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Flashcards in Exam 1 Deck (185):
1

Distinguish between structural and functional causes of disease

-Structural cause is tissue loss or gain, material deposits like from smoking, obstruction like a clot, or distention, rupture, displacement. (mechanical)
-While functional are secretion loss or gain like a hormone, or impaired conduction or contractility. (chemical)
**Identifying the cause of the disease is the basis for rational treatment.

2

Subdivisions of pathology and what they consist of

1. Experimental (pathogenesis-from beginning to symptoms, etiology, epidemiology)
2. Anatomical (Autopsy, surgical, cytology and hematopathology)- It involves biopsy and studying cells and bone marrow and lymph to look at morphology of cells and tissue **based off morphology
3. Clinical (chemistry, urinalysis, hematology, serology, microbiology, virology, molecular, TDM, toxicology, coagulation, transfer med, point of care, flow cytometry) Studies more biochemical alterations and some morphology

3

Differentiate basic categories of disease etiology

1. Genetic-mutation, copy number
2. Radiation- free radicals, DNA damage
3. Chemical/drug- corrosion, interactions, DNA damage
4. Mechanical-cell/tissue loss
5. Thermal- enzyme distruption, protein coagulation
6. Infection-inflammatory damage, toxins
7. Immunologic- antibody formation
8. Iatrogenic- secondary to treatment or diagnostic procedure

4

Used to see smears of cells for hematology and cytopathology

light microscopy

5

Tissue section techniques for light microscopy

1. Fixation
2. Embedded in wax or plastic, or frozen
3. 2-5 microns thick (single cell layer)
4. Slides
5. Stains, IHC

6

what color do proteins and starch stain

pink

7

what color do nucleic acids (DNA, RNA) stain

blue

8

what color do air, water, sugar, lipids stain

do not stain (make white bubble area)

9

what color do natually colored materials stain

black, brown, green (keep their pigment)

10

what color does bile stain

golden (yellow/brown/green)

11

what color do hemosiderin and lipofuschin (iron) stain

brown

12

what color does carbon and melanin stain

black

13

what does PAS stain

starch/sugar (darker pink)

14

what does prussian blue stain

iron

15

what does Oil Red O stain

lipids

16

what machine is used to cut thin slices of tissue

microtome

17

lab techniques used by scientist

1. microscopy
2. Immunohistochemistry

18

describe immunohistochemistry

-produce antibodies to specific molecules, usually proteins
-attach a visual maker of some kind to antibody
-expose a tissue section to the labeled antibody

19

what information is found on a pathology report

1. patient info
2. accession # (ex. S13-1297)
3. gross description
4. microscopic description
5. diagnosis
6. tumor or lesion size (in cm)
7. margins
8. Otherr: samples sent for other test or a second opinion, TNM staging

20

what does patient info include on pathology report

name, birth date, biopsy date

21

what does gross description include on pathology report

color, weight, size of tissue as seen by naked eye. lesions identified

22

what does microscopic description include on pathology report

how tissue section looks under microscope compared to normal cells

23

what does positive margins mean on pathology report

abnormal cells are found at the edge of the material removed

24

what does negative margins mean on pathology report

no abnormal cells are found at the outer edge

25

what does close margins mean on pathology report

usually within 1mm

26

increase in the number of cells without an increase in the size of cells

Hyperplasia

27

Usually happens with cells with no ability to divide (muscle, myocardial) in response to increased demand on a cell to do whatever it does

hypertrophy

28

Physiologic example is weight lifting, pathologic is cardiomegaly from HTN

hyperplasia

29

increase in cell size without an increase in the number of cells

hypertrophy

30

increased division and/or decreased loss

hyperplasia

31

physiologic example is glandular tissue in breast in response to puberty and pregnancy

Hyperplasia

32

pathologic example is breast growth during pregnancy or liver regrowing after transplant

hyperplasia

33

most cells undergo hypertrophy and hyperplasia. an example is

uterine smooth muscle during pregnancy

34

decrease in scell size w/o decreased number of cells

atrophy

35

physiologic example is thymus in adulthood or uterus and testes in old age

atrophy

36

pathologic example is diuse, ischemia, or starvation

atrophy

37

incomplete development or underdevelopment- not reversible and not adaptive

hypoplasia

38

no growth, usually an embryologic failure

aplasia

39

transformation of one normal cell type into another normal cell type

metaplasia "changed growth"

40

ex. is transition of ciliated glandular epithelium to squamous epithelium in respiratory tissue of smokers

metaplasia

41

transition of squamous epithelium to glandular epithelium in esophageal relux

metaplasia

42

____ is often a precurosr to dysplasia

metaplasia

43

Disorderly, but non-neoplastic growth

dysplasia

44

ex of dysplasia

HPV in cervix

45

Can regress but characterized by one or more:
-hyperplasia, especially w/ increased mitotic figures
-cellular atypia
-decreased differentiation
-loss of architectural orientation

dysplasia

46

loss of organization (appearance on a cell slide)

dysplasia

47

appearance of dysplastic cells

-atypia
-pleomorphism
-high nuclear to cytoplasm ratio
-hyperchromasia (too much color) of the nucleus

48

-variable cell size/shape
-variable nucleus size/shape

pleomorphism

49

"new growth"

neoplasia

50

unregulated growth of abnormal tissue

neoplasia

51

is neoplasma adaptive or reversible

no and no

52

may or may not be cancer, depending on clinical behavior (malignant vs benign)

neoplasia

53

Ways to injure the cell (6)

1. Mechanical distruption
2. Energy failure
3. Failure of membrane functional integrity*
4. Membrane damage
5. Blockage of metabolic pathways
6. DNA damage or loss

*irreversible

54

what type of cellular injury?
-trauma
-osmotic pressure

mechanical distruption

55

what type of cellular injury?
-oxygen lack
-glucose lack
-mitochondrial failure

energy failure (decrease in ATP)

56

what type of cellular injury?
-damage to ion pump
-complement or perforins
-bacterial toxins

failure of membrane functional intergrity

57

what type of cellular injury?
-free radicals

membrane damage

58

what type of cellular injury?
-interruption of protein synthesis
-respiratory poisons
-horomone/growth factor lack

blockage of metabolic pathways

59

what type of cellular injury?
-ionising radiation
-chemotherapy
-free radicals

DNA damage or loss

60

factors associated with irreversible injury

1. persistent or excessive injury
2. Mitochondrial dysfunction
3. Membrane dysfunction

61

cell cannot return to normal function

irreversible cellular injury

62

how does freezing injure a cell

cell membrane perforation by ice crystals, dehydration

63

what type of cellular injury affects cells with high metabolic requirements the most and cells with higher glycolytic capacity less?

hypoxia

64

what cell injury has increased Ca2+ which results in enzyme activation?

hypoxia

65

what cellular injury can result in Reperfusion injury, and what is the direct cause of Reperfusion injury?

hypoxia
-caused by free radicals
- tissue damage caused when blood supply returns to the tissue after a period of ischemia or lack of oxygen

66

how do toxins cause cell injury

block essential pathways

67

what organ is greatly affected by glucose deprivation

brain
25% of brain requires glucose

68

what type of cellular injury causes:
cyanide binds iron --> hemoglobin dysfunction, loss of ATP production

toxins

69

Immunity type?
for molecules shared by groups of related microbes and moleules produced by damaged host cells

innate

70

Immunity type?
has memory cells

adaptive

71

Immunity type?
is very specific for microbial and nonmicrobial antigens

adaptive

72

Immunity type?
very large and diverse, receptors are produced by somatic recombination of gene segments

adaptive

73

Immunity type?
doesn't have memory cells

innnate

74

Immunity type?
limited diversity; germline encoded

innate

75

Immunity type?
contains skin, mucosal epithelia; antimicrobial molecules

innate

76

Immunity type?
lymphyocytes in epithelia; antibodies secreted at epithelial surfaces

adaptive

77

Immunity type?
blood proteins include antibodies

adaptive

78

Immunity type?
cells include lymphocytes

adaptive

79

Immunity type?
cells include phagocytes, natural killer cells, innate lymphoid cells

innate

80

Immunity type?
blood proteins include complement, others

innate

81

Describe the mechanisms of innate immunity

-body’s immediate response, not very specific.
-Targets general or common microbes and damaged body cells.
-It accomplishes this via cellular and chemical barriers (skin, mucosa, antimicrobial molecules), blood proteins (complement system) and via phagocytes (neutrophils, monocytes or macrophages) natural killer cells, and dendritic cells

82

List examples of non-specific defenses of innate immunity

1. mechanical barrier (skin, mucosa, cilia)
2. Environmental factor- (stomach and urine pH, sebaceous secretions of skin, normal flora)

83

molecules that have toll-like receptors to recognize common molecules on the surface of pathogens

macrophages & neutrophils

84

what type of receptors can recognize altered self molecules (oxidized LDL, glycated proteins, amyloid, apoptoic cells)

scavenger receptors

85

what cells directly kill cells which it senses are "not right" (virally infected, neoplastic, injured, etc)

natural killer cells

86

what inhibits natural killer cells

the presences of normal MHC I molecules (need MHC to know the molecule belongs)

87

what cell mediators are released by natural killer cells and what do they do?

Perforin and granzymes
-induce apoptosis
(perforin make a pore for the granzymes can get in and kill the virus in an organized/clean way)

88

How can you activate the complement system

1. Lectin pathway
2. classic pathway
3. Alternative pathway
- all result in an enzyme cascade in the blood--> create C3 convertases--> 3 different consequences of the complement

89

how does the lectin pathway active the complement

by recognizing mannose carbohydrates via the protein MBL (mannose binding lectin) and binding them on microbes cell surface

90

How is the classical pathway activated

activated via antigen/antibody complexes

91

how is the alternative pathway activated

activated via complement proteins directly binding microbe surface

92

C3 convertases influence 3 different pathways. What molecules are effected and what is the end result?

1.) C5a, C4a, C3a--> inflammation and cell recruitment
2.) C3b --> opsonisation, and removal of immune complexes
3.) C5-9--> cell lysis (non-confined cell death)

93

what turns off C3 convertase

C3

94

what molecules it the main opsonin

C3b

95

who has C3b receptors

phagocytes, B-cells, and T-cell subset
**they are recruited via opsoniaztion

96

anaphylatoxins and their job

C5a, C4a, C3a
-chemotactic for monocytes and neutrophils

97

what makes the membrane attack complex for the complement

C5-9

98

what is the purpose of fluid phase regulators and cell-associated regulators

keep complement under control

99

What are the fluid phase regulators

Factor I
C1 inhibitor (classic and lectin pathways)
S- protein (for C5-9)
F I, H related proteins (alternative**, also in lectin and classical)

100

What are the cell associated regulators

MCP: CD46 (cofacor for Factor I cleavage---- not on erythrocytes)
DAF: CD 55 (day of C3 and C5 converases)
HRF and CD59 (C8 inhibition)

101

what immunity?
undergoes clonal expansion

adaptive

102

what does clonal expansion occur and what is its purpose

expand if their receptors get bound
- increases the number of antigen-specific lymphocytes to keep pace with microbes

103

what immunity?
prevents injury to the host during responses to foreign antigens

adaptive

104

What turns on the adaptive immune system and stimulate a specific immune response

antigens

105

small molecules that stimulate an immune reponse only when attacked to a larger molecule

hapten

106

part of the antigen that is recognized by the immune system

epitope

107

more epitopes on a protein may allow for ____

rapid expansion if different antibodies recognize different epitopes

108

3 types of antigen binding molecules

immunoglobulin (Ig)
T cell receptors (TCR)
MHC molecules

109

most stable antigen binding molecule

MHC molecules

110

what antigen binding molecule?
nature of antigen that may be bound: peptide

MHC molecules
*non-specific peptides

111

what antigen binding molecule?
nature of antigen that may be bound: macromolecules (proteins, lipids, polysaccharides) and small chemicals

immunoglobluin
*most diverse

112

what antigen binding molecule?
nature of antigen that may be bound: peptide-MHC complexes

T cell receptors

113

where are HLA I found and what alleles make up the subclasses

-found on all nucleated cells (not RBC)
- Alleles/subclasses: A, B, C

114

what HLA class binds with the help of CD8

HLA I

115

what HLA class displays mostly exogenous, ingested peptide

HLA II

116

WHere are HLA II found and what alleles make up the subclasses

-found on specialized antigen presenting cells
-alleles/subclasses: DP, DQ, DR

117

what HLA class binds with the help of CD4

HLA II

118

what HLA class displays mostly self peptides and viral antigens

HLA I

119

lymphocytes

T cells
B cells
macrophages

120

each lymphocyte has receptors for how many antigens

1 antigen!

121

how is a cell activated (colonal selection) for proliferation (colonal selection)

binding of antigen

122

what cells have receptors usually made from an alpha and beta chain

T cell

123

parts of a t cell receptor

variable region- recognizes a specific antigen
constatn region- embeds in plasma membrane

124

arrangment of what regions on the variable region of a T cell receptor cause diversity

rearrangment of V, D, J regions

125

negative selection of T lymphocytes

cells which respond to presented self antigesn undergo apoptosis

126

positive selection of T lymphocytes

cells which bind to self MHC get a survival signal

127

what T cells are CD4 + and activate complementary B cells (humoral immunity)

Helper T cells

128

What T cells are CD 8+ and attack cells bearing recognized antigen (cell-mediated immunity)

cytotoxic T cells

129

Helper T cells bind to what MHC

MHC II

130

Cytotoxic T cells bind to what MHC

MHC I

131

Antigen presenting T cells

1. Macrophages (Kupffer cells, microglia, histiocytes)
2. Dendritic cells (spleen and lymph nodes)
3. Langerhans cells (skin)
4. B cells
** bind to MHC II

132

lymphocytes/ antigen presenting cells need ___ in order to become responsive and become anergic

co-stimulation

133

when can naive B cells mature into plasma cells

after thye are stimulated by antigens

134

what cell secretes antibodies

plasma cells

135

what immunity relies on antibodies

humoral immunity

136

what receptors bind antigens

immunoglobulins
(B cell receptors)

137

How does class switching occur

-IgM is secreted by T cell independent B cell activation
-further stimulation of CD4- on a B cells by CD 40 ligand on an activated T cell
-causes a shift in heavy chain production to G, A, or E

138

What are antibodies composed of?

2 light chains (kappa or lambda)
2 heavy chains (G, A, M, E or D)

139

what chain determines the class of antibody

heavy chain

140

what part of the antiboy binds to the plasma membrane

the heavy chains

141

antibodies are encoded by what immunoglobulin genes

V, D, J (variable segment)
C (constant segment)

142

first type of antibody produced (pentamer), expressed on naïve B cells

IgM
*largest antibody

143

normally not in blood, expressed on surface of naïve B cells

IgD

144

small amount in blood, bind mast cells in allergic responses (plays a role with parasites)

IgE

145

found in mucosal secretions, some in blood (dimer)

IgA
*smallest antibody

146

monomer, usually most abundant antibody produced

IgG

147

the only antibody secreted with T cell independent B cell activation

IgM

148

this involves the use of antibodies produced by the b cells to attack any invading foreign bodies like bacteria, viruses (out of cell) etc. Production of memory cells also takes place for a faster response in case of a second infection.

humoral immunity

149

this involves the destruction of self-cells damaged by mutations or infected by viruses intracellular. This form of immunity includes cells like cytotoxic T cells.

cell mediated immunity

150

sequence of events in normal humoral immunity

• B cell receptors (immunoglobulin) bind antigen
• Ingestion
• Present peptides to helper T cell by MHC II ( the T receptor contains CD4)
• Costimulation (CD28 on T cell) (remember CD40 is for class switch)
• B cells become activated and produce more membrane-bound antibody (secretory B cells)
• Stimulation via bound antibody causes differentiation into plasma cells and secretion of antibodies
• In some cases, T-cell independent antigens are recognized by multiple receptors on a B cell

151

Normal immune response with cell mediated immunity

• Often begins with macrophage or APC showing via MHC II to T-helper who activates cytotoxic T cells
• Cytotoxic T cells recognize peptides expressed on cells by MHC I molecules
• Induce apoptosis of the presenting cell
– Perforin: polymerizes to form a pore in the cell membrane
– Granzymes: enzymes that activate apoptosis
• Also secrete cytokines which potentiate other parts of the immune response
• Antibody dependent cytotoxicity
– NK cells, monocytes and neutrophils

152

what are the layers of a normal lymph node (inner to outter)

1. Medulla- mostly macrophages and plasma cells
2. Paracortex- T cells (CD4+ mostly)
3. Follicles - mostly B cells
4. Cortex- contains APC
5. Capsule

153

what ducts are in a lymph node

multiple afferent ducts
1 efferent duct

154

layers of a secondary follicle (inner to outter)

1. germinal center (secretory B cells, IgG)
2. Mantle Zone, MZ (naive B cells, IgM, IgD)
3. Marginal zone, MRZ (memory B cells)

155

describe the organziation of the spleen

made of:
white pulp- has lymph nodes like functions and is minority of tissue
Red pulp- filters blood and contains macrophages ready to engulf molecules, bound antibodies or worn out RBCs

156

what are the most important HLA subclasses

A, B, DR

157

having numerous allelic forms

polymorphism

158

what is the most important polymorphic system

HLA

159

when is HLA most important

-self and non-self recognition
-solid organ and stem cell transplant

160

How is HLA type obtained and expressed

inherited one from each parent
-co-dominant expression (all expressed)

161

the chance of complete HLA match amongst 2 full siblings is ____%

25%

162

why are HLA so diverse

they are polymorphic because they have so many different alleles
(ex. A-2013, B-2605, C 1551 alleles
DR-1267, DQ-223, DP-189 alleles)

163

successful organ transplant requires:

1. matching
2. sufficient pharmacologic suppresion of immune system to prevent rejection
3. Caution not to over suppress

164

what can over suppressing the immune system cause

prediposition to opportunistic infections, tumors, graft-vs-host disease

165

donor immune T cells attack the recipient tissue

graft vs host disease

166

patient immune T cells attack the donor graft

rejection

167

rejection often occur with what organs

renal
cardiac
bone marrow

168

What to do before a transplant

1. type the recipient (ABO and HLA)
2. screen recipient for presence of exisiting antibodies

169

when is ABO matching crucial and when is it not as important

Crucial for solid organ transplant
-not as cruical for HSC transplant (hematopoietic stem cell)

170

When is HLA matching most crucial and when does it not matter as much

crucial for HSC transplant
-not as cruical for solid organ

171

kidney transplant requires what HLA matches

A, B, DR

172

heart and lung transplant requires what in regards to HLA

need to avoid prior HLA antibodies

173

liver transplant requires what in regards to HLA

HLA matchingnot crucial

174

causes of transplant rejection

MHC on allogenic graft cells seen as foreign by recipients T cells

175

Immune response to rejection

-T helper cells proliferate and secrete cytokines
-Cytotoxic T cells directly attack the graft

176

3 types of clinical transplant rejection

1. hyperacute
2. acute
3. Chronic

177

-Pre-formed anti-donor antibodies react with ABO or MHC I in donor kidney
-Complement is activated and get obstruction of vessels and ischemia
-Destruction of tissue then occurs to donor kidney.

hyperacute rejection

178

Since immunosuppression isn’t perfect, small amounts of damage occur over years and eventually destroy transplant.

chronic rejection

179

Immunosuppression fails and antibodies can attach donor organ in weeks or months following transplant
- Usually involves CD4 and CD8 T cells. Prompt treatment can reverse kidney damage.

acute rejection

180

what rejection can cause:
-activation of complement
-influx of PMNs
-platlet aggregation
-rapid destruction (within minutes to hours of transplant)

hyperacute rejection

181

what rejection involves CD4+ and CD8+ T lymphocytes that cause mononuclear inflammation

acute rejection

182

what rejection causes thickening of glomerular basement membrane, hyalinization of the glomeruli, intestitial fibrosis, and proliferation of endotheial cells

chronic rejection

183

what rejection causes a build up of collagen and closes off their own vessels

chronic rejection

184

Mostly attacks the liver, skin and GI tract causing jaundice, rash or bloody diarrhea. Treat with immunosuppression

graft vs host disease

185

Usually in immunocompromised or HLA similar patients. Causes fever, liver dysfunction, rash, diarrhea and bone marrow hypoplasia. Treated with steroids and supportive care

Transfusion-associated GVHD
(TA-GVHD)