Interferes w the synthesis of a # of clotting proteins; most importantly the synthesis of Vitamin K
• *Also used for pesticide, specifically rodenticide. (D-con mice poison = mouse anticoagulant)

• Anticoagulant
• Present in blood-draw tubes used for blood counts

• Anticoagulant
• Present in blood collection bags for blood donations

• Anticoagulant
• Inhibits platelet aggregation

• chemicals used in medicine that breakdown clots that have already formed
• Used for strokes, heart attack, emboli and thrombi

• tissue-plasminogen activator
• Drugs that are given to stroke/heart attack victims when they come into the hospital
• Gets rid of the clots they have ; activates the thrombinogen to become plasmin
• Therefore, activates the fibrinolytic system
• THE CLOT BUSTER DRUGS

ABO and Rh systems

The A and B antigens are genetically determined: A genes codes for A antigen, B gen codes for B antigen, O gene results in lack of either A or B

• Both A and B are dominant
• O is recessive
• Therefore, if a person doesn't inherit an A or B, they will lack the antigens and have O blood type

• A antigens on red cells, Will have B antibodies in the plasma
• B antigens on red cells, will have A antibodies in the plasma
• AB antigens on red cells, no A and B antibodies in the plasma
• No A or B antigens on the red cells, A and B antibodies in the plasma
• *The antigens are present at birth, but the antibodies are not. They are formed shortly after birth (within 6 months)

• identifies whether a person has the Rh antigen or not
• So simply just another marker on the cell
• If they have it, they are Rh⁺, if they don't they are Rh^-
• 85% of population has it
• *people do not normally have antibodies to the Rh antigen, but they can develop it if they are ever exposed to Rh⁺ blood (cause they don't have the antigen, it is foreign)

• you know what this is
• just remember, a whole blood transfusion is rare. 
• Just parts of the blood are given, such as red blood cells

• blood type O
• doesn't have any A or B antigen on the red blood cells, therefore there isn't anything for the immune system to see

• blood type AB
• doesn't have any A or B antibodies in their plasma
• their system already knows what A and B antigens look like, so they aren't foreign

• If pt receives wrong blood type, their antibodies to the corresponding antigens will cause the incorrect RBC's to be destroyed by the immune system
• This can cause pt to develop a fever, go into shock, or result in acute renal failure

• Hemolytic disease of the newborn
• caused by blood incompatibility btwn a fetus and mother
• Most serious cause is Rh incompatibility
• Problem arises if:
• -Dad is Rh⁺
• -Mom is Rh^-
• -Baby is Rh⁺ , due to genetics inherited from father
• *but note that mom and baby are incompatible. If mother is exposed to baby's blood (in childbirth, trauma, etc) mom develops antibodies against Rh. This can be a problem if she becomes prego again. 
• *Her antibody can cross placenta and target fetus' red cells

• It starts attacking Baby's red blood cells in the uterus
• Baby becomes anemic because of a loss of red blood cells; not getting enough oxygen
• To compensate, baby's heart starts pumping faster, trying to circulate the red cells it has left
• RESULTS IN HEART FAILURE

• The mothers who are Rh^- are given an injection (in late middle pregnancy and at delivery)  of Rhogam (IF baby is Rh⁺)
• Rhogam is a commercially produced Rh antibody
• *"Rh-" = Rh   "-gam" = gamma globulin

• helps get rid of the Rh+ cells from baby before the mother's immune system sees them.
• Does this by flagging any Rh⁺ cells to be destroyed BEFORE HER immune system sees them.  
• So the Rh⁺ are flagged to be destroyed by the shot
• In this way, she never develops the ability to make Rh- antibodies ON HER OWN.

• Its not a problem
• Baby is neg. So there isn't an Rh antigen to see
• Mom is Rh⁺, already has Rh antigen
• immune system doesn't make antibody to antigen it doesn't recognize as foreign

• System consisting of lymphatic vessels through which lymph passes
• Functions:
• Draining interstitial fluid
• Transporting dietary lipids absorbed by the gastrointestinal tract to the blood
• Facilitating immune responses

• Lymphatic fluid
• Lymphatic capillaries
• Lymphatic vessels
• Lymph nodes
• Lymphatic trunks
• Lymphatic ducts
• red bone marrow
• thymus
• spleen

• what lymph vessels begin as
• located throughout body in interstitial spaces
• have overlapping endothelium that allows interstitial fluid in, not out
• held in place by anchoring filaments (specialized fibers arising from capillaries and extending into tissue)
• As they converge, they form larger lyphatic vessels

• vessels which carry lymphatic fluid (lymph) one way, from the tissue back into the blood stream
• have thin walls and valves to encourage one-way fluid movements

• bean-shaped lymphatic organ surrounded by connective tissue capsule
• serve as a filter for lymph fluid
• Foreign objects are trapped and destroyed
• Approx 600 in body, present at intervals along the lymphatic vessels
• provide opportunity for lymph to come into contact w immune system
• like a specializing sampling process
• *Lymph enters through the afferent vessels, exits through the efferent vessels[

• The left lymphatic duct
• where all lymph from Left upper body and entire lower body
• DOESN'T INCLUDE RIGHT UPPER BODY OR EXTREMITY
• Located at meeting point btwn left internal jugular vein and left subclavian vein

• only drains the right upper body & extremity
• Also drains into blood stream at junction of Right internal jugular vein and right subclavian vein

• formed by plasma that is filtered by the capillary walls
• clear fluid
• less protein than plasma
• Most is reabsorbed back into the blood through venous end of capillary

• liquid component of blood
• filtered through capillary walls to form interstitial fluid
• Large proteins don't pass through the capillaries
• *still has clotting proteins

• Unaltered interstitial fluid in the lymphatic vessels (that fluid that is not reabsorbed)
• Absorbed dietary lipids
• essentially, just drainage from the tissue, so it is identical to interstitial fluid

• Pressure in interstitial space
• Skeletal muscle contraction: "milks" lymphatic vessels and encourages movement
• Respiratory movements: encourage lymph flow by increasing and decreasing thoracic and abdominal pressures
• *In both scenarios, valves present in lymphatic vessels restrict black-flow of lymph

• 1. Plasma in the blood vessels
• 2. Interstitial fluid
• 3. Lymphatic capillaries
• 4. Lymphatic vessels
• 5. Lymphatic ducts
• 6. Back into the blood stream

• Locations where stem cells divide to produce immune cells
• Bone marrow and thymus

• Locations of cell maturation and immune responses
• Includes lymph nodes, spleen, lymphoid tissue (tonsils, MALT)

• happens as a cell matures
• means they can facilitate an immune response

• located in mediastinum btwn sternum and aorta
• in infants, is approx 70 grams, with age shrinks to only 3 grams, but still continues to release some mature T cells

• one of the primary lymphatic organs
• stem cells here divide to produce both B lymphocytes and T lymphocytes

• begin as stem cells in the bone marrow
• Will remain in bone marrow to mature
• activated to become plasma cells WHICH the job of plasma cells is to make antibodies

• begin as stem cells in the bone marrow
• Will leave as pre-T lymphocytes and migrate to the thymus gland to become immunocompetent

• lymph nodes have a connective tissue capsule
• Lymphatic nodules do not have a capsule

are considered secondary lymphatic tissue

Ex: Peyer's patches in the intestinal tract, portions of the appendix, and the tonsils (pharyngeal, adenoid and palatine)

• stores blood and helps with blood supply
• helps get rid of dead red blood cells
• sits in left upper quadrant
• One of most common things injured in trauma; making it easy to bleed to death
• Full of immune cells

• Cervical
• Submandibular
• axillary
• inguinal

extensions of the lymph node capsule which divide the node into compartments

the cortex and the medulla

• lymph flows into node via afferent lymphatic vessel
• flows through cortex, where it sees lots of B lymphocytes, dendritic cells, and macrophages
• continues to flow through node into medulla
• there it is exposed to more B lymphocytes, plasma cells (activated B cells) and more macrophages
• lymph then exits through efferent vessels

• consists of a # of different cellular and chemical barriers
• Non-specific
• Non-adaptive - meaning it doesn't change from exposure to exposure
• Has two lines of defense

• skin
• mucous membranes
• cilia
• endogenous antimicrobials
• inflammation
• phagocytosis
• fever

• Provides the ability to respond against specific invaders 
• Is specific & adaptive
• Generates memory
• *sometimes considered 3rd line of defense

• skin
• mucous membranes
• lacrimation
• salivation
• flow of urine
• vaginal secretions
• defecation
• vomiting
• Each of these barriers protects the various external opening of the body

• Comprised of the internal defenses:
• Endogenous antimicrobials
• Complement system
• Iron-binding proteins
• Interferon (chemical which warns neighbors of invasion) 
• Phagocytes (wandering and fixed macrophages)
• NK cells

• Natural killer cells
• a type of lymphocyte
• make up 5 - 10% of our circulating lymphocytes
• Along with non-specific phagocytes, their role is to release chemicals from their granules to either induce apoptosis or cause lysis of targeted cell

• neutrophils - released in large #'s, very quickly, but life span is short
• macrophages - first released as monocytes from bone marrow, which enlarge and develop as they migrate to site of infection or injury (called wandering macrophages)
• fixed macrophages occupy specific tissues

• chemotaxis
• adherence
• ingestion
• digestion
• killing

• the phenomenon whereby cells direct their movements according to certain chemicals in their environment
• Referring to phagocytosis, when an infection begins, the body releases chemicals in order to attract the phagocytes to the site of infection

fixed macrophages of the liver

fixed macrophages of the lungs

fixed macrophages of the CNS

• Part of our non-specific internal defenses
• abnormally high body temp due to resetting of hypothalamic thermostat
• Non-specific response:
• speeds up body reactions
• increases effects of endogenous antimicrobials
• Sequesters nutrients from microbes

• big part of non-specific, non-adaptive, innate response; internal defenses
• process has three stages: 
• vasodilation and increased vascular permeability
• emigration of phagocytes from blood to tissue
• tissue repair

• redness
• pain
• heat
• swelling
• possible loss of tissue funtion

• Vasodilation leads to redness and heat due to increased blood flow
• (only happens in vascular tissue since it's mediated by things coming through blood vessels)

• increased vascular permeability for the emigration of phagocytes
• also leads to fluid and proteins leaking into the interstitial space and causing swelling

• Fluid, histamine, and broken cells release prostaglandins (which cause pain)
• is the result of targeted free nerve endings by cytokines and pro-inflammatory chemicals

• LYMPHOCYTES=
• T lymphocytes: include T-helper, T-cytotoxic, T-regulator & memory T-helper and T cytotixic cells
• B lymphocytes

• type of agranular leukocyte (WBC)
• They are classified by the location where they mature~
• T-lymphocytes originate from stem cells in bone marrow, leave as pre-T cells and mature in thymus
• B-lymphocytes originate and mature in bone marrow
• *So a lymphocyte will either be a T or B

• a substance that is recognized as foreign and reacts with products of the immune system
• 4 things determine the antigenicity of a substance: 
• recognition as foreign
• structural complexity
• size
• organic in nature
• *Recognition as foreign most important - something can fit all the others, but if the body deems it as part of itself, it will leave it alone

• a molecule that fits the criteria of an antigen, except for size
• doesn't trigger immune response (unless it binds w another molecule, making it big enough)

• also called antigenic determinants
• refers to different sites or antigens on a pathogen
• can react with the immune system IF IT IS LARGE ENOUGH ~ initiating an immune response
• A pathogen can have multiple sites (or antigens)
• *They are antigens which the body see's as foreign so it will induce immune response

• *Produced in bone marrow, mature in thymus
• Divide into:
• T helper (CD4) cells
• T-cytotoxic (CD8 - marker on cell) cells
• T-regulator cells
• Memory T-helper cells
• Memory T-cytotoxic cells

• CD for short
• old name used for T helper & T cytotoxic cells
• initially researchers though the markers of white cells indicated a specific cell type. Thought they occurred in groups or clusters

• also called CD4 T-cells, due to presence of CD4 marker
• The middle man or main "helper" of immune response ~ act as a co-stimulator for both the B cells and T cytotoxic cells
• receive info from non-specific phagocytic cells & pass that info on to generate specific response to a particular antigen
• *part of BOTH cell-mediated and antibody-mediated immunity

• T-cells which destroy abnormal cells
• virally-infected cells and cancerous cells are main target
• Also called CD8 T-cells
• Does cell-to-cell combat & kills bad cells

• keep immune system from getting out of control
• decrease the reactivity of other types of T-cells
• essential for maintaining self-tolerance

• produced w an initial exposure to an antigen to provide memory of the event and a rapid response if re-exposed to the antigen
• do not participate in the first time around

• Cell mediated immunity = Side w T cells
• Anti-body mediated immunity = humoral side - B cells ( humor meaning fluid: the antibody "missiles" made by B cells travel through blood to get to where they need to go)
• both triggered by exposure to specific antigens

• involves action of T-cytotoxic lymphocytes
• cell to cell combate
• detect and destroy abnormal cells
• Virally-infected cells, cancer cells, and cells infected by intracellular bacteria

• involves action of B-lymphocytes
• activated to become plasma cells and produce antibody
• also makes memory

• major histocompatibility complex = (Also called HLA) 
• a group of genes that codes for a group of transmembrane proteins 
• found on the surface of all nucleated cells
• Important in processing and presentation of antigen

• Human leukocyte antigens = code for transmembrane proteins
• was the old name for MHC
• it was originally thought the group of genes that codes for transmembrane proteins only existed on leukocytes
• Now it's known they are present on all nucleated cells. Therefore, name changed to MHC

• MHC Class I and MHC Class II
• are protein molecules
• could think of them as flag poles that fly a flag to rat out a foreign invader
• So they present antigen to rest of immune system

• present on all body cells, except red blood cells (cause they don't have a nucleus)
• Present antigens that were inside of cell

• present on surface of antigen-presenting cells (APC's)
• Present antigens that were outside of cell

• Antigen-presenting cells
• primary responsibility to present antigens to other components of immune system
• *They are like the sheriff's of immune system
• commonly phagocytes, but B cells can present antigen
• Processing differs slightly depending on whether or not the antigen was present outside the body cells or inside
• *required for cell-mediated and antibody-mediated immunity

• viral proteins within virally-infected cells
• toxins from intracellular bacteria
• abnormal proteins in cancer cells

• Occurs when a cell proliferates (increases it's numbers) and differentiates (matures)
• Regarding APC's, it's through this process the active T-helper cells and T-memory cells are produced

• Phagocytosis by antigen-presenting cells
• Digestion of antigen within vesicle
• Synthesis of MHC-class molecule
• Fusion of antigen fragment w MHD-class molecule
• Insertion of antigen-MHC class complex in the plasma membrane

• It's ready to meet the T-helper cell
• Through a specific T-cell receptor, an inactive T-helper cell will bind to antigen fragment (which is being presented by MHC class II molecule)
• Along with this binding, cytokine stimulation results in the activation and proliferation of the T-helper cell (clonal selection = more T-helpers & T-memory cells)

• An inactive T-cytotoxic cell binds to the abnormal cells presenting viral proteins or cancer proteins on MHC class-I molecule
• T-helper cells act as a co-stimulator
• This activates the T-cytotoxic cell, which then also undergoes clonal selection

• Is the last to be activated
• can be activated by 2 different mechanisms:
• by direct recognition of antigen through B-cell receptors
• OR
• Through T-helper cell activation
• Once activated, B-cells under go clonal selection - some new B-cell clones will become B-memory cells, others will mature into plasma cells and secrete antibodies specific to the particular antigen

• Ingestion of antigen
• Digestion of antigen into fragments
• Synthesis of MHC class-II molecules
• Vesicular packaging of class-II molecules
• Fusion of fragment and class-II molecules
• Binding of fragments to class-II molecules
• Insertion of the antigen-MHC class-II complexes in the plasma membrane for recognition

• Digestion of antigen into fragments
• Synthesis of MHC class-I molecules
• Binding of fragments to class-I molecules
• Vesicular packaging of class-I molecules
• Insertion of the antigen-MHC class-I complexes in the plasma membrane for recognition

• immunoglobulins = gamma globulins = antibodies
• produced in response to antigen through antibody-mediated immunity
• *they actually don't "destroy" anything; instead they signal antigen for destruction, and disable antigen

• they have specific structure that provides for their specificity
• Generally consist of 4 peptide chains: two heavy and two light
• Disulfide bonds link the chains together in Y-shaped arrangement
• Most are one Y-shaped unit (monomer)

Variable region: consists of distal segments of heavy and light chains - forms the antigen binding site (which gives the antibody it's specificity)

Constant region: differs slightly for the different classes of antibodies

• Neutralizing antigen
• Immobilizing bacteria
• Agglutinating and precipitating antigen
• Activating complement
• Enhancing phagocytosis

• Neutralizes toxins
• binds to viruses to restrict their binding to host cells

Restricts the spread of motile bacteria by binding to cilia or flagella

• Making what is soluble, insoluble
• Multiple antigen-binding sites can result in one antibody binding to 2 or more antigen, causing agglutination (clumping of cells)
• binding may cause soluble antigen to become insoluble

Antigen/antibody complexes initiate the classical complement pathway

opsonization (flag for phagocytosis)

• IgG
• IgM
• IgA
• IgE
• IgD

• One class of antibody
• Monomer w two antigen-binding sites
• 80% of the antibody in the blood
• Only class that can cross placenta
• Provide long-term immunity
• Found in: blood, lymph and intestines

• Once class of antibody
• Pentamer w ten antigen-binding sites
• First to be secreted by plasma cells
• great complement activator
• short-lived response

• One class of antibody
• Dimer w four antigen-binding sites
• Most numerous in body secretions: sweat, tears, saliva, mucus, breast milk, and gastrointestinal 
• Levels decrease during stress (so you probably have NONE)

• One class of antibody
• Monomer w two antigen-binding sites
• less than 0.1% of antibody in blood
• located on mast cells in tissue

• One class of antibody
• Monomer w two antigen-binding sites
• 0.2% of antibody in blood
• acts as antigen receptors on B lymphocytes

• Naturally - not gained through modern medicine
• Artificially - gained through artificial means
• Actively - body responds to a pathogen to make antibodies (long-term immunity)
• Passively - body receives antibodies w no effort of it's own
• Active is long-term; passive is short-term

• Naturally-acquired active immunity
• Naturally-acquired passive immunity
• Artificially-acquired active immunity
• Artificially-acquired passive immunity

• Immune products acquired following exposure to antigen
• Ex: Hep A stimulated production of anti-hep A antibodies

• Transfer of antibody from non-medical source
• Ex: IgG through the placenta, IgA through breast milk

• Immune products acquired through vaccination
• antigens given that are immunogenic but not pathogenic

Prepared injection of antibody

• a very powerful group of proteins that "complement" the action of the immune system
• Main proteins are C1 - C9
• Activated by multiple pathways in a step-wise or cascading fashion

• Encourages vasodilation and inflammation
• Antigen opsonization
• Destroys antigen

• by the formation of a membrane-attack complex
• this is a group of complement proteins that are inserted into the plasma membrane to form a port in the membrane of the microbe
• This causes extracellular fluid to flow into the cells and the lysis of the microbe

• Primary:
• 1st exposure
• 5-7 day delay
• Production of IgM antibodies followed by IgG

• Secondary:
• Second & subsequent exposures
• Very little delay due to memory T-helper and B cells
• Production of IgM followed by a long-lasting population of IgG

• is a test that detects the relative amount of antibody
• indicator for an antibody-mediated response

• Self-recognition: ability to recognize one's own cellular markers
• Self-tolerance: the immune system must leave self-antigens alone

Failure of self-recognition or self-tolerance results in autoimmune disease