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Immunology > Immunology 1 > Flashcards

Immunology 1 Flashcards

1
Q

What are the 4 different classes of pathogens protected by the immune system?

A

Bacteria
Viruses
Fungi
Parasites (protozoa and worms)

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2
Q

What are the recognition mechanisms of innate immunity (4)?

A

Rapid response
Fixed
Limited number of specificities
Constant during response

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3
Q

What are the recognition mechanisms of adaptive immunity (4)?

A

Slow response (days to weeks)
Variable
Numerous specificities
Improve during response

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4
Q

What features of pathogens do innate cells generally recognize?

A

Pathogen-associated molecular patterns (PAMPS)

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5
Q

What are PAMPS?

A

General features of some pathogens, like repeating subunits

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6
Q

PAMPS are recognized by _______.

A

Pattern Recognition Receptors (PRRs)

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7
Q

How do innate cells help to initiate acquired immunity?

A

By processing and presenting antigen to lymphocytes

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8
Q

T or F: Innate cells produce cytokines that modulate acquired immune responses.

A

T

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9
Q

Innate immune responses control infection until _______.

A

Acquired immune responses have developed

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10
Q

All cells of the immune system stem from ____.

A

Hematopoietic stem cells

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11
Q

What are the progenitor cells of the immune system?

A

Common lymphoid progenitor

Common myeloid progenitor

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12
Q

What do megakaryocytes produce?

A

Thrombocytes (Platelets)

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13
Q

What cells have an important role in clearance of immune complexes from the circulation?

A

Erythrocytes

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14
Q

T or F: Innate cells express highly specific receptors on their surface.

A

F: they express PAMPS or PRRs

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15
Q

T or F: Cells of the acquired immune system produce highly specific receptors that recognize specific features of a particular pathogen.

A

T

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16
Q

What is the site where all of the elements of the blood are derived from one type of progenitor cell?

A

Bone marrow

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17
Q

The myeloid progenitor is the precursor for ______(4).

A

Granulocytes
Macrophages
Dendritic cells
Mast cells

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18
Q

What are the features of neutrophils?

A
  • Short-lived, highly phagocytic cells
  • Have receptors that can bind to bacteria
  • Engulf and kill microbes
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19
Q

What is the most numerous immune cell in the body?

A

Neutrophils

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20
Q

What are the types of granulocytes?

A

Neutrophils
Eosinophils
Basophils

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21
Q

What are the features of eosinophils?

A
  • Have receptors that bind IgE antibody molecules
  • Have granules that contain inflammatory mediators and toxic compounds
  • Kill antibody coated parasites by releasing granule contents
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22
Q

What are the features of basophils?

A
  • Least abundant immune cell

- Functions a lot like eosinophils

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23
Q

What is the primary role of mast cells?

A

To expel parasite pathogens from the body

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24
Q

What do mast cell granules contain?

A

Histamine and other inflammatory mediators

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25
Q

What receptors do mast cells have on their surface?

A

IgE receptors – hijack IgE molecules from circulation and use them as antigen specific receptors

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26
Q

What are professional antigen presenting cells? What cells fall under this category?

A

Cells that have a critical role in the initiation of adaptive immune responses

  • dendritic cells
  • macrophages
  • B cells
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27
Q

What is the most potent antigen-presenting cell of the immune system?

A

Dendritic cell

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28
Q

What is the function of dendritic cells?

A

Take up antigen at the sites of infection/inflammation and then return to secondary lymphoid tissues and present antigens

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29
Q

What cells function in the activation of T cells and initiation of adaptive immune responses?

A

Dendritic cells

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30
Q

What is the circulating precursor of the macrophage?

A

Monocyte

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31
Q

T or F: Macrophages are components of both innate and acquired immune systems.

A

T

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32
Q

What are the functions of macrophages?

A
  • Have PRRs that allow them to recognize, phagocytose, and destroy microorganisms
  • Have complement and Fc receptors that allow it to find and destroy opsonized microbes
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33
Q

T or F: Granulocytes (PMNs) have important roles in the acquired immune response.

A

F

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34
Q

The common lymphoid progenitor gives rise to_______.

A

T cells and B cells (lymphocytes), and natural killer cells

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35
Q

_______ are the primary components of the acquired immune system.

A

Lymphocytes

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36
Q

What cells express receptor molecules on their surface that allow them to specifically recognize foreign antigens?

A

Lymphocytes

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37
Q

T or F: NK cells bear no antigen-specific receptor.

A

T

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38
Q

What is the function of NK cells?

A

Kill some virally infected cells

Are the effector cells of ADCC (antibody dependent cell-mediated cytotoxicity)

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39
Q

What are the effector cells of the acquired immune system?

A

B cells and T cells

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40
Q

What cells produce antibodies?

A

B cells

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41
Q

What cells produce signals that direct the action of other cells or are specific effectors of cell-killing?

A

T cells

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42
Q

What are plasma cells?

A

Fully differentiated B cells that serve as antibody factories

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43
Q

Where do all cells of the immune system originate?

A

Bone marrow

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44
Q

Lymphocytes migrate from the bone marrow to _________, where they differentiate.

A

Lymphoid organs

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45
Q

What defines a primary lymphoid organ and what are they?

A

Tissues where lymphocytes develop and mature

Bone marrow and thymus

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46
Q

Where do T cells mature?

A

Thymus

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47
Q

What defines a secondary lymphoid organ and what are they?

A

Tissues where adaptive immune responses are initiated; designed to trap antigens
-Spleen, lymph nodes, GALT (peyer’s patches, tonsils, adenoids, appendix), BALT, MALT

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48
Q

How does the spleen function in adaptive immune response?

A

It disposes of dead red blood cells

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49
Q

Most of the spleen is composed of ______, the site of RBC disposal.

A

Red pulp

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50
Q

What forms white pulp in the spleen?

A

Lymphocytes surround the arterioles that enter the spleen

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51
Q

What is the white pulp of the spleen divided into?

A

PALS (periarteriolar lymphoid sheath) containing mostly T cells and a flanking B cell corona

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52
Q

What is the makeup of lymph nodes?

A

B lymphocytes are in follicles, with T cells distributed in surrounding paracortical areas

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53
Q

What are germinal centers?

A

B cell follicles in which B cells are undergoing intense proliferation

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54
Q

T or F: Only the spleen has germinal centers.

A

F

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55
Q

What role do GALT perform in the immune system?

A

They capture antigen from the epithelial surfaces of the GI tract

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56
Q

What are the specialized cells of the Peyer’s patch and what do they do?

A

M cells: collect antigens along intestinal mucosa

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57
Q

What are the lymphoid tissues that protect the respiratory epithelium?

A

BALT and MALT

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58
Q

Phagocytes can initiate inflammatory responses by producing _______.

A

Cytokines

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59
Q

Inflammatory responses facilitate uptake of antigens by ______, and increase the flow of _______.

A

Phagocytes

Lymph

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60
Q

T or F: Inflammatory responses facilitate antigen transport to secondary lymphoid organs.

A

T

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61
Q

What is the clonal selection of lymphocytes?

A

When a lymphocyte is stimulated by binding of its receptor to its cognate antigen, the lymphocyte is activated to proliferate, giving rise to many new lymphocytes that have identical antigen-receptor specificity

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62
Q

The diversity of lymphocyte receptor molecules is generated by _________.

A

The unique organization of immunoglobulin genes

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63
Q

Interaction between a foreign molecule and a lymphocyte receptor capable of binding that molecule with high affinity leads to _________.

A

lymphocyte activation

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64
Q

What do T cell receptors recognize?

A

Peptide fragments of protein antigens presented on MHC molecules

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65
Q

T or F: Surface expressed antibodies can bind to proteins in their native or denatured conformation.

A

T

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66
Q

T or F: T cells have antigen-specific receptors on their surface that are secreted.

A

F: T cells do have antigen specific receptors, but they don’t secrete the receptor molecules.

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67
Q

Why are there two arms of acquired immune responses?

A
  1. Many pathogens live in extracellular spaces within the host (good for antibody immune responses)
  2. Other pathogens live inside cells of the host (good for T cell immune response)
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68
Q

What is an antigen?

A

Any ligand that binds to B cell or T cell receptors

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69
Q

Most antigens are composed of ______.

A

Protein

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70
Q

Where are MHC class I molecules found?

A

On almost all host cells

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71
Q

Where are MHC class II molecules found?

A

Only on immune cells (APCs)

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72
Q

What do MHC molecules do?

A

Bind to peptides and present them to T cells

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73
Q

What are the steps of B cell activation?

A
  1. B cell receptor binds to its antigen
  2. B cell endocytoses the antigen, breaks it up, and presents the antigen to a specific T helper cell (if it exists)
  3. T helper cell supplies a cytokine signal to the B cell, which activates it
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74
Q

What are the steps of T cell activation?

A
  1. T cells bind the cognate peptide antigen
  2. Co-stimulation signal by the antigen presenting cell
    T cells recognize peptide fragments of antigens that are presented to the T cell by an antigen presenting cell
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75
Q

T or F: T cell receptor can only bind to peptides that are presented on MHC molecules.

A

T

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76
Q

What are the main functions of antibodies?

A

Neutralization (of pathogen-derived toxins)
Opsonization
Complement activation

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77
Q

What is opsonization?

A

Some antibodies can coat antigens, which facilitates the uptake of antigen by phagocytes or NK cells

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78
Q

What role do antibodies play in complement activation?

A

Some antibodies serve as a receptor for the 1st component of the classic complement system. They fix complement, which helps destroy the antigen.

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79
Q

T or F: Antibodies play a role in the activation of NK cells for ADCC.

A

T

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80
Q

What are the primary populations of T cells?

A

Those that express CD8 on their surface and those that express CD4 on their surface

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81
Q

CD8+ T cells recognize antigen presented on ________.

A

MHC Class I molecules

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82
Q

What is the function of armed effector CD8+ T cells (aka cytotoxic T lymphocytes (CTLs))?

A

They kill cells that have the cognate peptide:MHC Class I complex on their surface

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83
Q

CD4+ T cells recognize antigen presented on _________.

A

MHC Class II molecules

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84
Q

Armed effector CD8+ cells are called ______, and armed effector CD4+ cells are called ______.

A

CD8+: killer T cells

CD4+: helper T cells

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85
Q

What is the function of helper T cells?

A

They secrete cytokines which modulate the activity of other immune cells

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86
Q

Activated CD4+ T cells can differentiate into at least 2 different types of effector cells that differ in ____________ (2).

A

The array of cytokines they produce

Effector functions that they participate in

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87
Q

What is the main function of T helper 1 CD4+ cells?

A

To supply cytokine signals to macrophages and up regulate their ability to kill ingested bacteria and present peptide antigens

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88
Q

What is the primary role of T helper 2 CD4+ cells?

A

To promote antibody-mediated immune responses by serving as helper cells for B cell activation and supplying cytokine signals so B cells will produce antibodies

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89
Q

What are two failures of the body’s immune defenses?

A
  1. Evasion of the immune system by pathogens

2. Inherited immunodeficiency diseases

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90
Q

What are 3 unwanted immune responses?

A
  1. Hypersensitivity reactions (i.e. allergic reactions, contact hypersensitivities, immune complex diseases)
  2. Autoimmunity (responses to self-tissue)
  3. Graft rejection
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91
Q

What is an antibody?

A

The secreted form of the immunoglobulin produced by a B cell

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92
Q

What are immunoglobulins?

A

Antigen-binding molecules of B cells

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93
Q

T or F: Antibodies are identical to the immunoglobulin component of the B cell receptor.

A

T

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94
Q

T or F: Each antibody produced by a single B cell has a different specificity for antigen.

A

F: Each antibody has the exact same specificity for antigen

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95
Q

T or F: Each B cell displays many copies of the same BCR on its surface.

A

T

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96
Q

Antibodies (have/don’t have) toxic properties, and (do/do not) destroy invading pathogens themselves.

A

Don’t have

Do not

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97
Q

When antibodies bind to a pathogen, they promote _________.

A

Uptake and destruction of the pathogen by phagocytes

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98
Q

What serve as ligands for the 1st component of the classical complement cascade?

A

Antibodies

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99
Q

Antibodies interact with ________ to promote clearance of infectious agents.

A

Host systems and cells

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100
Q

What is the main component of B cell surface receptors?

A

membrane-integrated forms of antibody molecules

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101
Q

T or F: Antibodies help provide protection from re-challenge by infectious agents.

A

T

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102
Q

What attaches the antibody light chain to the heavy chain and the heavy chains to each other?

A

Intrachain disulfide bonds

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103
Q

Heavy and light chains consist of (identical/similar) sequences encoded on (the same/separate) gene(s).

A

Similar; Separate

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104
Q

What is the advantage of antibodies’ unique tertiary structure?

A

It enables them to withstand environmental changes (changes in pH, salt concentration, proteolytic enzymes, etc) and maintain functionality.

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105
Q

Both constant and variable domains of antibodies are formed by ___________ that are covalently linked by a disulfide bond.

A

2 adjacent B-sheets that form a B-barrel

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106
Q

What is the primary difference in structure of constant and variable domains?

A

V domains are larger and have an extra loop of polypeptide chain

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107
Q

What forms the antigen-binding domains of antibodies?

A

The flexible loops of V domains

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108
Q

Where is there sequence variability in antibody molecules?

A

It’s confined to 3 hypervariable regions

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109
Q

What are framework regions?

A

Low variability regions between hyper variable regions of antibodies

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110
Q

Which regions of antibodies correspond to the beta sheets?

A

Framework regions

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111
Q

Which regions fo antibodies correspond to the loops between the beta sheets?

A

Hypervariable regions

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112
Q

T or F: Hypervariable regions are localized to a particular surface of the immunoglobulin molecule.

A

T

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113
Q

What are complementarity-determining regions?

A

Regions where the hyper variable regions of heavy and light chains are brought together, creating a single hypervariable site at the tip of the antibody.

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114
Q

The region of the antigen that is recognized by the antibody is known as ______.

A

Antigenic determinant or epitope

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115
Q

The antibodies that are most effective in fighting infection are those that bind to ________.

A

Surface exposed/accessible molecules of the pathogen

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116
Q

What is antibody binding mediated by? (4)

A

Electrostatic forces
Hydrophobic interactions
Van der Waals forces
Hydrogen bonding

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117
Q

What is an antigen?

A

Any molecule bound by an antibody or a T cell receptor

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118
Q

T or F: Antibodies have strict restrictions with respect to their binding.

A

F: they have few restrictions and can bind to proteins, peptides, carbs, nucleic acids, small molecules, and antigens

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119
Q

Antibodies produced in response to an infection usually have specificities for epitopes that are composed of _________.

A

Carbohydrate or protein

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120
Q

What are the surfaces of pathogens typically composed of? (4)

A

Glycoproteins
Polysaccharides
Glycolipids
Proteoglycans

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121
Q

What are the two types of multivalent antigens?

A
  1. Can have a single epitope repeated many times

2. Can have a number of distinct epitopes

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122
Q

Antibodies that have specificity for chemical structures other than carbohydrates or proteins are usually involved in __________.

A

Allergic reactions and autoimmune diseases

NOT in defense against infection

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123
Q

The antigen binding regions of antibody molecules are typically rich in ______ amino acids.

A

Aromatic

124
Q

The binding strength of an antibody to its particular antigenic determinant is known as _____.

A

Binding affinity

125
Q

What are the types of antigenic determinants that antibodies can bind to?

A
  1. Continuous epitopes: formed by a linear stretch of aa

2. Discontinuous epitopes: aa from different parts of a polypeptide brought together

126
Q

T or F: T cells cannot recognize linear epitopes.

A

F: T cells ONLY recognize linear epitopes

127
Q

What are the isotypes of antibody molecules?

A

IgA, IgD, IgE, IgG, IgM

128
Q

The amino terminal ends of the heavy and light chains contain the ______ regions of the polypeptide chains.

A

Variable

129
Q

How many variable and constant regions do light chains have?

A

1 variable, 1 constant

130
Q

How many variable and constant regions do heavy chains have?

A

1 variable, 3-4 constant

131
Q

Which isotypes have proline-rich hinge regions?

A

IgD, IgG, IgA

132
Q

What function does the hinge region confer?

A

It allows flexibility of the antibody, making it easier for antigenic determinants or immune components to bind

133
Q

What are the types of light chains?

A

Kappa and lambda

134
Q

How many kappa and lambda light chains are in an individual antibody molecule?

A

Only one type, 2 identical light chains per antibody molecule

135
Q

How many subclasses do IgA and IgG have?

A

IgA: 2 (IgA1 and IgA2)
IgG: 4 (IgG1, IgG2, IgG3, IgG4)

136
Q

Which isotypes have J chains, and what are J chains?

A

IgA and IgM

J chains are polypeptides that are disulfide linked to the tail pieces to confer stability

137
Q

What is the secretory component in mucosal secretions?

A

A polypeptide that is attached to the dimer non-covalently and helps with secretions (i.e. IgA secretions through epithelial cells)

138
Q

What main functions do secreted antibodies serve?

A
  1. Bridge between innate and acquired immune system
  2. Mark microbes for destruction by phagocytes (opsonization) or NK cells (ADCC)
  3. Activate complement pathway
139
Q

Which antibody isotype plays the biggest role in bodily secretions?

A

IgA

140
Q

Which antibody isotype is most efficiently transported across epithelium?

A

IgA

141
Q

What main function does IgD serve?

A

It serves with IgM as an antigen receptor on B cell membranes to help initiate antibody responses by activating B cell growth

142
Q

Most IgE is bound to ______, where it serves what function?

A

Fc receptors on mast cells

Serves as a receptor for allergens and parasitic antigens

143
Q

What isotype is important for protection against parasitic infection and anaphylactic hypersensitivity?

A

IgE

144
Q

Which antibody isotype can cross the placenta?

A

IgG

145
Q

What is the most efficient Ig for fixing complement?

A

IgM

146
Q

What isotypes are found on the surface of all naive B cells?

A

IgM and IgD

147
Q

T or F: IgM cannot cross efficiently into tissue.

A

T – too large because it’s a pentamer

148
Q

Which isotype is particularly important for immunity to polysaccharide antigens?

A

IgM

149
Q

Which antibody isotypes play a role in opsonization?

A

IgG1 and IgG3

150
Q

Which antibody isotypes play a role in neutralization of bacterial or viral pathogens and toxins?

A

IgG and IgA

151
Q

Which antibody isotypes help in activating the complement system?

A

IgM and IgG

152
Q

What is an idiotype?

A

The amino acid sequence within the variable region of an antibody

153
Q

T or F: The idiotype forms the mirror image of the epitope that the antibody recognizes.

A

T

154
Q

What is the Fc portion of an antibody?

A

The stem portion that interacts with complement components, macrophages, and NK cells to promote antigen clearance and activation of immune response

155
Q

What does papain cleavage of the hinge region yield?

A

A single Fc fragment and 2 Fab fragments (each Fab has a single antigen-binding site)

156
Q

What does pepsin cleavage of the hinge region yield?

A

A F(ab’)2 fragment (containing 2 antigen-binding domains) and a single pFC’ fragment

157
Q

The Fc portion of IgG1 and IgG3 antibodies are recognized by _______.

A

Fc receptors on macrophages and neutrophils

158
Q

The Fc portion of IgE binds to Fc receptors on _________.

A

Mast cells, basophils, and activated eosinophils

159
Q

The Fc portions of antibody:antigen complexes can bind to ________.

A

Complement, initiating the complement cascade

160
Q

T or F: Fc portion can help deliver antibody to sites they wouldn’t reach without active transport.

A

T

161
Q

What is the primary effector function of B cells?

A

Production of antigen-specific antibodies

162
Q

T or F: Each of the immunoglobulins produced by any one B cell all have the same antigen-specificity.

A

T

163
Q

If B cell receptors encounter and bind to their specific antigen, the B cell can be activated to proliferate and differentiate into _________.

A

Either plasma cells or memory cells

164
Q

Plasma cell

A

Terminally differentiated B cell whose primary function is to produce antibodiess

165
Q

IgG producing plasma cells migrate to ________, while IgA producers migrate to ________.

A

IgG: bone marrow
IgA: lamina propria of mucosal surfaces

166
Q

Memory B cell

A

Antigen-specific B call that results from antigenic stimulation of a naive B cell during the primary immune response

167
Q

Upon exposure to a specific antigen, memory B cells can be reactivated to differentiate into _________ as a component of ________.

A

Differentiate into plasma cells as a component of a secondary immune response

168
Q

The wide repertoire of B cells is randomly produced by _________.

A

Somatic recombination

169
Q

Light chain genes contain ____ and _____ gene segments which are combined to create the variable region. This variable region is then associated with _______ to form the complete light chain gene.

A

Variable and Joining

Constant

170
Q

Heavy chain genes consist of ________ gene segments which encode the variable region and combine with a constant region gene.

A

V, D, J

171
Q

Somatic recombination is (antigen dependent/antigen independent).

A

Antigen independent

172
Q

What enzymes mediate somatic recombination?

A

RAG1 and RAG2

173
Q

What are the types of light chain genes?

A

Kappa and lambda

174
Q

What’s the general organization of the lambda light chain?

A

There are approximately 30 V segments (each preceded by a leader sequence) followed by 4-5 J segments, and EACH of the J segments is associated with a C gene
(LV LV [LV x 30] J C J C J C)

175
Q

What’s the general organization of the kappa light chain?

A

There are approximately 35 V segments(each preceded by a leader sequence), followed by up to 5 J segments which are associated with a SINGLE C gene segment
(LV LV [LV x 35] JJJJJ C)

176
Q

What is the heavy chain gene organization?

A

There are approximately 40 V gene segments (each preceded by a leader sequence) followed by 23 D gene segments and 6 J gene segments
(LV LV [LV x 40] [D x 23] JJJJJJ)

177
Q

Why is the leader sequence important in Ig organization?

A

It directs the proteins into the cells secretory pathway following translation

178
Q

The rearrangements that take place in somatic recombination are (random/fixed) and take place during ________.

A

Random

Take place during B cell development in the bone marrow

179
Q

What is the relationship between somatic recombination and the interaction of the developing B cell with antigen?

A

They’re totally independent of each other

180
Q

What are the steps of light chain gene construction?

A
  1. Random rearrangement of a single V gene segment with a single J gene segment to form VJ junction
  2. Transcription
  3. RNA processing brings VJ junction together with the C gene segment to create the complete coding region for the light chain
181
Q

What are the steps of heavy chain gene construction?

A
  1. Random rearrangement of a single D segment with a single J segment to form a DJ junction
  2. Random rearrangement of a single V gene segment with the DJ junction to form a complete DNA sequence encoding the variable region
  3. Transcription
  4. RNA processing brings the VDJ junction together with the C mu segment to create the complete coding region
182
Q

What is allelic exclusion?

A

Only one allele is expressed while the other allele is silenced
(prevents simultaneous gene rearrangement on the other chromosome)

183
Q

T or F: The joining of the gene segments during heavy/light chain construction is precise.

A

F: It’s not precise and generates diversity of the recombined V region coding sequence

184
Q

The gaps between gene segments formed during heavy/light chain construction are filled by ________.

A

Random addition of nucleotides

185
Q

During light chain gene construction, the C segment is separated from the VJ junction by ______.

A

Non-coding (intronic) DNA sequence

186
Q

During heavy chain gene construction, the C segment is separated from the VDJ junction by _________.

A

Non-coding (intronic) DNA sequence

187
Q

T or F: Once the V region genes have rearranged to form VJ or VDJ junctions, no further rearrangement of that chromosome can take place.

A

T

188
Q

The only changes in the variable region genes of a rearranged B cell line arise from _______.

A

Somatic hypermutation

189
Q

What are the 3 main processes that help to generate antibody diversity, and when do these mechanisms occur?

A
  1. Different pairing of gene segments to form variable domains of both the light and heavy chains
  2. Imprecise joining of gene segments during somatic recombination
  3. Different pairing of light chains and heavy chains
    All of these occur during initial development of the B cell in the bone marrow
190
Q

Because of allelic exclusion, successful Ig gene rearrangement on one chromosome results in _______.

A

The shutting down of rearrangement on the second chromosome

191
Q

If no successful Ig gene rearrangement occurs on either chromosome, what happens?

A

The cell dies

192
Q

T or F: All antigen receptors on a lymphocyte will have the same amino acid sequence in the variable domains of the light and heavy chain proteins.

A

T

193
Q

What is somatic hypermutation?

A

Point mutations that occur at high frequency in the rearranged variable region DNA of Ig genes; It results in production of variant antibodies, some of which have higher affinity for the antigen and are stimulated to proliferate and differentiate.

194
Q

Most of the point mutations that occur during antibody construction are confined to what regions?

A

Complementarity-determining regions (CDRs) aka hypervariable regions

195
Q

How frequently do mutations in the hyper variable regions occur compared to the ordinary mutation rate for a gene?

A

Point mutations in the hyper variable regions occur at a rate 1 million times greater than the ordinary mutation rate for a gene

196
Q

Affinity maturation is (antigen dependent/antigen independent), and it occurs in _______.

A

Antigen dependent process

Occurs in secondary lymphoid tissues during a germinal center reaction

197
Q

Class switching is (antigen dependent/antigen independent).

A

Antigen dependent

198
Q

The V-region exons produced by any B cell are determined during the __________ stage of maturation.

A

Pro- and pre- B cell stage

199
Q

Except for ________, a given B cell and all of its progeny will express the same VL and VH genes.

A

Somatic hypermutation

200
Q

T or F: The CH-region genes expressed by a B cell line do not change as the response matures.

A

F: The CH-region genes expressed can change as response matures, but the VL and VH genes expressed will be the same

201
Q

Each B cell initially produces Ig_, which comes from C_.

A

M, mu

202
Q

T or F: Isotype switching to IgD does not occur.

A

T: Because IgM and IgD are simultaneously expressed on mature naive B cells

203
Q

How does class switching alter the light chain?

A

It doesn’t

204
Q

What’s the order of the heavy chain coding region?

A

Cmu(IgM) Cdelta(IgD) Cgamma3(IgG3) Cgamma1(IgG1) Calpha1(IgA1) Cgamma2 (IgG2) Cgamma4(IgG4) Cepsilon(IgE) Calpha2(IgA2)

205
Q

The cytokine signals produced by ______ promote class switching to a particular antibody isotype.

A

T helper cells (TH1 or TH2)

206
Q

Isotype switching only occurs after B cells have been stimulated by ______.

A

Antigen

207
Q

By what mechanism does class switching occur?

A

It occurs by a specialized recombination mechanism guided by DNA switch regions. The switch regions lie in introns between the C regions (except between Cmu and Cdelta). The switch regions are brought together and the intervening DNA is excised.

208
Q

The recombination events that occur during class switching are catalyzed by ______

A

Switch recombinase

209
Q

T or F: Once you class switch you can’t switch back.

A

T

210
Q

Does class switching affect the antigen-combining region of the antibody molecule?

A

No, but it does lead to functional diversity of the antibody repertoire by producing different isotypes of antibody that have the same specificity as the parental B cell.

211
Q

B cells are lymphocytes dedicated to making _____.

A

Immunoglobulings (antibodies)

212
Q

What are the 6 phases of B cell development?

A
  1. Expression of Igs and rearrangement of light and heavy chains
  2. Negative selection in bone marrow to remove B cells with selectivity for “self” antigens
  3. Positive selection of developing B cells that will mature
  4. Search for infection
  5. Activation and proliferation of B cells when they encounter antigen
  6. Proliferating B cells differentiate and give rise to plasma cells and memory cells
213
Q

What are the two stages of B cell maturation?

A
  1. Antigen independent

2. Antigen dependent

214
Q

What are the 4 phases of antigen-independent development of B cells?

A
  1. Pro-B cell
  2. Pre-B cell
  3. Immature B cell
  4. Mature B cell
215
Q

In what developmental cell does the rearrangement of heavy-chain Ig genes take place?

A

Pro-B cells

216
Q

D-J rearrangement occurs in ____ cells, and V-DJ rearrangement occurs in ______ cells.

A

D-J: early pro-B cell

V-DJ: late pro-B cell

217
Q

Light chain rearrangement occurs in ____ cells?

A

Pre-B cells

218
Q

Which cell stage migrates to the peripheral lymphoid tissues and undergoes self tolerance selection?

A

Immature B cells

219
Q

What is clonal deletion?

A

Immature B cells that specifically interact with”self” antigens in the bone marrow undergo apoptosis and are depleted from the B cell population

220
Q

What is anergy?

A

Immature B cells that specifically interact with soluble antigen in the bone marrow are signaled to down-regulate cell surface expression of IgM and are left unable to respond to specific antigen. Anergic cells can’t usually survive more than a few days.

221
Q

The process of developing into a mature B cell is complete when _______.

A

The B cell expresses both IgM and IgD on its surface

222
Q

What do non-lymphoidal stromal cells do?

A
  1. Make specific cell-surface contact with the B cells through interactions between their adhesion molecules
  2. They produce growth factors that are essential survival signals for B cells
223
Q

What growth factors are essential for B cells?

A

IL-7 and stem cell factor

224
Q

What happens to a B cell that doesn’t productively rearrange both its heavy and light chains and express IgM on its surface?

A

It dies :(

225
Q

Somatic recombination is dependent on which enzymes? What do they do?

A

RAG-1 and RAG-2. They make double stranded breaks in DNA during somatic recombination

226
Q

What does terminal deoxynucleotidyl transferase (TdT) do?

A

It catalyzes the addition of N nucleotides (not encoded in germline DNA) at the junctions between rearranging gene segments

227
Q

What does Bruton’s thymidine kinds (Btk) do?

A

It’s involved in the transduction of signals from cell-surface receptors during B cell development

228
Q

What is deficiency of Btk called, and what are the effects?

A

X-linked Agammaglobulinemia. They have little or no circulating antibody because B cell development stops at the pre-B cell stage

229
Q

What is a plasma cell?

A

A terminally differentiated B cell whose primary function is to produce antibodies

230
Q

IgG-producing plasma cells migrate to ______, and IgA-producers migrate to _____.

A

IgG: bone marrow
IgA: lamina propria of mucosal surfaces

231
Q

What is a memory B cell?

A

An antigen-specific B cell that results from antigenic stimulation of a naive B cell during the primary immune response. These cells can be reactivated to differentiate into plasma cells as a component of secondary immune response.

232
Q

Functions of the surface immunoglobulin

A
  1. Receptor for a specific antigen (delivers 1st activation signals to the B cell once it interacts with antigen)
  2. Delivers specific antigen to the interior of the B cell via receptor-mediated endocytosis, and here the antigen is degraded
233
Q

What happens after antigen is degraded inside the B cell?

A

Peptide fragments of the antigen are displayed on the surface of the B cell in association with MHC Class II. The peptide:MHC complex is recognized by T helper cells, which produce cytokines and CD40 ligand. These signals trigger B cells to proliferate and differentiate.

234
Q

Lymphokines are _____ produced by lymphocytes.

A

Cytokines

235
Q

Can class switching occur in individuals that don’t express CD40L?

A

No

236
Q

What forms can isotypes of antibody be produced in? Production of these two forms is achieved by ______.

A

Membrane-bound form or secreted form; Production achieved by alternative RNA processing

237
Q

All membrane-bound antibody molecules are in the _____ form of the antibody.

A

Monomeric

238
Q

The membrane-bound form of antibody molecules has a ______ that anchors the molecule into the membrane.

A

Transmembrane domain

239
Q

The secreted form of antibodies has what structural modification?

A

Secretory tail at the carboxyterminal end of each heavy chain

240
Q

What does activation-induced cytidine deaminase (AID) do?

A

It catalyzes class switching and is required for somatic hypermutation (affinity maturation)

241
Q

What is the major histocompatibility complex?

A

A large cluster of genes encoding specialized glycoproteins

242
Q

How was the major histocompatibility complex originally identified?

A

By its potent effects on the immune response to transplanted tissues

243
Q

What is the structure of MHC Class I molecules?

A

They consist of two chains: an alpha chain encoded by MHC and a B2-microglobulin chain not encoded by the MHC

244
Q

What is the structure of the alpha chain of MHC Class I molecules?

A

It has three domains (alpha 1-3): alpha 1 and 2 are brought together to form a peptide binding site and the alpha 3 domain spans the host cell membrane

245
Q

What is the structure of the B2-microglobulin chain of MHC Class I molecules?

A

It folds to form an Ig-like domain and associates with the alpha-3 domain of the MHC Class I alpha chain

246
Q

T or F: Everyone expresses an essentially identical B2-microglobulin.

A

T

247
Q

What is the structure of MHC Class II molecules?

A

They consist of a non covalent association of two polypeptide chains (alpha chain and beta chain)

248
Q

_______ only recognize peptides bound to MHC molecules.

A

T cells

249
Q

T or F: Antigen recognition by T cells is very similar to antigen:antibody recognition.

A

F: they’re very different

250
Q

What are the structures of the alpha and beta chains of MHC Class II molecules?

A

Both are glycosylated transmembrane proteins that have two domains:

  • a2 and B2 domains of these chains are similar to Ig domains
  • a1 and B1 domains form a cleft which binds to peptides
251
Q

How are the binding grooves of MHC Class I and MHC Class II molecules different?

A

MHC Class II binding groove is open at both ends, whereas MHC Class I binding groove is closed on the ends

252
Q

T or F: Each MHC molecule can bind to many different peptides.

A

T

253
Q

T or F: MHC Class I and II have the same peptide-binding characteristics.

A

F: They’re slightly different

254
Q

MHC Class I molecules bind to peptides ______ in length.

A

8-10 amino acids

255
Q

How is peptide binding stabilized in MHC Class I molecules?

A

By contacts between the amino terminal and carboxyterminal ends of the peptide and invariant sites found at the ends of the binding grooves

256
Q

MHC Class II molecules bind to peptides _______ in length.

A

At least 13 residues

257
Q

Which class of MHC molecules is more promiscuous with respect to peptide binding?

A

MHC Class II

258
Q

What is antigen processing?

A

The degradation of proteins into peptides that can bind to MHC molecules for presentation to T cells

259
Q

T or F: Antigens must be processed into peptides before they can be presented via MHC molecules.

A

T

260
Q

Where does antigen processing take place?

A
  1. Cytosol

2. Endocytic vesicles

261
Q

What degrades antigens into peptide fragments in the cytosol?

A

Proteasome

262
Q

What are proteasomes?

A

Large cylindrical complexes whose function is to recycle cytosolic proteins

263
Q

Peptides produced by the proteasome are actively transported to the ER by __________.

A

TAP transporter complex

264
Q

What happens after peptides are transported from the cytosol to the ER?

A

The peptides bind to MHC Class I molecules

265
Q

T or F: The TAP transporter complex is ATP-dependent.

A

T

266
Q

Why aren’t self peptides usually recognized by CD8+ effector cells?

A

Because most self-reactive T cells are clonal deleted during the negative selection process in the thymus

267
Q

Antigens that are phagocytosed are degraded by ___________ into peptide fragments.

A

Endosomal or lysosomal proteases

268
Q

T or F: Antigens in endosomal compartments can be processed by proteasomes.

A

F: They’re not available to proteasomes for processing

269
Q

Peptide fragments within endocytic vesicles bind to _______.

A

MHC Class II molecules

270
Q

Peptides bound to MHC Class II molecules are recognized by __________ cells.

A

CD4+

271
Q

What role does the invariant chain play in antigen processing?

A
  1. It associates with new MHC Class II molecules and prevents peptides in the ER from binding in the peptide-binding groove of these molecules
  2. Then MHCII:Invariant chain complexes are transported to acidified vesicles where the invariant chain is degraded
272
Q

When the invariant chain is degraded, _______ is left behind.

A

Clip (Class II Associated Invariant Peptide) in the binding groove

273
Q

When does MHC Class II release the clip peptide from the binding groove?

A

When MHC Class II interacts with the vesicle membrane protein HLA-DM.

274
Q

What happens to an MHC Class II molecule that doesn’t bind a peptide quickly.

A

It’s degraded

275
Q

Intracellular pathogens in any cell are processed by _________.

A

Proteasomes in the cytosol of the infected cell

276
Q

Intracellular pathogen peptides bind to _________.

A

MHC Class I molecules

277
Q

Intracellular pathogen peptides are presented to _______ cells.

A

CD8+

278
Q

Extracellular pathogens are endocytosed by ________________ (3).

A

Macrophages
Dendritic cells
B cells

279
Q

Extracellular pathogen peptides bind to _________.

A

MHC Class II molecules

280
Q

Extracellular pathogen peptides are presented to ___________ cells.

A

CD4+

281
Q

Why is it important that MHC Class I molecules are expressed on all nucleated cells?

A
  • Because virus can infect almost any nucleated cell

- CD8+ cells are programmed to kill any cell that presents their cognate antigen via MHC Class I molecules

282
Q

Where are MHC Class II molecules found?

A
  • Antigen presenting cells

- Thymic cortical epithelial cells

283
Q

Why is the expression of MHC Class II molecules important for thymic cortical epithelial cells?

A

They participate in positive selection of MHC-binding thymocytes during thymic maturation

284
Q

What are some examples of immune playerz encoded by the MHC gene complex?

A

TAP-1 and TAP-2
Proteasomes
Cytokines
Complement proteins

285
Q

T or F: MHC Class I and II genes are the most polymorphic genes in the mammalian genome.

A

T

286
Q

What properties of MHC make it difficult for pathogens to evade immune response?

A
  1. MHC is polygenic

2. MHC Class I and II genes are highly polymorphic

287
Q

MHC Class II genes are expressed by ________.

A

Most B cells, APCs, and thymic epithelial cells

288
Q

Diversity of MHC expression results from _________.

A

Polygeny for each individual and polymorphism within the population

289
Q

What’s an allele?

A

A naturally occurring variant of a particular gene

290
Q

What are isoforms?

A

The different forms of a protein that are encoded by the alleles of a gene or by different but closely related genes

291
Q

What’s a haplotype?

A

The set of alleles carried on a single chromosome for a linked set of polymorphic genes

292
Q

How many MHC Class I isoforms are there?

A

6: HLA-A, HLA-B, HLA-C, HLA-E, HLA-F, HLA-G

293
Q

Which of the MHC class I isoforms are the most polymorphic? What is different about these isoforms?

A

HLA-A, HLA-B, and HLA-C – These encode the MHC Class I molecules that present peptide antigens to T cells

294
Q

How many MHC Class II isoforms are there?

A

5: HLA-DR, HLA-DQ, HLA-DR, HLA-DM, and HLA-DO

295
Q

Which of the MHC Class II isoforms are highly polymorphic and what is different about these isoforms?

A

HLA-DP, HLA-DQ, HLA-DR – these bind to peptides and present them to CD4+ T cells

296
Q

The minimum number of HLA class I isoforms expressed by an individual is ____.

A

3

297
Q

The maximum number of HLA class I isoforms expressed by an individual is ___.

A

6

298
Q

The minimum number of MHC class II isoforms is ____.

A

6

299
Q

The maximum number of MHC class II isoforms is ____.

A

48

300
Q

The MHC class I heavy chain is stabilized by ________ until B2-microglobulin binds.

A

Calnexin

301
Q

T or F: MHC Class I and Class II pathways are mutually exclusive.

A

F

302
Q

Antibody-mediated immune responses are best for clearance of _________.

A

Extracellular pathogens

303
Q

T-cell mediated immune responses are best for clearance of __________.

A

Intracellular pathogens

304
Q

T or F: The more MHC isoforms you possess, the more potential you have for a functional immune response.

A

T

305
Q

What is the great mystery of life?

A

Why is the hotdog always longer than the hotdog bun?

Immunology (3 decks)

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