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Immuno > Immuno Exam 1 > Flashcards

Immuno Exam 1 Flashcards

1
Q

Immunology is the branch of biomedical science that studies…

A

resistance to infection and
mechanisms used by organisms to defend themselves against microorganisms or foreign particles

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2
Q

Define immune system

A

mechanisms used by organisms to defend themselves against microorganisms or foreign particles

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3
Q

Define immunity

A

state of being resistant to infection by a specific pathogen

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4
Q

When was Thucydides’ eyewitness account of immunity to plague?

A

430 BCE

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5
Q

When did Girolamo Fracastoro state that diseases were caused by seed-like entities transmitted by direct or indirect contact?

A

1546

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6
Q

Whose belief contributed to the eventual germ theory of disease?

A

Girolamo Fracastoro

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7
Q

What is the germ theory of disease?

A

diseases are caused by pathogens

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8
Q

Define pathogens

A

microorganisms with the potential to cause disease

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9
Q

Who are important figures related to the germ theory of disease?

A

Agostino Bassi
Ignaz Semmelweis
Louis Pasteur
Robert Koch

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10
Q

What are examples of early forms of vaccination?

A

inhalation of crusts from smallpox lesions in 1000 AD
variolation against smallpox (16th century)

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11
Q

Who developed the smallpox vaccine?

A

Edward Jenner

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12
Q

What was hypothesized to provide protection against smallpox?

A

cowpox

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13
Q

How did the developer of the smallpox vaccine provide an 8-year-old boy with smallpox immunity?

A

by inoculating him with cowpox pus

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14
Q

What latin word is “vaccine” derived from, and what does it mean?

A

vaccinus - “of the cow”

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15
Q

What did Paul Ehrlich discover?

A

granulocytes are part of the immune system

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16
Q

What did Ilya Mechnikov discover?

A

white blood cells are capable of phagocytosis
cellular theory of immunology

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17
Q

What did Emil von Behring and Shibasaburo Kitasato discover?

A

antitoxin to diptheria and tetanus in blood of infected individuals (antibody)
humoral theory of immunology

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18
Q

How do opportunistic pathogens cause disease?

A

only when the immune system is not functioning properly or enters a site where it can grow uncontrollably

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19
Q

What can be pathogenic organisms?

A

bacteria
viruses
fungi
protozoa
parasitic animals

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20
Q

What are examples of pathogenic bacteria, and what diseases do they cause?

A

Staphylococcus aureus - skin infection, meningitis, toxic shock
Haemonophilus influenzae - pneumonia
Salmonella typhimurium - food poisoning
Vibrio cholera - cholera

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21
Q

What are examples of pathogenic viruses, and what diseases do they cause?

A

Influenza A - influenza (flu)
Hepatitis B - hepatitis
Epstein–Barr - mononucleosis
Ebolavirus - hemorrhagic fever

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22
Q

What are examples of pathogenic fungi, and what diseases do they cause?

A

Candida albicans - yeast infection
Cryptococcus neoformans - meningitis
Aspergillus flavus - aspergillosis

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23
Q

What are examples of pathogenic parasites, and what diseases do they cause?

A

Plasmodium falciparum - malaria
Toxoplasma gondii - toxoplasmosis
Trypanosoma brucei - sleeping sickness

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24
Q

What are examples of pathogenic protozoa, and what diseases do they cause?

A

Giardia intestinalis - giardiasis
Leishmania - leishmaniasis

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25
Q

Where do extracellular pathogens reside?

A

outside of the cells of organisms they infect

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26
Q

Where do intracellular pathogens reside?

A

mainly within the organism’s cells

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27
Q

What are the lines of defense?

A

physical barriers
innate immunity
adaptive immunity

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28
Q

What are the physical barriers?

A

skin and mucosa

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29
Q

Define innate immunity

A

non-specific immunity present from birth

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30
Q

Define adaptive immunity

A

specific immunity learned after contact with a pathogen
protects upon subsequent exposure
identifies antigens

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31
Q

Define antigens

A

substances recognized as foreign

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32
Q

What type of cells are associated with humoral immunity?

A

B cells

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33
Q

Define B cells

A

immune cells that use cell-surface proteins to bind and recognize an antigen

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34
Q

What are the cell-surface proteins utilized by B cells called?

A

immunoglobulins

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35
Q

What happens after an immunoglobulin is used to bind and recognize an antigen?

A

activation and differentiation to produce an antibody

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36
Q

Define antibody

A

soluble form of immunoglobulin

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37
Q

What type of cells are associated with cell-mediated immunity?

A

T cells

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38
Q

Define T cells

A

immune cells that use T-cell receptor proteins to bind and recognize an antigen

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39
Q

What happens once an antigen is bound and recognized by T cells?

A

activation and differentiation to clear pathogens
support other immune cells to combat external pathogens or directly target and destroy pathogen-infected cells

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40
Q

What is another name for self-antigens?

A

autoantigens

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41
Q

Define self-antigens

A

components of normal tissue that stimulate an immune response

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42
Q

Does the immune system want to combat foreign antigens, self-antigens or both?

A

foreign antigens

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43
Q

Define tolerance

A

inactivation of immune response to self

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44
Q

When does tolerance occur?

A

during B and T cell development and in other ways throughout the body

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45
Q

What prevents entry of pathogens?

A

epithelium

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46
Q

What is produced by mucus membranes?

A

mucus

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47
Q

What is mucus?

A

destructive components that are constantly flushed and replenished

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48
Q

What do epithelial cells secrete?

A

antimicrobial substances
defensins
lysozyme

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49
Q

Define defensins

A

antimicrobial peptides that disrupt bacterial and viral membranes

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50
Q

What deters microorganisms?

A

low pH of skin, stomach and vagina

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51
Q

Define microbiota

A

collection of microorganisms that normally inhabit the body

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52
Q

What type of organisms make up the microbiota?

A

symbiotic

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53
Q

What are some characteristics of symbiotic organisms?

A

benefit from nutrient-rich environment
aid in digestion
compete with pathogens for nutrients and space
create environment inhibitory for pathogens
help develop immune system

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54
Q

What are the two main categories of leukocytes?

A

granulocytes and agranulocytes

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55
Q

What do granulocytes contain?

A

granules within cytoplasm

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56
Q

What are the granulocytes?

A

neutrophils
eosinophils
basophils
mast cells

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57
Q

What do neutrophils specialize in?

A

phagocytosis

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58
Q

What are the agranulocytes?

A

lymphocytes
monocytes

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59
Q

What are the lymphocytes?

A

B cells and T cells

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60
Q

What do monocytes differentiate into?

A

dendritic cells and macrophages

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61
Q

Define hematopoiesis

A

the process of formation of blood cells

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62
Q

What does hematopoiesis produce?

A

erythrocytes
megakaryocytes
leukocytes

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63
Q

What do hematopoietic stem cells differentiate into for a specific cell line?

A

progenitor cells

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64
Q

What do myeloid progenitor cells give rise to?

A

most cells involved in innate immunity and antigen presentation

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65
Q

What do antigen-presenting cells do?

A

process engulfed material into peptides
present peptides at surface for T cells

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66
Q

What cells are involved in innate immunity and antigen presentation?

A

antigen-presenting cells
granulocytes
monocytes
mast cells

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67
Q

What are macrophages?

A

long-lived cells that specialize in phagocytosis
inhabit specific organs in body areas

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68
Q

Macrophages are scavengers to eliminate what?

A

pathogens, dead cells or other debris from apoptosis

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69
Q

Define apoptosis

A

programmed cell death

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70
Q

What do macrophages secrete?

A

cytokines

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71
Q

What are dendritic cells important for?

A

phagocytosis and pathogen destruction

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72
Q

Dendritic cells link…

A

innate and adaptive immune response

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73
Q

What do dendritic cells play a major role in?

A

antigen uptake and presentation during innate immune response

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74
Q

What can dendritic cells process?

A

many different types of pathogens

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75
Q

Where do dendritic cells reside?

A

tissues of the body

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76
Q

Dendritic cells are able to leave the site of infection to…

A

display antigen
activate adaptive immunity

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77
Q

What do lymphoid progenitor (innate) cells give rise to?

A

innate lymphoid cells (ILCs)
natural killer (NK) cells

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78
Q

What do ILCs secrete, and what do they do?

A

cytokines - activate innate immune cells

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79
Q

What do NK cells do?

A

prevent viral infections
recognize and destroy viral-infected cells
secrete cytokines to minimize viral replication

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80
Q

What do lymphoid progenitor (adaptive) cells give rise to?

A

T cells
B cells

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81
Q

What do T cells differentiate into?

A

cytotoxic T cells
helper T cells

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82
Q

What do cytotoxic T cells do?

A

attack pathogen-infected cells

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83
Q

What do helper T cells do?

A

activate other cells

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84
Q

What do B cells differentiate into?

A

plasma cells

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85
Q

What do plasma cells do?

A

produce antibodies that bind and neutralize pathogens and toxins

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86
Q

What recognizes the pathogens that breach the skin and mucosal barrier?

A

proteins of the complement system
receptors of innate immune cells

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87
Q

What happens once pathogens are recognized after breaching the skin and mucosal barrier?

A

pathogens are removed or destroyed by membrane destabilization
pathogens are engulfed by phagocytosis and eliminated
induce inflammation

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88
Q

Define inflammation

A

increased fluid at the site of infection
can be acute or chronic

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89
Q

When does inflammation occur?

A

when innate immune cells recognize infection and release cytokines or inflammatory mediators

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90
Q

What occurs during inflammation?

A

vasodilation
secretion of complement proteins
recruit leukocytes to the site of infection
movement of dendritic cells and antigens to lymphoid tissue to activate adaptive immune response

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91
Q

What is a fever?

A

the byproduct of inflammation
rise in temperature caused by cytokines and inflammatory mediators
aids in immune system

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92
Q

How does fever aid the immune system?

A

lowers rate of replication of many pathogens
increases activity of the adaptive immune response

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93
Q

What immune response targets and destroys pathogens that evade the innate immune system?

A

adaptive

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94
Q

What receptors recognize a specific antigen in the adaptive immune response?

A

highly specific T cell and B cell receptors

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95
Q

What is the recognition process of highly specific T cell and B cell receptors of the adaptive immune response called?

A

clonal selection

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96
Q

What is clonal expansion?

A

cell proliferation and differentiation of the adaptive immune response

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97
Q

What is another name for daughter cells that recognize the same antigen as the highly specific T cell and B cell receptors?

A

effector cells

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98
Q

What is the key characteristic of adaptive immunity that allows for vaccines to work?

A

immunological memory

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99
Q

What is the primary immune response?

A

the first antigen encounter requires initial adaptive immune response after about 14 days

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100
Q

What do some of the effector cells produced in the primary immune response become?

A

memory cells

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101
Q

Define memory cells

A

long-lived cells capable of activation if exposed to the same pathogen

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102
Q

How long does the stronger, faster secondary immune response take?

A

2-3 days

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103
Q

What is primary lymphoid tissue?

A

sites where lymphocytes develop and mature

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104
Q

What takes place in bone marrow?

A

B cell and T cell production
B cell maturation

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105
Q

What are examples of primary lymphoid tissue?

A

bone marrow
thymus

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106
Q

What takes place in the thymus?

A

T cell development and maturation

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107
Q

What is secondary lymphoid tissue?

A

sites where antigen from pathogens is presented and lymphocytes are activated in response

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108
Q

What are examples of secondary lymphoid tissue?

A

lymph nodes
spleen

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109
Q

What are lymph nodes important in?

A

lymphocyte activation

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110
Q

Lymph nodes are the connection between…

A

circulatory and lymphatic systems

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111
Q

What is lymph?

A

extracellular fluid drained from tissues to blood by lymph nodes of the lymphatic system

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112
Q

What do lymph nodes facilitate?

A

antigen presentation and activation of the adaptive immune response

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113
Q

What is the name of the B-cell region contained by lymph nodes?

A

lymphoid follicles

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114
Q

What cells present T cells in T-cell area, also contained by lymph nodes, and what do they turn into?

A

dendritic cells, effector cells

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115
Q

Where do effector cells migrate, and what do they activate?

A

lymphoid follicles, B cells

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116
Q

What reside in the spleen?

A

macrophages and dendritic cells

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117
Q

What do the cells residing in the spleen do?

A

clear bloodborne pathogens
activate T cells and B cells circulating through the blood into the spleen

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118
Q

What are individuals without a spleen more prone to?

A

bloodborne bacterial infections

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119
Q

What occurs in the white pulp of the spleen?

A

antigen presentation
lymphocyte activation

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120
Q

What does MALT stand for?

A

mucosa-associated lymphoid tissue

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121
Q

Where is MALT found?

A

in the mucus membranes of the digestive, respiratory and urogenital tracts

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122
Q

What are the more-specific forms of MALT?

A

gut-associated lymphoid tissue (GALT)
bronchial-associated lymphoid tissue (BALT)

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123
Q

What is MALT structurally similar to but have different antigen delivery?

A

lymph nodes and spleen

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124
Q

How does MALT gain antigens for presentation to lymphocytes?

A

through M cells

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125
Q

What are the types of immune system malfunctions?

A

hypersensitivity reactions
autoimmune diseases
immunodeficiencies
cancer

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126
Q

What causes hypersensitivity reactions?

A

recognition of an allergen

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127
Q

Define allergen

A

a foreign but innocuous material

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128
Q

What are hypersensitivity reactions commonly known as?

A

allergies

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129
Q

What are severe and deadly hypersensitivity reactions called?

A

anaphylaxis

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130
Q

What do hypersensitivity reactions do?

A

activate granulocytes
induce localized symptoms to expel allergen

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131
Q

What are the localized symptoms induced by hypersensitivity reactions?

A

coughing
sneezing
vomiting
diarrhea

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132
Q

What happens when someone has an autoimmune disease?

A

B cells and T cells that recognize self-molecules enter circulatory and lymphatic systems, causing an adaptive immune response to tissues within the body

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133
Q

What is rheumatoid arthritis?

A

an autoimmune disease characterized by inflammation at recognition sites

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134
Q

What is type I diabetes?

A

an autoimmune disease characterized by destruction of the tissue at recognition sites

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135
Q

What causes immunodeficiencies?

A

lack of immune system function
can be inherited (genetic mutations) or acquired (environmental factors or infection)

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136
Q

What causes a higher likelihood of pathogen infection?

A

immune cells unable to mount proper response

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137
Q

What normally happens when individuals acquire random mutations in genes over a lifetime?

A

the immune system detects these changes as foreign and eliminates the cells that acquire them

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138
Q

What causes cancer?

A

the immune system fails to eliminate mutations occurring in genes controlling cell division, and cells begin to grow uncontrollably

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139
Q

What is the largest organ of the body?

A

skin

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140
Q

What else, besides skin, form a barrier?

A

cells that line the digestive tract and airways

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141
Q

What prevent entry by microbes between epithelial cells?

A

tight junctions

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142
Q

What continually removes microbes to prevent colonization?

A

secretion of fluids such as mucus and tears

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143
Q

What are chemical barriers?

A

acid pH
antimicrobial proteins
antimicrobial peptides
complement system

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144
Q

What is lysozyme?

A

an antimicrobial protein that digests bacterial cell walls

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145
Q

What are examples of phagocytes?

A

macrophages and neutrophils

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146
Q

What are recruited to the site of infection?

A

phagocytes

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147
Q

What do the cell surface receptors of phagocytes recognize?

A

opsonin or molecular pattern on pathogen surface

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148
Q

Clustering of receptors binding to pathogen induces ingestion of pathogen into membrane-enclosed…

A

phagosome

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149
Q

What is formed when a phagosome is fused with a lysosome?

A

phagolysosome

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150
Q

What does a phagolysosome have?

A

low pH and digestive enzymes for destruction and degradation of pathogen

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151
Q

What does PRR stand for?

A

pattern recognition receptor

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152
Q

What are PRRs?

A

receptors used by innate immune cells that recognize pathogen-associated molecular patterns (PAMPs)

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153
Q

What are PAMPs?

A

molecules that are characteristic of a broad range of microbes that are not normally present in the body

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154
Q

What are examples of PAMPs?

A

bacterial cell wall components, such as carbohydrates and lipids
viral or bacterial nucleic acids

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155
Q

What are the types of innate immune cell receptors?

A

toll-like receptors (TLRs)
lectin receptors
scavenger receptors
cytosolic innate receptors
opsonin receptors

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156
Q

What are TLRs, and where can they be found?

A

transmembrane proteins, cell surface and endosomes

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157
Q

What PAMPs do TLRs recognize?

A

lipopolysaccharide (gram-negative bacteria)
lipoteichoic acid (gram-positive bacteria)
single/double-stranded RNA (viruses)
some bacterial proteins

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158
Q

What do lectins do?

A

bind carbohydrates common to pathogen cell surfaces, which activates phagocytosis

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159
Q

What specific lectin recognizes sulfated sugars, polysaccharides with terminal mannose, fucose or N-acetylglucosamine?

A

CD206

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160
Q

What are examples of scavenger receptors?

A

SR-A and SR-B on macrophages

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161
Q

What do scavenger receptors do?

A

bind negatively charged ligands, such as sulfated sugars, lipoteichoic acid and lipopolysaccharide, which activates phagocytosis

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162
Q

What do cytosolic innate receptors recognize?

A

intracellular cytosolic PAMPs, such as viral nucleic acids and bacterial signaling molecules

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163
Q

What specific cytosolic innate receptor recognized viral RNA?

A

RIG-1

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164
Q

What type of cytosolic innate receptor recognizes bacterial cell wall components in the cytosol?

A

NOD-like receptors (NLRs)

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165
Q

What do cytosolic innate receptors do?

A

activate cell responses that inhibit growth of intracellular pathogens and recruit white blood cells to destroy infected host cells

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166
Q

What are two related examples of opsonin receptors, and what do they bind?

A

complement receptors CR3 and CR4, complement proteins bound to microbial cell surfaces

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167
Q

What is a single example of an opsonin receptor, and what does it bind?

A

Fc receptors, immunoglobulins bound to microbial cell surfaces or to soluble foreign molecules

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168
Q

What does binding of opsonin receptors trigger?

A

phagocytosis

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169
Q

What triggers intracellular signaling pathways?

A

receptor clustering

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170
Q

What leads to the production and secretion of cytokines?

A

changes in gene expression

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171
Q

What are cytokines?

A

secreted proteins that have signaling roles in the immune response

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172
Q

What are two inflammatory cytokines?

A

TNF-α and IL-1

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173
Q

What do inflammatory cytokines cause?

A

swelling and fluid accumulation
dilation of blood vessels
increased vascular permeability
induced local blood vessels to express cell surface proteins that bind and recruit immune cells

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174
Q

What are chemokines?

A

a type of cytokine that act as chemoattractants for immune cells, attract immune cells to site of infection, and lead to inflammation to better fight infections

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175
Q

What are antiviral cytokines?

A

a family of secreted proteins that includes IL-12, interferon-α and interferon-β

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176
Q

What do antiviral cytokines do?

A

activate NK cells to find and destroy virus-infected cells

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177
Q

Where are TLRs that recognize extracellular ligands located?

A

plasma membrane

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178
Q

Where are TLRs that recognize nucleic acids located?

A

endosomal membranes

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179
Q

How is the pathogen recognition domain of TLRs shaped?

A

has an overall C-shape and consists of repeating segments of the leucine-rich repeat (LRR) motif

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180
Q

What are required by TLRs to bind some ligands?

A

cofactors

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181
Q

What does ligand binding by TLRs activate via signaling pathways?

A

transcription factors

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182
Q

What is the cytosolic signaling domain of TLRs called?

A

toll-interleukin receptor (TIR) domain

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183
Q

What transcription factor is activated by TLRs that recognize bacterial PAMPs, and what does the signaling pathway start with?

A

NFκB, MyD88

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184
Q

What transcription factors are activated by TLRs that recognize nucleic acids, and what are involved in the signaling pathway?

A

IRF3 and IRF7
TRIF (toll-receptor-associated activator or interferon) and TRAM (toll-receptor-associated molecule)

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185
Q

What happens when TLRs that bind extracellular bacterial PAMPs activate the transcription factor?

A

ligand binding causes MyD88 to bind to the TIR domain
MyD88 brings the protein kinase IRAK4
IRAK4 phosphorylates and activates IRAK1
IRAK1 phosphorylates and activates TRAF6
TRAF6 modifies and causes destruction of NEMO and TAB to free and activate TAK1
TAK1 phosphorylates and activates IKK
IKK phosphorylates IκB and causes destruction of IκB to free NFκB to enter the nucleus and transcribe genes for cytokines IL-1 and TNF-α

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186
Q

What happens when TLRs that bind viral nucleic acids activate their transcription factors?

A

ligand binding causes TRIF and TRAM to bind to the TIR domain
TRIF and TRAM activate TRAF3
TRAF3 phosphorylates and activates IRF3 and IRF7
phosphorylated IRF3 and IRF7 enter nucleus to transcribe interferons and other genes that promote defense against viral infection

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187
Q

What are the functions of macrophages?

A

phagocytosis
inflammation

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188
Q

What is phagocytosis by macrophages facilitated by?

A

opsonin receptors

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189
Q

What causes inflammation due to macrophages?

A

TLR signaling activates transcription factor NFκB
NFκB induces production of inflammatory cytokines

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190
Q

What are key inflammatory cytokines produced by macrophages?

A

IL-1 and TNF-α
IL-6
CXCL8
IL-12

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191
Q

What do IL-1 and TNF-α do?

A

induce fever and increase vasculature permeability

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192
Q

What does IL-6 do?

A

induces fever and activates liver cells to produce acute phase response proteins

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193
Q

What does the CXCL8 chemokine do?

A

attracts neutrophils and basophils

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194
Q

What does IL-12 do?

A

recruits and activates NK cells

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195
Q

What is the inflammasome?

A

a complex of innate cytosolic receptors of NOD-like receptor proteins (NLRPs) and apoptosis-associated speck-like protein containing a CARD domain (ASC)

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196
Q

How is IL-1 activated?

A

NLRPs responding to viral infection as a part of the inflammasome activate Caspase 1 to cleave pro-IL-1 and generate active IL-1

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197
Q

Which of the following are more mobile: neutrophils or macrophages?

A

neutrophils

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198
Q

What percentage of circulating white blood cells do neutrophils comprise?

A

50%

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199
Q

How quickly do neutrophils die?

A

within hours of phagocytosing pathogens

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200
Q

What is extravasation?

A

neutrophil migration
neutrophils exit blood circulation via extravasation to sites of infection and inflammation

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201
Q

What does extravasation require?

A

cell adhesion molecule interactions

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202
Q

What are examples of cell adhesion molecule interactions?

A

glycoproteins on neutrophil surface binding to selectins on vascular endothelial cell surface
integrin on neutrophil surface binding to ICAM on vascular endothelial cell surface

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203
Q

What is the first step of extravasation?

A

rolling adhesion via weak interaction between neutrophil glycoproteins and selectins on endothelial cells

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204
Q

What is the second step of extravasation?

A

tight binding of neutrophil integrin LFA-1 to ICAM-1 in response to chemokine CXCL8

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205
Q

What is the third step of extravasation?

A

neutrophils cross the endothelial cell layer (diapedesis)

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206
Q

What is the fourth and final step of extravasation?

A

chemotaxis of neutrophils towards source of CXCL8 (migration)

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207
Q

What are effector (bacteriocidal) mechanisms?

A

fusion of phagosome with granules containing proteases and antimicrobial proteins and peptides
respiratory burst
neutrophil extracellular traps (NETs)

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208
Q

What does respiratory burst entail?

A

activation of NADPH oxidase in phagosomes consumes oxygen and generates superoxide radicals
superoxide dismutase and catalase convert superoxide radicals to water and oxygen gas

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209
Q

What are NETs?

A

extracellular fibers of DNA and granule contents

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210
Q

What are type-1 interferons?

A

IFN-α and IFN-β

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211
Q

Where and how are type-1 interferons induced?

A

in virus infected cells, by activation of endosomal TLRs and cytosolic innate receptors

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212
Q

What do type-1 interferons induce?

A

NK cell proliferation
RNAse L
p53 to trigger apoptosis of infected cells
expression of cell surface proteins that signal viral infection of NK cells

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213
Q

What do type-1 interferons activate?

A

protein kinase R to inhibit protein synthesis

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214
Q

How do inhibitory receptors recognize infected host cells?

A

bind cell surface proteins present on all healthy cells, which present peptide fragments from inside the cell

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215
Q

What do virus infections do regarding cell surface presentation of protein fragments?

A

they reduce cell surface presentation of protein fragments

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216
Q

How do activating receptors recognize infected host cells?

A

NKG2D binds MIC-A and MIC-B, which are expressed by target cells in response to cellular stress

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217
Q

What type of receptors may inhibitory and activating receptors be?

A

killer-cell immunoglobulin-like receptors (KIR)
lectin-like receptors

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218
Q

What activates NK cells?

A

signaling from activating receptors in absence of signaling from inhibitory receptors

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219
Q

What do NK cells have to create holes in cell membranes and initiate apoptosis?

A

granules with perforin and granzymes

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220
Q

Where do NK cells release granule contents?

A

toward the surface of stressed and altered target cells

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221
Q

What do dendritic cells do to pathogens?

A

phagocytose and transport pathogens to lymph nodes
process and present pathogen protein fragments to T cells

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222
Q

What do pattern recognition receptors do?

A

elicit production of cytokines to direct appropriate adaptive immune response

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223
Q

What do activated NK cells secrete?

A

IFN-γ, which recruits cytotoxic T cells

224
Q

What is a systemic infection?

A

infection that spreads through bloodstream

225
Q

During a systemic infection, what causes vasodilation throughout the body?

A

TNF-α

226
Q

What does rapid loss of blood pressure lead to?

A

septic shock

227
Q

What does septic shock cause?

A

organ failure of kidneys, liver, heart and lungs

228
Q

What does failure of TLR signaling cause?

A

lack of cytokine production

229
Q

What does inadequate innate immune response lead to?

A

greater susceptibility to infection

230
Q

What can defective macrophage function lead to?

A

persistence of infection

231
Q

What leads to granulomas?

A

defective neutrophil function
neutrophils phagocytose bacteria but fail to destroy them
macrophages attempt to clear infected neutrophils, fuse and form granulomas

232
Q

What causes chronic and recurrent viral infections?

A

defective NK cells

233
Q

Over how many different proteins related to the complement system are in blood plasma?

A

30

234
Q

A cascade of what type of reactions make up the complement system?

A

proteolytic cleavage reactions

235
Q

What does the complement system do?

A

tag proteins for phagocytosis and directly kill pathogens by creating holes in their membranes

236
Q

What tags proteins for phagocytosis?

A

opsonin

237
Q

What directly kills pathogens by creating holes in their membranes?

A

membrane attack complex (MAC)

238
Q

All pathways of complement activation converge at the point of creating which enzyme?

A

C3

239
Q

What is C3 cleaved to form?

A

C3a and C3b

240
Q

What is the smaller C3 fragment?

A

C3a

241
Q

What does C3a do?

A

acts as an anaphylatoxin to induce inflammation
recruit phagocytes and induce their degranulation

242
Q

What does C3b do?

A

covalently attaches to pathogen surface to induce phagocytosis, via a newly exposed reactive thioester group

243
Q

What are the three pathways of complement activation, from first to act to last?

A

alternative pathway
lectin pathway
classical pathway

244
Q

What do the three pathways of complement activation all form?

A

C3 convertase

245
Q

What pathway is spontaneous, already initiated and ready to go whenever pathogen enters the body?

A

alternative pathway

246
Q

What pathway is activated by recognition of bacterial oligosaccharides ending in mannose and fucose?

A

lectin pathway

247
Q

What pathway is best activated by antibodies bound to pathogen surface?

A

classical pathway

248
Q

Where is C3 always present?

A

plasma

249
Q

What is “tickover” in regards to the spontaneous reaction undergone by C3 in the alternative pathway?

A

reaction of its internal thioester bond with water to form iC3

250
Q

What are the steps of “tickover”?

A

iC3 binds factor B
factor B bound to iC3 is cleaved by factor D to form Ba and Bb fragments
Bb fragments remain bound to iC3 to form iC3Bb, a soluble C3 convertase
iC3Bb cleaves C3 to form C3a, a small soluble peptide, and C3b, which attaches to the surface of a pathogen

251
Q

How is alternative pathway C3 convertase (C3bBb) formed?

A

C3b bound to pathogen surface binds factor B
factor B bound to C3b is cleaved by factor D, and the larger Bb fragment remains bound to C3b

252
Q

How does alternative C3 convertase form more alternative C3 convertase?

A

alternative C3 convertase cleaves more C3 to form C3b that covalently attaches to pathogen surface to react with factor B and factor D

253
Q

How is the alternative pathway regulated?

A

alternative C3 convertase (C3bBb) forms more C3 convertase in positive feedback loop
accelerators stabilize C3bBb on pathogen surfaces
brakes destabilize C3 convertase on host cell surfaces

254
Q

Is attachment of C3b to cell surface specific or non-specific?

A

non-specific

255
Q

What are plasma protein regulators?

A

properdin (factor P)
factor H

256
Q

What is the accelerator plasma protein regulator?

A

factor P

257
Q

What is the brake plasma protein regulator?

A

factor H

258
Q

What does factor P do?

A

stabilizes C3bBb on pathogen cell surfaces

259
Q

What does factor H do?

A

binds to C3b and promotes cleavage of C3b by factor I to form inactive iC3b
binds preferentially to host cell membranes via interaction with sialic acid

260
Q

What are the host cell surface regulators?

A

decay accelerating factor (DAF)
membrane cofactor protein (MCP)

261
Q

What does DAF do?

A

inactivates C3bBb by promoting dissociation of Bb from C3b

262
Q

What does MCP do?

A

binds to C3bBb and promotes both dissociation of Bb and cleavage of remaining C3b by factor I to form inactive iC3b

263
Q

What does C3b bind to on macrophages to stimulate phagocytosis?

A

complement receptor CR1

264
Q

What do iC3b bind to on macrophages to stimulate phagocytosis?

A

complement receptors CR3 and CR4

265
Q

How is the membrane attack complex formed?

A

C3bBb recruits another molecule of C3b to form C3b2Bb (alternative C5 convertase)
alternative C5 convertase cleaves C5 to C5a, an anaphylatoxin, and C5b
C5b associates with C6 and C7
exposed hydrophobic region of C7 allows association of C5b67 with pathogen membrane
addition of C8 nucleates polymerization of C9 molecules in the target cell membrane to form a pore

266
Q

How are host cells protected from the membrane attack complex?

A

soluble plasma proteins inhibit recruitment of C6 and C7 to C5b
membrane proteins on host cells inhibit C9 polymerization

267
Q

What soluble plasma proteins inhibit recruitment of C6 and C7 to C5b?

A

S protein
clusterin
factor J

268
Q

What membrane proteins on host cells inhibit C9 polymerization?

A

protectin (CD59)
homologous restriction factor (HRF)

269
Q

What do C3a and C5a have in common?

A

they are both anaphylatoxins

270
Q

What does C3 convertase cleave, and what is released?

A

C3, small diffusible peptide C3a

271
Q

What does C5 convertase cleave, and what is released?

A

C5, small diffusible peptide C5a

272
Q

How do both C3a and C5a provoke inflammation?

A

bind to endothelial cells to increase vascular permeability
induce degranulation of mast cells and basophils
act as chemoattractants for phagocytes
increase expression of complement receptors on phagocytes

273
Q

What does C3a produced by alternative C3 convertase recruit and activate?

A

innate immune cells

274
Q

What does C3b act as?

A

an opsonin

275
Q

What are lectin and classical pathway initiator proteins secreted by in response to inflammatory cytokines?

A

liver cells

276
Q

What does MBL bind to?

A

mannose on pathogen cell surfaces

277
Q

What does the MBL hexamer complex with?

A

proteases MASP-1 and MASP-2

278
Q

What are the lectin and classical pathway initiator proteins?

A

mannose binding lectin (MBL)
C-reactive protein

279
Q

What does C-reactive protein bind to?

A

phosphocholine on pathogen cell surfaces

280
Q

What does C-reactive protein on pathogen cell surfaces bind?

A

C1q hexamer complexed with proteases C1r and C1s

281
Q

What do MBL and C-reactive protein both act as?

A

opsonins

282
Q

What have receptors for MBL and C-reactive protein?

A

monocytes and macrophages

283
Q

The initiation of parallel and homologous pathways by MBL and C-reactive protein form what?

A

classical C3 convertase

284
Q

What does MBL binding activate?

A

associated MASP-1 and MASP-2

285
Q

What does C1q binding to C-reactive protein or immunoglobulin complexes activate?

A

associated C1r and C1s

286
Q

Activated proteases in both parallel and homologous MBL and C-reactive protein pathways cleave what to make what?

A

C4 to C4a and C4b
C2 to C2a and C2b

287
Q

How is C4b similar to C3b?

A

C4b attaches to cell surface by thioester bond

288
Q

What does C2b associate with, and what is the name of that complex?

A

C4b, C4bC2b

289
Q

What is C4bC2b also known as?

A

the classical C3 convertase

290
Q

What homologs were identified in echinoderms?

A

C3 and factor B

291
Q

Homologs of C3 were also identified in…

A

fruit flies

292
Q

Homologs identified in echinoderms and fruit flies enhance…

A

phagocytosis

293
Q

Homologs identified in echinoderms and fruit flies are upregulated by…

A

bacterial infection

294
Q

What are components of lectin and classical pathways found in?

A

urochordates, close relatives of vertebrates

295
Q

What does the blood coagulation system do?

A

minimizes blood loss
hinders entry of pathogens into blood circulation

296
Q

Why do platelets release prostaglandin and other factors?

A

to boost innate immune response

297
Q

What does bradykinin do?

A

cause vasodilation
attract innate immune cells

298
Q

Why do many pathogens release proteases?

A

to aid in tissue breakdown and invasion

299
Q

What percentage of plasma proteins are protease inhibitors?

A

10%

300
Q

What does α2 macroglobulin do?

A

undergoes shape change to enclose protease and prevent access to other substrates

301
Q

What does protease attack do to α2 macroglobulin?

A

expose their internal thioester that then bonds with protease

302
Q

What are defensins?

A

small amphipathic peptides

303
Q

How small are defensins?

A

35-40 amino acids

304
Q

What are α-defensins made by?

A

neutrophils, Paneth cells of small intestine

305
Q

What are β-defensins made by?

A

various types of epithelial cells

306
Q

What are among the evolutionarily oldest of immune defense mechanisms?

A

defensins

307
Q

What happens when there is a deficiency in complement?

A

abnormal clearance of gram-positive bacteria
difficulty removing immune complexes
recurring bacterial infections

308
Q

What happens when there is abnormal clearance of gram-positive bacteria?

A

PAMPs are masked from PRRs of innate immune cells
opsonization by complement facilitates clearance by phagocytes

309
Q

What happens when there is difficulty removing immune complexes?

A

classical pathway tags immune complexes
accumulation of soluble immune complexes can lead to hypersensitive reactions, autoimmunity

310
Q

What cells are a part of the innate immune system?

A

phagocytes
granulocytes

311
Q

What cells are a part of the adaptive immune system?

A

B cells
T cells

312
Q

What type of immunity is unable to recognize novel pathogens?

A

innate immunity

313
Q

What type of immunity is capable of recognizing novel foreign molecules?

A

adaptive immunity

314
Q

How does innate immunity function?

A

by using PRRs that recognize common pathogen-associated molecular patterns (PAMPs)

315
Q

How does adaptive immunity function?

A

through the use of diverse receptors specific for particular molecules on particular pathogens

316
Q

What cells have immune memory?

A

subset of B cells and T cells whose receptors recognize the pathogen

317
Q

How does immune memory work?

A

increasing numbers of daughter B cells and T cells with the same specificity serve to combat future infections by the same pathogen more quickly and effectively

318
Q

What are T-cell receptors?

A

transmembrane proteins with very short cytoplasmic tails
heterodimers

319
Q

What is the most common type of T-cell receptor?

A

alpha-chain and beta-chain

320
Q

What is not the most common type of T-cell receptor?

A

gamma-chain and delta-chain

321
Q

What does each chain of a T-cell receptor have?

A

N-terminal variable region
constant region closer to the membrane

322
Q

What do the variable regions of the two chains of a T-cell receptor form?

A

antigen binding site

323
Q

What does each T cell start with?

A

its own unique T-cell receptor

324
Q

What kind of peptide do most T-cell receptors bind?

A

short peptides

325
Q

What must the peptides bound to T-cell receptors be “presented” by?

A

MHC molecule

326
Q

What are most T cells able to recognize?

A

a particular peptide from a specific pathogen

327
Q

What do MHC molecules bind?

A

peptide, T-cell receptor and a coreceptor

328
Q

What does a class I MHC present?

A

peptides from degradation of proteins in cytosol

329
Q

What does a class I MHC bind to?

A

CD8 coreceptor on CD8+ T cells

330
Q

What does a class II MHC present?

A

peptides from externally acquired proteins degraded in lysosomes

331
Q

What does a class II MHC bind to?

A

CD4 coreceptor on CD4+ T cells

332
Q

What is the MHC genetic locus called in humans?

A

human leukocyte antigen (HLA) locus

333
Q

How can an MHC protein differ in different people?

A

differing amino acid sequence and peptide binding specificities

334
Q

What are immunoglobulins also known as?

A

antibodies

335
Q

What serve as B-cell receptors when expressed as a cell surface protein with a transmembrane domain?

A

immunoglobulins

336
Q

What do immunoglobulins serve as when secreted by activated and differentiated B cell progeny?

A

soluble effector molecule

337
Q

What are differentiated B cell progeny called?

A

plasma cells

338
Q

What is the basic structure of an immunoglobulin?

A

four polypeptide chains with two identical heavy chains plus two identical light chains held together by disulfide linkages

339
Q

What do both heavy and light chains of immunoglobulins have?

A

variable and constant regions

340
Q

What forms a single antigen-binding site?

A

a heavy chain variable region and a light chain variable region

341
Q

How many identical antigen-binding sites does each immunoglobulin have?

A

two

342
Q

How many different secreted soluble immunoglobulin isotypes are there?

A

five

343
Q

What are the effector functions of secreted soluble immunoglobulins?

A

neutralization of foreign particle or pathogen
opsonization
complement activation
activation of innate immune cells
protection of internal mucosal surfaces

344
Q

What type of cells express multiple PRRs encoded in their genome?

A

innate immune cells

345
Q

What express just one antigen receptor from genes that undergo recombination to generate diversity?

A

lymphocytes

346
Q

What cells have receptors for constant regions of immunoglobulins?

A

innate immune cells

347
Q

What can activate the classical pathway of complement activation?

A

immunoglobulins

348
Q

What cells present peptide antigens to T cells?

A

dendritic cells

349
Q

What immune system can clear most common pathogens?

A

innate

350
Q

What immune system can target novel pathogens or pathogens expressing new antigens?

A

adaptive

351
Q

How long does the adaptive immune system require to respond to a new pathogen?

A

several days to two weeks

352
Q

Why do relatively few T cells and B cells recognize a new pathogen?

A

adaptive immune system receptor diversity

353
Q

What must antigens from a pathogen go through in order to be presented to T cells?

A

they have to be processed and delivered to secondary lymphoid organs such as lymph nodes

354
Q

What must antigen-specific B cells and T cells go through before their progeny migrate to sites of infection?

A

they must be activated, proliferate and differentiate in secondary lymph nodes

355
Q

Where to T cells mature?

A

thymus

356
Q

Where do B cells develop?

A

bone marrow

357
Q

What do both T cells and B cells undergo?

A

somatic recombination of their receptor genes
selection for functional receptors that don’t recognize self-antigens

358
Q

What do dendritic cells do at the site of infection in regards to antigen processing and presentation?

A

phagocytose pathogens and migrate to lymph nodes

359
Q

What do dendritic cells do in lymph nodes?

A

present peptide fragments to circulating T cells that interact via cell-adhesion molecules

360
Q

Where are cytosolic pathogen proteins processed, and where are their peptide fragments presented?

A

cytosol, on class I MHC molecules

361
Q

Where are extracellular pathogen proteins processed, and where are their peptide fragments presented?

A

phagolysosomes, class II MHC molecules

362
Q

What results in the signaling and activation of the T cell?

A

T-cell receptor and co-receptor engagement with MHC and peptide

363
Q

What happens once the T cell is activated?

A

CD8 T cells engaged with a class I MHC differentiate into cytotoxic T cells
CD4 T cells engaged with a class II MHC differentiate into various types of helper T cells

364
Q

Where do some helper T cells migrate to, and what do they interact with?

A

part of a lymph node, circulating B cells

365
Q

What happens to B cells that recognize the same pathogen as a T cell?

A

they become activated, divide and differentiate

366
Q

What determines what B cells differentiate into?

A

cytokine signals from helper T cells

367
Q

What do some B cells differentiate into?

A

antibody-secreting plasma cells

368
Q

What do some progeny B cells become?

A

memory B cells

369
Q

What are some refinements undergone by the B-cell receptors of some B cells?

A

higher affinity for the antigen
different heavy chain type

370
Q

What generates B cells with higher affinity for the antigen, and what is this process called?

A

somatic hypermutation and selection
affinity maturation

371
Q

What results in a different heavy chain type of a B cell, and what is this process called?

A

recombination of heavy chain constant region genes
isotype switching

372
Q

What are the genetic mechanisms for T-cell and B-cell receptor diversity?

A

recombination of different randomly selected variable gene segments
addition or removal of random nucleotides at junctions of recombined variable gene segments
combination of different subunits

373
Q

What are the different subunits that can be combined for T-cell receptors?

A

alpha-chain and beta-chain

374
Q

What are the different subunits that can be combined for B-cell receptors?

A

heavy chain and light chain

375
Q

What process splices DNA segments?

A

somatic recombination

376
Q

What segments for T-cell receptor alpha-chain and immunoglobulin light chain undergo somatic recombination?

A

V and J segments

377
Q

What segments for T-cell receptor beta-chain and immunoglobulin heavy chain undergo somatic recombination?

A

V, D and J segments

378
Q

In what type of cells does antigen receptor gene rearrangement (somatic recombination) occur?

A

developing T cells and B cells

379
Q

What are expressed as a result of antigen receptor gene rearrangement?

A

spliced gene segments

380
Q

How does alpha-chain T-cell receptor gene rearrangement occur?

A

alpha-chain joins a single randomly selected Vα to a single randomly selected Jα segment
many different combinations

381
Q

How does beta-chain T-cell receptor gene rearrangement occur?

A

beta-chain first joins Dβ to Jβ segment
then join a Vβ segment
many different combinations

382
Q

What happens to the possible number of unique T-cell receptors as a result of alpha-chain and beta-chain combination?

A

multiplied

383
Q

What type of rearrangement is heavy chain immunoglobulin gene rearrangement similar to?

A

T-cell receptor beta-chain rearrangement

384
Q

How does heavy chain immunoglobulin rearrangement take place?

A

a VH segment combines with a DH and a JH to form many possible VHDHJH segments

385
Q

What types of immunoglobulin light chains are there?

A

κ and λ

386
Q

Each immunoglobulin light chain recombines to form multiple of what combinations?

A

VκJκ or VλJλ

387
Q

Each B cell expresses how many unique heavy and light chains?

A

a single unique heavy chain with a single unique light chain, either a κ or λ

388
Q

What further immunoglobulin gene changes do activated B cells undergo?

A

somatic hypermutation (affinity maturation)
isotype switching

389
Q

What does B cell somatic hypermutation do?

A

improves receptor binding to the same antigen

390
Q

What does B cell isotype switching do?

A

changes only the constant region of the heavy chain and affects function but not antigen binding

391
Q

What are the key proteins of V(D)J recombinase?

A

RAG1 (recombination activating gene 1) and RAG2

392
Q

What enzymes are involved with V(D)J recombinase?

A

enzymes in the non-homologous end joining (NHEJ) DNA repair pathway

393
Q

What do RAG1/RAG2 bind and recognize?

A

recombination signal sequences (RSSs) that border V, D and J DNA segments

394
Q

What do RSSs contain?

A

heptamer sequence
nonomer sequence
either a 12-bp or 23-bp spacer between

395
Q

What does RAG1/RAG2 recombinase cutting at the RSSs create?

A

hairpins

396
Q

What does nicking by Artemis create?

A

single-strand palindromic overhangs that create P-nucleotides

397
Q

What do exonucleases and terminal deoxynucleotidyl transferase do?

A

delete and add random nucleotides, respectively, called N-nucleotides

398
Q

What amplifies receptor diversity?

A

junctional sequence diversity

399
Q

How do jawed fish and all higher vertebrates use V(D)J recombinase with RAG1/RAG2?

A

to diversify lymphocyte receptors

400
Q

What have recombinases that cut and join DNA segments with specific border sequences, similar to V(D)J recombination at RSSs?

A

DNA transposons

401
Q

What do DNA transposons produce?

A

changes in sequence at sites of insertion

402
Q

What are self-tolerance mechanisms?

A

processes that generate receptor diversity that create receptors that recognize self-molecules

403
Q

What does positive selection select?

A

cells with functional receptors

404
Q

What does negative selection select against?

A

cells with self-reactive receptors

405
Q

How do T-cell receptor and immunoglobulin gene rearrangements proceed?

A

in defined sequence

406
Q

What happens after each T-cell receptor and immunoglobulin recombination event during positive selection?

A

the protein product is tested for functionality

407
Q

What does failure to produce functional protein product cause during positive selection?

A

apoptosis of developing T cell or B cell

408
Q

What does successful production of functional protein allow during positive selection?

A

cell to proceed to next step of development

409
Q

What is tested during negative selection, and what are they tested for?

A

lymphocytes with functional antigen receptors
reactivity to self molecules

410
Q

What do cells in thymus express?

A

many self peptides on MHC molecules to test developing T cells

411
Q

During negative selection, T cells that recognize self-peptide:MHC complexes too well are…

A

induced to undergo apoptosis

412
Q

During negative selection, T cells that recognize self-peptide:MHC complexes only moderately…

A

survive

413
Q

What do positive and negative selection test developing lymphocytes for?

A

functional receptors that do not react with self-molecules

414
Q

What do lymphocytes do once they pass positive and negative selection?

A

mature and enter circulation

415
Q

Why do MHC molecules present peptides on the surface of a cell?

A

for inspection by T cells

416
Q

What are removed by negative selection in the thymus?

A

self-reactive T cells

417
Q

What are most of the peptides presented by MHC molecules derived from?

A

normal cell proteins that are not recognized by T cells

418
Q

During an infection, what do some MHC molecules present that can be recognized by some T cells?

A

peptides from pathogens

419
Q

What do class I MHC molecules present?

A

peptides from proteins made inside the cell

420
Q

What do class II MHC molecules present?

A

peptides from extracellular proteins taken into phagolysosomes

421
Q

What transmembrane chains act when class I MHC molecules present peptides, and what do they do?

A

transmembrane alpha chain forms peptide binding pocket plus β2-microglobulin

422
Q

What transmembrane chains act when class II MHC molecules present peptides, and what do they do?

A

transmembrane alpha and beta chains together form peptide binding pocket

423
Q

What do class III genes include?

A

immune regulatory proteins
some complement proteins

424
Q

What is step one of MHC class I peptide presentation in most cells?

A

proteins in the cytoplasm are digested to peptide fragments by the proteasome

425
Q

What is step two of MHC class I peptide presentation in most cells?

A

peptide fragments transported into ER and loaded onto class I MHC molecules

426
Q

What is step three of MHC class I peptide presentation in most cells?

A

class I MHC:peptide complexes exit ER, travel to plasma membrane via secretory pathway

427
Q

What is step four of MHC class I peptide presentation in most cells?

A

a CD8 T cell that recognizes the class I MHC:peptide complex can be activated

428
Q

What is step one of MHC class II peptide presentation in professional antigen-presenting cells?

A

proteases in phagolysosomes degrade endocytosed or phagocytosed proteins into peptide fragments

429
Q

What is step two of MHC class II peptide presentation in professional antigen-presenting cells?

A

phagolysosomes then fuse with secretory vesicles that contain MHC class II proteins

430
Q

What is step three of MHC class II peptide presentation in professional antigen-presenting cells?

A

class II MHC:peptide complexes travel to plasma membrane

431
Q

What is step four of MHC class II peptide presentation in professional antigen-presenting cells?

A

a CD4 T cell that recognizes the class II MHC:peptide complex can then be activated

432
Q

What type of cytoplasmic tails do the T-cell receptor α and β (or γ and δ) chains have?

A

short cytoplasmic tails

433
Q

What do T-cell receptors associate with?

A

other transmembrane proteins that form the CD3 complex

434
Q

What type of cytoplasmic tails do proteins of the CD3 complex have?

A

cytoplasmic tails with signaling motifs

435
Q

What coreceptors have important signaling roles?

A

coreceptors of CD4 or CD8

436
Q

What activates T cells?

A

T-cell receptor signaling

437
Q

What are effector T cells?

A

cytotoxic T cells (CTLs) from CD8 T cells

438
Q

What does the effector T cell TH1 do?

A

activates macrophages

439
Q

What does the effector T cell TH2 do?

A

helps activate B cells

440
Q

What does the effector T cell TH17 do?

A

activates neutrophils

441
Q

What do natural killer (NK) T cells act like?

A

CTLs

442
Q

What do regulatory T cells do?

A

induce tolerance

443
Q

What can form memory T cells?

A

all activated T cells

444
Q

What do naive B cells have?

A

cell surface IgM and IgD, with transmembrane forms of µ and δ heavy chains, that act as the B-cell receptor

445
Q

What do B-cell receptors associate with?

A

two proteins Igα and Igβ that have cytoplasmic domains with signaling motifs

446
Q

What does signaling from a B-cell receptor complex activate?

A

B cells to differentiate into antibody-secreting cells

447
Q

What do naive B cells initially secrete?

A

IgM

448
Q

What can IgM undergo to produce IgG, IgA or IgE?

A

class switching

449
Q

When does the primary immune response take place?

A

the first exposure to an antigen

450
Q

What contributes to the time required by the primary immune response?

A

antigen processing
migration of dendritic cells to lymph nodes
presentation to T cells
activation and differentiation of T cells and B cells

451
Q

What may happen when antigen-specific T cells and B cells proliferate?

A

some of their progeny turn into memory T cells and memory B cells

452
Q

What do memory cells do?

A

increase the number of antigen-specific T cells and B cells
primed to respond faster if/when the same antigen re-enters the body

453
Q

Because of the great diversity of receptors, how many T cells and B cells may exist in the body when a pathogen infects?

A

relatively few

454
Q

What can encounter each other in lymph nodes?

A

dendritic cells presenting antigen
circulating T cells
circulating B cells

455
Q

What facilitate and speed up activation of T cells and B cells?

A

lymph nodes

456
Q

What happens during the secondary immune response?

A

memory cells encounter antigen faster, respond more quickly and more strongly

457
Q

What do memory B cells produce?

A

antibodies with better affinity

458
Q

How long may the primary response take to clear an infection?

A

weeks

459
Q

How long does the secondary response take to clear an infection?

A

within a few days

460
Q

What is the basis for vaccines and immunity after recovery from an infection?

A

immune memory

461
Q

What is the primary lymphoid organ responsible for T-cell development and maturation?

A

thymus

462
Q

What migrate from the bone marrow and blood to the thymus?

A

undifferentiated lymphocyte precursor cells

463
Q

How many lobes does the thymus have?

A

two

464
Q

What does each lobe of the thymus contain?

A

outer cortex
inner medulla

465
Q

What are immature T cells called?

A

thymocytes

466
Q

What happens to immature T cells?

A

they undergo key developmental steps to ensure proper TCR expression in the cortex

467
Q

What takes place in the medulla

A

mature thymocytes undergo negative selection and finish their development into naive T cells

468
Q

What do resident cells of the thymus do?

A

drive the development of thymocytes into naive T cells

469
Q

What are resident cells of the thymus?

A

thymic epithelial cells (TECs)
macrophages
dendritic cells
Hassall’s corpuscles

470
Q

What are characterized by cell-surface markers present on the stem cell precursors, along with the absence of lineage-specific markers?

A

hematopoietic stem cells

471
Q

What are expressed on both human and mouse T cells?

A

CD34 and CD38

472
Q

What are precursors to several cell types, and what must they receive to commit to a differentiate cell type?

A

lymphoid progenitors
appropriate signal

473
Q

What regulates cell proliferation and differentiation?

A

the Notch signaling pathway

474
Q

What is Notch?

A

a cell-surface receptor protein that interacts with transmembrane ligands on adjacent cells

475
Q

What does not express either coreceptor (CD4 or CD8)?

A

double-negative thymocyte

476
Q

Where are double-negative thymocytes found?

A

thymic cortex during initial development

477
Q

What do double-negative thymocytes begin?

A

somatic recombination at the TCR loci

478
Q

What do double-negative thymocytes continue until?

A

both subunits of the receptor have properly rearranged, and both coreceptors are expressed

479
Q

What expresses a fully rearranged TCR, and both CD4 and CD8?

A

double-positive thymocytes

480
Q

What are the possible fates of double-positive thymocytes?

A

develop into regulatory T cells
develop into NK T cells
begin the process of positive and negative selection to test the TCR and select for a single coreceptor

481
Q

What thymocytes have a single coreceptor?

A

single-positive thymocyte

482
Q

How does the initial development of the double-negative thymocyte in humans differ from in mice?

A

in regard to the cell-surface molecules present during the developmental process

483
Q

What is the first stage of double-negative thymocyte initial development?

A

human lymphoid progenitor cells in the thymus shut down expression of the step cell marker CD34 and begin expressing the adhesion and signaling molecules CD2, CD5 and CD7

484
Q

As double-negative thymocytes continue to develop, they begin to express…

A

CD1 at their cell surface

485
Q

What are the critical checkpoints that a thymocyte must pass to continue development and become a functional naive T cell?

A

checkpoint of the γδ subunit of the T-cell receptor
checkpoint of the beta subunit of the T-cell receptor
checkpoint of the alpha subunit of the T-cell receptor

486
Q

What percentage of T cells in mice do γδ T cells represent?

A

0.5%

487
Q

What percentage of T cells in humans do γδ T cells represent?

A

3.5%

488
Q

Why are γδ T cells important?

A

they protect the fetus during development
in adults, they play an important role in protecting mucosal surfaces

489
Q

What produces all cell types of the circulatory system from a common stem cell?

A

hematopoiesis

490
Q

Where do T cells begin their life as a lymphoid progenitor?

A

bone marrow

491
Q

What commit the common lymphoid progenitors to the T-cell lineage?

A

migration of common lymphoid progenitors to the thymus
signals given by cells

492
Q

What is somatic recombination activated through?

A

the expression of the RAG1 and RAG2 proteins

493
Q

Where do recombination events begin?

A

at the β, γ and δ loci of the TCR

494
Q

What happens if productive rearrangements occur at the γ and δ loci?

A

thymocyte becomes a γδ T cell

495
Q

How many possible productive beta-chain rearrangements are there?

A

four

496
Q

Most T cells will express which chain?

A

beta-chain

497
Q

What must the developing thymocyte assemble to test for a productive arrangement of the beta chain?

A

a surrogate T-cell receptor complex

498
Q

What occurs once the beta-chain checkpoint has been passed?

A

recombination of the alpha-chain locus

499
Q

What is the name of a surrogate alpha chain?

A

pre-T alpha chain (pTα)

500
Q

What is the pTα?

A

it assembles with the rearranged beta chain and the CD3 complex to form the pre-TCR

501
Q

What does the pre-T cell receptor complex do?

A

ensures that a functioning T-cell receptor can signal via the same transduction pathways used to activate T cells

502
Q

Once through the beta-chain checkpoint, what does the cell do?

A

proliferates
expresses RAG1 and RAG2 again
begins recombination at the other T-cell receptor loci (α, γ and δ)
undergoes allelic exclusion

503
Q

What must be tested to ensure TCR function?

A

rearrangement of the alpha chain

504
Q

Where is the alpha chain tested?

A

ER membrane

505
Q

If the expressed alpha chain does not function properly, what happens to the alpha-chain locus?

A

it is further rearranged

506
Q

If a functional alpha chain is produced, what happens to the developing thymocyte?

A

it continues development into a naive T cell

507
Q

What are the later stages of development in which thymocytes continue through after successfully passing through both checkpoints?

A

positive selection
negative selection

508
Q

What does positive selection do?

A

promotes the selection of thymocytes that can bind to self-MHC molecules (MHC restriction)

509
Q

What does negative selection do?

A

prevents the release of thymocytes that can recognize MHC-self-peptide complexes with high-affinity (self-tolerance)

510
Q

What does development of T cells in the thymus involve?

A

somatic recombination of T-cell receptor loci

511
Q

What receptor loci can thymocytes rearrange?

A

α and β
γ and δ

512
Q

What do double-positive thymocytes interact with to test the affinity of the TCR with MHC-peptide complexes at the cell surface?

A

cortical thymic epithelial cells (cTECs)

513
Q

What can cTECs express?

A

both MHC class I and class II molecules

514
Q

Why can cTECs present a variety of self-peptides?

A

to promote positive selection of double-positive thymocytes based on the affinity of the T-cell receptor for the MHC-peptide complexes

515
Q

What does positive selection of double-positive thymocytes positively select?

A

those with the ability of the TCR to interact with MHC

516
Q

What are the three possible outcomes of selection within the thymic cortex?

A

death by neglect
negative selection
positive selection

517
Q

What is death by neglect?

A

double-positive (DP) thymocytes cannot interact with any MHC-peptide complexes

518
Q

What is negative selection within the thymic cortex?

A

DP thymocytes bind too tightly with an MHC-peptide complex

519
Q

What is positive selection within the thymic cortex?

A

DP thymocytes with TCRs that can interact with an MHC-peptide complex with a low or intermediate affinity survive and proliferate

520
Q

What happens during selection within the thymic cortex?

A

DP thymocytes further develop and express only a single coreceptor (either CD4 or CD8)

521
Q

What is lineage commitment?

A

commitment of a thymocyte to express a single coreceptor

522
Q

What play roles in lineage commitment?

A

transcriptional control
epigenetics

523
Q

What are the two proposed models of lineage commitment?

A

instructive and kinetic signaling

524
Q

What type of selection is the instructive model?

A

interaction-driven selection

525
Q

What happens if a TCR engages an MHC class I molecule presenting a peptide in the instructive model?

A

the interaction will also promote CD8 interaction with the complex and shut down CD4 expression

526
Q

What happens if a TCR engages an MHC class II molecule presenting a peptide in the instructive model?

A

the CD4 coreceptor will engage in the interaction, and the thymocyte will receive a signal to prevent CD8 expression

527
Q

What type of selection is the kinetic signaling model?

A

signal strength-driven selection

528
Q

What will positively selected thymocytes become if the T-cell receptor/coreceptor signal is continuous in the kinetic signaling model?

A

CD4+

529
Q

What will positively selected thymocytes become if the T-cell receptor/coreceptor signal is interrupted in the kinetic signaling model?

A

CD8+

530
Q

When can negative selection occur within the thymic medulla?

A

if the T-cell receptor:MHC-peptide complex has too high an affinity

531
Q

What is central tolerance?

A

negative selection processes that occur in primary lymphoid tissues that are responsible for the removal of self-reactive lymphocytes

532
Q

What is AIRE?

A

a transcriptional activator (autoimmune regulator) which allows cells to express genes not normally expressed by epithelial cells of the thymus (promiscuous gene expression)

533
Q

What domains does AIRE contain?

A

CARD domain (caspase recruitment)
SAND domain (SP100, AIRE1, NucP41/PP75 and DEAF1)
two PHD domains (plant homeodomain)

534
Q

What acts as a “gas pedal” for RNA polymerase II?

A

AIRE

535
Q

What does the “gas pedal” for RNA polymerase II cause?

A

transcription of tissue-restricted genes and presentation of tissue-specific antigens on MHC I within mTECs

536
Q

What can engulf mTECs and present tissue-specific antigens via MHC class II?

A

medullary thymic dendritic cells

537
Q

What does the engulfing of mTECs allow for?

A

negative selection of CD4+ thymocytes that bear a TCR that interacts too strongly with an MHC class II–tissue-specific antigen peptide

538
Q

What does negative selection drive and limit, respectively?

A

central tolerance
the circulation of self-restrictive T cells

539
Q

What will a subset of CD4 T cells that express a self-reactive TCR begin to express?

A

the transcription factor FOXP3

540
Q

What cells continue development to become natural regulatory T cells (nTregs)

A

CD4+ and FOXP3+

541
Q

When nTregs are released into circulation, what do they promote?

A

peripheral tolerance

542
Q

Where to T cells undergo both positive and negative selection after rearranging their T-cell receptor loci?

A

thymus

543
Q

Why do T cells undergo positive selection?

A

to ensure that they have a functional receptor

544
Q

Why do T cells undergo negative selection?

A

to ensure that they are not self-reactive

545
Q

What provides further means of tolerance?

A

the action of regulatory T cells

546
Q

What can regulatory T cells inactivate?

A

self-reactive T cells in the periphery

547
Q

How to T cells target pathogens for destruction?

A

directly or by activating other immune system components

548
Q

What receptor do the majority of circulating T cells express?

A

αβ T-cell receptor

549
Q

What can αβ T-cells do when activated?

A

differentiate into effector cells that activate a range of innate or adaptive immune responses
directly destroy an infected cell

550
Q

What may αβ T-cells be a target for?

A

infection and destruction by SARS-CoV-2, the virus responsible for COVID-19

551
Q

What receptor do a small subset of T cells in the body express?

A

γδ T-cell receptor

552
Q

Where do γδ T-cell receptors mainly reside?

A

within the gut mucosa as intraepithelial lymphocytes

553
Q

What do expressed γδ T-cell receptors behave like?

A

pattern recognition receptors of the innate immune system

554
Q

What is T-cell diversity driven in part by?

A

the number of V, D and J subunits present for all chains associated with the receptor
junctional diversity
random association of subunits

555
Q

What is junctional diversity?

A

adding or removing P and N nucleotides during recombination

Immuno (2 decks)

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