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BMS150 - Biomedicine > Week 1 - Immunology > Flashcards

Week 1 - Immunology Flashcards

1
Q

What are the functions of the immune system?

A
  • Protection from microbial pathogens
  • Protection from “foreign” cells that may have malignant potential
  • Detection of damaged tissue and facilitates regeneration of those tissues
  • Permits microflora to aid in: protection and provision of nutrients
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2
Q

Allergy and autoimmune disease are ____ diseases, whereas acute and chronic inflammatory states are ____ diseases

A

immune-mediated
outside of immune-mediated

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3
Q

A “bystander” is damage that happens when attacking a ____

A

pathogen

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4
Q

The components of the immune system contribute to 3 things:

A

1) Recognizing foreign molecules, microbes, or cells
2) Destroying foreign molecules, microbes, or cells (cell membrane disruption, cellular damage from free radicals, catalyzing degradation of cellular components)
3) Communicating between these two activities

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5
Q

What are the 2 major functional divisions of the immune system?

A
  1. Innate immunity - “1st line of defense”
  2. Adaptive immunity - activated when innate
    defenses are breached (delayed)
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6
Q

What are the features of innate immunity?

A

less specific - each cell or molecule recognizes a range of targets
genetically “hard-wired” - cells and molecular effectors
don’t change during the lifespan of the organism

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7
Q

What are the features of adaptive immunity?

A

highly specific - each cell or molecule recognizes a particular target
genetically “changeable” - cells and molecular effectors change their germline DNA to produce unique receptors/effectors during the lifespan of the organism

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8
Q

When is adaptive immunity activated?

A

when innate defenses are breached (delayed)

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9
Q

What is the response time for innate and adaptive immunity?

A

innate: hours to days
adaptive: days to 2 weeks

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10
Q

The innate immune system has no ____

A

memory
- fixed responses with repeated exposures (to antigen)

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11
Q

In adaptive immunity ____ is present and response can improve in specificity and rapidity of response with repeated exposures

A

memory

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12
Q

The innate immune system often recognizes ____

A

patterns

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13
Q

The adaptive immune system recognizes very ____

A

specific entities

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14
Q

What is the difference in diversity between the innate and adaptive immune system?

A

Innate: limited (though large) repertoire of entities that can be recognized and neutralized/destroyed
Adaptive: Extremely large number of entities can be recognized and neutralized/destroyed

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15
Q

Recognition of a foreign molecule by high-affinity binding to a receptor occurs in ____

A

adaptive immunity

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16
Q

True or False: In adaptive immunity, the affinity can increase as the receptor is modified over time

A

True

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17
Q

True or false: In adaptive immunity, receptors are generated by genetic recombination (gene shuffling)

A

True

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18
Q

An ____ is a substance that can bind to a receptor of the adaptive immune system

A

antigen

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19
Q

Receptors include:

A

B-cell and T-cell receptors

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20
Q

____ receptors can be released from a ____ into the ECF forming an antibody

A

B-cell
B-cell

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21
Q

An ____ is a substance that can generate an adaptive immune response

A

immunogen

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22
Q

The molecular entity that binds to the receptor is called a:

A

epitope

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23
Q

A substance that can bind to an antibody, but CANNOT generate an immune response is called a:

A

hapten

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24
Q

True or false: no two naive T or B cells are activated by the same molecule

A

true

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25
Q

In adaptive immunity, diversity is accomplished by randomly “shuffling” portions of genes for lymphocyte receptors and selecting receptors that are___ and ______

A

functional
do not recognize self

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26
Q

The set of antigen (Ag) receptors in a given individual’s immune system is known as:

A

lymphocyte receptor repertoire

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27
Q

True or false: Clonal Selection Theory is a part of innate immunity

A

False
Clonal Selection Theory is a part of adaptive immunity

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28
Q

In Clonal Selection Theory, each lymphocyte bears a single type of ____ with a ______

A

receptor
unique specificity

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29
Q

In Clonal Selection Theory, receptor binding is required for _____

A

cell activation

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30
Q

In Clonal Selection Theory, the differentiated effector cells derived from an _______ bear receptors of identical specificity as the ________

A

activated lymphocyte
parent cell
(they are clones of the parent cell - exact genetic copies with the same receptor)

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31
Q

In Clonal Selection Theory, lymphocytes bearing receptors for self molecules are ______ at an early stage

A

destroyed
- we select functional receptors that do not bind to self

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32
Q

Naive B cells express ____ on their surface, where they are called _____

A

antibodies
B-cell receptors

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33
Q

Once naive B cells are activated, they secrete _____ into the blood

A

antibodies

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34
Q

B cell receptors are made up of:

A

2 light chains and 2 heavy chains - each with variable and constant regions

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35
Q

The ____ regions of a B cell receptor are the portions that are “shuffled” and that can bind to an antigen

A

variable

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36
Q

True or false: some antigens can be bound by many different antibodies

A

true
- different epitopes on the same antigen

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37
Q

Most antibodies bind to ____ antigens

A

protein
- distinct sequences of amino acids

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38
Q

A recognized amino acid sequence can be either _____ or ______

A

Continuous (aka linear)
Discontinuous (aka conformational)

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39
Q

True or false: antibodies can also bind to lipid, nucleic acid, and carbohydrate moieties

A

true
- a wide range of molecules can be recognized

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40
Q

T cell receptors are composed of 2 chains, they are:

A

1 alpha, 1 beta - each with a variable region and a constant region

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41
Q

T cell receptors are best at recognizing _____

A

protein antigens

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42
Q

T cell receptors are never _____ , they always stay attached to the membrane

A

secreted

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43
Q

T cell receptors only recognize antigens by close communication with molecules on other cells, this is called _______

A

antigen presentation

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44
Q

Exposure of the adaptive immune system to an antigen _____ its ability to respond to the same or closely related antigen following ______

A

increases
re-exposure

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45
Q

Secondary immune responses are generally faster, larger, qualitatively different and often involve _______

A

high-affinity B-cell receptors

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46
Q

Control and down-regulation of the _______ is quite specific, as it activation

A

adaptive immune system

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47
Q

Immune responses to self can result in ______ , and immunological unresponsiveness to self can result in ______

A

autoimmunity
tolerance

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48
Q

A cell that has not reached a point where it can become activated –
usually refers to cells of the adaptive immune system, is called:

A

an immature cell

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49
Q

A mature cell that has not yet been activated – always refers to the adaptive
immune system, is called:

A

a naive cell

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50
Q

A cell (or group of cells) that is currently an active
participant in an immune response is called:

A

an activated or effector cell

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51
Q

A cell that responds to receptor binding by deactivation of the cell – it
“goes to sleep”, is called:

A

an anergic cell

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52
Q

A group of effector T/B cells that express the same antigen receptor and are
derived from the same parent cell, is called:

A

a clone

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53
Q

What are the 2 groups of hematopoietic stem cells?

A

Myeloid cells and lymphoid cells

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54
Q

What are the myeloid cells?

A

granulocytes
- neutrophils
- basophils
- eosinophils
- mast cells
monocytes
- macrophages
dendritic cells

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55
Q

What additional cells are derived from myeloid cells?

A

RBCs and platelets

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56
Q

What are the lymphoid cells?

A

T cells
B cells
NK cells
dendritic cells

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57
Q

What is the most abundant cell type?

A

neutrophils

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58
Q

What is the least abundant cell type?

A

basophils

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59
Q

Monocytes circulate in the blood & differentiate into _____ upon migration into tissue (long-lived)

A

macrophages

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60
Q

Macrophages are phagocytic, and are the mature form of a ______

A

monocyte

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61
Q

Macrophages often produce soluble ______ that help orchestrate
a wide range of adaptive and innate immune responses

A

messengers

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62
Q

What cells present antigens to T cells?

A

monocytes/macrophages
dendritic cells

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63
Q

True or false: dendritic cells are resident in the body’s tissues

A

true

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64
Q

During infection _____ cells recognize infection and transports antigens to lymphoid organs

A

dendritic

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65
Q

Antigen presentation to T-cells is important in T-cell activation during ______ responses

A

adaptive immune

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66
Q

_______ are phagocytic and short-lived, enter sites of infection and die in infected tissues which forms pus

A

neutrophils

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67
Q

_____ defend against parasites and are involved in hypersensitivity responses

A

eosinophils

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68
Q

_____ along with mast cells, protect mucosal body surfaces & release histamine in hypersensitivity responses

A

basophils

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69
Q

______ reside in all connective tissues and orchestrate hypersensitivity responses (i.e., seasonal allergies), important in mucosal immune responses

A

mast cells

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70
Q

Mast cells participate in the expulsion of parasites from the body through the release of _____ containing histamine and other active agents

A

granules

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71
Q

Neutrophils kill microorganisms through _______

A

phagocytosis

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72
Q

Eosinophils kill antibody-coated parasites through the release of ______

A

granule contents

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73
Q

B-cells are derived from ______ , and upon activation differentiate into ______

A

bone marrow
antibody-secreting plasma cells

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74
Q

T-cells are derived from the _______ (though they originate in bone marrow)

A

thymus

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75
Q

What type of cells can T cells can become?

A

helper T cells (Th)
cytotoxic T lymphocytes (CTL)

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76
Q

What type of T cell activates other cells like macrophages and B cells?

A

helper T cells (Th)

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77
Q

What type of T cell kill cells that express foreign molecules?

A

cytotoxic T cells

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78
Q

True or false: T and B lymphocytes look alike, each having receptors for specific antigen

A

true

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79
Q

_________ are important in the innate immune system, lack antigen-specific receptors and kill infected/altered cells

A

Natural killer (NK) cells

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80
Q

What cells are absolutely key in presenting antigens to T-lymphocytes?

A

dendritic cells and macrophages

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81
Q

Many innate immune cells produce _____ that inform helper T-cells about how to help other immune cells

A

cytokines

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82
Q

True or false: certain subsets of helper T-cells are dedicated to ONLY aiding
innate immune responses

A

true

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83
Q

What cells are
important at helping to clear antigens that are bound by
antibody

A

Mast cells, neutrophils, eosinophils, and macrophages

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84
Q

Lymphoid tissues are organized tissues where lymphocytes interacts with ______ cells

A

non-lymphoid

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85
Q

true or false: lymphoid tissues are important in the initiation/maturation of adaptive immune
responses

A

true

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86
Q

What are the 2 types of lymphoid tissues?

A

1) primary (central) lymphoid organs
2) secondary (peripheral) lymphoid organs

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87
Q

Primary lymphoid organs where lymphocytes are generated and mature include:

A

bone marrow and thymus

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88
Q

Both B and T cells are generated in the bone marrow, however B cells mature in the ____ and T cells mature in the ____

A

bone marrow
thymus

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89
Q

For B cells, additional maturation steps can occur in the ____

A

spleen

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90
Q

Once lymphocytes mature, they leave primary lymphoid organs and are capable of responding to an ____

A

antigen

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91
Q

Secondary lymphoid organs are where adaptive immune responses are _____

A

initiated
- antigens and B/T Cell receptors encounter each other

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92
Q

Secondary lymphoid organs exist to bring antigen and lymphocytes together and include:

A

lymph nodes, spleen and MALT

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93
Q

Lymph nodes lie at junctions of ______ , collect _____ and return it to the blood via lymphatics

A

lymphatic vessels
ECF/lymph

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94
Q

Afferent lymphatics drain _____ and _____ from tissues, carrying it to the nodes where antigen is _____

A

lymph
antigens
trapped

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95
Q

The ____ filters for blood, collects blood-borne antigens and destroys aged RBCs

A

spleen

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96
Q

B-cells in the ____ produce large quantities of ____ and secrete them into the bloodstream

A

spleen
antibodies

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97
Q

The spleen organ is divided into _____ and _____

A

red pulp
white pulp

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98
Q

What division of the spleen does the destruction of RBCs take place?

A

red pulp

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99
Q

What division of the spleen is where lymphocytes surround arterioles entering the organ?

A

white pulp

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100
Q

White pulp can be further subdivided into _____ and _______

A

corona
periarteriolar lymphoid sheath (PALS)

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101
Q

Mucosa-associated lymphoid tissues (MALT) includes:

A

gut associated lymphoid tissues (GALT) and bronchial- associated lymphoid tissues
BALT

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102
Q

The purpose of MALT is to collect _____ from mucosal surfaces

A

antigens

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103
Q

______ is a specialized lymphoid tissue at the body’s “wet” surfaces required due to large surface area, and is rich with potential pathogens

A

MALT

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104
Q

______ includes tonsils, adenoids, appendix and Peyer’s Patches (PP)

A

GALT

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105
Q

______ collect antigens from epithelial surfaces of the GI tract via M cells

A

peyer’s patches

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106
Q

_______ are composed of distinct T and B cell areas

A

peyer’s patches

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107
Q

True or false: only when innate defenses are overwhelmed/bypassed/evaded is an adaptive immune response required

A

true

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108
Q

What are the 3 barriers of the immune system?

A

1) mechanical
2) chemical
3) microbiological

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109
Q

What are the mechanical, chemical and microbiological barriers of the skin?

A

mechanical
- epithelial cells joined by tight junctions
- flow of fluid, perspiration, sloughing off of skin
chemical
- antimicrobial peptides (defensins)
- sebum (fatty acids, lactic acid, lysozyme)
microbiological
- normal flora of the skin

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110
Q

What are the mechanical, chemical and microbiological barriers of the GI tract?

A

mechanical
- epithelial cells joined by tight junctions
- flow of fluid, mucus, food, and saliva
chemical
- antimicrobial peptides (defensins)
- acidity, enzymes (proteases)
microbiological
- normal flora of the GI tract

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111
Q

What are the mechanical, chemical and microbiological barriers of the respiratory tract?

A

mechanical
- epithelial cells joined by tight junctions
- flow of fluid and mucus e.g., by cilia, air flow
chemical
- antimicrobial peptides (defensins)
- lysozyme in nasal secretions
microbiological
- normal flora of the respiratory tract

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112
Q

What are the mechanical, chemical and microbiological barriers of the urogenital tract?

A

mechanical
- epithelial cells joined by tight junctions
- flow of fluid, urine, mucus, sperm
chemical
- antimicrobial peptides (defensins)
- acidity in vaginal secretions, spermine and zinc in semen
microbiological
- normal flora of the urogenital tract

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113
Q

What are the mechanical, chemical and microbiological barriers of the eyes?

A

mechanical
- epithelial cells joined by tight junctions
- flow of fluid, tears
chemical
- antimicrobial peptides (defensins)
- lysozyme in tears
microbiological
- normal flora of the eyes

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114
Q

Chemical barriers include _____ and ______

A

lysozymes
antimicrobial peptides - defensins

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115
Q

Lysozymes present in secretions and uses _____ to break apart the peptidoglycan wall, causing lysis of the bacterial cell wall

A

hydrolysis

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116
Q

Antimicrobial peptides/defensins are small, heterogenous, cationic peptides that kill _____ and _____ bacteria, some enveloped viruses and fungi

A

Gram-negative
Gram-positive

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117
Q

What are the antimicrobial effects of antimicrobial peptides/defensins?

A
  • Destabilize membranes and Pore formation in bacterial cell walls
  • Proteolytic degradation of bacterial proteins
  • Inhibit viral binding and entry
  • Inhibit virus particle assembly
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118
Q

Defensins are prototypical AMPs that can act as a chemical barrier when they are secreted by _______ in a variety of mucosal surfaces

A

epithelial cells

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119
Q

Defensins and other AMPs (i.e. cathelicidins) are also stored
in _______ and can be released within tissues in
response to inflammation

A

neutrophil granules

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120
Q

Defensins and other AMPs (i.e., cathelicidins) can kill microbes _____ when neutrophils die during inflammation, and _____ after a cell phagocytoses a pathogen

A

extracellularly
intracellularly

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121
Q

Phagocytes are a _____ of defense as they can recognize, ingest and destroy many pathogens without the aid of an adaptive immune response

A

first line

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122
Q

True or false: Phagocytosis can also occur after an antibody (signal) has bound to an antigen and triggers phagocytosis

A

true

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123
Q

What are the 2 major phagocytes in the body?

A

macrophages and neutrophils

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124
Q

Pro-monocytes are found in the ____, monocytes are found in the ____ and macrophage/macrophage-like cells are found in the ____

A

bone marrow
blood
tissues

125
Q

_____ are a non-dividing short-lived cell type in the blood (dominant WBC), and are derived from hematopoietic precursors in the bone marrow

A

neutrophils

126
Q

Review the stages of phagocytosis:

A

1 - bacterium binds to pattern recognition receptors on membrane evaginations called pseudopodia
2 - bacterium is ingested, forming phagosome
3 - phagosome fuses with lysozyme
4 - bacterium is killed and then digested by low pH activated lysosomal enzymes
5 - digestion products are released from cell

127
Q

Evolutionarily conserved mechanism for
recognizing common, conserved ‘signs’ of microbial
infection, physiological stress, or other damage is known as:

A

pattern recognition

128
Q

True or false: Pattern recognition is immediate, does not require prior
recognition, and activates several arms of the
innate (and adaptive) immune response

A

true

129
Q

Responses are elicited via the engagement of
Pattern Recognition Receptors (PRRs) found on
phagocytes, in response to:

A
  • Pathogen Associated Molecular Patterns (PAMPs)
  • Danger Associated Molecular Patterns (DAMPs)
130
Q

Pattern recognition receptors include:

A
  • Toll-like receptors
  • Nod-like receptors
  • Lectins
131
Q

Pattern recognition receptors illicit responses such as:

A

phagocytosis and cytokine secretion

132
Q

In step 1 of the phagocytosis process, a pattern-recognition-receptor (PRR) binds to a microbe or bit of
debris, OR an ____ created by
another cell binds to the microbe

A

opsonin

133
Q

An opsonin is a
soluble, secreted PRR
that enhances the
effectiveness of
_____

A

phagocytosis

134
Q

An opsonin coats a
microbe, the ____
has receptors for parts of
that opsonin

A

phagocyte

135
Q

Lectin receptors (i.e., mannose receptor) recognize _____

A

carbohydrate patterns

136
Q

Scavenger receptor examples are:

A

SR-A and SR-B

137
Q

Complement receptors (i.e., CR3) binds to _____

A

complement opsonins

138
Q

Fc receptors are receptors for the _____ region of an antibody

A

constant

139
Q

In step 2 of the phagocytosis process (microbe engulfment), the PRR receptors signal the
________ to
approach, coat and
surround the sites where
the receptor is bound.

A

cell membrane

140
Q

In step 2 of the phagocytosis process, we form a ____ , mediated by intracellular signaling events and actin polymerization

A

phagosome

141
Q

PI3 kinase is important in which step of phagocytosis?

A

the 2nd step

142
Q

In step 3 of the phagocytosis process (microbe killing), phagosomes fuse with _____ as well as primary and secondary ______

A

lysosomes
granules

143
Q

Phagosomes have many molecules that are effective at cellular killing. Major groups include:

A
  • Reactive oxygen species
  • “pore”-forming proteins or peptides
  • Hydrolytic enzymes
  • pH changes – i.e. acidic
    environment of the
    lysozyme
144
Q

In step 3 of the phagocytosis process (microbe killing), the microbe remnants are either _______ or can be excreted from the phagocyte

A

digested and used

145
Q

After the microbe has been phagocytosed, the phagosome will
dock with a ____ and/or neutrophil granules

A

lysozyme

146
Q

What are the characteristics of lysozymes?

A
  • they can pretty much break down anything (acid hydrolases)
  • they have a low pH of a lysozyme which is unpleasant for many bacteria
147
Q

The NADPH oxidase complex becomes associated with the membrane of the ____ and uses a large amount of ____

A

phagolysosome
oxygen

148
Q

True or false: If a particle is too large to phagocytose, macrophages will surround
it and “place” their NADPH oxidases close to it to try to kill it

A

true

149
Q

Macrophages are also capable of killing cells by inducing the synthesis of ______ at high concentrations

A

nitric oxide

150
Q

Neutrophils have a multitude of pore-forming molecules within their _____ , that will fuse with the phagosome

A

granules

151
Q

Neutrophil granules include:

A

defensins
cathepsin
cathelicidins
lysozyme
lactoferrin

152
Q

Defensins causes lysis and are very rich in ____

A

cysteine

153
Q

Defensins form voltage-dependent pores in ____ that are permeable to water

A

bacteria

154
Q

Cathepsin is a type of ___

A

protease

155
Q

Cathelicidans are pore-forming molecules that causes ____

A

lysis

156
Q

Lysozome is a glycoside hydrolase that doesn’t require an ____, is found in a variety of glandular secretions, and is great at killing gram ____

A

acidic pH
positive bacteria

157
Q

Lactoferrin is an iron-binding protein that interferes with _____ in microbes

A

iron metabolism

158
Q

When neutrophils are in an environment with many bacteria, they can lyse and release their ____ into the ___

A

DNA
ECF

159
Q

NETs are neutrophil extracellular traps that are sticky and contain ____ where most bacteria are trapped

A

chromatin

160
Q

True or false: histones are toxic to many bacteria

A

true

161
Q

True or false: the granule contents will remain close to the NETs and
help with killing bacteria, even after the neutrophil itself is dead

A

true

162
Q

LPS, dsRNA, ssRNA, DNA, and Flagellin are all examples of ____

A

toll-like receptor ligands

163
Q

Cytokines secreted in response to TLR’s include:

A

inflammatory cytokines (IL-1b, IL-6, CXCL8, IL-12, TNFa) and interferons

164
Q

What are the functions of inflammatory cytokines?

A

small protein messenger secreted by many cells that can:
- Influence the differentiation of a wide variety of cells,
including leukocytes
- Mediate – activate or inactivate – the activity of many cells, including leukocytes
- Increase or decrease the production of a wide variety of stem/hematopoietic cells

165
Q

What are the types of interferons (IFN)?

A

alpha, beta, and lambda (IFNa, IFNb, IFNl)

166
Q

Interferons are autocrine and paracrine signaling molecules that are effective in activating _____ and ____ cells, and inducing an _____ state

A

macrophages
NK
antiviral

167
Q

MyD88 is an essential adaptor in ___ signaling

A

TLR

168
Q

People with MyD88 deficiency suffer frequent and severe _____ infections, while antiviral responses are generally unaffected

A

bacterial

169
Q

People with constitutively active MyD88 are prone to developing ____ and ____

A

blood disorders
blood cancers
- overproduction or dysregulated production of igM
- B cell lymphoma, marginal cell lymphoma

170
Q

Nod-like receptors are a family of intracellular receptors found in the ____ that detect products derived from the intracellular degradation of phagocytosed pathogens

A

cytoplasm

171
Q

True or false: Nod-like receptors can recognize DAMPs associated with cellular stress

A

true

172
Q

Nod-like receptors activate expression of _______

A

inflammatory cytokines

173
Q

What are the 3 steps of acute inflammation?

A

1) alteration of vascular caliber - vasodilation
2) enhancement of vascular permeability
3) emigration and activation of leukocytes

174
Q

Vasodilation leads to increases in blood flow at the capillary bed due to _____ dilation, dilation of precapillary sphincters

A

arteriolar

175
Q

What components contribute to vasodilation in acute inflammation?

A
  • Nitric oxide and histamine
  • Prostaglandins (PGI2, PGE2, PGD2)
  • Platelet activating factor (at low concentrations – higher
    concentrations cause vasoconstriction)
  • Complement (C5a and C3a stimulate histamine release)
176
Q

At low concentrations _____ is a potent vasodilator

A

nitric oxide

177
Q

At high concentrations ____ is capable of destroying both microbes and host cells since it’s a _____

A

nitric oxide
free radical

178
Q

In macrophages, higher concentrations of nitric oxide are produced by an inducible _____

A

nitric oxide synthase

179
Q

Vasodilation and fluid loss due to increase permeability lead to slower blood flow known as ______ , which helps with margination of leukocytes

A

vascular congestion

180
Q

Prostaglandins and leukotrienes are produced when PLA2
generates ______ from membrane phospholipids

A

arachidonic acid

181
Q

Different types of cyclooxygenases produce different types
of prostaglandins from ______

A

arachidonic acid

182
Q

What prostaglandins cause vasodilation and increase vascular permeability?

A

PGE2, PGD2, and PGI2

183
Q

Different types of 5-lipoxygenase produce different types of leukotrienes from _____ that are
important in lung tissue

A

arachidonic acid

184
Q

LTB4 is a leukotriene that is an important _____

A

chemotactic agent

185
Q

Many leukotrienes increase vascular permeability and _______

A

smooth muscle constriction

186
Q

Lipoxins are generated from arachidonic acid by 12-lipoxygenase and they decrease ____

A

inflammation

187
Q

Capillaries and venules become more “leaky” with the release of numerous mediators:

A
  • Histamine and serotonin (released by activated
    platelets)
  • Prostaglandins (PGD2 and PGE2)
  • Leukotrienes (LTC4, LTD4, LTE4)
  • Platelet activating factor
  • C3a and C5a
  • Bradykinin
188
Q

Increased vascular permeability is due to contraction of
_______ , which is often short-lived and occurs mainly in the ____

A

endothelial cells
venules

189
Q

Vascular permeability can also occur through ______ caused by trauma, burns and microbial damage, or leukocyte-mediated damage to the _____ , which is longer-lived

A

endothelial damage
endothelium

190
Q

Increased transcytosis can result in ____ of plasma components into the _____

A

leakage
interstitial space

191
Q

Active, vesicle-mediated transport across the capillary endothelial cell is known as:

A

transcytosis

192
Q

In transcytosis, larger molecules can move across the endothelium via _____ and _____

A
  • Pinocytosis (caveolin
    pathway)
  • Receptor-mediated
    endocytosis
193
Q

Mechanisms of increased vascular permeability:

A

Retraction of endothelial cells –> endothelial injury –> leukocyte-mediated vascular injury –> increased transcytosis

194
Q

A interstitial fluid accumulates during inflammation, pressure increases in the interstitial space and _____ increases

A

lymphatic drainage

195
Q

Excess fluid, microbes, debris, and leukocytes all migrate into the ____ during inflammation

A

lymph

196
Q

When lymphatic vessels themselves become inflamed this is called:

A

lymphangitis

197
Q

During emigration and activation of leukocytes, neutrophils, monocytes, eosinophils, and basophils will all migrate from the circulation into _____

A

inflamed tissue

198
Q

What are the 5 steps of leukocyte migration?

A

1) Margination
2) Rolling (Mediated by binding of selectins and
cellular adhesion molecules to their respective ligands on leukocytes)
3) Adhesion (Mediated by binding of selectins and
cellular adhesion molecules to their respective ligands on leukocytes)
4) Diapedesis
5) Chemotaxis of leukocytes to sites of injury or infection

199
Q

What are the functions of cytokines?

A

1) Influence the differentiation of a wide variety of cells, including leukocytes
2) Mediate – activate or inactivate – the activity of many cells,
including leukocytes
3) Increase or decrease the production of a wide variety of stem/hematopoietic cells

200
Q

What are the functions of chemokines?

A

1) Bind to cell-surface receptors (usually leukocytes)
2) Induce movement of leukocytes along the chemokine concentration
gradient
3) Mediate adhesion of leukocytes for the purposes of:
* Differentiation
* Inflammation/migration

201
Q

What are the 2 major chemokine families?

A

CXC and CC

202
Q

CXC chemokines attract ____ and are ____

A

neutrophils
angiogenic

203
Q

In CXC chemokines, the “X” indicates the location of a _____ bond

A

disulphide

204
Q

CC chemokines act on/attract a wide variety of _____

A

leukocytes

205
Q

Review the steps for emigration and activation of leukocytes:

A

a) Margination – leukocytes migrate towards vessel wall
b) Rolling – formation & dissociation of adhesion bonds between
leukocytes and endothelial cells
c) Stable/Tight Adhesion – Formation of tight/stable
adhesion bonds between leukocytes and endothelial cells
d) Diapedesis/Transmigration – leukocyte migrates through
endothelium
e) Chemotaxis of
leukocytes to sites of injury or infection

206
Q

Activation by chemokines presented on endothelial cells is required before the leukocyte can form ______

A

stable adhesion

207
Q

When an endothelial cell presents a chemokine that stimulates the activation of leukocytes, this increases the affinity of leukocyte integrin for it’s ____ , allowing _____ to form

A

ligand
stable/tight adhesion bonds

208
Q

What are the 3 families of endothelial and leukocyte adhesion molecules?

A

selectin, integrin and Ig

209
Q

How does histamine and thrombin increase the ability of leukocytes to migrate to a target?

A

rolling and selectin expression by endothelial cells

210
Q

How does TNF and IL1 increase the ability of leukocytes to migrate to a target?

A

ICAM expression by endothelial cells

211
Q

How do chemokines increase the ability of leukocytes to migrate to a target?

A

increased integrin affinity

212
Q

Chemotactic agents are produced in higher concentrations at sites of _____

A

cellular damage/pathogen invasion
- i.e., leukotriene B4, bacterial products containing N-formyl-methionine, activated complement (C5a), chemokines (IL-8, RANTES, eotaxin)

213
Q

Leukocytes can “follow the breadcrumbs” to the site of pathology via the _______

A

chemotactic agent concentration gradient

214
Q

What is the complement system?

A

A blood-borne molecular defense system that “complements” the immunity provided by antibodies

215
Q

What 3 functions does the complement system aid in?

A

1) phagocytosis - some complement components are opsonins
2) destruction of microorganisms - the end result of complement activation is formation of a large, antimicrobial protein complex
3) inflammation - some complement components are potent inflammatory mediators

216
Q

How is the complement system activated?

A

Through a tightly-controlled enzyme-triggered cascade
- cascade = enzymatic reactions that activate protein effectors in a sequence

217
Q

What are the 3 pathways of complement activation?

A

1) Alternative pathway
- complement component 3 (C3) acts as a PRR binding to the surface of a pathogen
2) Mannose-binding-lectin (MBL)
- triggered by binding of MBL, a PRR, to mannose-containing CHO on bacteria/viruses
3) Classical pathway
- when antibodies bind to a pathogen, C1q binds to the Fc portion of those antibodies

218
Q

The _____ pathway and ______ pathway have a similar activation mechanism

A

mannose-binding-lectin
classical

219
Q

C3 convertase cleaves C3 into ___ and ___

A

C3b
C3a

220
Q

C3b is an important ____ , forms part of the _____ convertase, and causes progression through the rest of the complement cascade

A

opsonin
C5

221
Q

C5 convertase cleaves C5 into ___ and ___

A

C5a
C5b

222
Q

C5b becomes associated with the cell wall/membrane of the microbe and causes ____ as it activates other components of the complement system

A

lysis

223
Q

What complement molecules all associate to form a large pore in the microbial membrane and cause lysis

A

C5b, C6, C7, C8, C9

224
Q

True or false: C3a and C5a are incorporated into the microbes membrane and also mediate inflammation

A

true

225
Q

The classical and lectin pathways have the same ___ and ___ convertases, and C1q and MBL look very similar

A

C3
C5

226
Q

C3 forms C3a and C3b spontaneously in the bloodstream, but is ____ quickly under normal conditions

A

degraded

227
Q

Factor B, a circulating proteins is spontaneously ____ to a protein known as ____

A

cleaved
Bb (complexes with C3b to form C3bBb)

228
Q

C3bBb is a C3 convertase and can convert C3 into ___ and ___

A

C3a
C3b

229
Q

C3bBb is rapidly inactivated in the ____. If an bacterium is present, then it will bind to the _____

A

uninfected host
bacterial membrane

230
Q

C3Bb bound to the bacterial membrane is a stable _____

A

C3 convertase

231
Q

As more C3b is generated, more ___ is formed

A

C3Bb

232
Q

The circulating protein, properdin helps stabilize the alternative pathway complex to form the stable ___ and ___ convertases

A

C3 and C5

233
Q

C3bBbC3b and properdin are components of the C5 convertase of the _____ pathway. They need to bind to the bacterial membrane to stay stable and keep converting C5 into ___ and ___

A

alternative
C5a
C5b

234
Q

When C1q detects a bound antibody or MBL detects mannose on a membrane, they bind ______ proteins, and these proteins cleave ___ and ___

A

complement-activating
C2
C4

235
Q

C4b2a is formed from the cleavage of ___ and ___ upon C1q or MBL activation

A

C4
C2

236
Q

The membrane attack complex (MAC) generates a ___ in lipid bilayer membranes

A

pore

237
Q

What is the sequence of events for cell lysis in the MAC?

A
  1. C5b triggers the assembly of complexes C5b, C6, C7 and C8
  2. Upon binding to C7, C8 inserts into the membrane
  3. Polymerization of C9, forming a pore in the membrane
238
Q

True or false: The MAC and the pro-inflammatory effects of C5a and C3a can be extremely damaging to cells if they are not tightly regulated

A

true

239
Q

___ and ___ both cause vasodilation, increased vascular permeability, smooth muscle contraction (i.e., bronchoconstriction) and histamine release from mast cells

A

C3a
C5a

240
Q

____ is a chemotactic agent for a wide variety of cells (neutrophils & macrophages)

A

C5a

241
Q

Inadequate complement proteins C2, C3, C4, C5, MBL, and MAC complex tend to make patients vulnerable to _____ infection

A

bacterial

242
Q

Deficiencies in ___ highly predispose patients to systemic lupus erythematosus

A

C1q

243
Q

C1q helps macrophages to clear _____ bodies and initiate the ____ pathway, as it recognizes phosphatidylserine

A

apoptotic
classical

244
Q

The alternative pathway is the first responder, while the lectin/classical pathways are more effective later because ___ is always present in the bloodstream and is constantly being produced by the liver, cleaved and degraded

A

C3

245
Q

Mannose-binding lectin does not circulate in high ____ unless it is secreted by the liver in response to pro-inflammatory signals

A

concentrations

246
Q

What do toll-like receptors 1-4 detect?

A

TLR1 - can detect mycobacteria (like Tb) and gram-negative bacteria
TLR2 - can detect peptidoglycans (major component of cell wall of gram-positive bacteria)
TLR3 - can detect double stranded RNA (only found in viruses)
TLR4 - can detect lipopolysaccharide (LPS) (major component of gram-negative bacteria)

247
Q

TLRs tend to recognize PAMPs in the ____ or in ___

A

ECF
endosomes

247
Q

C-type lectin receptors detect ____ components of many microbes, and are found on the cell membrane of a wide variety of _____ cells

A

carbohydrate
immune

248
Q

True or false: C-type lectin receptors are found on the cell membrane and detect pathogens in the cytosol

A

false
- they do NOT detect pathogens in the cytosol

249
Q

NOD-like receptors (NLRs) are present in the ____ of a wide range of immune cells and non-immune cells (i.e., epithelial cells)

A

cytosol

250
Q

Most NLRs detect ____ or parasite cell walls and some can also detect ____

A

bacteria
viruses

251
Q

Activation of ____ leads to activation of NF-KB and AP-1

A

NLRs

252
Q

RIG-like receptors (RLRs) are present in the ___ of many immune cells and non-immune cells. They detect viral ___ and activate NF-KB and transcriptions factors which leads to the production of antiviral ____

A

cytosol
RNA
cytokines (interferons)

253
Q

DAMPs are molecular signals that are present when a cell is damaged but they can also present as crystals including:

A

cholesterol crystals (cellular damage or oxidized LDL)
uric acid crystal (gout)

254
Q

When a DAMP activates NLRP3, it associated with caspase 1 and activates it by forming a large molecular complex known as an ____

A

inflammasome

255
Q

What are the 2 major effects of caspase 1 activation?

A

1) activation of pro-IL-1-beta to IL-1-beta
2) insertion of a cell membrane pore - gasdermin - into the cell membrane

256
Q

If enough gasdermin is produced, the cell will ____ , and release more ____

A

lyse/die (pyroptosis)
DAMPs

256
Q

Inflammasomes are a molecular assembly that activates _____

A

caspase 1

256
Q

IL-1 leaves the cell via ____

A

gasdermin pores

257
Q

True or false: The release of DAMPs can lead to activation of neighboring cells

A

true

258
Q

Review the 2-step process of IL-1 generation/release:

A

1) Priming - detection of PAMPs or DAMPs leading to synthesis and storage of pro-IL-1
2) release - continued or larger DAMP or PAMP stimuli, causing NLRP3 activation leading to caspase 1 activation and the conversion of pro-IL-1 to IL-1, releasing IL-1

258
Q

What cells are cellular sentinels/important DAMP and PAMP detectors?

A

Resident macrophages, endothelial cells, epithelial cells

258
Q

Il-1-beta is one of the most important _____, and is released in large quantities by macrophages in response to _____ or _____

A

pro-inflammatory cytokines
significant infection
tissue damage

259
Q

What cells express most PAMP and DAMP receptors and can secrete large quantities of pro-inflammatory cytokines?

A

Langerhans cells - dermis and epidermis
Kupffer cell - liver
Alveolar macrophages - lung
Microglia - brain
Resident macrophages also found in connective tissue
Spleen (and other secondary lymphoid organs)

260
Q

Endothelial cells in the blood and lymph vessels express TLRs and RLRs, and when they detect a PAMP they do 2 things:

A

1) increase the expression of ICAMs and selectins
2) increase the production of pro-inflammatory cytokines and chemokines

261
Q

The PRRs in epithelial cells (found in skin and mucosal surfaces) tend to result in increased production of local ______ peptides

A

antimicrobial

262
Q

Chemokines and cytokines in epithelial cells can be produced if more ____ need to be recruited from circulation

A

leukocytes

263
Q

What are the major pro-inflammatory cytokines?

A

IL-1-beta, IL-6, IL-12, CXCL8, and TNF-alpha

263
Q

What are the important cellular sources for IL-6?

A

Macrophages/monocytes, dendritic cells, NK cells, epithelial cells, endothelial cells

263
Q

What are the important cellular sources for IL-1?

A

Macrophages/monocytes, dendritic cells, keratinocytes, epithelial cells, endothelial cells

264
Q

What are the important cellular sources for TNF-alpha?

A

Macrophages/monocytes, dendritic cells, mast cells, NK cells, epithelial cells

264
Q

Which 3 cytokines have redundant and pleiotropic effects?

A

IL-1, IL-6, TNF-alpha

265
Q

IL-1-beta, IL-6 and TNF-alpha all act on the ____ to cause fever, participate in the synthesis and release of acute-phase proteins by the ____, and increase vascular permeability

A

hypothalamus
liver

266
Q

IL-1-beta and TNF-alpha both increase ____ molecules on vascular endothelium, produce the chemokine ____, and IL-6

A

adhesion
CXCL8

267
Q

What are the mechanisms of higher body temperature?

A
  1. peripheral vasoconstriction (blood flows away from the periphery to the core)
  2. shivering
  3. increased metabolic rate
267
Q

What is the benefit to fever?

A

adaptive immune mechanisms in general are more effective at higher temperatures

267
Q

The hypothalamic set-point is altered by increased levels of _____

A

pro-inflammatory cytokines

268
Q

IL-1-beta and TNF-alpha can induce fever at low ____ , and IL-6 induces fever at higher (10X) ____

A

serum concentrations
concentrations

269
Q

Pro-inflammatory cytokines cause elevation of ____ E2 production by cells in the 3rd ventricle, which leads to signaling that changes the _____ setpoint

A

Prostaglandin
hypothalamic

270
Q

What are the 5 major acute phase proteins?

A
  1. C-reactive protein (CRP)
  2. Ferritin
  3. Hepcidin
  4. Mannose-binding lectin (MBL)
  5. Serum amyloid protein A (SAA)
271
Q

Blockers of cyclooxygenase activity (i.e., tylenol) are effective _____

A

anti-pyretics

272
Q

Elevated levels of inflammatory cytokines cause the ____ to increase the secretion of useful ___ into the bloodstream, known as acute _____

A

liver
proteins
phase proteins

273
Q

C-reactive protein (CRP) includes ___ which binds to phosphorylcholine. CRP can activate ____ to trigger the classical complement cascade.

A

opsonin
C1q

273
Q

True or false: CRP is a common lab measurement ordered to diagnose inflammatory disease

A

true

273
Q

Ferritin binds to ____ with high affinity, and many microbes depend on ____ for their metabolism

A

serum iron
iron

274
Q

Mannose-binding lectin is the PRR that initiates the ______ cascade

A

lectin complement

274
Q

Hepcidin interferes with intestinal transport of ___ into the bloodstream

A

iron

274
Q

Serum amyloid protein A modulates/increases the activation of the ____ and ____, and also opsonizes ____ bacteria

A

inflammasome
TLRs
gram-negative

275
Q

IFN-alpha and IFN-beta are secreted by:

A

macrophages, dendritic cells and cells that have detected viruses via PRRs

275
Q

What are the 2 major groups of interferons?

A

1) Group 1 - interferon-alpha (IFN-alpha) and interferon-beta (IFN-beta)
2) Group 2 - interferon-gamma (IFN-gamma)

276
Q

The role of IFN-alpha and IFN-beta is to:

A

interfere with viral replication

277
Q

IFN-gamma is secreted by ___ cells and ___ cells, and it activates ____to push the adaptive immune system to a cell-mediated response

A

Th
NK
macrophages

278
Q

Type 1 interferons act in an ___ and ___ fashion to provide a rapid, innate protection to viral infection

A

autocrine
paracrine

279
Q

If type-1 IFNs and the NK response is inadequate, then we rely on the ______

A

adaptive immune response

280
Q

What are the 3 ways type 1 interferons protect against viral infection?

A

1) induce resistance to viral replication in all cells
2) increase MHC class I expression and antigen presentation in all cells
3) activate NK cells to kill virus-infected cells

281
Q

How do interferons interfere with viral replication inside cells?

A
  • they inhibit protein translation in the presence of viral RNA
  • they degrade viral mRNA
  • they inhibit viral protein assembly
282
Q

Natural killer cells are specialized cells derived from the ____ lineage, and has a non-specific way of detecting cancer cells or virally-infected cells

A

lymphoid

283
Q

Large lymphocytes that are activated by Type 1 IFNs and IL-12 do 2 things:

A

1) kill cells that are infected by viruses
2) secrete cytokines that predispose the adaptive immune system to adopt a response that relies on cellular effectors rather than antibodies

284
Q

NK cells survey the body for ___ or ____ abnormal cells

A

infected
stressed

285
Q

What are the two types of NK cell receptors?

A

1) NK activating receptors (NKARs)
2) NK inhibitory receptors (NKIRs)

286
Q

_____ detect molecules expressed on the membrane of cells that are infected by viruses or have developed into cells that may be malignant, while ____ detect molecules that are typically expressed by normal cells

A

NKARs
NKIRs

286
Q

NKG2D is an NKAR that detects _____ molecules on cells

A

strange MHC-I

286
Q

KIR is an NKIR that detects -_____ molecules on a cell membrane

A

normal MHC-I

287
Q

While normal MHC-I proteins can present intracellular ____, abnormal MHC-I proteins cannot and are typically expressed by virally-infected cells or cells with damaged genomes.

A

antigens

288
Q

Before NK cells can be activated, they need to be licensed to make sure their ____ are functional. This is done by _____

A

NKIRs
dendritic cells (protect body from indiscriminate NK-killing and tissue damage)

288
Q

Once NK cells are activated an licensed, they travel to areas of ____ and ___ the cells

A

damage/inflammation
survey

289
Q

If a cell expresses mostly normal MHC-I proteins, ____ over-rule ____ and vice versa for abnormal MHC-I proteins

A

NKIRs
NKARs

290
Q

When NKARs are activated, it kills the cell by:

A

1) receptor-mediated apoptosis via Fas-Fas ligand interaction
2) secretion of the proteins perforin and granzyme
- perforin pokes holes in membrane
- granzyme activated BH3-only apoptotic protein Bid and executioner caspase 3

BMS150 - Biomedicine (2 decks)

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