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COT > Quiz 6 > Flashcards

Quiz 6 Flashcards

1
Q

what are the major components of innate immunity

A

complement protiens
neutrophils
macrophage
innate lymphoid cells

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2
Q

what are the major mechanisms of the innate immune system

A

-invaders may be distroyed directly through reconition of foreign molecules of lack of self-MHCs
-the signaling action of cytokines ramps up the cellular response
-phagocytes recognize opsonizing “tags” and opsonized antibodies & destroy marked cells

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3
Q

what are the 3 pathways to activate the complement cascade

A

classical
lectin
alternative

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4
Q

what is the classical complement cascade?

A

recognition of antigens by antibodies produced by B-lymphocytes

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5
Q

what is the lectin complement cascade

A

recognition of foreign sugars in cell membrane

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6
Q

what is the alternative complement cascade?

A

automatic destruction of cells that can’t inactivate C3

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7
Q

what is the life cycle of a neutrophil?

A

-born in marrow
-“marginal pool” stored in marrow, usually in adult form,
waiting to release
-released in circulation, usually in adult form, but possibly as band cell
-enters connective tissue via rolling adhesion and diapedesis
-“dies” upon use

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8
Q

what do tertiary granules in neutrophils do

A

facilitate migration to
target; disolve tissue in it’s way

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9
Q

what do specific granules of neutrophils do?

A

kill bacteria with enzymes and reactive oxygen compounds

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10
Q

what do azurophilic granules in neutrophils do?

A

lysosomal enzymes digest bacteria

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11
Q

pyrogen

A

a substance that causes a rise in temperature (fever reaction) in a human or animal through the activation of the innate immune system

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12
Q

what is pus made out of

A

dead neutrophils

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13
Q

what is the cell that turns into a macrophage

A

Formed in marrow as a monocyte
Migrates via diapedesis through endothelium to connective tissue & differentiates to become a macrophage

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14
Q

what are the organ specific macrophages in the lungs

A

alverolar macrophages

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15
Q

what are the liver specific macrophages

A

kupffer cell

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16
Q

how do macrophages kills cells

A

1 - recognizing a foreign substance
2 - engulfing it in a phagosome
3 - killing it by attaching lysosomes
macrophages are also antigen presenting cells

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17
Q

how do macrophages recruit other cells

A

via cytokine release

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18
Q

describe the macrophages activated states

A

marcophages can acts differently depending on the envirnment
there are many ddifferent activated macrophage states

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19
Q

what is the macrophage classical activation for

M1

A

phagocytosis

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20
Q

what is the macrophages alternative activation for

M2

A

tissue remodeling and repair

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21
Q

what do Lymphocytes, non-B, non-T, CLP-derived do

A

They promote inflammation and tissue repair

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22
Q

what do group 1 Innate Lymphoid Cells (ILC) target?

A

intracellular pathogens

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23
Q

what do group II Innate Lymphoid Cells (ILC) target?

A

parasites

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24
Q

what so group III Innate Lymphoid Cells (ILC) target?

A

bacteria and fungi

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25
Q

what is the main role of the adaptive immune system

A

produce antibodies

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26
Q

what do B-cells do?

A

-extracellular pathogens
- when activated, become Ig-producing plasma cells

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27
Q

what do Tc-cells do

A

-MHC1 recognition
-direct killing of cells by lymphotoxins
-recognize intracellular pathogens

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28
Q

what surface receptor do Tc-cells have?

A

CD8

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29
Q

what do Th-cells do

A

-MHC2 recognition
- indirect killing of cells by lymphokine signaling

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30
Q

what suface receptor is with Th-cells

A

CD4+

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31
Q

what are the antigen presenting cells

A

B-cells for their specific antigens
macrophages
dendritic cells

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32
Q

what is the structrure of antibodies

A

heavy chain, light chain and constant regions

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33
Q

all antibodies are specific for how amny antigens

A

1

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34
Q

what are the two forms antibodies come in

A

membrane bound or free flotting

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35
Q

what does The Fc (constant) region of a n antibodies do

A

allows for easy recognition & binding by other proteins

is the Ig class

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36
Q

which part of the antibodies gives antigen specificity

A

Fab

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37
Q

what antibodies do B -cells first secrete?

A

B-cells make IgM antibodies first, but in the presence of cytokines, B-cells can switch the class of antibodies that they make

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38
Q

IgG

A

-most common antibody in blood and CT
- good diffusibility
- only antibody that crosses placenta, provides “passive” immunity of fetus

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39
Q

IgD

A
  • the mysterious one
  • present on naive B-cells during development, together with IgM
  • may regulate B-cell maturation
  • does not bind complement
  • present at very low levels in blood
    & secretions
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40
Q

IgE

A
  • mast cell IgE receptors trigger degranulation
  • great for parasitic infections
  • responsible for allergies and anaphylaxis
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41
Q

IgM

A
  • pentamer (sometimes hexamer) of IgGs
  • excellent at bringing together multiple C1 complement molecules that will then start the complement cascade
  • excellent at early response to infection
  • more sensitive to the amount of antigen present
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42
Q

IgA

A

-prodominant in the intestines
-protects mucosal sufaces
-secreted in breast milk
-“clip” region confers resistance to acids does not bind complement
-passive defender of the gut

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43
Q

describe the activation of B-cells

A

Critical density of antigen causes “activation”

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44
Q

what are memory B-cells

A

A small population differentiate to
memory B-cells, specific to the antigen that caused activation, and persist throughout life

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45
Q

what antibodies do naive B-cells express

A

IgD & IgM

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46
Q

what happens after a B-cell is activated?

A

Upon ‘activation’, divides and differentiates to a plasma cell which secretes antibodies

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47
Q

where does a B-cells become specfic for an antibody?

A

in the bone marrow

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48
Q

T-cell receptor

A

on T-cells which recognizes antigens bound to
MHC and tells other cells their Identity

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49
Q

MHC-1

A

-exists on almost all cells
-recognized by Tc (CD8+)
-displays a protein being produced so passing cells can see what the cell is making

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50
Q

what is one cell that does not have MHC-1

A

syntrophoblasts in the placenta

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51
Q

MHC-2

A

exists on APCs
only recognized by Th (CD4+)
displays an internalized protein

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52
Q

what does Th1 do

t helper

A

-helps Tc response and recruits macrophages
-helps aganits intracellular viruses

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53
Q

what do Th2 cells do

A

-helps B-cell response
-recruits eosinophils and basophils
-active against worms and allergies

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54
Q

what does Th17 do

T helper

A

recruits neutrophils
-attacks extracellular bacteria

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55
Q

what do Treg do

T cells

A

dampen the immune response

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56
Q

Stages of an Adaptive Immune Response

A

1 - activation of naive cells
2 - effector cell differentiation, clonal expansion
3 - contraction of population & production of memory cells

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57
Q

Primary (generative) Immune Organs

A

bone marrow
thymus

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58
Q

Secondary (effector) Immune Organs

A

peripheral MALT (including tonsils)
lymph nodes
spleen
liver

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59
Q

Thymocytes

A

thymic lymphocytes

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60
Q

where is The thymic stroma is derived from

A

endoderm

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61
Q

involution

A

replacement of tissue by adipose tissue

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62
Q

when is the thymus most active?

A

The thymus is most active in childhood

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63
Q

ERC role

The Epithelioreticular Cells

A

”nurse” (or maybe “teacher”) cells for the thymocytes

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64
Q

“positive” selection

A

happens in thymic cortex -
assurance that TCR is functional and can recognize antigen
-AKA T-cell have a functional receptor (CD3, CD4, CD8)

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65
Q

“negative” selection

A

-occurs in the thymic medulla
- assures the antigen is not a “self” antigen
- the cells that are self reactive are killed by thymic macrophages

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66
Q

myasthenia gravis

A

-autoimmune response to nAchR is the most common disorder associated with thymic neoplasias

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67
Q

where do Liver, gall bladder, bile duct and pancreas derive from

A

endoderm foregut

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68
Q

The liver receives a systemic circulation via the

A

hepatic artery

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69
Q

The liver receives the majority of its blood from the digestive tract through a

A

venous portal system

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70
Q

Blood is returned through the ___BLANK______ which drain to the__BLANK______

A

hepatic vein
inferior vena cava

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71
Q

portal hypertension

A

increased blood pressure
in the portal vein

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72
Q

gall bladder

A

stores and concentrates bile

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73
Q
A
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74
Q

what is the flow of Lymphatics of the Liver

A

1) lymph drains (through space of Mall) via portal triad lymphatics to hilar nodes & cisterna chyli
2) lymph follows space around central vein & exits with hepatic vein
3) lymph drains to pericapsular regions & exits through capsule adventitial to diaphragm

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75
Q

what is the apical surface of a hepatocyte

A

the bile canaliculus

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76
Q

what is the lateral surface of the hepatocyte

A

hepatocyte faces other hepatocytes, and is separated from the apical surface via tight junctions

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77
Q

what is the basal surface of the hepatocyte

A

faces the space of Disse and the sinus (sinusoidal) capillaries

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78
Q

where are the hepatocyte microville

A

extend from the basal surface into the space of Disse and from the apical surface into the bile canaliculus

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79
Q

zone 3 in hepatocytes

A

pericentral

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80
Q

zone 1 in hepatocytes

A

periportal

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81
Q

what varies between the hepatic zones

A

Oxygen tension & metabolite concentrations in the blood also change dramatically with these zones

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82
Q

what is this pointing to

A

Kupffer cells

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83
Q

what are kupffer cells

A

-resident macrophages in the liver
-phagocytose blood-borne pathogens
-break down RBCs
-hemoglobin into bile pigment
-sits in sinus

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84
Q

what cells are these

A

Hepatic Stellate Cells

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85
Q

what are the major functions of a hepatic stellate cell

A

Vitamin A storage and
fibrosis during injury

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86
Q

where does the hepatocyte stem cell reside

A

the canal of Hering, the connection of the bile ductules with the hepatocyte plates

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87
Q

Activation of hepatic stellate cells causes what

A

initiates inflammation and wound healing response

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88
Q

cirrhosis

A

chronic fibrosis that is not reversible

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89
Q

steatosis

A

fatty accumulation in hepatocytes

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90
Q

Factors that commonly lead to cirrhosis of the liver

A

Hepatitis C virus
Alcoholic liver disease
non-alcoholic steatohepatitis (NASH) metabolic disorders
drug toxicity

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91
Q

jaundice

A

yellow coloration caused by systemic bilirubin pigment, not broken down

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92
Q

ascites

A

abdominal distention due to peritoneal fluid accumulation because of portal hypertension

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93
Q

fetor hepaticus

A

“liver stink” portal hypertension causes systemic shunting to the lungs. Thiols, normally removed by the liver, can be detected in expelled air

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94
Q

what cell is appart of the largerst resident macrophagee population in the body

A

Kupffer cells

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95
Q

what happens when liver transplants are coupled to skin or heart transplants in mice

A

Liver transplants in mice are protective to simultaneous skin or heart transplants

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96
Q

how is Hepatitis (B, C) linked to liver

A

hepatitis B and C take advantage of the liver’s unique immune system

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97
Q

fact about liver transplants

A

Liver transplants can thrive without immunosuppressant drugs

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98
Q

what is complement

A

proteins that can kill and tag (opsonization) the invader

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99
Q

how are antibodies to one specific antigen selected for each B-cell

A

chosen at random through the process of VDJ recombinatio

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100
Q

how do B-cells switch to produce another anitbody

A

-under the influence of cytokine signals
-has to have the same class specificity

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101
Q

sphincter of Oddi

A

controls bile and pancreatic secretions

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102
Q

what is the exocrine product of the liver

A

bile

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103
Q

cholangiocytes

A

-bile ductules are lined by these distinctive cuboidal cells
-sensing lumenal bile with a primary cilium, modifying bile composition via a variety of transporters, signalling the immune system, and occasionally contributing to liver pathologies

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104
Q

Glisson’s capsule

A

connective tissue that surrounds the liver

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105
Q

how does metistatic cancer affect Kupffer cells

A

In the setting of metastatic cancer, Kupffer cells have been shown to delete activated T-cells from circulation, facilitating metastases and causing immunotherapy to be ineffective

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106
Q

what is endomitosis and what cells does it

A

-chromosome duplication without cell division
-megakaryocyte

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107
Q

what cells is this

A

megakaryocyte

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108
Q

what disease is this?

A

Paget’s disease
too much bone reabsorbtion

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109
Q

what happens to the thalymus with age

A

it involutes

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110
Q

label a lobe, cortex, medulla, and capule

A
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111
Q

what is special about thymic capillaries

A

they are sheathed and surrounded by an ERC call and endothelial cell

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112
Q

what happens to lymphocytes in the thymic medulla

A

-negative Selection
-either CD8+ or CD4 + T-cell receptors pass test to not recognize self-antigens
-If don’t pass test eaten by thymic macrophages

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113
Q

what happens to lymphocytes in the thymic cortex

A

-positive selection
-both CD8+ and CD4+ lose either CD8 or CD4
-T-cells pass test to recognize antigens

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114
Q

label

A
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115
Q

what are these and what are they made of

A

-Hassall’s corpuscles
-These are sheets of squamous ERCs, piled up like the layers of an onion
-cytokeratin that comprises them is characteristic of a specific subtype of medullary ERCs

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116
Q

red marrow

A

marrow containing predominately hematopoietic cells

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117
Q

where is red marrow most often found in adults

A

-long bones, in the vertebral column, and conveniently in the pelvis
-The crest of the ilium is the preferred biopsy site

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118
Q

what is this showing

A

an involuted thymus

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119
Q

what is this showing

A

cross-section of bone with yellow marrow

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120
Q

what is this diagram called

A

the classic liver lobule

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121
Q

what is this diagram called

A

portal lobule

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122
Q

what is this diagram called

A

liver acinus

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123
Q

label

A
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124
Q

what is the central structure called

A

central vein

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125
Q

what is this pointing to

A

bile duct/ canniliculi

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126
Q

liver sinusoidal endothelial cell

A

The endothelial cell of the liver is of a distinct lineage, differing in gene expression from other endothelia and producing proteins that are important to the immune system

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127
Q

what is this pointing to

A

gisson’s capsule

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128
Q

what is this pointing to?

A

kupffer cell

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129
Q

what is going on with is liver

A

chronic alcoholism affects hepatocyte fat metabolism, so you are left with more adipocytes, which become stored in your liver

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130
Q

what is going on with this liver

A

cirrhosis
fibrosis caused by alcoholism is harder to reverse but still possible b/c liver can regerate

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131
Q

what is this pointing to

A

adventitia between the liver and gallbladder

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132
Q

what is the evolution of the sites of hematopoiesis

A

-Yolk Sac: hematopoietic islands form here in the 3rd-4th week of gestation, peaking in 2nd month
-Liver: hematopoiesis begins here in the 5th week, peaks at 5-6 months gestation
-Bone Marrow: hematopoiesis begins here in the
5th month of gestation, continues to adulthood
-Red Marrow: limited to specific locations after
puberty.

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133
Q

what is the most important site of heamatopoiesis in the fetus

A

liver

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134
Q

what is the most important site of heamatopoiesis in the fetus

A

liver

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135
Q

where are macrophages stored

A

spleen

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136
Q

where is the largest site for marginated neutrophils

A

postcepillary venules of the lug

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137
Q

Vasculogenesis

A

creation of new blood vessels in the mesoderm layer

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138
Q

where do early blood vessels originate from

A

extraembryonic (lateral sphlancnic) mesoderm

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139
Q

Angiogenesis

A

The sprouting of vessels from existing vessels

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140
Q

how does vasculature migrate

A

medially and dorsally - some of the first major vessels are the perineuronal vascular plexus surrounding the neural tube.

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141
Q

what do angiogenesis tip cells do?

A

direct the formation of stalk cells into vascular lumens

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142
Q

parenchyma

A

developing blood cells (hematopoietic islands)

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143
Q

what do bone marrow stromal cells do?

A

all marrow stromal cells
are active in regulating and supporting hematopoiesis

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144
Q

describe which can regerate between stem ells, progenitor cells, and percursor cells

A

stem cells are pluripontent, progenitor cells are more resitricted in lineage, precursor cells are totally restricted to lineage

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145
Q

CMP gives rise to

common myeloid progenitor

A

eosinophils, basophils, neutriphils, monocytes, erythrocytes

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146
Q

what do CLP give rise to

common lymphoid progenitor

A

lymphocytes

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147
Q

as we get further down in differentiation what happens to the likelyhood of trans differentiation

A

it goes down

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148
Q

can progenitors make more of themselves

A

Progenitors (the CFUs) can make more of
themselves; precursor cells cannot

149
Q

which cells have a CD33 marker

A

granulocyte lineage

150
Q

which cells have a CD45 marker

A

CMP progenitors

151
Q

what cells have a CD14 marker

A

monocytes and mature neutrophils

152
Q

what cells have a CD34 marker

A

CLP and CMP

153
Q

what is the erthythrocyte lineage in order

A

blast, basophillic erythroblast, polychromatophillic erythroblast, orthrochromatophilic erythroblast ,reticulocyte

154
Q

what is the neutrophil lineage in order

A

blast, promyelocyte,
early neutrophillic myelocyte, late neutrophilic myelocyte, neutrophilic metamyelocyte, band cell, mature neutrophil

155
Q

what is the eosinophil lineage in order

A

blast, promyelocyte, early eosinophillic myelocyte, late eosinophilic myelocyte, eosinophilic metamyelocyte, mature eosinophil

156
Q

how is EPO regulated?

A

-Oxygen levels
-Renin-Angiotensin system (sensing blood pressure)
-other hormones like insulin

157
Q

BFU-E

A

erythrocyte progenitor cell
requires several cytokines for survival
high proliferative potential
14 days to RBCs in culture
motile – can be present in peripheral blood (!)

158
Q

CFU-E

A

progenitor cell
highly dependent on EPO
7 days to RBCs in culture non-motile, found in marrow only

159
Q

what cell is in the last stage for mitosis in the erythrocyte lineage?

A

Polychromatophilic erythroblast

160
Q

what cell do erythrocyte precursers leave as

A

recticulocytes

161
Q

what percent of circulating recticulocytes is normal

A

1%

162
Q

what stain is used for reticulocyte count

A

methylene blue

163
Q

what is the shape of a reticulocyte

A

Shape is intermediate between spheroid and biconcave

164
Q

how do reticulocytes leave the marrow

A

-Reticulocytes leave the marrow by piercing through endothelial cells
-endothelium controls release by making holes

165
Q

what stage do granulocytes leave the marrow

A

mature

166
Q

what percent of granulocytes in normal in peripheral blood

A

3%

167
Q

what do each neutrophil granule do

A

-primary (azurophilic): lysosomes
-secondary (specific) :kill bacteria with enzymes and reactive oxygen compounds
-tertiary: chemotactic

168
Q

what granules do basophils have?

A

histamine (vasodilator)
heparin (anticoagulant)

169
Q

what triggers fast degranulation in basophils

A

binding of IgE surface antibodies
triggers fast degranulation

170
Q

compound exocytosis

A

stacking of granules at cell membrane for future relsease

171
Q

what cell is this

A

band cell
C-shaped nucleus, without chromatin bridges
-normally present in peripheral blood in small quantities but over 2% can indicate pathology

172
Q

what is the monocyte lineage

A

monoblast, promonocyte, circulating monocyte, in tissue can become, macrophages, dendritic cells,
osteoclasts

173
Q

whatis the lymphocyte lineage

A

lymphoblast, prolymphocyte, circulating lymphocyte

174
Q

how are platlets formed

A

Platelets from megokaryocytes next to megokaryocytes sit sinus and dangle tendrils out of sinus and platlets bud off

175
Q

what is endomitotic division and what cell does it

A

megokaryocytes
copies chromosome a fails to devide
~128n cell

176
Q

what is the megakaryocyte lineage

A

(Pro-) Megakaryoblast →
(Pro-) Megakaryocyte

177
Q

what gives platelets their shape

A

microtubles

178
Q

alpha granules in platelets

A

α granules contain fibrinogen and coagulation factors

179
Q

δ granules in platelets

A

δ granules contain factors that promote the clotting cascade - they are also called “dense bodies” or “dense core granules”

180
Q

λ granules in platlets

A

λ granules are lysosomes

181
Q

where are platelets stored?

A

“stored” in circulation

182
Q

what activated platelets

A

clotting factors

183
Q

how long do platelets last

A

10 days

184
Q

what does G-CSF cytokine recruit

A

neutrophils

185
Q

what does the GM-CSF cytokine recruit

A

leukocytes

186
Q

what does the EPO cytokine recruit

A

erythrocytes

187
Q

what does the IL-2 cytokine recruit

A

T-cells

188
Q

what is anemia

A

Reduction in the oxygen carrying capacity of the blood

189
Q

what are common causes of anemia

A

-Blood loss via trauma or genetic defects
– Kidney disease (kidney and liver make erythropoietin) – Bone marrow cancer

190
Q

polycythemia

A

Too many RBCs
↓ ability of tissues to get O2 blood is very viscus and can’t flow properly

191
Q

Leukemia

A

disorders of white blood cells

192
Q

what is the leukemia basic classification

A
  • First letter:
    – A for Acute – few mature circulating WBCs
    – C for Chronic – abnormal function in circulating WBCs
  • Second letter:
    – M for Myelogenous = affecting myeloid cells
    – L for Lymphocytic = affecting lymphatic cells
  • Third letter:
    – L for Leukemia = abnormal proliferation of leukocytes, sometimes called ‘cancer of the blood’
193
Q

Acute Leukemias characteristics

A
  • Very few mature leukocytes (WBC’s) in blood. Blood may contain cells normally found in marrow.
  • Marrow is full of rapidly dividing immature cells that do not differentiate.
  • Anemia and bleeding are common as normal cells in marrow are affected by crowding.
194
Q

treatment for Acute Leukemias

A

drugs, radiation, bone marrow transplants and autologous stem cell transplants

195
Q

purpose of a bone marrow biopsy

A

used to evaluate the overall composition of the marrow, including bone and stroma

196
Q

autologous bone marrow trasnplant

A

-stem cells are harvested prior to irradiation, will not stimulate immune system
-risk of the same disease recurring

197
Q

allogenic stem cell transplants

A

*cells from an HLA-matched donor are used
*risk of graft-vs-host disease
-effective a transplantation o f an
Immune system

198
Q

Activating pain neurons has what effect

A

shown in mice to mobilize HSCs into circulation

199
Q

which cells have white nucleolus

A

blasts and promyleocytes

200
Q

big cell in middle

A

blast

201
Q
A

blast

202
Q
A

promylocyte

203
Q
A

promylocyte

204
Q

what cell is this?
large cells with echromatic nuclei
and visible nucleoli
no azurophilic granules

A

blast

205
Q

what cell is this?
-large cell w/ nucleoli and azurophilic granules

A

promylocyte

206
Q
A

early neutrophilic myelocyte

207
Q
A

late neutrophilic myelocyte

208
Q
A

neutrophilic metamyelocyte

209
Q
A

band cell

210
Q

cell in middle

A

early eosinophilic myelocyte

211
Q
A

late eosinophilic myelocyte

212
Q
A

eosinophilic metamyelocyte

213
Q
A

basaphilic erythroblast

214
Q
A

polycromatophilic erythroblast

215
Q
A

orthochromatophic erythroblast

216
Q
A

megakaryocyte

217
Q

what is wrong with this blood smear

A

acute monocytic mleukemia
too many nucleated cells to be in normal blood

218
Q

what are the main secondary lymphatic cells and patches

A

1)MALT, GALT, BALT, peyer’s patches
2)tonsils

219
Q

what are the main secondary lymphatic organs

A

lymph nodes
spleen

220
Q

lymph consists of

A
  • extracellular interstitial fluid from connective
    tissue
  • immune cells, chiefly lymphocytes, also DCs
  • bound Ig molecules Cantibodies
  • lipids (e.g. central lacteals)
  • macromolecules & particulates
221
Q

what is the path of lymphatic vessels

A

lymphatic vessels originate in the periphery, and carry lymph from connective tissue all over the body,
through a system of lymph nodes, back to the venous circulation near the heart

222
Q

what are the main 3 functions of the lymphatic system

A

1) clearance of extracellular proteins & return
of fluid to circulation
2) transport antigens or experienced
immune response lymph node to mount an immune response
3) absorb fats (chylomicra) from the gut

223
Q

where do lymphatics sprout from

A

veins

224
Q

Reticulated Epithelium

A

-Immune tissue envades epithelia
-leaky basement membrane
-reduced # of desmosomes

225
Q

where is cancer most likly to metasticize

A

at the 1st lymph node

226
Q

Superficial
cervical
nodes drain what

lymph notes

A

head and neck

227
Q

Axillary nodes drain what

lymph nodes

A
  • lateral (drains arm)
  • apical (drains upper quadrant of breast)
  • anterior (drains some chest)
  • central (secondary)
228
Q

Epitrochlear nodes drain what

lymph nodes

A

distal arm

229
Q

Inguinal nodes drain what

A

proximal leg

230
Q

Popliteal nodes drain what

lymph nodes

A

distal leg

231
Q

Hilar nodes drain what

A

lungs

232
Q

Mediastinal nodes drain what

A

heart, esophagus, diaphragm

233
Q

lymph nodes are what kinds of structures

A

advential

234
Q

most common site of leukocyte extravasation to CT

A

postcapillary venues

235
Q

whaat is special about High Endothelial Venues

A

-highly active endothelial cells undergo reversible metaplastic transition to cuboidal shape & euchromatic nucleus
-add lymphocytes to CT

236
Q

Lymph node - the antibody response

A

-Processing of antigen
- APC cells present to Th
-Selection - of appropriate B cells for that antigen
-Proliferation (clonal expansion) of selected cells; dependent on Th co-activation need T-helper cells to proliferate B -Cells
-Differentiation - to antibody-producing plasma cells

237
Q

how are the spleen and the lymph nodes similar

A

where blood cells can leave the vasculature

238
Q

Flow cytometry

A

can be used to measure cell morphology, useful for blood and marrow, or to separate cells based on immunological markers

239
Q

immunohistochemistry

A

can be used in situ to demonstrate the location of marked proteins. Tagging a fluorescent molecule to the antibody is a common technique

240
Q

ELISA

A

uses antibodies to measure the presence of proteins in multiple samples – commonly used clinically
usefull for solubilized things

241
Q

PCR

A

is a technique to amplify DNA so that it can be readily detected. Cycle threshold (CT) is important. For example, COVID is typically detected with between 14-45 cycles, but there’s no universal standard

242
Q

how does a flow cytometry work?

A

1) put a sample down a tube and flash a light at it
2) a computer measures the forward and side scatter
3) forward scatter relates to cell size and side scatter relate to granularity

243
Q

If there is a pathogen in your environment, what are the three options for dealing with it

A

Avoidance
Resistance
Tolerance

244
Q

what are examples of avoidance

A

skin
mucosal surfaces

245
Q

what is the tolerance antigen

A

igA

246
Q

autoimmune disease results from a lack of

A

-an appropriate tolerance response
-specifically, B- and T- lymphocytes must tolerate proteins that belong

247
Q

what is going on here

A

celiac disease
only crypts no villi

248
Q

gluten is digested to what

A

gliadin

249
Q

what immune reponse happens in celiac disease

A

Production of IgG against gliadins leads to inflammation & eventual tissue destruction in the presence of gluten

250
Q

M-cells

A

-M-cells and thinner and are
specialized for the transport of lymphocytes
-some organisms take advantage of M-cells to gain entry in the cell

251
Q

HIV

A

-“hides” in Th cells
-evades the “sterilization” that is the usual endpoint of adaptive immunity
-leaves the individual “immunocompromised”
-has a slow rate of replication
-decreases T-helper cells until the person dies from a infection or autoimmune disease

252
Q

what is the theory about how to prevent allergies

A

early exposure to antigens lowers rates of allergies
-allergies are more prevalent in western societies

253
Q

ppl with allergies produce what antibody

A

IgE

254
Q

Antigen binding to IgE causes what

A

mast cells to degranulate

255
Q

B-cells produce what antibody

A

IgE

256
Q

Th cells regulate what

A

allergic reponse

257
Q

M2 macrophages promote what

A

tissue homeostasis

258
Q

what is the morphology of the ddisease asthma

A

-acute changes driven by Th2 cytokines, IgE
-also causes chronic tissue remodeling( local cells producing cytokines and unregulation)

259
Q

what is the difference between alveolar and intersitial macrophage immune responses

A

-alveolar macrophages patrol the lumen and they usually dont have a huge reaction when they see something forgein becasue they see that shit all the time
-interstitial macrophages if it sees promotes inflammation because this means that something has crossed the barrier

260
Q

what is the arrow pointing to?

A

hyaline membrane

261
Q

function of tonsils

A

Tonsils are merely folds in the epithelium, creating tonsilar crypts, which trap food and extrinsic substances together with saliva or other secretions for a length of time sufficient to permit immune surveillance

262
Q

Typically 80-95% of cells in lymph are what

A

B- and T- lymphocytes

263
Q

where to lymph vessels mainly drain

A

thoracic duct and right lymphatic duct(upper right quadrant of the body)

264
Q

Effete RBCs

A

those which can no longer deform themselves adequately to fit through small capillaries. Splenic macrophages may also recognize and remove senescent cells through investigation of their various surface markers

265
Q

wat are the connective tissue structures that divide the spleen

A

trabeculae

266
Q

what is the series of vasculature of the speen in order of entry

A

splenic artery, and courses in succession through trabecular arteries, central arteries, radial arteries, penicillar arteries, sheathed capillaries, splenic sinuses, trabecular veins and the splenic vein

267
Q

where is the rgion of the lowest flow rate in the spleen

A

white pulp

268
Q

splenic nodules

A

lymphoid follicles of the spleen

269
Q

what is the role of reticular fibers in the spleen

A

form a circle around splenic sinus and mechanically prevent defective erythrocytes from entering the splenic sinuses

270
Q

how do Mycobacterium tuberculosis evade termination

A

the TB bacteria is able to modify the phagosome membrane to make it incapable of binding to the lysosome

271
Q

what cells are targeted in diabetes mellitus type 1

A

pancreatic islet β-cells

272
Q

what cells are attacked in myasthenia gravis

A

Ach receptors

273
Q

what cells are attacked in pemphigus vulgaris

A

desmogleins of desmosomes

274
Q

what cells are attacked in rheumatoid arthritis

A

citrullinated proteins of cartilage - fibrinogen, vimentin, collagen type II, α-enolase

275
Q

what cells are attched in multiple sclerosis

A

myelin basic protein of myelin sheath

276
Q

what is the traditional method for generating antibodies for staining for IHC

A

raise an animal (typically mouse or rabbit) in a pathogen-free environment, expose it to the antigen of interest (possibly bound to a carrier protein), harvest plasma and harvest the resulting antibodies from plasma. Antibodies thus produced are often tagged with their species of origin

277
Q

what is the function of the tonsils

A

allow the various lymphocytes access to potential ingested foreign substance

278
Q

what is this showing

A

reticular epithelium

279
Q

what is this showing

A

intraepithelial lymphocyte: a lymphocyte within an epithelial layer

280
Q

what cells are in each area

A
281
Q

what structure is this

A

lymph node

282
Q
A
lymph node
283
Q

in the lymph node what is this pointing to

A

macrophoges

284
Q

what are these collectively called and where were they seen

A

mitotic figures
in the center of a lymphatic follice

285
Q

where is practically the only place in the body where erythrocytes are “allowed” to exist outside of an endothelium-lined space

A

spleen

286
Q

marginal zone

A

-at the interface of the red and white pulp
-where blood leaves the systemic circullation

287
Q

what is this

A

marginal zone

288
Q

trabecular artery

A

as the name suggests, this is an artery that runs within the trabeculae. You can recognize one because it is surrounded by dense connective tissue

289
Q

central artery

A

unlike trabecular arteries, the central arteries are surrounded by white pulp

290
Q

splenic sinus

A

These are the venules into which blood must return if it is to exit the spleen. Blood cells, both white and red, must traverse first the rings of reticular fibers then the epithelium in the basal to apical direction.

291
Q

what are the smallest vessels of the arterial vascularization of the spleen

A

penicillar arteries

292
Q

what is the arrow pointing at

A

splenic sinus

293
Q

what are these showing

A

These are regions within the red pulp where reticular fibers encircle the splenic sinuses. Specifically, they are attached to the basement membrane of the sinus endothelium. Thus, blood must squeeze first through the reticular fibers, and second through the endothelial cells, in order to re- enter the sinus

topology is often described as “staves and hoops of a barrel”.

294
Q

what cells can caner occur in

A

Can occur in any nucleated Cells AKA not RBC’s

295
Q

what type of cancers are more common

A

cancers from epithelial cells

296
Q

Hodgkin lymphoma

A

Cancer of blood cells in lymph that move of lymph

297
Q

what is this pointing to?

A

Reed-Sternberg cells (defective plasma cells) are the hallmark of a Hodgkin’s Lymphoma diagnosis

298
Q

what are the key behavior characteristics of solid tissue tumors

A

-Commitment to division
mitosis - metaplasia
loss of original cell functions
loss of MHC-1
no time to carry out the role always dividing
-Migration
EMT:epithelial morphologymesenchymal
loss of attachment proteins (cadherin proteins)
-Nutrition seeking behavior
entosis
recruitment of vasculature

299
Q

what are driver mutations

A

-promote mutations
-directly drive cancer initiation and progression

300
Q

what are passenger mutations

A

-accumulate over the lifetime, may change phenotype or drug response
-may stear mutaion toward a cancer state

301
Q

p53

A

Proteins exist (for example, ATM, ATR, p53) that detect DNA damage and arrest the
cell cycle, giving cellular machinery time to repair the damage
*If damage is irreparable, apoptosis (programmed cell death) is an option
*If checkpoint mechanisms are damaged, cancer may result

302
Q

what signals can p53 respond to

A

-lack of nucleotides
-UV radiation
-ionizing radiation
-oncogene signaling
-hypoxia
-blockage of transcription

303
Q

what responses can p53 initate

A

-cell cycle arrest
-DNA repair
-block angiogenesis
-apoptosis

304
Q

examples of EMT

A

neural crest

305
Q

examples of MET

A

blood vessel formation coelomic epithelium mesonephric duct

306
Q

which cancer is predisposed to go through EMT

A

meanoma because melanocytes are motile

307
Q

what are the tumor types where EMT has a key role

A

breast, skin, pancreatic, lung, colorectal, hepatocellular, blader

308
Q

when a cell becomes a cell of the CT what happens

A

there is much more M2 (antinflammatory) and tolorgenic responses

309
Q

Cannibalism

A

he engulfment of live or dead cells or debris by cancer cells - a marker of malignancy

310
Q

Entosis

A

the uptake of live cells into other cells through an invasive mechanism, typically involving cell-cell adhesion proteins and actin-myosin mediated contraction

311
Q

Emperitosis

A

NK cells
entotically invading cancer
cells and dying intracellularly

312
Q

VEGF

A

-a potent angiogenic factor
-Many types of cancers synthesize VEGF

313
Q

how does EMT affect tumor vascularization

A

EMT allows for better tumor vascularization

314
Q

metastasize

A

-take advantage of the lymphatic and ultimately systemic circulation to travel to sites distant from the site of origin
-may take up residence elsewhere in the body

315
Q

what is this showing

A

metastasis of
primary pancreatic cancer

316
Q

how do you stage Epithelial Cancers

A
317
Q

what is the seed and soil theory of metastases

A

metastases occur when the local conditions match the growing preferences of tumor cells

318
Q

what are the main sites of metastases

A

brain bone lung liver

319
Q

whta is the gold standard of cancer imaging

A

PET scan
uses radioactive glucose to visualize the cancer

320
Q

which cancer responds well to treatment

A

bladder cancer

321
Q

what cancer respond poorly to treatment

A

pancreatic (exocrine) cancer

322
Q

what are some cancer treatmentscancer treatments

A

-radiation
-surgery
endocrine therapy
-gene therapy
-marrow transplantation
-chemotherapy
-targeted therapy
-combination therapy

323
Q

how does radition work

A

kills dividing cells

324
Q

how does chemotherapy work?

A

target DNA REPLECATION

325
Q

what is the most effective cancer treatment

A

combination therapy

326
Q

Cancers curable with chemotherapy alone

A

choriocarcinoma
childhood ALL (Dr. Sidney Farber, 1947)
Burkitt lymphoma
Hodgkin disease
acute promyelocytic leukemia
large follicular center cell lymphoma embryonal carcinoma of testis
hairy cell leukemia

327
Q

how does age affect cancer risk

A

cancer risk goes up with age

328
Q

what cancer is second most frequent cause of cancer deaths in US

A

breast cancer

329
Q

how does age affect breast cancer

A

breast cancer has a huge age dependence

330
Q

what genes are involved in familial breast and ovarian cancers

A

BRCA1 & BRCA2 tumor suppressor genes

331
Q

what percent of brest cancers are ductal and lobular

A

Ductal (80%)
Lobular (10%)

332
Q

what is this showing

A

lactiferous duct biopsy- breast cancer

333
Q

what stains can you use on breast tissue

A

estrogen and progesterone

334
Q

HER2 receptor

A

The HER2 receptor is one of a class of surface receptors that respond to growth factors. These signaling pathways are potentially relevant in many different cancers

335
Q

what is one way you can tailor cancer treatment

A

Classification by receptor status lets us choose a treatment that is most effective

336
Q

ER+ breast cancer

A

estrogen receptor
– tamoxifen (anti-estrogen) is a drug of choice

337
Q

HER2/neu breast cancer treatment

A

can sometimes be treated with monoclonal antibodies
-herceptin/trastuzumab

338
Q

Triple negative breast cancer

A

hardest to treat, no cell surface receptors, hard to make drugs against

339
Q

what are the ABCD’s of melanoma

A

A for asymmetry
B for border irregularity
C for color
D for diameter
E for evolving

340
Q

what is the most important ABCDE of melanomas

A

E for evolving

341
Q

what are the Categories of Biomarkers

A

diagnostic
prognostic
predictive

342
Q

Melanoma S100 antibody

A

-diagnostic marker
-labels neuroectoderm and melanocytes are the only cells from the neural creast

343
Q

Melan A antibody

A

diagnostic and predictive marker good for prognosis

344
Q

which cells mediate tumor cell death

A

Tc and NK cells

345
Q

FASL and TRAIL

A

cell death ligands
kill cell via apoptosis

346
Q

PD-1

A

-PD-1 is the repector for PDL-1 (programmed death ligand)
-Activation of PD-1 on a T-cell may trigger T-cell apoptosis. This is a mechanism of immune regulation.
-Tumor cells upregulate PDL-1 in an attempt to evade immune detection

347
Q

oncolytic virus

targeted immunotherapies

A

a virus that selectively invades tumor cells and causes their destruction by normal immune mechanisms

348
Q

anti-CTLA4

targeted immunotherapies

A

CTLA4 is a surface receptor on Tregs responsible for inhibiting their function

349
Q

anti-PD1

targeted immunotherapies

A

Programmed Death Receptor & Ligand - PD1 is a surface receptor on Th that negatively regulates them. Blocking it keeps Th alive.

350
Q

CAR-T

targeted immunotherapies

A

Chimeric Antigen Receptor - select (or design) a population of T-cells that fight the tumor and expand them ex vivo

351
Q

pembrolizumab

A

-blocks programmed cell death (PD-1) receptor
encourages Immune system to stay active
-treats melanoma

352
Q

Adoptive T-cell therapy

A

We harvest tumor T-cells
to encourage immune System

353
Q

ADC - Antibody-Drug Conjugate molecules

A

-We can find a drug that kills the tumor and use antibodies to bring the drug right to the tumor
-help us use very toxic drugs

354
Q

Targeted therapies for melanoma

A

IFN-α
CTLA-4 MEK/MAPK KIT

355
Q

what color are the azurophilic granules

A

blue
in the promyleocyte

356
Q

what color are the secondary granules

A

eosinophilic and basophilic
in the myelocyte

357
Q

Asthma is driven by what antibody

A

IgE

358
Q

allergies are driven by what antibody

A

IgE

359
Q

what antibody is involved in celiac disease

A

IgG

360
Q

what is the tolerace antigen

A

IgA

361
Q

in the lung the principle sites of metastasis are

A

brain, bone, adrenal gland, and liver

362
Q

in the breast the principle sites of metastasis are

A

bone, lung, liver, and brain

363
Q

in the prostate the principle sites of metastasis are

A

bone

364
Q

in the colon the principle sites of metastasis are

A

liver and lung

365
Q

in the pancreas the principle sites of metastasis are

A

liver and lung

366
Q

in the skin the principle sites of metastasis are

A

Lung, brain, and liver

367
Q

in the sarcoma the principle sites of metastasis are

A

lung

368
Q

in the uveal the principle sites of metastasis are

A

liver

369
Q

Keratomas

A

from keratinocytes

COT (8 decks)

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