Pbl Exam 1 Case 4

Front 1

1. Two kinds of joints

Back 1

1. Solid (Non-synovial)
2. Cavitated (synovial)

Front 2

2. Solid joints

Back 2

Known as synarthroses; provide structural integrity and allow for minimal movement

No joint space; grouped according to type of connective tissue by bridges at end of bones

Front 3

3. Cavitated joints

Back 3

Synovial joints

Have a joint space that allows for a wide range of motions

At the ends of bones formed by endochondral ossification; strengthened by dense fibrous capsule and reinforced by tendons and ligaments; has a synovial membrane.

Front 4

4. Synoviocytes

Back 4

Surface lining of synovial joints;

Cuboidal cells; 1-4 layers deep; lacks a basement membrane and merges w/underlying loose CT

Front 5

5. Synovial fluid

Back 5

Filtrate of plasma containing hyaluronic acid

Front 6

6. Osteoarthritis

Back 6

AKA degenerative joint disease

Most common type of joint disease

Characterized by progressive erosion of articular cartilage

Not a disease of inflammation but rather a disease of articular cartilage in which biochemical metabolic processes result in the breakdown

Front 7

7. Secondary osteoarthritis

Back 7

Involves 1 or more predisposed joints; i.e. sports injuries

Hands more commonly affected in women

Hips more commonly affected in men

Front 8

8. Normal articular cartilage (Function)

Back 8

1. Bathed in synovial fluid ensures friction free movement w/in the joint

2. Spreads the load across the joint surface to allow underlying bones to absorb shock and weight w/o being crushed

Front 9

9. Aging and mechanical effects

Back 9

Mechanical stresses important role in osteoarthritis

Increasing age = increasing freq of arthritis

Increasing occurrence in weight bearing joints

Increasing freq in conditions that predispose joints to abnormal mechanical stress

Front 10

10. Genetic factors in osteoarthritis

Back 10

Appears to play a role in susceptibility esp in hand and hips

Specific genes not identified linkage to chromosome 1 and 2 has been suggested

Front 11

11. Risk of osteoarthritis

Back 11

Increased in direct proportion to bone density

High levels of estrogens also associated w/increased risk

Front 12

12. Early characterizations of osteoarthritis

Back 12

Degenerating cartilage contains:

1. increased water content
2. decreased concentration of proteoglycans
3. appears to have a weakening of the collagen network -> presumed decreased local synthesis of Type II collagen and increased breakdown of existing collagen
4. apoptosis also increased in chondrocytes but chondrocytes proliferate

Front 13

13. Characteristics/symptoms of osteoarthritis

Back 13

Patients w/primary disease are asymptomatic until 5th decade

1. Achy pain that worsens w/use
2. Morning stiffness
3. Crepitus
4. Limited range of motion
5. Impingement on spinal foramina by osteophytes results in cervical and lumbar nerve root compression
6. Typically, only one or a few joints are involved

Front 14

14. Joints commonly involved in osteoarthritis

Back 14

1. Hips
2. Knees
3. Lower lumbar/cervical vertebrae
4. Proximal and distal IP joints of fingers
5. First carpometacarpal joints
6. First tarsometatarsal joints in feet

Front 15

15. Heberden nodes

Back 15

Characteristic in women but not in men

Prominent osteophytes at the distal IP joints of the fingers.

Easily seen on XRay

Front 16

16. Bone eburnation

Back 16

Exposed subchondral bone plate becomes new articular surface and friction smooths and burnishes the new bone giving it the appearance of polished ivory

Front 17

17. Joint mice

Back 17

Small fractures are common and the dislodges pieces of cartilage and subchondral bone tumble into the underlying joint

Front 18

18. Subchondral cyst

Back 18

The fractured gaps allow synovial fluid to be forced into subchondral regions in one way ball valve-like mechanism.

The trapped fluid collection increases in size forming a fibrous walled cyst

Front 19

19. Synovial pannus

Back 19

Fibrotic tissue that covers the diseased part of the joint

Front 20

20. Rheumatoid arthritis

Back 20

Chronic systemic inflammatory disorder that may affect tissues and organs (skin, blood vessels, heart, lungs, muscles) but principally attacks the joints producing a non-suppurative proliferative and inflammatory synovitis that often progresses to destruction of the articular cartilage and ankylosis of the joints

Cause is unknown but autoimmunity plays a pivotal role in its chronicity and progression

Front 21

21. Morphological alterations of Rheumatoid arthritis

Back 21

Initially, synovium becomes edematous, thickened and hyperplastic transforming its smooth contour to one covered by delicated and bulbous fronds.

Front 22

22. Histological features of Rheumatoid arthritis

Back 22

1. Infiltration of synovial stroma by dense perivascular inflammatory cells (B cells, CD4+ helper T cells, plasma cells, and macrophages)
2. Increased vascularity (caused by vasodilation and angiogenesis)
3. Aggregation of organizing fibrin covering portions of the synovium
4. Rice bodies floating in the joint space
5. Accumulation of neutrophils in the synovial fluid and synovium
6. Osteoclastic activity in the underlying bone which forms juxta-articular erosions and subchondral cysts and osteoporosis
7. Pannus formation

Front 23

23. Rheumatoid arthritis nodules

Back 23

Rheumatoid nodules are most common cutaneous lesions in rheumatoid arthritis

They form in regions of skin that are subjected to pressure (i.e. elbows, occiput, and lumbosacral area)

Less commonly they form in the lungs, spleen, peri and myocardium, heart valves, aorta, and other viscera

Firm, non-tender and round to oval in shape

Front 24

24. Rheumatoid vasculitis

Back 24

Potentially dangerous complication of RA; particularly when if affects vital organs

Freq segments of small arteries are obstructed by an obliterating endarteritis resulting in peripheral neuropathy, ulcers, and gangrene.

Leukocytoclastic venulitis produced purpura, cutaneous ulcers and nail bed infarction.

Front 25

25. Pathogenesis of RA

Back 25

Autoimmune disease triggered by exposure of genetically susceptible host to an unknown arthritogenic antigen.

Activation of CD4+ helper T cells and other lymphocytes, and local release of inflammatory mediators and cytokines that ultimately destroy the joint.

Front 26

26. Autoimmune reaction in RA

Back 26

Activated CD4+ T cells and B lymphocytes as well

Target antigen unknown

T cells function by stimulating other cells in joint to produce cytokines that are essential mediators of the synovial reaction

Evidence that immune complex deposition may play some role in joint destruction

Front 27

27. Mediators of joint injury

Back 27

1. Cytokines
2. TNF
3. IL-1
4. TNF and IL-1 stimulate synovial cells to proliferate and produce various mediators (matrix metalloproteinases that contribute to cartilage destruction)

Front 28

28. RANKL

Back 28

Produced by activated T cell and synovial fibroblasts

Activates osteoclasts and promotes bone destruction

Front 29

29. Genetic susceptibility of RA

Back 29

Class II HLA locus (specifically a region of 4 AAs located in the antigen binding cleft)

May bind and display the arthritic antigen to T cells

The AA sequence in the cleft is inherited

Front 30

30. Characteristics/symptoms of RA

Back 30

1. Malaise
2. Fatigue
3. Generalized musculoskeletal pain after which joints become involved
4. Small joints involved before larger ones
5. Swollen, warm, painful, and stiff joints upon arising or after painful activity

Front 31

31. Radiographic hallmarks of RA

Back 31

Juxta-articular osteopaenia and bone erosions w/narrowing of the joint space from loss of articular cartilage

Front 32

32. Lab Dx of RA

Back 32

No specific lab tests but many patients have RF factor and IgM antibody reacted w/Fc portions of the patients own IgG

May not be present, but also included in differentials of other diseases so not 100% indicative

Front 33

33. Synovial analysis of RA

Back 33

1. Nonspecific inflammatory arthritis
2. Neutrophils with high protein content and low mucin content

Front 34

34. Clinical features for Dx of RA

Back 34

Need at least 4 of the following criteria:

1. Morning stiffness
2. Arthritis in 3 or more joints
3. Arthritis of typical hand joints
4. Symmetric arthritis
5. Rheumatoid nodules
6. RF factor
7. Typical radiographic changes

Front 35

35. Treatment of RA

Back 35

1. Glucocorticoids
2. NSAIDS
3. Anti-Rheumatic drugs (methotrexate)
4. TNF blockers

Front 36

36. Juvenile RA

Back 36

Begins before age 16 and must be present for a duration of at least 6 wks

2:1 female ratio

Front 37

37. Differences btwn adult and juvenile RA

Back 37

1. Oligoarthritis more common in juvenile
2. Systemic onset is more frequent in juvenile
3. Large joints affected more often in juvenile
4. Rheumatoid nodules and factor usually absent in juvenile
5. Anti-nuclear antibodies seropositivity is common in juvenile

Front 38

38. Similarities btwn adult and juvenile RA

Back 38

1. Genetic association w/HLA haplotypes
2. Mycobacterial or viral infection
3. Abnormal immunoregulation w/CD4+ T cells w/in the involved joints
4. Cytokine production

Front 39

39. Systemic onset of juvenile RA

Back 39

1. High spiking fever
2. Migratory and transitory skin rash
3. Hepatosplenomegaly
4. Serositis

Front 40

40. Seronegative spondyloarthropathies

Back 40

Produce inflammatory peripheral or axial arthritis and inflammation of the tendinous attachment


Included:
1. Ankylosing spondyloarthritis
2. Reactive arthritis
3. Psoriatic arthritis

Front 41

41. Ankylosing spondyloarthritis

Back 41

A chronic inflammatory joint disease of axial joints, esp the SI joints
-chronic synovitis w/destruction of articular cartilage
-bony alkylosis in SI and apophyseal joints
-inflammation of tendinoligamentous insertion points leading to bony outgrowths

Become symptomatic in 2nd or 3rd decades of life

Analogous to RA

Front 42

42. Reactive arthritis

Back 42

Episode of non-infection arthritis that occurs w/in 1 month of a primary infection localized elsewhere in the body

Associated w/genitourinary infections in the 2nd and 3rd decades of life

Wax and wanes over a period of several weeks to 6 months

Front 43

43. Psoriatic arthritis

Back 43

1. Distal IP joint involvement w/nail pitting
2. Asymmetrical oligoarthropathy of both large and small joints
3. Arthritis mutilans, a severe form
4. Symmetrical polyarthritis
5. Spondyloarthropathy

Front 44

44. Infectious arthritis

Back 44

Caused by microorganisms lodging in joints during hematogenous dissemination

Includes:
1. Suppurative arthritis
2. Tuberculous arthritis
3. Lyme arthritis
4. Viral arthritis

Front 45

45. Suppurative arthritis

Back 45

Caused by bacterial infection

Individuals w/sickle cell are prone to infection

Presents w/:
1. Acutely painful hot and swollen joint w/restricted range of motion
2. Fever
3. Leukocytosis
4. Elevated sedimentation rate

Occurs in hip, shoulder, elbow, wrist, and sternoclavicular

Front 46

46. Tuberculous arthritis

Back 46

Chronic progressive, monoarticular disease, usually develops w/adjoining osteomyelitis or after dissemination of infection from lungs

Results in:
1. Severe destruction w/fibrous ankylosis and obliteration of joint space
2. Weight bearing joints are usually affected

Front 47

47. Lyme arthritis

Back 47

Arthritis caused by lyme disease.

Infected synovium takes the form of:

1. Chronic papillary synovitis w/synoviocyte hyperplasia
2. Fibrin deposition
3. Mononuclear cell infiltrites
4. Onion-skin thickening of arterial walls

Front 48

48. Viral arthritis

Back 48

Occurs w/viral infections including parvovirus, rubella, and Hep-C

Symptoms: variable and range from acute to subacute

Front 49

49. Gout

Back 49

Metabolic disorder that includes acute and chronic arthritis, uric acid deposits in and around joints and skin, renal stones, and hyperuricemia

Leads to chronic gouty arthritis, and tophi deposits

Front 50

50. Accumulation of uric acid

Back 50

Results from

1. Defect in the purine uric acid metabolism leading to overproduction of uric acid
-OR-
2. Result of primary defects of renal clearance

Front 51

51. Plasma urate levels

Back 51

Above 7 mg/dL is considered elevated at normal body temp and pH

Front 52

52. Two pathways involved in purine synthesis

Back 52

1. de novo pathway in which purines are made from non-purine precursors

2. *Salvage pathway; free purine bases are derived from breakdown of AAs of endo or exogenous origins

*uses the enzyme HGPRT

Front 53

53. Factors that lead to gout

Back 53

1. Age
2. Genetic predisposition
3. Heavy EtOH consumption
4. Obesity
5. Certain drugs (i.e. thiazides)
6. Lead toxicity

Front 54

54. Morphology of gout

Back 54

1. Acute arthritis
2. Chronic tophaceous arthritis
3. Tophi deposits
4. Gouty nephropathy

Front 55

55. Chronic tophaceous arthritis

Back 55

Evolves from the repetitive precip of urate crystals which may heavily encrust the articular surfaces and form visible deposits on the synovium.

Synovium forms a pannus which destroys the underlying cartilage.

Fibrous or bony alkylosis ensues in severe cases

Front 56

56. The pathognomonic hallmark of gout

Back 56

Tophi!!!

Formed by large aggregates of urate crystals; surrounded by intense inflammatory reaction of macrophages, lymphocytes, and large foreign body giant cells which may have partially or completely engulfed masses of crystals.

Front 57

57. Gouty nephropathy

Back 57

Renal disorder associated w/deposition of monosodium urate crystals in the renal medullary interstitium.

Sometimes forms tophi, intratubular precipitations or free uric acid crystal (form kidney stones)

Front 58

58. Four stages of gout

Back 58

1. Asymptomatic hyperuricemia
2. Acute gouty arthritis
3. Intercritical gout
4. Chronic tophaceous gout

Front 59

59. Locations of gout

Back 59

First attacks are monoarticular and 50% occur in the first metatarsophalangeal joint

1. Insteps
2. Ankles
3. Heels
4. Knees
5. Wrists
6. Fingers
7. Elbows

Takes 12 years from initial attack to reach the tophaceous stage

Front 60

60. Dx of gout

Back 60

Acute onset of monoarthritis in joint of lower extremity

Intracellular needle shaped, -negatively- bifringent crystals are essential to Dx of acute gouty arthritis

Urate crystals may also be seen in tophaceous deposits into which a joint has ruptured tophaceous deposits

Front 61

61. Treatment of gout

Back 61

1. Colchicine
2. NSAIDS
3. Glucocorticoids

Front 62

62. Treatment of intercritical gout

Back 62

1. Colchicine
2. NSAIDS
3. Probenecid
4. Allopurinol

Front 63

63. Pseudogout

Back 63

AKA Calcium pyrophosphate crystal disease (CPPD)

Intra-articular crystal formation

Altered activity of the matrix enzymes that produce and degrade pyrophosphate, resulting in its accumulation and eventual recrystallization with calcium.

Front 64

64. Three forms of pseudogout

Back 64

1. Sporadic
2. Hereditary
3. Secondary types

Front 65

65. Hereditary form of pseudogout

Back 65

The crystals develop relatively early in life and forms severe osteoarthritis.

The autosomal dominant form of the disease has been shown to be related to a mutation in the ANKH gene, which encodes a transmembrane-inorganic pyrophospate transport channel

Front 66

66. Secondary form of pseudogout

Back 66

Associated w/various disorders, including previous joint damage, hyperparathyroidism, hemochromatosis, hypomagnesmia, hypothyroidism, ochronosis, and diabeted.

Front 67

67. Morphology of pseudogout

Back 67

The crystals first develop in the articular matrix, menisci, and intervertebral discs, and may rupture and seed the joint if large enough.

Once released into the joint, they elicit the production of IL-8 which helps produce an inflammatory reaction rich in neutrophils.

The neutrophils produce damage thru the release of oxygen metabolites, catabolic enzymes, and cytokines.

Front 68

68. Dx of pseudogout

Back 68

May mimic other disorders such as osteoarthritis or RA.

Joint involvement may be monoarticular or polyarticular

Crystals are weakly birefringent and have geometric shapes; they are rarely deposited in masslike aggregates simulating tophi.

Front 69

69. Joint involvement in pseudogout

Back 69

1. Knees
2. Wrists
3. Elbows
4. Shoulders
5. Ankles

Therapy is supportive; no known treatment prevents or retards crystal formation.

Front 70

70. Ganglion

Back 70

A small 1 to 1.5 cm cyst that is almost always located near a joint capsule or tendon sheath.

It arises as a result of cystic or myxoid degeneration of connective tissue; the cyst wall lakes a true cell lining.

Fluid that fills the cyst is similar to synovial fluid; however, there is no communication with the joint space.

Front 71

71. Synovial cyst

Back 71

Herniation of synovium through a joint capsule or massive enlargement of a bursa may produce a synovial cyst.

Synovial lining may be hyperplastic and contain inflammatory cells and fibrin but is otherwise unremarkable.

Front 72

72. Villonodular synovitis

Back 72

A term for several closely related benign neoplasms that develop in the synovial lining of joints, tendon sheaths, and bursae.

They arise from a clonal proliferation of cells and are neoplastic.

Front 73

73. Pigmented villonodular synovitis (PVNS)

Back 73

The normally smooth joint synovium, most often the knee, is converted into a tangled mat by red-brown folds, finger like projections, and nodules.

Aggressive tumors erode into adjacent bones and soft tissues

Usually presents as a monoarticular arthritis that affects the knee in 80% of cases.

Treatment is surgery

Front 74

74. Giant cell tumor of tendon sheath (GCT)

Back 74

AKA localized nodular tenosynovitis

Usually occurs as a discrete nodule on a tendon sheath and may be attached to the synovium by a pedicle.

Slow growing painless mass that frequently involves the tendon sheaths along wrists and fingers.

Treatment is surgery

Front 75

75. Location of hyaline cartilage

Back 75

1. Epiphyseal plates
2. Articular surface of synovial joints
3. Costal cartilages of the rib cage
4. Cartilages of the nasal cavity
5. Larynx
6. Rings of trachea and plates in the bronchi

Front 76

76. Function of hyaline cartilage

Back 76

1. Resistance to compression
2. Cushioning
3. Smooth and low friction surface for joints
4. Structural support in respiratory system
5. Endochondral bone formation
6. Bone growth

Front 77

77. Does hyaline cartilage have a perichondrium?

Back 77

Yes (except articular cartilage and epiphyseal plates)

Front 78

78. What cell types are present in hyaline cartilage?

ECM?

Back 78

1. Chondroblasts
2. Chondrocytes

The ECM contains Type II collagen fibrils and aggrecan, which is the most important proteoglycan

Front 79

79. Location of elastic cartilage

Back 79

1. Pinna of external ear
2. External acoustic meatus
3. Auditory tube
4. Cartilages of the larynx

Front 80

80. Function of elastic cartilage

Back 80

Provides flexible support

Front 81

81. Perichondrium in elastic cartilage?

What about calcification?

Back 81

There is a perichondrium in elastic cartilage.

Elastic cartilage does not undergo calcification.

Front 82

82. Cell types present in elastic cartilage

ECM?

Back 82

1. Chondroblasts
2. Chondrocytes

ECM contains Type II collagen fibrils and elastic fibers as well as aggrecan

Front 83

83. Location of fibrocartilage

Back 83

1. Intervertebral disks
2. Symphysis pubis
3. Articular disks (sternoclavicular and termporomandibular joints)
4. Menisci
5. Wrist joint
6. Insertion of tendons

Front 84

84. Function of fibrocartilage

Back 84

Resists deformation under stress

Front 85

85. Does fibrocartilage have a perichondrium?

What about calcification?

Back 85

No, fibrocartilage does not have a perichondrium

Fibrocartilage does, however, undergo calcification

Front 86

86. Cell types present in fibrocartilage

ECM?

Back 86

1. Chondrocytes
2. Fibroblasts

ECM contains Type I and Type II collagen fibers, versican, and proteoglycan secreted by fibroblasts

Front 87

87. Four zones of articular cartilage (a form of hyaline cartilage)

Back 87

1. Superficial (tangential zone)

2. Intermedial (transitional zone)

3. Deep (radial) zone

4. Calcified zone; separated from the deep zone by a heavy calcified line called the "tidemark"

Front 88

88. What is the distinguishing characteristic in elastic cartilage?

Back 88

Elastic cartilage is distinguished by the presence of elastin in the cartilage matrix.

Front 89

89. What two kinds of growth is cartilage capable of?

Back 89

1. Appositional growth
2. Interstitial growth

Front 90

90. Appositional growth

Back 90

The process that forms new cartilage at the surface of an existing cartilage

Front 91

91. Interstitial growth

Back 91

The process that forms new cartilage within an existing cartilage mass

Front 92

92. Chondrogenesis

Back 92

Process of cartilage development

1. Aggregation of chondroprogenitor mesenchymal cells to form a mass of rounded, closely apposed cells.
2. Expression of SOX-9 triggers diferentiation of these cells into chondroblasts
3. Chondroblasts secrete cartilage matrix and become surrounded by matrix material
4. When these cells are completely surrounded by matrix material, they are call chondrocytes

Front 93

93. How doe blood leukocytes and tissue cells derived from leukocytes work together to combat infectious and toxic agents?

Back 93

1. Actually destroying invading bacteria or viruses by phagocytosis

2. Forming antibodies and sensitized lymphocytes, one or both which may destroy or inactivate the invader.

Front 94

94. White blood cells

Back 94

AKA leukocytes, are the mobile units of the body's protective system. They are formed partially in the bone marrow (granulocytes and monocytes and a few lymphocytes) and partially in the lymph tissue (lymphocytes and plasma cells). After formation, they are transported in the blood to different parts of the body where they are needed.

The real value of the white blood cells is that most of them are specifically transported to areas of serious infection and inflammation, thereby providing a rapid and potent defense against infectious agents.

Front 95

95. Six types of white blood cells

Back 95

1. Neutrophils*
2. Eosinophils*
3. Basophils*
4. Monocytes
5. Lymphocytes
6. Plasma cells

*are considered granulocytes due to multiple nuclei

Front 96

96. Which white blood cell has the highest concentration in the body?

Least?

Back 96

Most: Neutrophils

Least: Eosinophils

Front 97

97. What are the two major lineages in which white blood cells are formed?

Back 97

1. Myelocytic lineage
-begins w/the myeloblast

2. Lymphocytic lineage
-begins w/the lymphoblast

Front 98

98. Where are granulocytes and monocytes formed?

Back 98

Only in the bone marrow

Front 99

99. Where are lymphocytes and plasma cells formed?

Back 99

Produced mainly in the various lymphogenous tissue, esp the lymph glands, spleen, thymus, tonsils, and various lymphoid tissue.

Front 100

100. Life span of granulocytes

Back 100

normally 4 to 8 hours circulating in the blood and another 4 to 5 days in tissues where they are needed.

In times of serious tissue infection, this total life span is often shortened to only a few hours because the granulocytes proceed even more rapidly to the infected area, perform their functions, and, in the process, are themselves destroyed.

Front 101

101. Life span of monocytes

Back 101

Monocytes also have a short transit time, 10 to 20 hours in the blood, before wandering through the capillary membranes into the tissues. Once in the tissues, they swell to much larger sizes to become tissue macrophages, and, in this form, can live for months unless destroyed while performing phagocytic functions.

These tissue macrophages are the basis of the tissue macrophage system.

Front 102

101. Life span of lymphocytes

Back 102

Lymphocytes enter the circulatory system continually, along with drainage of lymph from the lymph nodes and other lymphoid tissue. After a few hours, they pass out of the blood back into the tissues by diapedesis.

Then, still later, they re-enter the lymph and return to the blood again and again; thus, there is continual circulation of lymphocytes through the body.

The lymphocytes have life spans of weeks or months; this life span depends on the body's need for these cells.

Front 103

102. Neutrophils and tissue macrophages

Back 103

These cells are responsible for attacking and destroying invading bacteria, viruses, and other injurious agents.

Macrophages start as monocytes, but then swell up to 5x their size to become mature macrophages

Front 104

103. Diapedesis

Back 104

Neutrophils and monocytes can squeeze through the pores of the blood capillaries by diapedesis. That is, even though a pore is much smaller than a cell, a small portion of the cell slides through the pore at a time; the portion sliding through is momentarily constricted to the size of the pore

Front 105

104. Chemotaxis

Back 105

Chemical substances in the tissues cause both neutrophils and macrophages to move toward the source of the chemical; it depends on the concentration gradient of the chemotactic substance.

Front 106

105. Three selective procedures of phagocytosis

Back 106

1. First, 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. Second, 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 them subject to phagocytosis.
3. Third, the immune system of the body develops antibodies against infectious agents. The antibodies then adhere to the bacterial membranes and thereby make the bacteria especially susceptible to phagocytosis. (called opsonization)

Front 107

106. What do neutrophils and macrophages contain in abundance?

Back 107

Lysosomes filled w/proteolytic enzymes especially geared for digesting bacteria or other foreign matter.

Also contain bactericidal agents (hydrogen peroxide, superoxide)

Macrophages (but not neutrophils) also contain large amounts of lipases, which digest the thick lipid membranes of some bacteria.

Front 108

107. Reticuloendothelial system

Back 108

Monocyte-macrophage system

The total combination of monocytes, mobile macrophages, fixed tissued macrophages, and a few specialized endothelial cells in the bone marrow, spleen, and lymph nodes.

Front 109

108. Histiocytes

Back 109

Tissue macrophages in the skin and subcutaneous tissues

Front 110

109. General organization of the lymph node

Back 110

1. Afferent lymph vessels
2. Nodal medullary sinuses
3. Hilus
4. Efferent lymph vessels

Front 111

110. Kupffer cells

Back 111

These cells line the liver sinusoids

They are tissue macrophages that are an extremely effective particulate filtration system.

Front 112

111. Red pulp of the spleen

Back 112

The trabeculae of the red pulp are lined w/vast numbers of macrophages, and the venous sinuses are also lined w/macrophages.

Good way of filtering the blood

Front 113

112. Five characteristics of inflammation

Back 113

1. vasodilation of local blood vessels w/increased blood flow
2. increased permeability of the capillaries
3. clotting of the fluid in the interstitial spaces
4. migration of large numbers of granulocytes and monocytes into the tissue
5. swelling of the tissue cells

Front 114

113. "Walling-off" effect of inflammation

Back 114

One of the first results of inflammation is to "wall off" the area of injury from the remaining tissues.

Tissue spaces and lymphatics in the inflamed area are blocked by fibrinogen clots.

This process delays the spread of bacteria or toxic products;

Important to note that the intensity of inflammation is direction proportional to the degree of tissue injury

Front 115

114. Lines of defense in inflammation response (Four lines)

Back 115

1. Tissue macrophages

2. Neutrophil invasion of the inflamed area
-Acute increase in number of neutrophils in the blood (neutrophilia)

3. Second macrophage invasion into the inflamed tissue

4. Increased production of granulocytes and monocytes by the bone marrow.

Front 116

115. Five important factors in inflammation control

Important role?

Back 116

1. TNF
2. IL-1
3. Granulocyte-monocyte colony stimulating factor
4. Granulocyte colony stimulating factor
5. Monocyte colony stimulating factor

These factors are formed by activated macrophage cells in the inflamed tissues and in smaller quantities by other inflamed tissue cells.

They provide an important feedback mechanism for the deveolpment of defensive white blood cells that help remove the cause of inflammation

Front 117

116. Pus

Back 117

When neutrophils and macrophages engulf large numbers of bacteria and necrotic tissue, essentially all the neutrophils and many of the macrophages eventually die.

After several days, a cavity is often excavated in the inflamed tissues that contains varying portions of necrotic tissue, dead neutrophils, dead macrophages, and tissue fluid. This mixture is commonly known as pus.

Front 118

117. Eosinophils

Back 118

Constitute about 2% of all blood leukocytes

They are weak phagocytes and they exhibit chemotaxis.

*Produced in large numbers in response to parasitic infections*

They attach themselves to parasites and release substances that kill many of the parasites

Front 119

118. How do eosinophils kill parasites?

Back 119

1. Release hydrolytic enzyme from their granules, which are modified lysosomes
2. Release highly reactive forms of oxygen that are lethal to parasites
3. Release major basic protein from the granules (very larvacidal)

Front 120

119. Eosinophil chemotactic factor

Back 120

Released by mast cells and basophils and causes eosinophils to migrate toward the inflamed allergic tissue.

The eosinophils are believed to detox some of the inflammation inducing substances released by the mast cells and basophils.

Front 121

120. Basophils

Back 121

Basophils liberate heparin into the blood (prevents blood coagulation) as well as histamine, bradykinin, and serotonin.

However, it is mainly the mast cells in inflamed tissues that release these substances during inflammation.

Front 122

121. Mast cells and basophils in allergic reactions

Back 122

IgE has a special propensity to become attached to mast cells and basophils.

Front 123

122. Leukopenia

Back 123

Occurs when the bone marrow produces very few white blood cells, leaving the body unprotected against many bacteria and other infectious agents.

Front 124

123. What is leukemia?

What are the two types?

Back 124

Uncontrolled production of white blood cells caused by cancerous mutation of a myelogenous or lymphogenous cell.

Two types of leukemia:
1. Lymphocytic
2. Myelogenous

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124. Lymphocytic leukemias

Back 125

Caused by cancerous production of lymphoid cells, usually beginning in a lymph node or other lymphocytic tissue and spreading to other areas of the body.

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125. Myelogenous leukemias

Back 126

Begins by the cancerous production of young myelogenous cells in the bone marrow and then spread throughout the body so that cancerous white blood cells are produced in many extramedullary tissues, especially in the lymph nodes, spleen, and liver.

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126. Acute vs. chronic leukemia

Back 127

The more undifferentiated the cell, the more acute is the leukemia, often leading to death within a few months if left untreated.

With some of the more differentiated cells, the process can be chronic, sometimes developing slowly over 10 to 20 years.

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127. Effects of leukemia on the body

Back 128

1. Metastatic growth of leukemic cells in abnormal areas of the body (bone and bone fractures)
2. Almost all leukemias eventually spread to the spleen, lymph nodes, liver.
3. Development of infection, sever anemia, and lack of platelets (easily bleed)
4. Excessive use of metabolic substrates by the growing cancerous cells (the leukemic tissues reproduce new cells so rapidly that tremendous demands are made on the body reserves.

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129. Innate immunity

Back 129

The innate immune system comprises the cells and mechanisms that defend the host from infection by other organisms, in a non-specific manner.

This means that the cells of the innate system recognize, and respond to, pathogens in a generic way, but unlike the aquired immune system, it does not confer long-lasting or protective immunity to the host.

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130. Examples of innate immunity

Back 130

1. Phagocytosis of bacteria and other invaders by white blood cells
2. Destruction of swallowed organisms by the acid secretions of the stomach and the digestive enzymes
3. Resistance of the skin to invasion by organisms
4. Presence in the blood of certain chemical compounds that attach to foreign organisms and destroys them (lysozymes, basic polypeptides, complement complexes, natural killer cells)

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131. Acquired immunity

Back 131

AKA adaptive immunity

The body has the ability to develop extremely powerful specific immunity against individual invading agents such as lethal bacteria, viruses, toxins, and even foreign tissues from other animals

Caused by a special immune system that forms antibodies and/or activated lymphocytes that attack and destroy the specific invading organism or toxin.

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132. Two basic types of acquired immunity

Back 132

1. Humoral immunity (B-cell immunity)

2. Cell mediated immunity (T-cell immunity)

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133. Importance of antigens

Back 133

Each toxin or each type of organism almost always contains one or more specific chemical compounds in its makeup that are different from all other compounds.

These are proteins or large polysaccharides and it is they that initiate the acquired immunity.

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134. What is the importance of lymphocytes?

Back 134

They are responsible for acquired immunity

They include the T lymphocytes which form the activated lymphocytes that provide "cell mediated immunity"

and the B lymphocytes which form the antibodies that provide "humoral immunity"

Both types of cells derived from pluripotent hematopoietic stem cells.

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135. Where are T lymphocytes preprocessed?

Back 135

In the thymus gland

They migrate to the thymus from the bone marrow and divide rapidly and at the same time develop extreme diversity for reacting against different specific antigens.

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136. Selective processing of the thymus

Back 136

It's thymic education, baby.

The thymus makes certain that any T lymphocytes leaving will not react against proteins or other antigens that are present in the body's own tissue.

It selects which ones will be released by first mixing them with all the specific "self-antigens" from the body's own tissues. If it reacts, it is destroyed and phagocytized instead of being released.

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137. Where are B lymphocytes preprocessed?

Back 137

In the liver and bone marrow

Instead of the whole cell developing reactivity against an antigen, the B lymphocytes actively secrete antibodies that are the reactive agents.

B lymphocytes also have a greater diversity than T lymphocytes.

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138. Origin of the many clones of lymphocytes

Back 138

The whole gene for forming each type of T cell or B cell is never present in the original stem cells from which the functional immune cells are formed. Instead, there are only "gene segments"-actually, hundreds of such segments-but not whole genes. During preprocessing of the respective T- and B-cell lymphocytes, these gene segments become mixed with one another in random combinations, in this way finally forming whole genes.

For each functional T or B lymphocyte that is finally formed, the gene structure codes for only a single antigen specificity. These mature cells then become the highly specific T and B cells that spread to and populate the lymphoid tissue.

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139. Activating clones of B lymphocytes

Back 139

Each B lymphocyte has on the surface of its cell membranes about 100,000 antibody molecules that will react highly specifically w/only one specific type of antigen.

When the appropriate antigen comes along, it immediately attaches to the antibody in the cell membrane; this leads to the activation process.

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140. Activating clones of T lymphocytes

Back 140

Molecules similar to antibodies, called surface receptor proteins (or T-cell markers), are on the surface of the T-cell membrane, and these, too, are highly specific for one specified activating antigen.

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141. Role of macrophages in the activation process

Back 141

Most invading organism are first phagocytized and partially digested by the macrophages and the antigenic products are liberated into the macrophage cytosol.

The macrophages then pass these antigens by cell-to-cell contact directly to the lymphocytes, thus leading to activation of lymphocytic clones.

They also secrete IL-1 which also promotes growth of lymphocytes.

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142. Role of T cells in the activation of the B lymphocytes

Back 142

Some of the T cells that are formed, called "helper cells", secrete specific substances (lymphokines) that activate the specific B lymphocytes.

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143. Formation of antibodies by plasma cells

Back 143

On entry of a foreign antigens, macrophages in the lymphoid tissue phagocytize the antigen and then present it to adjacent B lymphocytes.

In addition, the antigen is presented to T cells at the same time, and activated helper T cells are formed.

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144. Formation of memory cells

Back 144

The B-cell population of the specifically activated clone becomes greatly enhanced, and the new B lymphocytes are added to the original lymphocytes of the same clone.

They spread throughout the body and remain dormant until activated once again by a new quantity of the same antigen.

Subsequent exposure will cause a much more rapid and potent antibody response the second time around.

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145. Differences between primary and secondary responses

Back 145

The primary responses usually have a 1-week delay, weak potency, and a short life.

The secondary response begins rapidly after exposure to the antigen, is far more potent, and forms antibodies for many months rather than only a few weeks.

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146. What are antibodies?

Back 146

They are gamma globulins called immunoglobulins; they are composed of light and heavy polypeptide chains.

They have a variable portion (for antibodies) and a constant portion (determines properties of antibody).

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147. Specificity of antibodies

Back 147

Each antibody is specific for a particular antigen; when the antibody is highly specific, there are so many bonding sites that the antibody-antigen coupling is exceedingly strong and is held together by:

1. Hydrophobic bonding
2. Hydrogen boding
3. Ionic attractions
4. van der Waals forces

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148. Ka (affinity constant)

Back 148

A measure of how tightly the antibody binds with the antigen

Ka= [Bound antibody-antigen]/([antibody]*[antigen])

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149. Classes of antibodies (five)

Back 149

1. IgM - primary response
2. IgG - 75% of antibodies
3. IgA
4. IgD
5. IgE - involved in allergies

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150. Two mechanisms of action of antibodies

Back 150

1. Direct attack
2. Activation of the "complement system"

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151. Direct action of antibodies

Back 151

1. Agglutination (clumping)
2. Precipitation
3. Neutralization
4. Lysis

Front 152

152. Complement system for antibody action

Back 152

"Complement" is a collective term that describes a system of about 20 proteins, many of which are enzyme precursors.

All these are present normally among the plasma proteins in the blood as well as among the proteins that leak out of the capillaries into the tissue spaces. The enzyme precursors are normally inactive, but they can be activated mainly by the so-called classic pathway.

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153. Classic pathway

Back 153

Initiated by an antigen-antibody reaction

when an antibody binds with an antigen, a specific reactive site on the "constant" portion of the antibody becomes uncovered, or "activated," and this in turn binds directly with the C1 molecule of the complement system, setting into motion a "cascade" of sequential reactions, beginning with activation of the proenzyme C1 itself.

The C1 enzymes that are formed then activates successively increasing quantities of enzymes, so that from a small beginning, an extremely large amplified reaction occurs.

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154. Important effects of the classic pathway

Back 154

1. Opsonization and phagocytosis
2. Lysis
3. Agglutination
4. Neutralization of viruses
5. Chemotaxis
6. Activation of mast cells and basophils
7. Inflammatory effects

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155. Release of activated T cells

Back 155

Principal difference from B cells is that instead of releasing antibodies, whole activated T cells are formed and released into the lymph, circulating again and again throughout the body.

Front 156

156. T-lymphocyte memory cells

Back 156

Formed in the same way that B memory cells are formed in the antibody system.

When a clone of T lymphocytes is activated by an antigen, many of the newly formed lymphocytes are preserved in the lymphoid tissue to become additional T lymphocytes of that specific clone.

These memory cells spread throughout the body and are more rapidly released upon second exposure.

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157. How do T lymphocytes respond to antigens?

Back 157

They respond only when they are bound to specific molecules called MHC proteins on the surface of antigen-presenting cells in the lymphoid tissues.

Front 158

158. Three major types of antigen presenting cells

Back 158

1. Macrophages
2. B lymphocytes
3. Dentritic cells.

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159. MHC proteins

Back 159

The MHC proteins are encoded by a large group of genes called the major histocompatibility complex (MHC). The MHC proteins bind peptide fragments of antigen proteins that are degraded inside antigen-presenting cells and then transport them to the cell surface.

There are two types of MHC proteins: (1) MHC I proteins, which present antigens to cytotoxic T cells, and (2) MHC II proteins, which present antigens to T helper cells.

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160. Three major groups of T cells

Back 160

1. Helper T cells
2. Cytotoxic T cells
3. Suppressor T cells

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161. Helper T cells

Back 161

Most numerous of the T cells; major regulators of all immune functions

Form a series of protein mediators called lymphokines that act on other cells of the immune system as well as on bone marrow cells; without lymphokines the immune system would be paralyzed

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162. Lymphokines formed by helper T cells

Back 162

1. IL-2
2. IL-3
3. IL-4
4. IL-5
5. IL-5
6. Granulocyte-monocyte colony-stimulating factor
7. Interferon-γ

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163. Interleukin-2

Back 163

The lymphokine interleukin-2 has an especially strong stimulatory effect in causing growth and proliferation of both cytotoxic and suppressor T cells.

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164. B-cell stimulating factors

Back 164

Almost all the interleukins participate in the B-cell response, but especially:

1. IL-4
2. IL-5
3. IL-6

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165. Activation of the macrophage system by T-cells

Back 165

1. They slow or stop the macrophages after they migrate via chemotaxis causing great accumulation

2. They activate the macrophages to cause far more efficient phagocytosis

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166. Feedback Stimulatory Effect on the Helper Cells

Back 166

Some of the lymphokines, especially interleukin-2, have a direct positive feedback effect in stimulating activation of the helper T cells themselves. This acts as an amplifier by further enhancing the helper cell response as well as the entire immune response to an invading antigen.

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167. Cytotoxic T cells

Back 167

A direct attack cell that is capable of killing micro-organisms an at times, even some of the body's own cells.

The receptor proteins on the surfaces of the cytotoxic cells cause them to bind tightly to those organisms or cells that contain the appropriate binding-specific antigen. Then, they kill the attacked cell.

After binding, the cytotoxic T cell secretes hole-forming proteins, called perforins, that literally punch round holes in the membrane of the attacked cell. Then fluid flows rapidly into the cell from the interstitial space. In addition, the cytotoxic T cell releases cytotoxic substances directly into the attacked cell. Almost immediately, the attacked cell becomes greatly swollen, and it usually dissolves shortly thereafter.

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168. Suppressor T cells

Back 168

They are capable of suppressing the functions of both cytotoxic and helper T cells.

It is believed that these suppressor functions serve the purpose of preventing the cytotoxic cells from causing excessive immune reactions that might be damaging to the body's own tissues.

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169. Examples of autoimmune diseases caused by the failure of the tolerance mechanism

Back 169

1. Rheumatic fever
2. Glomerulonephritis
3. Mayastenia gravis
4. Lupus erythematosus

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170. Immunization

Back 170

Immunity can be achieved against toxins that have been treated with chemicals so that their toxic nature has been destroyed even though their antigens for causing immunity are still intact. This procedure is used in immunizing against tetanus, botulism, and other similar toxic diseases

And, finally, a person can be immunized by being infected with live organisms that have been "attenuated." That is, these organisms either have been grown in special culture media or have been passed through a series of animals until they have mutated enough that they will not cause disease but do still carry specific antigens required for immunization. This procedure is used to protect against poliomyelitis, yellow fever, measles, smallpox, and many other viral diseases.

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171. Passive immunity

Back 171

Temporary immunity can be achieved in a person without injecting any antigen.

This is done by infusing antibodies, activated T cells, or both obtained from the blood of someone else or from some other animal that has been actively immunized against the antigen.

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172. Delayed reaction allergy

Back 172

Caused by activated T cells and not by antibodies.

Usually results in serious tissue damage

Example: poison ivy

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173. Allergic tendency

Back 173

Called atopic allergies b/c they are caused b a nonordinary response of the immune system.

Usually passed from parent to child.

Characterized by the presence of large quantities of IgE antibodies in the blood. These antibodies are called reagins or sensitizing antibodies to distinguish them from the more common IgG antibodies.

When an allergen (defined as an antigen that reacts specifically with a specific type of IgE reagin antibody) enters the body, an allergen-reagin reaction lakes place, and a subsequent allergic reaction occurs.

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174. Special characteristic of IgE antibodies

Back 174

strong propensity to attach to mast cells and basophils. Indeed, a single mast cell or basophil can bind as many as half a million molecules of IgE antibodies.

Front 175

175. Anaphylaxis

Back 175

When a specific allergen is injected directly into the circulation, the allergen can react with basophils of the blood and mast cells in the tissues located immediately outside the small blood vessels if the basophils and mast cells have been sensitized by attachment of IgE reagins.

Therefore, a widespread allergic reaction occurs throughout the vascular system

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176. Urticaria

Back 176

Urticaria results from antigen entering specific skin areas and causing localized anaphylactoid reactions.

Histamine released locally causes (1) vasodilation that induces an immediate red flare and (2) increased local permeability of the capillaries that leads to local circumscribed areas of swelling of the skin within another few minutes. The swellings are commonly called hives.

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177. Hay Fever

Back 177

In hay fever, the allergen-reagin reaction occurs in the nose. Histamine released in response to the reaction causes local intranasal vascular dilation, with resultant increased capillary pressure as well as increased capillary permeability.

Both these effects cause rapid fluid leakage into the nasal cavities and into associated deeper tissues of the nose; and the nasal linings become swollen and secretory.

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178. Asthma

Back 178

Asthma often occurs in the "allergic" type of person. In such a person, the allergen-reagin reaction occurs in the bronchioles of the lungs.

Here, an important product released from the mast cells is believed to be the slow-reacting substance of anaphylaxis, which causes spasm of the bronchiolar smooth muscle.