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Pathology > Pathology I (end page 16) > Flashcards

Pathology I (end page 16) Flashcards

1
Q

Pathway responsible for decreasing cell number

A

Apoptosis

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2
Q

Pathway responsible for decreasing cell size

A

Ubiquitin-Proteosome

degradation/autophagy..ubiquitin is a tag, proteosome is they degradation powerhouse

vauoles - lysosomes - hydrolytic enzymes

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3
Q

Metaplasia

A

induced by stress
metaplastic cells are better able to handle stress

classic example - barrets esophagus - due to acid reflux

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4
Q

Barrets Esophagus

A

metaplastic change from nonkeratinized squamous (which is able to handle friction of food bolus) to squamous non ciliated mucin producing cells (better able to tolerate acid)

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5
Q

Is Metaplasia reversible?

A

yes if stressor is removed in time e.g. treating GERD

however, if it persists, can progress to dysplasia, e.g. barrets progressing to adenocarcinoma

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6
Q

Apocrine Metaplasia of The Breast

A

metaplasia induced, however even if persistent, carries no increased risk of cancer

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7
Q

Vitamin A Metaplasia

A

ketaomalacia of the conjunctiva - conversion of goblet cell columnar to keratinized squamous

induced by vitamin A defeciency; vit A needed for proper differentiation of conjunctival tissue

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8
Q

Myositis Ossificans

A

connective tissue in muscle changes to bone, during healing, after trauma

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9
Q

Dysplasia

A

disordered cell growth
typically a precancerous growth

can stem from hyperplasia (endometrial hyperplasia) or metaplasia (barrets esophagus)

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10
Q

Aplasia

A

aplasia is a failure of cell production during embryogenesis

example: unilateral renal agenesis

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11
Q

Hyoplasia

A

decrease in cell production in embryogenesis

results in small organ

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12
Q

Streak Ovary

A

Turner Syndrome

example of small organ formation from hypoplasia

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13
Q

slow developing ischemia

A

e.g. renal artery atherosclerosis

results in atrophy

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14
Q

acute ischemia

A

e.g. renal artery embolus

results in injury

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15
Q

Final electron acceptor in oxidative phorphorylation

A

oxygen

hypoxia can impair pathway; impair ATP production

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16
Q

Causes of Ischemia

A

decreased arterial perfusion (atherosclerosis)
decreased venous drainage (Budd-Chiari Syndrome)
shock (generalized hypotension)

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17
Q

Hypoxemia

A

arterial pressure (o2)

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18
Q

Causes of Hypoxemia

A 
high altitude (decreased barometric pressure)
hypoventilation (increased pCO2 and decreased O2)
Diffusion Defect - can't push as much oxygen into blood
V/Q Mistmatch - blood bypasses oxygenated lung or oxygenated air cannot reach the lung
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19
Q

Diffusion Defect

A

can’t push as much oxygen into blood

e.g. pulmonary interstitial fibrosis

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20
Q

V/Q Mistmatch

A
  • blood bypasses oxygenated lung (right to left shunt)

- or oxygenated air cannot reach the lung (ventilation problem; atelectasis)

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21
Q

Anemia

A

decrease in mass of RBC

saturation of oxygen and arterial oxygen pressure are NORMAL

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22
Q

Carbon Monoxide Poisoning

A

CO binds Hgb more closely than O2
classic sign - cherry red skin
early sign of exposure - headaches

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23
Q

Methemoglobinemia

A

iron in heme oxidized to 3+ instead of 2+
can’t bind oxygen as well
saturation goes down
arterial pressure remains same

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24
Q

Where do you see Methemoglobinemia?

A

oxidant stress (sulfa and nitrate drugs) or in newborns

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25
Q

Classical Findings of Methemoglobinemia

A

cyanosis

chocolate colored blood

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26
Q

Treatment of Methemoglobinemia

A

IV metheylene Blue - helps turn Fe 3+ to 2+

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27
Q

Hallmark of Reversible Cell Injury

A

cell swelling

initial phase of cell injury is reversible

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28
Q

Initial Phase of Cell Injury

A

reversible
loss of microvilli
membrane blebbing
swelling of rER - dissociation of ribosomes - decreased protein synthesis

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29
Q

Hallmark of Irreversible Injury

A

Membrane Damage **

end result of irreversible injury is cell death

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30
Q

Result of Membrane Damage (irreversible injury)

A 
enzyme leakage (serum troponin)
additional calcium enters the cell **
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31
Q

Mitochondrial Damage

A

loss of electron transport chain (inner mitochondrial membrane)
cytochrome c leaks into cytosol

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32
Q

Cytochrome C leakage

A

leaks into cytosol from cell damage

activates apoptosis

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33
Q

Morphological Hallmark of Cell death

A

Loss of a nucleus

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34
Q

Loss of Nucleus

A

nuclear condensation (pyknosis)
fragmentation (karyorrhexis)
dissolution (karyolysis)

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35
Q

2 mechanisms of cell death

A
  • necrosis and apoptosis *
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36
Q

necrosis (ALWAYS PATHOLOGICAL)

A

followed by acute inflammation

has several gross patterns

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37
Q

Coagulative Necrosis

characteristic of ischemic infarcts

A

tissue remains firm
cell shape/organ structure preserved by coagulation of proteins
nucleus disappears
wedge shaped on gross exam; pale appearance

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38
Q

Characteristic of Ischemic Infarcts

A

Coagulative Necrosis ** (except for brain)*

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39
Q

Red Infarctions

A

occurs if blood re enters loosley organized tissue following a coagulative necrosis

e.g. pulmonary and testicular infarcts*

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40
Q

Liquefactive Necrosis

A

necrotic tissue becomes liquefied; enzymatic lysis

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41
Q

Liquefactive Necrosis is characteristic of:

A

Brain Infarction* - proteolytic enzymes from microglial cells

Abscess* - proteolytic enzymes from neutrophils

Pancreatitis* - proteolytic enzymes from pancreas liquify parenchyma

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42
Q

3 places you will find Liquefactive Necrosis

A

Abscess
Brain Infarct
Pancreatitis

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43
Q

Gangrenous Necrosis

A
  • coagulative necrosis that resembles mummified tissue (dry gangrene)
  • ischemia of lower limb and GI tract
  • if superimposed infection then can get liquefactive necrosis on top of it (wet gangrene)
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44
Q

Caseous Necrosis

A

soft and friable necrotic tissue with cottage cheese appearance

combination of coag. and liquefactive necrosis

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45
Q

Ischemia of lower limb and GI tract

A

Gangrenous Necrosis

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46
Q

Wet Gangrene vs. Dry Gangrene

A

Wet - gangrenous necrosis with superimposed infection that precipitates liquefactive necrosis

Dry - coagulative necrosis that resembles mummified tissue

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47
Q

Common Places you will find Caseous Necrosis

A

granulmatous inflammation due to TB or fungal infection

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48
Q

Granulamatous inflammation due to TB or Fungal Infection

A

Caseous Necrosis is a common feature*

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49
Q

Fat Necrosis

A

chalky white appearance due to calcium deposition

fatty acids released from damage to fat e.g. breast or pancreatitis mediated damage of peripancreatic fat

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50
Q

Fat Necrosis and Saponification

A

Saponification - fatty acids join with calcium
- saponification is an example of dystrophic calcification in which calcium deposits on dead tissues

necrotic tissue acts as a nidus for calcification in setting of NORMAL serum calcium and phosphate

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51
Q

Saponification and Dystrophic Calcification

A

necrotic tissue acts as a nidus for calcification in setting of NORMAL serum calcium and phosphate

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52
Q

Fat Necrosis and Metastatic Calcification

A

unlike dystrophic calcification…occurs when there is HIGH serum calcium and phosphate levels

leads to calcium deposition in tissues (hyperparathyroidism leading to nephrocalcinosis)

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53
Q

Fibrinoid Necrosis

A

necrotic damage to blood vessel
leakage of fibrin
bright pink staining
malignant hypertension and vasculitis

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54
Q

2 common pathologies with fibrinoid necrosis

A

malignant HTN and Vasculitis

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55
Q

Apoptosis

A 
ATP dependent
Examples 
- endometrial shedding
- removal of cells durng embryogenesis
- CD8 T cell mediated killing of virally infected cells
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56
Q

CD8 T cell mediated killing of Virally infected cells

A

Apoptosis

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57
Q

Morphology of Apoptosis

A

Dying cell - shrinks, cytoplasm will become more eosinophlic (pink)

Nucleus condenses and fragments in organized manner

apoptotic bodies fall from cell and removed from macrophages

no inflammation follows

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58
Q

Does Inflammation Follow Apoptosis?

A

No

59
Q

Apoptosis and Caspases

A

Apoptosis is mediated by Caspases that activate proteases and endonucleases

  • proteases break down the cytoskeleton
  • endonucleases break down DNA
60
Q

Activation of Caspases

A
  1. Intrinsic Mitochondrial Pathway
    - loss of Bcl2
  2. Extrinsic Receptor Ligand Pathway
    - FAS death receptor (CD95)
    - TNF
  3. Cytotoxic CD8 T Cell Pathway
    - perforins
    - granyzmes
61
Q

Activation of Caspases - Intrinsic Pathway

(discuss Bcl2)

A
  1. Intrinsic Mitochondrial Pathway
    - cell injury, DNA damage, or decreased hormonal stimulation leads to inactivation of Bcl2
    - lack of Bcl2 allows cytochrome c to leak from inner mitochondrial matrix into the cytoplasm and activate caspases
62
Q

Activation of Caspases - Extrinsic Pathway

example is negative selection of thymocytes in thymus

A
  1. Extrinsic - Receptor Ligand Pathway
  • FAS ligand binds FAS death receptor (CD95) on target cell activating caspases
  • TNF binds tumor necrosis factor receptor on target cell activating caspases
63
Q

Activation of Caspases - Cytotoxic CD8 Pathway

A
  1. Cytotoxic CD8 T Cell Pathway
  • perforins secreted by CD8 T cell creates pores in membrane of target cell
  • Granzyme from CD8+ T cell enters pores and activates caspases
  • CD8+ T cell killing of virally infected cells is an example
64
Q

PHYSIOLOGIC generation of free radicals occurs during:

A

oxidative phosphorylation.

  1. cytochrome c oxidase (complex IV) transfers electrons to O2
  2. partial reduction of O2 yields superoxide, H202, and OH radicals
65
Q

PATHALOGIC generation of free radicals occurs during:

A

arises with:

  1. ionizing radiation - water to hydroxyl radical
  2. inflammation - NADPH oxidase generates superoxide during oxygen dependent killing by neutrophils
  3. Metals - Fe 2+ for example generates OH radicals via Fenton Reaction
  4. Drugs - P450 metabolizes drugs in liver, generates free radicals
66
Q

Elimination of Free Radicals

A
  1. Antioxidants (Vitamins A, C, E) / Glutathione
  2. Enzymes
    i - superoxide dismutase (mitochondria)
    ii - Glutathioine Peroxidase (mitochondria)
    iii - Catalase (peroxisomes)
  3. Metal Carrier Proteins
    - e.g. transferrin and ceruloplasmin
67
Q

Location of Enzymes that Eliminate Free Radicals

A

i - Superoxide Dismutase (mitochondria)

ii - Glutathioine Peroxidase (mitochondria)

iii - Catalase (peroxisomes)

68
Q

Examples of Free Radical Injury - Carbon Tetrachloride

A

CCl4

  • dry cleaning industry
  • converted to CCl3 free radical by P450
  • cell swells - ribosomes detach - protein syn. is shot
  • decreased apolipoproteins
    • leads to fatty change in the liver
69
Q

Examples of Free Radical Injury - Reperfusion Injury

A
  1. Return of blood to ischemic tissue results in production of Oxygen derived free radicals which further increases damage tissue
  2. leads to continued rise in cardiac enzymes **
    - (e.g. troponin) after reperfusion to infarcted Myocardium
70
Q

Basic Principles of Amyloidosis

A

Amyloid = misfolded protein that deposits in extracellular space, thereby damaging tissues

Multiple proteins can deposit as amyloid; shared features:

  • **beta pleated sheet configuration ***
  • **Congo red staining and apple green birefringence when viewed under polarized light ***

Deposition can be systemic or localized

71
Q 
Systemic Amyloidosis (deposition in multiple organs)
(Primary)

[AL Amyloid)

A
  1. Primary
    - deposition of AL Amyloid (derived from immunoglobulin light chain)
    - associated with plasma dyscrasias (multiple myeloma)
72
Q 
Systemic Amyloidosis (deposition in multiple organs)
(Secondary)

[AA Amyloid)

A
  1. Secondary
    - deposition of AA amyloid which is derived from serum amyloid associated protein (SAA)
  • SAA is an acute phase reactant that is increased in chronic inflammatory states, malignancy, and Familial Mediterranean Fever (FMF)
73
Q

FMF (Familial Mediterranean Fever)

A
  • FMF is due to a dysfunction of neutrophils (autosomal recessive) and occurs in persons of Med. Origin
  • Presents with episodes of fever and acute serosal inflammation (can mimic appendicits, arthritis, or MI)
  • High SAA during attacks deposits as AA amyloid in tissue
74
Q

Classic Clinical Findings of Systemic Amyloidosis*

A
  1. Nephrotic Syndrome - kidney is most commonly involved organ
  2. Restrictive Cardiomyopathy or Arryhtmia
  3. Tongue Enlargement, malabsorption, hepatosplenomegaly
75
Q

Diagnosis of Systemic Amyloidosis

A

needs tissue biopsy

abdominal fat pad and rectum easily accessible targets

76
Q

Organ Damage From Systemic Amyloidosis

A

organs must be transplanted because you cannot remove amyloid*

77
Q

Localized Amyloidosis

A

confined to a single organ

Senile Cardiac Amyloidosis

Familial Amyloid Cardiomyopathy

Non Insulin Dependent Diabetes Mellitus

Alzheimers

Dialysis-associated amyloidosis

Medullary Carcinoma of Thyroid

78
Q

Senile Cardiac Amyloidosis

A

NON-mutated form of serum transerythrin deposits in the heart

usually asymptomatic - present in 25% of ppl over 80

79
Q

Familial Amyloid Cardiomyopathy

A

MUTATED serum transerythretin deposits in the heart leading to restrictive cardiomyopathy

5% of African-Americans carry the mutated gene

80
Q

Non Insulin Dependent Diabetes Mellitus

A

Amylin (derived from insulin) deposits in the islets of pancreas

81
Q

Alzheimers

A

alpha beta amyloid derived from beta amyloid precursor protein, deposits in the brain

gene for beta - APP is on chromosome 21
- therefore, most individuals with Down’s syndrome develop Alzheimer disease by age 40 (early onset)

82
Q

Dialysis-associated amyloidosis

A

beta 2 microglobulin deposits in joints

83
Q

Medullary Carcinoma of Thyroid

A

calcitonin deposits witin tumor

“tumor cells in an amyloid background”

84
Q

Acute Inflammation

A

edema and neutrophils **

innate resposne with limited specificity (innate immunity)

85
Q

Edema and Neutrophils

A

hallmark of acute necrosis

86
Q

Mediators of Acute Inflammation

A

Toll Like Receptors

Arachiadonic Acid

Mast Cells

Complement

Factor XII (Hageman Factor)

87
Q

Toll Like Receptors (TLRs)

A

present on innate immune system cells like macrophages and dendritic cells

activated by PAMP patterns commonly shared by microbes

TLRs are present on cells of adaptive immunity
(lymphocytes) and hence play role in chronic inflammation

88
Q

TLRs and PAMP

Upregulation of NF-kB

A
  1. CD14 (co receptor for TLR4) on macrophages recognizes LPS (a PAMP) on outer membrane of gram- bacteria

TLR activation leads to upregulation of NF-kB which is a transcription factor that leads to upregulation of nuclear transcription factor that activates production of immune mediators

89
Q

Arachadionic Acid (AA)

A

released from phospholipid cell membrane by phospholipase A2 and then acted on by COX enzyme or 5-Lipoxygenase

COX produces PGs

  1. PGI2, PGD2, and PGE2 mediate vasodilation and permeability
  2. PGE2 also mediates pain and fever
90
Q

5 Lipoxygenase

A

makes LTs

LTB4 attracts and activates neutrophils

LTC4, LTD4, LTDE4 (slow reacting substancs of anaphylaxis mediate vasoconstriction, bronchospasm, and increased cell permeability.

91
Q

Mast Cells

A

widely distributed in connective tissue

activated by tissue trauma, C3a, C5a, cross linking of IgE by antigen

Immediate response = histamine release - vasodilation/ permeability

delayed response = production of AA and metabolites (esp LTs)

92
Q

Activation of Complement (3 routes)

A
  1. classical pathway - C1 binds IgG or IgM bound by antigen
  2. alternate pathway - microbial products directly activate complement
  3. Mannose Binding Lectin (MBL) Pathway
    - MBL binds to mannose on microbes and activates complement
93
Q

Convergence of Complement Activation

A

All pathways will result in production of C3 convertase which mediates C3a and C3b production from C3

This in turn produces C5 convertase - which will yield C5a and C5b

94
Q

C5b

A

complexes with C6-9 to form membrane attack complex (MAC)

95
Q

C3a and C5a (anaphylotoxins)

A

trigger mast cell degranulation resulting in histamine mediated inflammation / permeability

96
Q

C5a

A

chemotactic for neutrophils

97
Q

C3b

A

opsonin for phagocytosis

98
Q

MAC

A

lyses microbes (“MAC attack”

99
Q

Hageman Factor (Factor XII) Activation

A

inactive proinflammatory protein made by liver

activated upon exposure to subendothelial tissue or tissue collagen

100
Q

Activated Factor XII (Hageman Factor) in turn activates:

A

activates

  1. coagulation and fibrinolytic systems
  2. complement
  3. Kinin System - kinin cleave high molecular weight kinogen (HMWK) to bradykinin

bradykinin mediates vasodilation and pain

101
Q

What are the cardinal signs of inflammation?

A
  • Redness, Warmth (rubor, calor)
    • due to vasodilation (histamine, prostaglandins, bradykinin)
  • Swelling (tumor)
    • leakage of post capillary venules (exudate)
  • Pain (dolor)
    • PGE2 and bradykinin
  • Fever
    • pyrogens (LPS from bacteria) cause macrophages to release IL-1 and TNF which causes COX activity to increase in perviascular cells of hypothalamus
102
Q

PGE2 and Bradykinin

A

sensitize pain receptors

increase in PGE2 raises temperature

103
Q

Fever

A

pyrogens (LPS from bacteria) cause macrophages to release IL-1 and TNF which causes COX activity to increase in perviascular cells of hypothalamus

increase in PGE2 raises temperature

104
Q

Key Steps of Neutrophil Arrival And Function

A
  1. Margination
  2. Rolling

3 Adhesion

  1. Transmigration and Chemotaxis
  2. Phagocytosis
  3. Destruction of Phagocytosed Material
  4. Resolution
105
Q

What is Margination

A

vasodilation slows blood flow in postcapillary venules

cells marginate* from the center of flow to the periphery

106
Q

What is the Rolling Phase?

A

selectin “speed bump” upregulation on endothelial cells

P selectin release from Weibel Palade bodies is mediated by histamine

E selectin induced by TNF and IL-1

Selectins will bind sialyl Lewis X on leukocytes

interaction results in leukocytes rolling on vessel wall

107
Q

What is the Adhesion phase?

A

cell adhesion molecules ICAM and VCAM are upregulated on endotheleium by TNF and IL-1

LTB4 and C5a upregulates integrins on leukocytes

CAM and integrins will interact

108
Q

Leukocyte Adhesion Deficiency

A

most commonly due to autosomal recessive defect of integrins (CD18 subunit)

Clinical Features
- delayed separation of umbilical cord, increased circulating neutrophils (due to impaired adhesion of marginated pool of leukocytes), and recurrent bacterial infections that lack pus formation

109
Q

Clinical Features of Leukocyte Adhesion Deficiency

A

delayed separation of umbilical cord,

increased circulating neutrophils (due to impaired adhesion of marginated pool of leukocytes)

recurrent bacterial infections that lack pus formation

110
Q

Transmigration and Chemotaxis

A

leukocytes transmigrate across the endothelium of postcapillary venules and move toward chemical attractants (chemotaxis)

neutrophils are attracted by bacterial products
(IL-8, C5a, LTB4)

111
Q

Phagocytosis

A

consumption of pathogens or necrotic tissue; phagocytosis is enhanced by opsonins (IgG and C3b)

pseudopods extend from leukocytes to form phagosomes, internalized /merge with with lysosomes - form phagolysosomes

112
Q

C3b and IgG

A

enhance phagocytosis

113
Q

Chediak Higashi

A

protein trafficking defect (autosomal recessive) characterized by impaired phagolysosome formation

Features

  • increased risk of pyrogenic infection
  • neutropenia (due to intramedullary death of neutrophils)
  • giant granules in leukocytes (due to fusion of granules arising from the golgi apparatus)
  • defective primary hemostasis (abnormal dense granules in platelets)
  • albinism
  • peripheral neuropathy
114
Q

Clinical Features of Chediak Higashi

A
  • increased risk of pyrogenic infection
  • neutropenia (due to intramedullary death of neutrophils)
  • giant granules in leukocytes (due to fusion of granules arising from the golgi apparatus)
  • defective primary hemostasis (abnormal dense granules in platelets)
  • albinism
  • peripheral neuropathy
115
Q

Destruction of Phagocytosed Material

A
  1. oxygen dependent killing is most effective mechanism possible
  2. HOCl generated by oxidative burst in phagolysosomes destroys phagocytosed microbes
    i) oxygen converted to Oxygen radical by NADPH (oxidase) (oxidative burst)
    ii) oxygen radical converted to H2O2 by superoxide dismutase (SOD)
    iii) H202 is converted to HOCl (bleach) by myeloperoxidase (MPO)
116
Q

Oxidative Burst

A

i) oxygen converted to Oxygen radical by NADPH (oxidase) (oxidative burst)
ii) oxygen radical converted to H2O2 by superoxide dismutase (SOD)
iii) H202 is converted to HOCl (bleach) by myeloperoxidase (MPO)

117
Q

Chronic Granulmatous Disease (CGD)

A

characterized by poor oxygen dependent killing

NADPH oxidase defect (autosomal recessive or X linked)

recurrent infection / granuloma formation with catalase organisms

118
Q

Key organisms with CGD disease*

A 
staph aureus
pseudomonas capacia
settatia marcescens
nocardia
aspergillus
119
Q

How to Screen For CGD

A

Nitroblue Tetrazolium

leukocytes are incubated with NBT dye, which turns blue if NADPH oxidase can convert oxygen to oxygen radical

will remain colorless if defective

120
Q

MPO Defeciency

increases risk to Candida infection

A

defective conversion from H202 to HOCl

i) increased risk for candidal infections, however most patients are asymptomatic
ii) NBT is normal; respiratory burst (oxygen to H202) works normally

121
Q

Resolution Step of Neutrophil Activation

A

neutrophils undergo apoptosis and disappear within 24 hrs after resolution of the inflammatory stimulus

122
Q

Macrophages

A

peak 2-3d after neutrophils
derived from blood monocytes

manage next step of inflammatory process:
1. resolution and healing - IL-10 and TGF beta

  1. continued acute inflammation - IL-8, key feature is persistent pus formation
  2. abscess - fibrogenic surrounding process
  3. chronic inflammation - antigen presentation
123
Q

IL-10 and TGF Beta

A

made by macrophages - anti-inflammatory cytokines

124
Q

IL-8

A

from macrophages - recruits additional neutrophils

125
Q

macrophages and abscess

A

acute inflammation surrounded by fibrosis

macrophages mediate fibrosis via fibrogenic growth factors and cytokines

126
Q

macrophages and chronic inflammation

A

macrophages present antigen to activate CD4 helper cells which will secrete cytokines that promote inflammation

127
Q

Chronic Inflammation

A

charicterized by presence of lymphocytes and plasma cells in tissue

delayed response, but more specific (adaptive immunity) than acute inflammation

stimuli:

  • persistent infection (most common cause)
  • infection with viruses, mycobacteria, parasites, fungi
  • autoimmune disease
  • foreign material
  • some cancers
128
Q

T Lymphocytes

A

produced in bone marrow as progenitor T cells

further develop in the thymus where the T cell receptor (TCR) undergoes rerrangement and progenitor cells become CD4+ helpter T cells OR CD8 cytotoxic T cells

129
Q

Further Development of T Lymphocytes

A

rearrangement of TLR - progenitors become CD4 or CD8

T cells use TCR complex (TCR and CD4) for antigen surveillence

TCR complex recognizes antigen presented on MHC molecules

  • CD4+ T cells - MHC class II
  • CD8+ T cells - MHC class I

Activation of T Cells requires

1) binding of antigen/MHC complex
2) an additional second signal

130
Q

CD4 Helper T cell activation

A
  1. extracellular antigen (foriegn protein) is phagocytosed, processed, and presented on MHC class II, which is expressed by antigen presenting cells (APCs)
  2. B7 on APC binds CD28 on CD4 helper T cells providing the additional second signal
  3. Activated CD4 helper T cells secrete cytokines which help inflammation and are divided into 2 subsets
131
Q

B7 on APC

A

Binds CD28 on CD4 helper T cells providing the additional second signal

Activated CD4 helper T cells secrete cytokines which help inflammation and are divided into 2 subsets

  1. TH1 subset secretes interferon gamma
  2. TH2 secretes IL-4, IL-5, IL-13
132
Q

TH1

A

secretes interferon gamma

activates macrophages

promotes B cell class switching from IgM and IgG

promotes TH1 phenotype and inhibits TH2 phenotype

133
Q

TH2

A

secretes IL-4, IL-5

IL-4: facilitates B cell class switching to IgE

IL-5: eosinophil chemotaxis and activation, and class switching to IgA

IL-13: functions similar to IL-4

134
Q

CD8 Cytotoxic T Cell Activation

A

antigen presented on MHC class I

IL-2 from CD4 TH1 cell provides 2nd activation signal

cytotoxic T cells activated for killing

killing occurs via

  • perforin and granzyme secretion
  • expression of FasL, binds Fas on target cells, activating apoptosis
135
Q

Mechanism of Killing via Cytotoxic T Cells

A

perforin and granyzme secretion

expression of FasL which binds Fas on the target, activating apoptosis

136
Q

B Lymphocytes

A

Immature B cell made in bone marrow and undergo immunoglobulin rearrangment to become native B cells that express IgM or IgD

137
Q

B cell activation

A
  1. antigen binding by surface IgM or IgD resulting in maturation to IgM or IgD secreting plasma cells
  2. B cell antigen presentation to CD4 helper T cells via MHC class II
    i) CD40 receptor on B cell binds CD40L on helper T cell, providing 2nd activation signal
    ii) Helper T cell then secretes IL-4 and IL-5 (mediates B cell isotype swithing, hypermutation, and maturation plasma cells)
138
Q

Granulomatous Inflammation is a subtype of:

A

chronic inflammation

139
Q

Granulmatous Inflammation is charicterized by:

A

granulomas
- collection of epitheloid histiocytes (macrophages w/ abundant pink cytoplasm) usually surrounded by giant cells and a rim of lymphocytes

divided into caseating and non caseating subtypes

140
Q

Non Caseating vs. Caseating

A

Ceaseating
- these granulomas exhibit central necrosis and are charicteristic of fungal and TB infections

Non Caseating
- lack central necrosis

141
Q

Common Etiologies of Non-Caseating Granulomas

remember that NON caseating is NON central necrosis

A

rxn to foriegn material

sarcoidosis

beryllium exposure

crohn’s disease

cat scratch fever

142
Q

Granuloma Formation

A
  1. Macrophages process and present antigen via MHC Class II to CD4 helper T cells
  2. Interaction leads macrophages to secrete IL-12, inducing CD4 helper T cells to differentiate into TH1 subtypes
  3. TH1 cells secrete IFN gamma, which converts macrophages to epitheloid histiocytes and giant cells
143
Q

Granulomas and IFN-gamma

A

TH1 cells secrete IFN gamma, which converts macrophages to epitheloid histiocytes and giant cells

Pathology (2 decks)

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