Hemostasis is the process of stopping bleeding through vascular spasms, platelet plug formation, and coagulation. Key events include vasoconstriction, platelet aggregation, thromboxane A2 release, fibrinogen conversion to fibrin strands, and clot stabilization. Clot retraction and repair occur through platelet contraction and growth factor release. Fibrinolysis removes unneeded clots. Factors that limit clotting include antithrombin III and protein C. Disorders include deep vein thrombosis and hemophilia.
6. Vascular spasms
Vascular spasm is the immediate response
to blood vessel injury, which involves
constriction of the damaged blood vessel
(vasoconstriction).
7. Platelet plug formation
Serotonin enhances the vascular response.
ADP is a potent aggregating agent that
attracts more platelets to the area and causes
them to release their contents.
8. Thromboxane A2 is a short lived
prostaglandin derivative that is generated
and released by platelets, that stimulates
both events.
PGI2 (prostacyclin) is a prostaglandin
produced by the endothelial cells that is
limited to the immediate area.
9. Coagulation
Coagulation (blood clotting) is a three
phase process during which blood is
transformed from a liquid to a gel.
Factors that enhance clot formation are
called coagulation factors (procoagulants).
Factors that inhibit clotting are called
anticoagulants.
10. Clotting may be initiated by either the
intrinsic pathway or the extrinsic pathway,
and both are triggered by the same tissue
damaging events.
PF3 is a phospholipid associated with the
external surfaces of aggregated platelets,
that is a pivotal molecule in both
mechanisms.
11. When blood is exposed to an additional
factor released by injured cells, called tissue
factor (tissue thromboplastin), the extrinsic
mechanism is triggered.
12. When factor X (an intermediate) has been
activated, it complexes with tissue factor or
PF3 and calcium ions to form prothrombin
activator.
Prothrombin activator catalyzes the
transformation of the plasma protein
prothrombin to the active enzyme thrombin.
13. Thrombin catalyzes the polymerization of
fibrinogen.
Fibrin strands are long, hair-like insoluble
proteins that are formed from fibrinogen.
Factor XIII (fibrin stabilizing factor) is an
enzyme that binds the fibrin strands tightly
together and strengthens and stabilizes the
clot, in the presence of calcium ions.
14.
15.
16. Clot retraction and repair
Clot retraction is a platelet-induced process
that causes the clot to be stabilized further.
Serum is plasma minus the clotting
proteins,which gets squeezed from the clot
as the platelets contract.
Platelet-derived growth factor (PDGF)
stimulates smooth muscle and fibroblasts to
divide and rebuild the wall.
17. Fibrinolysis
Fibrinolysis is a process that removes
unneeded clots when healing has occurred.
Plasmin is a fibrin-digesting enzyme that
dissolves clots, produced upon the
activation of plasminogen.
18. The presence of a clot in and around the
blood vessel causes the endothelial cells to
secrete tissue plasminogen activator (tPA).
19. Factors limiting Clot growth or
formation
Thrombin not adsorbed to fibrin is quickly
inactivated by antithrombin III, which is an
alpha-globulin protein present in plasma.
Protein C is another protein produced in the
liver, that also inhibits the activity of other
intrinsic pathway procoagulants.
20. Heparin is a natural anticoagulant contained
in the granules of basophils, mast cells and
endothelial cells that inhibits thrombin by
enhancing the activity of antithrombin III.
21. Disorders of hemostasis
A clot that develops and persists in an
unbroken blood vessel is called a thrombus.
If a thrombus breaks away from the vessel
wall and floats freely in the bloodstream, it
becomes an embolus.
22. Aspirin is an antiprostaglandin drug that
inhibits thromboxane A2 formation, and
therefore blocks platelet aggregation and
platelet plug formation.
Warfarin (Coumadin) is an anticoagulant by
interfering with the action of vitamin K.
23. Thrombocytopenia is a condition in which
the number of circulating platelets is
deficient, causing spontaneous bleeding
from small blood vessels.
24. Hemophilia is a term that refers to several
different sex-linked, hereditary bleeding
disorders that have similar symptoms.
Classical hemophilia results from a
deficiency of factor VIII (antihemophilic
factor).
25. Origin Substance Primary Effects
Platelets Serotonin Enhance vascular spasm
Platelets ADP Aggregating agent
Platelets Thromboxane A2 Vascular spasm and aggregation
Platelets Platelet-derived growth factor (PDGF) Stimulates smooth muscle and fibroblasts to rebuild vessel wall
Endothelium PGI2 (prostacyclin) Inhibitor of platelet aggregation
Endothelium Tissue Plasminogen activator (tPA) Converts plasminogen into plasmin, which digests fibrin
Endothelium Tissue Thromboplastin (TF) Activates extrinsic pathway
Endothelium, Basophils & Mast Cells Heparin Enhances activitiy of antithrombin III
Plasma Protein Antithrombin III Inactivation of thrombin
Plasma Protein (produced in liver) Protein C Inhibits activity of intrinsic pathway procoagulants
Synthetic Aspirin Inhibits thromboxane A2 formation
Synthetic Warfarin (Coumadin) Inhibits action of vitamin K
27. Transfusion of whole blood
Whole blood transfusion are performed
when blood loss is substantial and when
treating thrombocytopenia.
Whole blood from which most of the
plasma has been removed, called packed
red cells, are used for infusions to treat
anemia.
28. Red blood cell antigens that promote
agglutination are called agglutinogens.
ABO blood groups are based on the
presence or absence of two agglutinogens,
type A and type B.
29. Agglutinins are preformed antibodies that
act against RBCs carrying ABO antigens
that are not present on a person’s own red
blood cells.
30.
31. There are at least eight different types of Rh
agglutinogens, each of which is called an
Rh factor.
Pregnant Rh- women who carry Rh+ babies
will form anti-Rh antibodies, which, during
the second pregnancy, will destroy the
baby’s RBCs in a condition known as
erythroblastosis fetalis.
32. When mismatched blood is infused, a
transfusion reaction occurs in which the
donor’s red blood cells are avidly attacked
by the recipient’s plasma agglutinins.
Groups O blood cells have neither the A not
the B antigen, so the blood group is known
as the universal donor.
33. Group AB plasma is devoid of antibodies to
both A and B antigens, so the blood group
known as the universal recipient.
When a patient predonates their own blood,
and has it stored so that it is immediately
available if needed during or after an
operation, it is known as an autologous
transfusion.
34. Plasma and blood volume
expanders
When plasma is not available, various
colliodal solutions, or plasma expanders,
can be infused.
36. A differential white blood cell count is a
diagnostic tool used to determine the
relative proportion of individual leukocyte
types.
The amount of prothrombin present in
blood is assessed by determining the
prothrombin time.
37. A platelet count is performed when
thrombocytopenia is suspected.
A complete blood count (CBC), which
includes counts of the different types of
formed elements, a hematocrit, and tests for
clotting factors, is performed during
physical examinations and before hospital
admissions.
39. Skin and mucosae
A pathogen is a harmful or disease causing
microorganism.
Lysozyme is an enzyme, found in saliva
and lacrimal fluid, that destroys bacteria.
40. Phagocytes
Macrophages are the primary phagocytes,
and are derived from monocytes.
Neutrophils are the most abundant type of
white blood cell, and become phagocytic
when they encounter infectious material in
the tissues.
41. Natural killer cells
Natural killer cells are defensive cells that
can lyse and kill cancer cells and virus-
infected body cells before the immune
system is activated.
NKs are part of a large group of
lymphocytes called third population cells,
which recognize glycolipids on the
membrane of infected cells.
42. Inflammation
The purpose of the inflammatory response
is to prevent the spread of damaging agents
to nearby tissues, and dispose of cell debris.
Important inflammatory chemicals released
into the extracelluar fluid by injured tissue
cells include histamines, kinins,
prostaglandins, complement and
lymphokines.
43. Hyperemia is congestion of the affected
area with blood.
Exudate is fluid containing proteins that
seeps from the bloodstream into tissue
spaces, due to the effect of the
inflammatory chemicals on the capillaries.
44. Phagocyte mobilization
Chemicals called leukocytosis-inducing
factors released by injured cells promote
rapid release of neutrophils from red bone
marrow.
Chemotactic agents are inflammatory
chemicals that attract neutrophils to the site
of the injury.
45. Margination is the binding of neutrophils to
each other when complementary CAMS
connect, which concentrates neutrophils
along the inflamed capillary walls.
Diapedesis is the squeezing of neutrophils
through the capillary walls en route to the
infection site.
46. Pus is a mixture of dead or dying
neutrophils, broken down tissue cells, and
living and dead pathogens.
47. Antimicrobial proteins
Antimicrobial proteins, such as complement
and interferon, attack microorganisms
directly or hinder their ability to reproduce.
Complement refers to a group of about 20
plasma proteins that provide a mechanism
for destroying foreign substances in the
body by enhancing the effectiveness of the
body’s defenses.
48. The classical pathway is a method of
activating complement, that is linked to the
immune system due to the binding of C1 to
the antigen-antibody complex, in a step
called complement fixation.
49. The alternative pathway to the activation of
complement is triggered by interaction of
certain plasma proteins with
polysaccharides in the cell wall of
pathogenic microorganisms.
50. When C3b complement binds to the targets
cell’s surface, it triggers the insertion of
complement proteins called membrane
attack complex (MAC) into the cell’s
membrane, which opens a hole in the
membrane.
51. Interferons are molecules that diffuse to
nearby cells where they stimulate synthesis
of PKR, which inhibits protein synthesis in
infected cells.
52. Fever is abnormally high body temperature
in a systemic response to infection.
Pyrogens are chemicals secreted by
leukocytes and macrophages that raise the
body’s thermostat in response to infection.
54. The immune system is the body’s built in
specific defense system, which stalks and
eliminates almost any type of pathogen that
enters the body.
Humoral immunity is provided by
antibodies present in the fluids, whereas
cellular immunity is provided by the
lymphocytes themselves.
55. Complete antigens and haptens
Antigens are substances that can mobilize
the immune system and provoke an immune
response, and are considered intruders, or
nonself.
56. Complete antigens exhibit immunogenicity,
which is the ability to stimulate
proliferation of specific lymphocytes, and
reactivity, which is the ability to react with
the products of these reactions (antibodies).
57. A hapten is an incomplete antigen that is
not immunogenic unless it combines with
the body’s own proteins, in which case an
immune response is initiated.
59. MHC proteins
Self-antigens are proteins that line the
surface of all body cells, and are therefore
not considered foreign to the immune
system.
MHC proteins (class I and II) are
glycoproteins that mark a cell as self.
60. Lymphocytes
Immunocompetence is the ability of
lymphocytes to recognize a specific antigen
by binding to it, and is determined by where
in the body the lymphocytes mature.
Self-tolerance is the relative lack of
responsiveness of lymphocytes to self-
antigens.
61. Antigen-presenting cells
Antigen-presenting cells engulf foreign
particles and present fragments of these
antigens on their own membranes, where
they can be recognized by T cells.
62. Clonal selection and
differentiation of B cells
Clonal selection is the stimulation of B
cells, by cross-linked receptor/antigen
complexes, to grow and multiply rapidly.
A clone is one of many cells that are
derived from the same ancestor cell by
clonal selection.
63. Plasma cells are the antibody-secreting
effector cells of the humoral response.
Memory cells are long-lived clone cells that
do not differentiate into plasma cells, but
can mount an almost immediate humoral
response if the same antigen is encountered
again.
64. Immunological memory
The primary immune response is the
cellular proliferation and differentiation
which occurs on the first exposure to a
particular antigen.
65. A secondary immune response occurs when
someone is re-exposed to the same antigen,
and is faster, more prolonged, and more
effective than the primary response.
Memory cells that initiate the secondary
response provide immunological memory.
66. Active and passive humoral
immunity
Active humoral immunity is the production
of antibodies against encountered antigens.
Vaccines induce artificially acquired active
immunity, because antigens from weak or
dead pathogens are artificially injected into
the body.
67. In passive humoral immunity, the acquired
antibodies are obtained from the serum of
an immune human or animal donor.
68. Antibodies
Antibodies (immunoglobulins) are soluble
proteins secreted by activated B cells or by
plasma cells in response to an antigen, and
are capable of binding specifically with that
antigen.
69. When the four polypeptide chains of an
antibody are combined, they form an
antibody monomer with two identical
halves consisting of heavy and light chains,
and having a T or Y shape.
70. A variable and constant region exists on
each of the four chains.
Antibodies responding to different antigens
have different variable regions, but their
constant regions are the same in all
antibodies of a given class.
71. The variable regions of antibodies all
combine to form an antigen-binding site
shaped to fit a specific antigen, whereas the
constant regions determine how the
antibody will function in antigen
elimination.
72. Secretory IgA is one of five classes of
immunoglobulins, and is responsible for
preventing pathogens from gaining entry
into the body.
73. Somatic recombination is the process of
recombining gene segments when a B cell
become immunocompetent, in order to code
for antibodies that are specific to the vast
number of antigens the body may
encounter.
74. Antigen-antibody complexes are the result
of the binding of antibodies with their
specific antigens, and serve to inactivate the
invaders for later destruction by other cells.
Complement fixation occurs as a result of
the binding of antibodies to the antigens on
cells, which exposes complement binding
sites on their constant regions.
75. Neutralization occurs when antibodies
block specific binding sites on viruses or
bacterial exotoxins.
Agglutination is clumping of cells as a
result of cross-linking of antibody-antigen
complexes.
76. Precipitation is the cross-linking of soluble
molecules into large complexes that
precipitate out of solution.
Monoclonal antibodies are produced by
descendants of a single cell, and are pure
antibody preparations specific for a single
antigenic determinant.
77. Clonal selection and
differentiation of T cells
Class 1 MHC proteins display fragments of
proteins synthesized in the cell from
endogenous antigens.
Endogenous antigens are foreign proteins
that are synthesized within a body cell
78. Class II MHC proteins are found only on
the surfaces of mature B cells, some T cells,
and antigen presenting cells, and are from
exogenous proteins.
Exogenous proteins are foreign proteins.
79. TCRs are T cell antigen receptors.
MHC restriction reflects the preference for
a specific class of MHC proteins by helper
and cytotoxic T cells.
The process in which the T cells adhere to
and crawl over the surface of other cells
examining them for antigens is called
immunologic surveillance.
80. Costimulatory signals, such as the binding
of macrophage proteins, are required for the
proliferation of T cells.
Anergy is a state of T cell unresponsiveness
to antigens due to binding without
costimulatory signals.
81. Cytokines are chemical mediators involved
in cellular immunity.
Lymphokines are soluble glycoprotein
cytokines released by activated T cells.
82. Monokines are cytokines secreted by
monokines
T cell proliferation is enhanced by two
cytokines that act as costimulators:
interleukin 1 is released by macrophages
costimulates bound T cells to liberate
interleukin 2, which is a key growth factor.
83. Helper T cells are regulatory cells that play
a central role in the immune response by
stimulating the proliferation of other T cells
and B cell already bound to antigens.
84. T cell-independent antigens activate B cells
without the help of the T cells themselves.
Most antigens, (T cell-dependent antigens),
require T cell costimulation to activate B
cells.
85. Cytotoxic T cells (killer T cells) are the
only T cells that can directly attack and kill
other cells.
86. When a cytotoxic T cell performs a lethal
hit, it binds tightly t the target cell and
inserts the cytotoxic chemical perforin into
the plasma membrane of the target cell.
Some cytotoxic T cells produce
lymphotoxin, which causes fragmentation
of the target cell’s DNA.
87. Some Tc cells release tumor necrosis factor,
which slowly kills the target cell.
Another secretion of Tc cells is gamma
interferon, which stimulates macrophages to
killer status and indirectly enhances the
killing process.
88. Suppressor T cells are regulatory cells that
release lymphokines to suppress the activity
of both T and B cells.
Delayed-type hypersensitivity cells appear
to promote allergic reactions called delayed
hypersensitivity reactions.
89. Organ transplants and
prevention of rejection
Autografts are tissue grates transplanted
from one body site to another in the same
person.
Isografts are grafts donated by genetically
identical individuals, the only example
being identical twins.
90. Allografts are grafts transplanted from
individuals that are not genetically identical
by belong to the same species.
Xenografts are grafts taken from another
animal species.