phagocytosis to transfusion
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PHAGOCYTOSIS TO TRANSFUSION || DR. MYRNA ESPIRITU
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PHAGOCYTOSIS most important function of macrophages and neutrophils cellular ingestion of foreign organisms Selective – recognize which agent or cell is foreign or normal
*Whether phagocytosis will occur depends especially on three selective procedures.1. Most natural structures in the tissues have smooth surfaces , which resist phagocytosis.
But if the surface is rough, the likelihood of phagocytosis is increased.2. Most natural substances of the body have protective protein coats that repel the phagocytes .
Most dead tissues and foreign particles have no protective coats, which makes themsubject to phagocytosis.
3. Opsonization- bacteria are altered in such a manner that they are readily and more efficientlyengulfed by phagocytes (more digestible)
The immune system of the body develops antibodies against infectious agents such as bacteria. The antibodies then adhere to the bacterial membranes and thereby make the bacteria especially susceptible to phagocytosis. To do this, the antibody molecule alsocombines with the C3 product of the complement cascade, which is an additional part ofthe immune system discussed in the next chapter. The C3 molecules, in turn, attach toreceptors on the phagocyte membrane, thus initiating phagocytosis.
Opsonizing agents:o IgGo C3b- product of complement cascade
Steps in Phagocytosis
1. Recognition and attachment IgG – contains FC fragments presented to Macrophage FC receptor for recognition
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Attachment – specific receptorsEx. Mannose and Scavenger receptors
2. Engulfment3. Killing and degradation
Phagolysosome – vacuole is surrounded by cell’s own membrane (initiate killing) Oxygen dependent
Activates: Hexose monophosphate shunt – toxic free radicals Myeloperoxidase Halide system
Oxygen independent Lysozymes Major basic proteins
Phagocytosis by Neutrophils enter tissue as mature cells – can immediately begin phagocytosis single neutrophil – phagocytize 3-20 bacteria before it becomes inactive and dies Neutrophils- “suicide commandos”
Phagocytosis by Macrophages end stage products of monocytes that enter tissues from the blood they need to undergo transformation and activation when activated: more powerful than neutrophils – can phagocytize as many as 100 bacteria have the ability to engulf much larger particles like whole RBCs and occasionally, malaria parasite after digesting particles, macrophage can extrude residual products and survive and function for
many more months
MONOCYTE – MACROPHAGE CELL SYSTEM (RETICULOENDOTHELIAL SYSTEM) total combination of monocytes, mobile macrophages, fixed tissue macrophages and a few
specialized endothelial cells in the bone marrow and spleen
A. Tissue macrophages in the skin and subcutaneous tissue (Histiocytes) perform usual functions of attacking and destroying the infectious agents first line of defense
B. Macrophages in the lymph nodes if foreign particles are not destroyed locally in the
tissue, they enter the lymph and flow to the lymphnodes located intermittently along the course of thelymph flow
the foreign particles are then trapped in the nodes in
a meshwork of sinuses lined by tissue macrophage
C. Alveolar macrophages in lungs large numbers of tissue macrophages as integral
components of the alveolar walls phagocytize particles trapped in the alveoli
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D. Macrophages (Kupffer Cells) in the liver sinusoids important because the liver is connected to the gastrointestinal
tract Portal circulation- Kuppfer cells form an effective particulate
filtration system not allowing bacteria from GI to pass throughinto the general systemic circulation
E. Macrophages of the spleen and bone marrow when an invading organism succeeds in entering the circulation In both these tissues, macrophages have become entrapped by the reticular meshwork of the two
organs, and when foreign particles come in contact with these macrophages, they are phagocytized.
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INFLAMMATION When tissue injury occurs, whether caused by bacteria, trauma, chemicals, heat, or any other
phenomenon, multiple substances are released by the injured tissues and cause dramaticsecondary changes in the surrounding uninjured tissues.
Double-edged sword- Necessary because without it the body will succumb to infection but in the
process, some parts of the body will be destroyed.
ENDOGENOUS AND EXOGENOUS AGENTS Cause injury Provoke inflammatory response (host response)
RESPONSES1. Vascular response – earliest response
vasodilatation increase capillary permeability
2. Migration and activation of leukocytes 3. Systemic reactions – ex. Fever, body malaise
SEQUENCE OF EVENTS 1. Release of chemicals that will serve as mediators e.g. Bradykinins, Interleukins, Prostaglandins2. Reaction of Blood Vessels3. Accumulation of fluids and leukocytes4. Process of repair
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Purpose of Inflammation1. Dilute2. Destroy3. Wall – off injurious agent
Two main components1. Vascular Reaction2. Cellular Reaction
Inflammation is characterized by: vasodilatation and leakage increase capillary permeability clotting of fluid in interstitial space migration of large number of granulocytes and monocytes into the tissues swelling of the tissue cells – inflammatory edema – exudation fluid
Intravascular cells Neutrophils M onocytes eosinophils lymphocytes basophils platelets – not really cells
Connective Tissue Cells mast cells fibroblast macrophages
Extracellular Matrix Components Collagen and elastin Adhesive glycoproteins Proteoglycans
Chemical Mediators (may be cell-derived or plasma-derived) Serotonin - responsible for initial vasodilation Histamine – allergy Bradykinin – pain prostaglandin complement factors coagulation factors interleukins – first seen to be expressed by leukocytes; intercellular communication
First Line of defense Tissue macrophage - rapid enlargement and activation
Second Line of defense Neutrophil invasion- within few hours of acute severe inflammation
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Third Line of defense Second wave of macrophage invasion- need
several days for build up to occur
Fourth Line of defense Increase production of granulocytes and
monocytes by the bone marrow Occurs with stimulation of progenitor cells in the
bone marrow
FEEDBACK CONTROLFactors:1. Tumor necrosis factor (TNF)2. Interleukin 1 (IL – 1)3. Granulocye – monocyte colony – stimulating factor(GM – CSF)4. Granulocyte colony – stimulating factor (G-CSF)5. Monocyte colony – stimulating factor (M-CSF)
EXTRAVASATION OF LEUKOCYTES (FROM VESSELS TO TISSUES)
A. Margination:- in normal blood flow, nucleated elements are in the center of the flow, via margination the WBC
go to the periphery of the blood vessels- leukocyte accumulation along the peripheral positionsB. Rolling:- Tumble slowly along the endothelium and adhere transiently.C. Adhesion:- WBC come to rest at some point and firmly adhere to the endothelium.- Resembles pebbles over which a stream runs.- “Pavementing” appearance -endothelium lined by white blood cells.D. Transmigration/diapedesis:- Insert pseudopods into junctions between endothelial cells.
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- Squeeze through between these junctions in endothelial cells and BV and eventually escape intothe extravascular space. They now proceed to tissues.
E. Chemotactic factors- Attract WBC towards the injured tissue.- Endothelial cells produce some amount of chemotactic substances to attract WBC intravascularly
Inflammation
- process by which leukocytes are delivered to site of injury- Activated to perform normal function in host defense but has to be done in a very exact manner to
avoid tissue damage and prolonged inflammation in which case it becomes pathologic.
Central SIGNS of inflammation
- RUBOR (redness) due to blood vessel dilatation.
- DOLOR (pain) due to release of chemical mediators e.ge. Bradykinin- CALOR (heat) due to vasodilatation- TUMOR (swelling) due to escape of fluids from IV to EV space.- FUNCTIO LAESSA (loss of function)
ACUTE VERSUS CHRONIC INFLAMMATION
CRITERIA ACUTE INFLAMMATIONCHRONIC
INFLAMMATION
Onset Rapid Slow
Duration Short (lasting for minutes, hoursor a few days)
Longer
Predominant cellsinvolved
Neutrophils Monocytes andLymphocytes
Maincharacteristics
1. Exudation of fluid andplasma protein
2. Emigration of leukocytes
1. Proliferation of bloodvessels (represents thebody’s attempt torepair)
2. Fibrosis (body’sattempt to repair)
3. Tissue Necrosis(represents activeinflammation anddestruction)
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IMMUNOHEMATOLOGY
Immunohematology ( BLOOD BANKING)
- the area of laboratory dealing with:1. the preparation of blood and blood components for transfusion2. the selection of appropriate, compatible components for transfusion
- screen for the eligibility of the donor- screen for: HIV, Hepatitis B Virus, Hepatitis C Virus, Syphilis, Malaria
- assures the appropriateness and safety of blood transfusion - BLOOD TRANSFUSION: HELPFUL… BUT POSSIBLY HARMFUL
HISTORY
Blood- “living force of the body”
*Egyptians- blood baths
*Rome- spectators rush to drink the blood of dying gladiators *Middle ages- blood was considered as a tonic for rejuvenation and treatment of diseases *William Harvey- discovery of circulatory system *Adreas Libavius (1619)- first to advocate blood transfusion *Blood Tranfusion from animals to humans
o Richard Lower- blood from artery to veins of dogs *Summer of 1492
o Pope innocent VIII received the first blood transfusions from 3 young boys whichapparently were not effective since the pope died in the summer. The 3 boys also died.
*Modern ages
o Donath Landsteiner The discovery in 1990 of the ABO blood group of antigens by Landsteinerestablished the immmunologic basis for blood transfusion reactions.
Very important person. He also discovered the Rh antigens and the tests that were developed to determine
the blood group antigens made the transfusion of blood from one human to another a practical and useful clinical procedure.
Antigenicity
- Causes formation of antibodies-
Causes immune reactions in blood
Immune reaction - Reaction against a foreign body- One way is by forming an antibody.- A substance that can cause formation of antibody is an antigenic substance - Blood is antigenic- There are 30 commonly occurring antigens and other hundred rare antigens.
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- Most antigens are weak- The 2 strongest antigens most likely to cause a transfusion reaction are ABO and Rh antigens
THE ABO SYSTEM
- Determined by type of agglutinogen (antigen capable of causing agglutination) present on theRBC surface.
- The blood group of a person would be determined by the antigen present on the surface of theRBC. A and B antigen by Lansteiner.
- When neither A or B agglutinogen is present on the RBC surface, the blood type is O.- When only type A agglutinogen is present, the blood type is A. - When only type B, blood type is B .- Both A and B agglutinogens are present, blood type AB.
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Genetic Determination of blood type
- Two genes for blood type. One on each of two paired chromosomes (A,B,O)
Genotypes
- AA BB AB AO BO OO, however the O gene is a recessive gene, so there are only 4 Phenotypes.
Phenotypes:
A 41%B 9%
AB 3%O 47%
- In a persons’ serum, antibodies against the agglutinogen he does not possess are present.(agglutinins: antibody.)
Blood Type Agglutinogen AgglutininType A Antigen A Anti B
Type B Antigen B Anti AType AB Antigen A and B NoneType O None Anti A and B
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O: universal donor. AB: universal recipient.
LABORATORY DETERMINATION OF BLOOD TYPE
CRITERIA DIRECT METHOD INDIRECT METHOD
Description Use of antisera to detect antigenspresent on RBC
Use of RBC antigens to detectantibodies in serum
Sample RBC of patient Serum of patient
Reagent Anti-sera Red cell suspension
Mismatching
- The RBCs Agglutinate as a result of the agglutinins attaching themselves to the RBC.- This involves physical distortion of the cells or attack by the phagocytic WBC, so the RBC
membranes are destroyed, releasing hemoglobin into the plasma (HEMOLYSIS)
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- Lysis of RBC can also occur by activation of the complement system.
Hemolytic transfusion reaction manifestation
- Fever, chills, hypotension, hemoglobinuria, renal failure, DIC.
Rh BLOOD GROUP SYSTEM
*Nomenclature
Fisher Race : DCE, cde (D is most antigenic)
Weiner’s : Rh-hr
Rosenfield : Rh1-5
Rho D 1rh’ C 2rh’’ E 3hr’ c 4hr’’ e 5
- Rho, D and 1 (only test for this, most clinically significant among all non-ABO antigens)
*Rh Incompatibility
- Rh incompatibility also affects intrauterine life.- In adults: Rh transfusion reaction - In utero: erythroblastosis fetalis
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*Rh Transfusion Reaction
Giving Rh positive blood to an Rh negative patient (transfusion reaction) 97% of asians are (+), most of caucasians are (-). Rh antibodies do not pre-exist but may be developed. So asymptomatic at first, but after 2-4 weeks, antibodies are now active, there is a delayed
transfusion reaction. First case is mild. Second transfusion reaction, there is now an acute reaction, which is as great as an ABO antibody
reaction. For emergency cases: GIVE O- BLOOD
*Erythroblastosis fetalis
Agglutination and phagocytosis of the fetus’ red blood cells. Mother: Rh Negative Father: Rh Positive First pregnancy: Baby is Rh+ Mother: develops anti-Rh antibodies Second pregnancy: Baby Rh+, anti Rh antibodies attack the baby’s RBC’s, hemoglobin is
released, converted to bilirubin that causes jaundice. Hyperbilirubinemia causes kernicterus (brain damage because of hyperbilirubinemia) Clinical picture:
o Jaundice, anemia, hepatosplenomegaly, nucleated RBC’s in the circulation.