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MLT immunology > Unit 1 > Flashcards

Unit 1 Flashcards

1
Q

What is immunology?

A

Study of a hosts reactions to foreign substances that are introduced into the body

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2
Q

What is an antigen?

A

A substance that reacts with an antibodies or sensitized cells but may or may not be able to elicit an immune response

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3
Q

What is immunity?

A

Condition of being resistant to infection

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4
Q

What was the first vaccine and what is used to create it?

A

1st → smallpox
Composed of cowpox

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5
Q

Who is the father of immunology and why is he considered this?

A

Louis Pasteur.he created the first attenuated vaccine

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6
Q

What is attenuation?

A
  • Makes pathogen less virulent
    -takes place through heat, aging and chemicals
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7
Q

What is phagocytosis?

A

Cells that eat cells

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8
Q

What is humoral immunity?

A
  • Protection from disease resulting from substances in the serum/plasma (antibodies and acute phase reactants)
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9
Q

Describe cell mediated immunity

A

-When recognition antigen occurs in the secondary lymphoid tissue, T cells are activated and differentiate into functionally active small lymphocytes that produce cytokines
-activities of specific cytokines include assisting B cells in commencing antibody production, eliminating tumor and other target cells, rejecting grafts, stimulating hematopóiesis in the bone marrow and initiating delayed hypersensitivity

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10
Q

What are the two parts of the adaptive immune response?

A
  • Cellular
    -humoral
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11
Q

Describe humoral immunity function

A

Involves production of antibodies by B cells and plasma cells

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12
Q

What are antibodies?

A

Serum protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses.

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13
Q

What is innate immunity?

A

An individuals ability to resist infection by means of normally present body functions

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14
Q

What are characteristics of innate immunity?

A
  • Nonspecific
    -no memory
    -immediate exposure
  • same response for all pathogens
    -influenced by nutrition, age, fatigue, stress, and genetic determinants
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15
Q

What is adaptive immunity?

A

-resistance that is characterized by specificity for each individual pathogen

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16
Q

List characteristics of adaptive immunity

A
  • Delayed response
  • stronger response
  • specific
  • has memory
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17
Q

What is the function of WBCs?

A

Defend against invasion by bacteria, virus, fungi, and other foreign substances

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18
Q

What are the 5 types of WBC?

A

-monocytes
- eosinophils
- basophils
-neutrophils
-lymphocytes

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19
Q

Which WBC is part of the adaptive immunity?

A

Lymphocytes

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20
Q

What are the main cells found in tissue?

A
  • dendritic cells
  • macrophages
  • mast cells
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21
Q

What is a hematopoietic stem cells (HSC)?

A

All blood cell types arise from this cell

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22
Q

Where are WBCs produced? And how much?

A
  • Bone marrow
  • one and a half billion daily
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23
Q

How do WBCs form?

A

HSC gives rise to two distinct types of precursor cells, myeloid precursors (CMP) and common lymphoid precursors (CLP)

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24
Q

What do CMPs do?

A

-Give rise to WBC that participate in phagocytosis.
-also known as myeloid line

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25
Q

What is the life span of a neutrophil?

A

Several days

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26
Q

What is the size of a neutrophil?

A

10-15 um

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27
Q

Describe the nucleus of a neutrophil

A
  • 2-5 lobes
    -has lots of granules
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28
Q

What percentage of WBCs are neutrophils?

A

50-70%

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29
Q

What stain is used on neutrophils?

A

Wright stain

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30
Q

What is the main function of neutrophils?

A

Phagocytosis

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31
Q

What is diapedsis?

A

Movement through blood vessel wallsm

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32
Q

What are chemotaxins?

A

Chemical messengers that cause cells to migrate in particular direction

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33
Q

What do neutrophils do when an acute infection occurs?

A

Neutrophils increase almost immediately in the blood and go to infection site rapidly

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34
Q

What is the size ofan eosinophil?

A

10-15 um

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35
Q

What percentage of WBCs are eosinophils?

A

1-4%

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36
Q

What stain is used for eosinophils?

A

Eosin stain

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37
Q

Describe the nucleus of eosinophils

A

-bilobed/ellipsoïdal nucleus
-eccentrically located

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38
Q

What are the functions of eosinophils

A

①phagocytosis (not efficient as neutrophils)
②neutralize basophils and mast cells
③kills parasites using cationic proteins

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39
Q

What is the most important role of eosinophils?

A

Regulation of adaptive immune response through cytokine release

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40
Q

What percent of WBCs are basophils?

A

Less than 1% WBC

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41
Q

What is the size of basophils?

A

Smallest, 10-15 um

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42
Q

Describe the nucleus of a basophil

A

-deep purple- blue granules
-bilobed, hard to see

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43
Q

What is the life span of a basophil?

A

A few hours

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44
Q

What happens to basophils in the spleen?

A

Removed and destroyed by macrophages

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45
Q

What are the 3 functions of basophils?

A

①induce and maintain allergic reactions
②regulate some t-helper cell response
③stimulate B-cells to produce IgE antibody

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46
Q

What does histamine do?

A

Contracts smooth muscle

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47
Q

What does heparin do?

A

It is an anticoagulant

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48
Q

What is the size of a monocyte?

A

Largest, 12-20 um

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49
Q

Describe the nucleus of a monocyte

A

-irregular horseshoe or folded nucleus
- occupies 1/2 or more of cell

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50
Q

What percentage of WBCs are monocytes?

A

2-10%

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51
Q

What is the lifespan of monocytes?

A

30 hours, then travels to tissues and become macrophages

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52
Q

What are 2 types of granules in monocytes?

A

1st→ contains peroxides, acid phosphate, and arylsulfatase
2nd→ containsbeta-glucuronidase, lysozyme, and lipase (No alkaline phosphate)

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53
Q

What does monocytes contain that macrophages do not?

A

Peroxidase

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54
Q

What are macrophages in the lungs called?

A

Alveolar macrophages

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55
Q

What are macrophages called in the liver?

A

Kupffer cells

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56
Q

What are macrophages in the brain called?

A

Microglial cells

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57
Q

What are macrophages in bone called?

A

Osteoclasts

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58
Q

What are macrophages in connective tissue called?

A

Histiocytes

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59
Q

Why are neutrophils more efficient at phagocytosis than macrophages?

A

Macrophages are slower

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60
Q

Why are neutrophils more efficient at phagocytosis than eosinophils?

A
  • Less eosinophils
  • eosinophils lack of digestive enzyme
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61
Q

What is the lifespan of a macrophages?

A

A few months

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62
Q

What are the innate immunity functions?

A

① phagocytosis
②microbial killing
③anti-tumor activity
④intracellular parasite eradication
⑤secretion of cell membrane

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63
Q

What enhances “killing” of foreign substances?

A

When macrophages become activated by cytokines

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64
Q

How do macrophages play an important role in the adaptive system?

A

By presenting phagocytosized antigens to T cells

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65
Q

What is the lifespan of mast cells?

A

9-18 months

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66
Q

Where can mast cells be found?

A
  • Located in variety of tissues
  • resembles a basophil
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67
Q

What is the size of mast cells?

A

Larger than basophil,up to 20 um

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68
Q

What are the functions of mast cells?

A

①act to increase vascular permeability and increase blood flow to affected area
② role in allergic reactions
③ APC

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69
Q

Describe the appearance of dendritic cells

A

-Covered with long, membranous extensions that resemble nerve cell dendrites

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70
Q

What are dendritic cells?

A

-APC that links innate and adaptive immunity and are critical for the induction of immune response
- classified according to location

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71
Q

What is to the most potent phagocytic cell?

A

Dendritic cells

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72
Q

What percentage of WBC are lymphocytes?

A

20-40%

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73
Q

What are the size of lymphocytes?

A

7-10 um (similar to RBC)

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74
Q

Describe the lymphocytes nucleus

A
  • Large, rounded, and indented
    -has narrow ring
    -chromatin stains deep blue
  • sparce cytoplasm
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75
Q

Why are lymphocytes granules unique?

A

They arise from HSC

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76
Q

What are the 3 categories of lymphocytes?

A

-T cells
-B cells
-innate lymphoid cells

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77
Q

What is the most prominent innate lymphoid cells?

A

Nk cells

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78
Q

what percent of lymphocytes are B-cells?

A

10-20%

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79
Q

What percentage of lymphocytes are T-cellsz

A

61-80%

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80
Q

What percentage of lymphocytes are Nk cells?

A

10-15%

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81
Q

What is cluster of differentiation?

A

Protein found on cell surfacesthat can be used to identify specific cell types and stages of differentiation

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82
Q

What are the primary lymphoid organs?

A

Bone marrow
Thymus

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83
Q

What is the largest tissue in the body?

A

Bone marrow

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84
Q

What is bone marrow the main source of?

A

HSC

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85
Q

What can HSC develop into?

A

-RBCs
- granulocytes
-monocytes
-platelets
- lymphocytes

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86
Q

What occurs when lymphocytes remain in the bone marrow?

A

Mature and become Nk cells or B cells

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87
Q

What occurs when lymphocytes travel to the thymus?

A

Mature and become T cells

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88
Q

Describe the thymus

A

Filled with epithelial cells that play central role in differentiation process

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89
Q

How long does it take T- cells to mature?

A

3 weeks

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90
Q

What are mature T-cells released from?

A

Medulla of thymus

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91
Q

What are the four secondary lymphoid organs?

A
  • Spleen
  • lymph nodes
    -CALT
    -MALT
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92
Q

After lymphocytes mature in primary lymphoid organs, what happens next?

A

They make their way to the secondary lymphoid organs

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93
Q

Where does main contact of foreign antigens occur?

A

-Secondary lymphoid organs
-T cells and B calls meet here as well

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94
Q

Where do lymphocytes spend most of their time?

A

The tissues

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95
Q

How do lymphocytes travel to blood stream?

A

Via. Thoracic duct

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96
Q

What is the largest lymphatic vessel?

A

Thoracic duct

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97
Q

What are T cells?’

A

Effector cells that serve a regulatory roles in adaptive and innate immunity

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98
Q

What do B cells do?

A

Produce antibodies

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99
Q

What is lymphopoiesis?

A

Multiplication of lymphocytes

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100
Q

Describe the spleens location

A

-upper left quadrant
-below diaphragm
- largest secondary organ

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101
Q

What does the spleen do?

A

Removes old/damaged cells and foreign antigens from the blood

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102
Q

What types of pulp is found in tissue?

A

Red and white

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103
Q

What is the function red pulp?

A
  • To destroy old RBCs, platelets, and pathogens
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104
Q

What is rich in red pulp?

A

Macrophages

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105
Q

What is the total volume of red pulp found a in the spleen?

A

50%

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106
Q

What is the total volume of white pulp found a in the spleen?

A

20%

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107
Q

Describe white pulp of the tissues

A
  • Contains lymphoid tissue arranged around arterioles (periarterolar lymphoid sheath: PALS)
  • sheath contains mostly T cells
  • primary follicles contains B cells
  • marginal zone containing dendritic cells that trap antigens
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108
Q

Describe lymph nodes

A

-located along lymphatic ducts and numerous joints attacking appendages
- provide ideal environment for contact with foreign antigens that have penetrated tissue

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109
Q

What is the main function of the lymph nodes?

A

-filtration of interstitial fluid from around cells in tissues
-important because it -allows contact between lymphocytes and foreign antigens that have penetrated tissue

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110
Q

What are the layers of the lymph node tissues?

A
  • Outer cortex
    -para cortex
    -inner medulla
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111
Q

What is lymph fluid?

A

A filtrate of the blood and arises from the passage of water and low molecular weight solutes out of blood vessel walls and into the interstitial spaces between cells

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112
Q

Describe flow of lymph nodes

A
  • Some return to blood streams through venules
    -portion flows through tissues and collected in lymphatic vessel
  • flow through place called sinuses lined with macrophages
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113
Q

What structure do lymphocytes and foreign antigens enter the lymph nodes through?

A

Afferent vessels

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114
Q

How do lymphocytes enter the lymph nodes from blood stream?

A

By means of the high endothelial venules

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115
Q

What cells could be found in a primary follicle of the lymph nodes?

A

-unstimulated B cells
- Macrophages
-follicular dendritic

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116
Q

What can be found in a secondary follicle of the lymph nodes?

A

Antigen stimulated proliferating B cells

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117
Q

What is the center of a secondary follicle of the lymph nodes called?

A

Germinal center

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118
Q

What happens when B cells come in contact with antigens?

A

Plasma cells and memory cells form

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119
Q

Where in the lymph nodes can T cells be found?

A

Para cortex

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120
Q

What structure does lymph fluid and lymphocytes exit the lymph nodes?

A

Efferent lymphatic vessels

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121
Q

What is the main function of plasma cells?

A

Actively secrete antibodies

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122
Q

What is the main function of memory cells?

A

Can quickly change into plasma cells

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123
Q

Where can MALT be found?

A

-appendix
-GI tract
-ileum
-peyers patch
-respiratory tract
-tonsils
-urogenital tract

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124
Q

Why are macrophages and lymphocytes localized in MALT?’

A

Mucousal surface are main ports of entry for a foreign antigen

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125
Q

What’s cells can be found in CALT?

A
  • Dendritic cells
  • Macrophages
  • monocytes
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126
Q

What do all secondary organs function as?

A

As potential sites for contact with foreign antigens and increase probability of immune response

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127
Q

What are the innate phagocytic cells?

A
  • Dendritic cells
    -Macrophages
    -monocytes
    -neutrophils
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128
Q

What can recognize B cells?

A

-CD19
-CD20
-surface antibody

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129
Q

Where do T cells acquire specificity?

A

Thymus

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130
Q

What are the two subtypes of T cells?

A

-CD4+ (Th or treg cells)
-CD8+ (Tc cells)

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131
Q

What marker is present on all subtypes of T-cells?

A

CD3

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132
Q

What are NK cells?

A

Can kill virally infected or cancerous target cells without previous exposure to them

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133
Q

Which WBC is capable of further differentiation in tissues?

A

Monocytes

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134
Q

How are T cells different from NK cells?

A

Only NK cells are able to kill target cells without prior exposure to them

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135
Q

What is the most potent phagocytic cell?

A

Dendritic cells

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136
Q

What is a distinguishing feature of B cells?

A

Presence of surface antibody

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137
Q

What is the main function of T-cells?

A

Produce cytokines that regulate both innate and adaptive immunity

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138
Q

What is the function of antibodies?

A

Neutralize bacterial toxins

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139
Q

What blood cell kills parasites?

A

Eosinophils

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140
Q

What are the 2 systems of innate immunity?

A
  • External defense system
    -internal defense system
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141
Q

What is the external defense system?

A

-contains chemical, physical, and biological factors that work together to prevent most infections agents from entering the body

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142
Q

What is the internal defense system?

A

-Triggered within minutes and clears invaders as quickly as possible

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143
Q

Why do external and internal defense systems work together?

A

To promote phagocytosis

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144
Q

What orchestrates the healing process?

A

Phagocytosis and resulting inflammation brings cells and humoral factors to the injuried area

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145
Q

What is the barrier of the external defense system?

A

Skin and mucosal membrane surfaces

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146
Q

Describe the outer layer of the external defense barrier?

A

-outer layer of skin is the epidermis and contains several layers of tightly packed epithelial cells
-protein coated cell called keratin

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147
Q

What is the role of keratin in the epidermis?

A

Makes skin impermeable to most infections agents

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148
Q

How often does the outer layer of skin renew?

A

Every couple of days

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149
Q

What is the layer under the epidermis?

A

Dermis

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150
Q

Describe the dermis

A

-thicker than epidermis
- connective tissue with bloodvessel, hair follicles, sebaceous glands,and WBC

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151
Q

What cells are found in the dermis?

A
  • Dendritic cells
    -macrophages
    -mast cells
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152
Q

Why does skin have several secretions?

A

Discourage growth of microorganisms

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153
Q

What is secreted on skin to maintain pH balance?

A

-fatty acids and lactic acids
-they prevent growth of microorganisms

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154
Q

What is a balanced pH of skin

A

~5.6

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155
Q

What is psoriasin?

A
  • Produced by skin
  • has antibacterial effects, especially for gram-negative bacteria
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156
Q

What is the respiratory tracts external defense system?

A

-mucous secretion block adherence
- coughing and sneezing clear out pathogens

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157
Q

What is the geniturinary tracts external defense systems?

A

-flushing out urine
- acidity helps to remove many potential pathogens
- lactic acid of vagina maintains pH of 5

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158
Q

What is the external defense for the digestive tract?

A
  • Hydrochloric acid keeps pH as low as 1 to kill pathogens brought in by food and drink
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159
Q

What are lysosomes role in the external defense system?

A
  • Attack cell wall of microorganisms, especially gram positive bacteria
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160
Q

What are microbiota?

A

A mix of bacteria that are normally found at species body sites and do not typically cause disease.

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161
Q

What is the microbiotas role in the external defense system?

A

Helps keep pathogens from establishing themselves

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162
Q

-*.3
Explain the internal defense

A
  • Composed of both cells
  • soluble factors that have specific and essential functions
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163
Q

What is the function of phagocytes?

A

They engulf and destroy most foreign cells or particles that enter the body

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164
Q

What is phagocytosis enhanced by?

A

Cell receptors on cells that capture invaders through identification of microbiota

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165
Q

What is the main function of soluble factors in the internal defense system?

A

-helps facilitate contact between microbes and phagocytic cells and bind to and recycle important proteins after phagocytosis
- soluble factors = acute phase reactants

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166
Q

What is the percent of macrophages and dendritic cells in total cell population of tissues?

A

10-15%

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167
Q

What are the most important cells in pathogen recognition?

A
  • Dendritic cells
  • macrophages
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168
Q

What is the main function of pattern recognition receptors? (PRRs)

A

Able to distinguish pathogens from normally present molecules in the body by means of receptors

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169
Q

What are pattern recognition receptors encoded by?

A

Hosts genomic DNA

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170
Q

What happens when PRRs binds to pathogen?

A

①phagocytic cells activate and are better able to engulf and kill organisms
② activated cells secrete proinflammatory cytokines and chemokines
③cytokines and chemokines also trigger adaptive immune response

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171
Q

What are pathogen associated molecular patterns?(PAMPs)

A

Substance that allows PRRs to have ability to distinguish self from non-self

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172
Q

What had a large impact on understanding innate immunity?

A

Toll-like receptors (TLRs)

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173
Q

What protein originally was discovered on a fruit fly?

A

Toll

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174
Q

Where are the highest concentrations of TLRs found?

A

-dendritic cell
-macrophages
-monocytes

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175
Q

Which TLRs are found in cytoplasm?

A

-TLR1
-TLR2
-TLR4
-TLR5
-TLR6

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176
Q

What TLRs are found in the endosomal compartment of cells?

A

-TLR3
-TLR7
-TLR8
-TLR9

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177
Q

What does TLR1 recognize?

A

Lipopeptides found in mycobacteria

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178
Q

What does TLR2 recognize?

A

Peptidoglycan, lipoprotein, and zymosan found in gram positive bacteria, mycobacteria, and yeasts

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179
Q

What does TLR4 recognize?

A

Lipopolysaccharides,fusion proteins, and Annan found in gram-negative bacteria, respiratory syncytial virus, and fungi

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180
Q

What does TLR5 recognize?

A

Flagellin found on bacteria with flagella

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181
Q

What does TLR6 recognize?

A

Lipopeptides, lipoteichoic acid, and zymosan found on mycobacteria - gram positive bacteria, and yeasts

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182
Q

What does TLR3 recognize?

A

Double stranded RNA found on RNA viruses

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183
Q

What does TLR7 recognize?

A

Single stranded RNA found on RNA viruses

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184
Q

What does TLR8 recognize?

A

Single stranded RNA found on RNA viruses

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185
Q

What does TLR9 recognize?

A

Double stranded DNA found on DNA viruses and bacterial DNA

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186
Q

What does TLR10 recognize?

A

Unknown

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187
Q

Describe the structure of TLRs

A

Membrane spanning glycoproteins that share a common structural element called leucine-rich repeats (LRRs)

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188
Q

What occurs once TLRs bind to their particular substances?

A

①host immune responses rapidly activated by production of cytokines and chemokines
②neutrophils are then recruitedto area because of increased capillary permeability
③macrophages and dendritic cells have expression of adhesion molecules on their surfaces

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189
Q

What are c-type lectin receptors? (CLRs)

A
  • Plasma membrane receptors that bind to Mannan and beta-glucans found in fungal cell walls
    -has production of cytokines and chemokines to microbes
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190
Q

What cells can CLRs be found on?

A

-B cells
-dendritic cells
-macrophages
-monocytes
- neutrophils
-T cells subsets

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191
Q

What are retinoisacid-inducable gene I-like receptors? (RLRs)

A

-recognize RNA from RNA viruses.
-induce production of inflammatory cytokines/ type I interferon

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192
Q

Describe serum amyloid A

A

-major protein who concentration can increase X1000 in response to infection/injury
-apolipoprotein synthesized in liver
-acts like cytokines, chemical messenger (activates monocytes and macrophages)

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193
Q

When does serum amyloid A reach peak?

A

24-48 hours after acute infection

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194
Q

Why would serum amyloid A be increased?

A
  • Chronic inflammation
    -atherosclerosis
  • cancer
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195
Q

Describe complement

A
  • Series of serum proteins that are normally present and contribute to inflammation
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196
Q

What are the functions of complement?

A

① opsonization
② chemotaxis
③lysis of cells

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197
Q

Describe alpha1-antitrypsin (AAT)

A
  • 52-KD protein that is primarily synthesized in liver
  • major component of alpha-band when serum electrophoreses
    -acts against trypsin
    -atleast 75 alleles of gene coding for AAT
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198
Q

What are the functions of alpha1-antitrypsin?

A

-general plasma prohibitor of proteases released from leukocytes
-acts to counteract effects of neutrophils (elastase) during inflammation
-regulates expression of proinflammatory cytokines
-inhibits monocytes and neutrophils

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199
Q

What is elastase?

A

An enzyme secreted by neutrophils during inflammation that can degrade elastin and collagen

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200
Q

What are the proinflammatory cytokines?(specific types)

A
  • TNF-alpha
    -interleukin-1beta
    -interleukin-6
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201
Q

Describe haptoglobin

A

-an alpha1-globulin with a molecular weight of 100,000
-binds irreversibly to free hemoglobulin
-acts as antioxidant to protect against oxidative damage from free hemoglobin

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202
Q

Describe fibrinogen

A

-acute phase protein involved in coagulation pathway
- small portion cleaved by thrombin to form fibrils that create a fibrils clot
-340,000 daltons

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203
Q

What do fibrin clots do?

A
  • Increases strength with wound and stimulate endothelial cell adhesion and proliferation
  • creates barrier of microorganisms further into the body
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204
Q

What is the effect of fibrinogen on blood?

A
  • Makes blood move viscous and serves to promote aggregation of RBCs and platelets
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205
Q

What can increased fibrinogen lead to?

A

An increased risk for developing coronary artery disease

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206
Q

Describe ceruloplasmin

A
  • Consists of a single polypeptide chain with a molecular weight of 132,000 daltons
    -copper transporting protein in human plasma
    -acts as enzyme, converting the toxic ferrous ion (Fe^2+) to non toxic ferric form (Fe^3+)
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207
Q

Depletion of ceruloplasm is found in what disease?

A

Wilsons disease

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208
Q

What is Wilsons disease?

A

-autosomal recessive genetic disorder characterized by massive increase of copper in the tissues and accumulate in liver.

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209
Q

What is the normal range for serum amyloid A?

A

5-8 mg/dl

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210
Q

What is the normal range for haptoglobin?

A

40 -290 mg/dl

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211
Q

What is the normal range for fibrinogen?

A

200-400 mg/dl

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212
Q

What is the normal range for ceruloplasm?

A

20-40 mg/dl

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213
Q

What is inflammation?

A

Body’s overall reaction to injury or invasion by an infectious agent

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214
Q

What are the cardinal signs of inflammation?

A

-erythema (redness)
-edema (swelling)
-heat
-pain

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215
Q

What are steps of the inflammation process?

A

①macrophages and mast cells at site of infection release chemokines that cause vasodilation and induce selections (red/heat)
②selectins loosely bind circulating leukocytes and cause them to roll along vascular wall (swell)
③chemokine induced integrins on leukocytes and bind firmly to the endothelial cells (neutrophils)
④ integrins enable the leukocytes to crawl between endothelial cells (diapedesis)(peaks at 16-48 hours)
⑤ leukocytes then follow the chemokine concentration gradient to the site of infection (chemotaxis)

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216
Q

During inflammation, how long does it take for neutrophils to mobilize?

A

30-60 minutes

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217
Q

What is the acute inflammatory response?

A

Acts to combat the early stages of infection and also begins a process that repairs tissues damage

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218
Q

What is it called when inflammation occurs for an extended period of time?

A

Chronic inflammation

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219
Q

What is the main purpose of the inflammatory response?

A

Attract cells to the site of infectionand remove foreign cells or pathogens by means of phagocytosis

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220
Q

What do acute phase reactants enhance?

A

Phagocytosis

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221
Q

What cells are most active in phagocytosis ?

A
  • Dendritic cells
    -macrophages
    -monocytes
    -neutrophils
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222
Q

What are the steps of phagocytosis?

A

① physical contact between the WBC and foreign cell
②outflowing of the cytoplasm to surround the microorganism
③formation of a phagosome
④fusion of lysosomal granules with the phagosome
⑤formation of a phagolysosome with release of lysosomal contents
⑥digestion of microorganisms by hydrolytic enzymes
⑦release of debris to the outside of the cell by exocytosis

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223
Q

What are selectins?

A

Adhesion molecules on endothelial cells lining blood vessels

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224
Q

What are integrins?

A

Adhesion molecules on endothelial cell wall

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225
Q

What is chemotaxis?

A
  • Cells are attracted to site of inflammation by chemical substances such as soluble bacteria factors and acute phase reactants
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226
Q

What cells already exist in tissue before phagocytosis?

A
  • Dendritic cells
    -macrophages
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227
Q

What enhances the binding process during phagocytosis?

A

Opsonins

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228
Q

What are opsonins?

A

Serum proteins that attach to a foreign cell or pathogen and make it more susceptible to phagocytosis

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229
Q

What do opsonins do to enhance binding?

A

Act by neutralizing the surface charge on the foreign particle.

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230
Q

What are phagosomes?

A

Pseudopodia fuse to completely enclose pathogen

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231
Q

What are phagolysosome?

A

Lysosomal granule fused to phagosome

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232
Q

What are the two processes that occur to eliminate pathogens?

A
  • Oxygen-dependent pathway
    -oxygen-independent pathway
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233
Q

Describe oxygen dependent pathway

A

-increase in oxygen consumption (oxidative burst) occurs in cell as the pseudeopodia enclose particles within vacuole
- generates considerable energy through oxidative metabolism

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234
Q

What is an important bacterial agent in oxygen dependent process?

A

Hydrogen peroxide

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235
Q

In oxygen dependent pathway, NAPD oxidase depolarizes the membrane when fused with phagosome. Why does this occur?

A

Allow hydrogen and potassium to enter vacuole, and thus alters the pH

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236
Q

Describe the oxygen-independent pathway

A
  • Defensins kill gram-negative bacteria, many fungi, and some viruses
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237
Q

What are defensins?

A

Small cationic proteins that cleave segments without benefit of oxygen

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238
Q

What is the importance of NAPDH oxidase in the oxygen independent pathway?

A

Eliminate microbes

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239
Q

What happens after phagocytosis?

A
  • Macrophages and dendritic cells mature and are able to process peptides from pathogens for presentation of T cells
  • T cells then interact with B cells to produce antibodies
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240
Q

What cell is the first line of defense against virally infected cells, tumor cells,and cells infected with intracellular pathogens?

A

Natural killer cells (NK)

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241
Q

Describe NK cells

A
  • Have ability to recognize damaged cells and target cells and eliminate them without prior exposure
    -No specificity because they are early defenders
    -peaks at 3 days
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242
Q

What is NK cell activity enhanced by?

A

Exposure to cytokines → interleukin-12, interferon-alpha and interferon-beta

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243
Q

What occurs after NK cells are activated?

A

-they become major producer of cytokines such as interferon-gamma and TNF- alpha that help recruit T cells
-they also release various colony-stimulating factors that act on developing granulocytes and macrophages

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244
Q

What is cytotoxicity?

A

The degree to which a substance can cause damage to a cell

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245
Q

What are the two main binding receptors for NK cells ?

A

① inhibitory receptors
②activating receptors

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246
Q

What do inhibitory receptors do?

A

Deliver inhibitor signals

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247
Q

What do activating receptors do?

A

Delivers signals to activate cytotoxic mechanism

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248
Q

Inhibitory signals are based on recognition of what?

A

Class I MHC proteins which are expressed on all healthy cells

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249
Q

What happens when NK cells and MHC I class react with one another?

A

Natural killing process is inhibited

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250
Q

What are perforins?

A

Proteins that form channels in target cell membrane

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251
Q

What are granzymes?

A

Packets of enzymes that may enter through channels and mediate cell lysis

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252
Q

Describe antibody-dependent cellular cytotoxicity

A

-NK cells recognize and lysis antibody-coated target cells
-binding occurs through surface receptors, CD16 and CD32, which bind to Fc portion of immunoglobulins
-destruction occurs outside of NK cells

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253
Q

What is an important contributor to the anti-tumor activity?

A

Antibody-dependent cellular cytotoxicity

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254
Q

In antibody-dependent cellular cytotoxicity, what does lysis of target cells require?

A

Contact with NK cells, followed by release of cytotoxic fixation

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255
Q

Describe innate lymphoid cells

A
  • Growing family of immune cells that develop from the common lymphoid progenitor but does not express markers of lymphocytes lineage
    -primarily found in mucosal sites
256
Q

Where does the creation of hypochlorite and hydroxyl ions occur?

A

Oxygen dependent pathway of phagocytosis

257
Q

What is the function of hypochlorite and hydroxyl ions in phagocytosis?

A

Damage protein irreversibly

258
Q

How are phagolysomes formed?

A

By fusion of engulfed material and enzymatic granules within the phagocytic cell

259
Q

Presence of human microbiota acts as a defense mechanism by what method?

A

Competing with potential pathogens

260
Q

What can measurements of CRP levels be used for?

A

-tracking progress of organ transplant
- monitoring drug therapy with anti-inflammatory agents
-determining active phases of RA

261
Q

What is the response time for C-reactive protein?

A

4-6 hours

262
Q

What is the normal concentration of c-reactive protein?

A

0.5 mg/dl

263
Q

How much can c-reactive proteins increase?

A

1000 x

264
Q

What are the functions of C-reactive protein?

A

① ospinization
② complement activation

265
Q

What is the response time for serum amyloid A?

A

24 hours

266
Q

How much can serum amyloid A increase by?

A

1000X

267
Q

What is the function of serum amyloid A?

A

Activates monocytes and macrophages

268
Q

What is the response time for alpha1- antitrypsin?

A

24 hours

269
Q

What is the normal concentration for alpha1- antitrypsin?

A

200-400 mg/dl

270
Q

What is the function MAIN of alpha1- antitrypsin?

A

Proteases inhibitor

271
Q

What is the response time for fibrinogen?

A

24 hours

272
Q

How much can fibrinogen increase by?

A

2-5x

273
Q

What is the function of fibrinogen?

A

Clot formation

274
Q

What is the response time for haptoglobin?

A

24 hours

275
Q

How much can haptoglobin increase by?

A

2- 10x

276
Q

What is the function of haptoglobin?

A

Binds hemoglobin

277
Q

What is the response time for ceruloplasmin?

A

48-72 hours

278
Q

How much can ceruloplasmin be increased by?

A

2x

279
Q

What is the function of ceruloplasmin?

A

Binds cooper and oxidizes iron

280
Q

What is complement C3 response time?

A

48- 72 hours

281
Q

What is the normal concentration for complement C3?

A

60-140 mg/dl

282
Q

How much can complement C3 increase by?

A

2x

283
Q

What are the functions of complement C3?

A

①opsonization
② lysis

284
Q

What causes increased vasodilation and vasopermability?

A

Inflammation

285
Q

Are all immunogen antigens?

A

Yes

286
Q

Are all antigens immunogens?

A

No

287
Q

What is a distinct difference between immunogen and antigen?

A

Immunogens successfully stimulate an immune response

288
Q

What are factors that influence an antigens immunogenicity?

A
  • Can arise from host
    -outbred/unique traits
    -age, health, genetics
    -dosage and route of exposure
    -not all antigens are equivalentin their ability to stimulate an immune response
289
Q

What is immunogenicity?

A

The ability of an antigen to stimulate a immune response

290
Q

What factors affect the strength of immunogenicity?

A

① macromolecule size
② foreignness
③the ability to be processed and presented with MHC molecules
④chemical composition
⑤ molecular complexity

291
Q

How large does an immunogen have to be recognized by the immune system?

A

10,000 daltons, (the larger, the more potent)

292
Q

What occurs to prevent the immune system from attacking the body’s own cells and tissues?

A
  • Lymphocytes are selected during development to ensure that the pool of mature lymphocytes responds only to antigens not recognized as self
293
Q

The more taxonomically distant an antigen is from the host, the greater the likelihood that host lymphocytes will do what?

A

React to it

294
Q

What are the most effective immunogens?

A
  • Proteins (strongest)
    -polysaccharides
295
Q

Explain the structure of proteins

A
  • Composed of subunits known as amino acids that are covalently linked together in polypeptide chains of various lengths
296
Q

Describe the structure of a proteins primary structure?

A

structure made up of subunits of amino acids and covalently linked together in polypeptide chains in varying links

297
Q

Describe the structure of proteins secondary structure?

A

Interactions between amino acids within primary structure causes chain to band/kink/ loop creating 3D shapes

298
Q

What are the two common secondary structures found in proteins?

A

①alpha-helices
②beta- pleated sheets

299
Q

Describe the alpha- helices in secondary structure of protein

A

Peptide chains that twist to form a spiral

300
Q

Describe the beta pleated sheet secondary structure proteins

A

Chains of undulating zig zags that have a planar shape

301
Q

Describe the tertiary structure of proteins

A

Secondary fold upon themselves once again, bringing distant regions of amino acid chains together and embodying the 3D orientation of the entire molecule

302
Q

Describe the quaternary level of proteins

A

Two or more polypeptide chains come together,forming a multimeric unit.

303
Q

How do activating receptors of T cells react with certain proteins?

A

-detect small fragments of protein (peptides) and rely on MHC molecules to cradle these peptides for antigen recognition to occur
- “sees” the primary structures

304
Q

How do activating receptors of B cells react with certain proteins?

A

-by binding to amino acids on a proteins exterior
- “sees” tertiary and quaternary structures of a protein

305
Q

An effective B cell response to most antigens requires “help” from what?

A

-T cells
-they must be activated so they can provide necessary physical and chemical signals to B cells

306
Q

Why are polysaccharides less immunogenic than proteins?

A

-their small size
-T cells do not recognize carbohydrates

307
Q

As immunogens, carbohydrates most often occur in what form?

A
  • Glycolipids
    -glycoproteins
308
Q

What are not immunogenic by themselves?

A
  • Pure nucleic acids
  • lipids
309
Q

What is required for a substance to elicit an immune response?

A

-must be subject to antigen processing

310
Q

What is antigen processing?

A

-involves enzymatic digestion to create small peptides that can be completed by MHC molecules for presentation to responsiveness of an specific antigen

311
Q

What is a haptan?

A

A substance that isn’t immunogenic by itself but is able to form a new antigenic determinant when combined with larger carrier molecule

312
Q

Are haptens considered a antigen or an immunogen?

A

Antigen

313
Q

What do haptens do once bound to a carrier?

A

Initiates production of antibodies that can react with the hapten even in the absence of the carrier

314
Q

Who discovered ABO blood groups?

A

Karl Landsteiner

315
Q

What is an epitope?

A

-part of antigen that hosts immune system recognizes, eliciting the immune response to an invading pathogen
- specifically binds to the corresponding antigen receptor on the immune cell

316
Q

What are the two types of epitopes that B cells recognize?

A

① linear epitopes
② conformational epitopes

317
Q

Describe linear epitopes

A

Consist of sequential amino acids on a single polypeptide chain

318
Q

Describe conformational epitopes

A

Results from the folding of one or more polypeptide chains, bringing together amino acids that may distant fromeach other so that they are recognized together

319
Q

What does triggering of a B cell response require?

A

-Epitopes found on the surface of a molecule
-accessible to the cell receptors, and that these sites contain more than one copy of epitopes so that cross- linking of B-cell receptors may occur

320
Q

What is an autoantigen

A

-antigens that belong to host
- does not evoke an immune response under normal circumstances

321
Q

What happens if an immune response does occur to autoantigens?

A

May result in autoimmune disease

322
Q

What is an alloantigen?

A

From other members of the hosts species and are capable of eliciting an immune response

323
Q

When are alloantigens important to consider?

A

-tissue transplant
-blood transfusion

324
Q

What is a heteroantigen?

A

From other species, such as other animals, plants or microorganisms

325
Q

What is a heterophil antigen?

A
  • Heteroantigens that exist in unrelated plants or animals but are either identical or closely related in structures so that an antibody against either antigen will cross-react with each other
326
Q

What is an important consideration in selecting the correct blood type for blood transfusions?

A
  • The presence of naturally occurring antibodies
327
Q

Describe the first laboratory assay for infectious mononucleosis (IM)

A

-based on a heterophil antibody reaction
- found to react with sheep RBC
- causative agent in Epstein Barr virus

328
Q

Describe the current rapid screening tests for IM

A

-detect heterophil antibodies presentin the serum of infected patients that cross react with horse or bovine RBC antigens

329
Q

How did MHC molecules get their name?

A

-they determine whether transplanted tissues is histocompatible and accepted by the recipientor if it is recognized as foreign and rejected

330
Q

Where are MHC molecules Found?

A
  • on all nucleated cells
331
Q

What do MHC molecules play a pivotal role in?

A

-the developmentof both humoral and cell-mediated immunity

332
Q

What is the main immune function of MHC molecules?

A

-Bring antigens to the cell surface for recognition by the T cells.
-only when the antigen is combined with the MHC molecules does the T cell activation occur

333
Q

What is B cell recognition?

A

Surface receptors bind to antigen directly

334
Q

What is T cell recognition?

A

Requires antigens to be cradled within MHC molecules

335
Q

What are MHC molecules encoded by?

A

The most polymorphic gene system found in humans

336
Q

Where does gene coding for MHC molecules in humans occur?

A

On short arm of chromosome 6 and are divided into 3 classes

337
Q

Where are class I MHC molecules genes found?

A

-3 loci’s
- A, B, and C

338
Q

Where are class II MHC molecule genes found?

A

-D region
-broken down into DR, DQ, and DP

339
Q

How is gene coding of class I and class II MHC molecules different?

A

-class I → only one gene coding for each particular molecule
-class II → have one gene that codes for the alpha-chain of the molecule and one or more genes that codes for beta-chain

340
Q

Where are class III MHC molecules found?

A

Lies between the class I and class II regions on chromosome 6

341
Q

What complement proteins does class III genes code for?

A
  • C4a
    -C4b
    -C2
    -B
    -TNF
342
Q

Describe class III MHC molecules

A

-are secreted protein that have an immune function, but they are not expressed on cell surfaces

343
Q

Why is the MHC system described as highly polymorphic?

A

There are so many possible alleles at each location.

344
Q

What is codominant

A

All alleles that an individual inherits code for products that are expressed on cells

345
Q

What is a haplotype?

A
  • Group of alleles in an organism that are inherited together from a single parent
    -one haplotype is inherited from each parent
346
Q

Why does the uniqueness of the HLA antigens cause a major problem when matching organ donors to recipients?

A

The antigens are highly immunogenic

347
Q

What is a helpful identification tool in paternity cases?

A

Polymorphisms

348
Q

Where are class I MHC molecules found?

A

-on all nucleated cells
-levels of expression can vary among various cell types

349
Q

Where are class II MHC molecules found?

A

Primarily on antigen- presenting cells (APC)

350
Q

Class I expression is highest on what cells?

A
  • Lymphocytes
  • myeloid cells
351
Q

Class I expression is lowest/nonexistent on what cells?

A

-liver hepatocytes
-neural cells
-muscle cells
- sperm

352
Q

What are the most important class I MHC antigens to match for transplantation?

A

-HLA-A antigens
-HLA-B antigens

353
Q

Describe class I antigens structure

A

Glycoprotein dimer made up of two noncovalently linked polypeptide chains

354
Q

What is the weight of the class I alpha chain?

A

44,000 daltons

355
Q

What is the weight of the class I beta2-microglobulin chain?

A

12,000 daltons

356
Q

Explain the folding of the class I alpha chain

A

-fold into 3 domains: alpha 1, alpha 2, and alpha 3
- its inserted into the cell membrane via a hydrophobic transmembrane segement

357
Q

What do the 3 external domains of class I alpha chain consist of?

A

90 amino acids each

358
Q

Describe the transmembrane domain of the class I alpha chain?

A
  • Has 25 hydrophobic amino acids along with short stretch of about 5 hydrophilic amino acids, as well as an anchor of 30 amino acids
359
Q

Give a brief description of beta2-microglobulin

A
  • Does not penetrate cell membrane
  • essential for proper folding of the alpha chain
360
Q

What structure can be found in alpha1 and alpha2 domains of class I MHC molecules?

A

Alpha-helix

361
Q

What happens to the alpha helixes in the tertiary structure of molecules?

A
  • Brought to together to form the walls of a deep grove
    -this functions as peptide binding site (able t hold peptides between 8-11 amino acids long)
362
Q

Where does the most polymorphism reside in a class I MHC molecules?

A

Alpha1 and alpha2 regions

363
Q

Describe HLA-E and HLA-F

A

-non classical I class MHC that are generally not expressed on the surfaces of calls and don’t present peptide to cytotoxic T cells
- they do play an important role in immunity

364
Q

Describe HLA-G

A

Primarily expressed on fetal trophoblasts during first trimester of pregnancy

365
Q

What APCs have class II molecules?

A

-B cells
- dendritic cells
- macrophages
-monocytes

366
Q

What are the major class II molecules?

A

HLA-DP
HLA-DQ
HLA-DR

367
Q

Describe class II molecules structure

A

-consists of two noncovalently bound polypeptide chains that are encoded by separate genes in the MHC gene complex
- this protein structure is called a heterodimer
- comprises of two dissimilar polypeptide chains

368
Q

What HLA-D region is expressed at the highest level and why?

A

-HLA-DR
- it accounts for about one-half of all the class II molecules found on a particular cell

369
Q

What gene in class II MHC molecules is the most polymorphic?

A

-HLA-DR beta
- over 3,300 different alleles are known at this time

370
Q

What gene in class II MHC molecules is found in short supply?

A

HLA-DP

371
Q

How many domains are in the alpha chain and beta chain of class II MHC molecules?

A

-two domains each
-numbered 1and 2

372
Q

Describe the heterodimic quaternary structure of class II MHC molecules

A
  • The alpha1 and beta1 domains each contribute an alpha helix, forming the peptide binding sites
    -both ends of peptide binding sites are sites are open, allowing capture of longer peptides
373
Q

What are the non classical class II MHC genes?

A

HLA-DM
HLA-DN
HLA-DO

374
Q

Describe the nonclassical class II MHC genes HLA-D

A
  • Play regulatory role in antigen processing
    -DM help to load peptides onto class II molecules
    -DO modulates antigen binding
    DN is unknown
375
Q

Describe antigen presentation

A

Process by which peptide fragments derived from degraded proteins are transported to the plasma membrane, allowing recognition by T lymphocytes

376
Q

What does the class I MHC molecules mainly present?

A

Cytoplasmic peptide antigens to CD8 T cells (cytotoxic)

377
Q

What does the class II MHC molecule mainly present?

A

-extracellular antigens to CD4 T cells ( helper)

378
Q

What is the function of class I MHC molecule?

A

Watchdogs of viral, tumor and intracellular bodies

379
Q

What is the function of class II MHC molecule?

A

-help to mount an immune response to bacterial infections or other pathogens usually found outside of cells

380
Q

In either class of MHC molecules, what needs to occur for a T cell response to be triggered?

A

-peptides must be available in adequate supply for MHC molecule to bind
- must be able to bind effectively
-they must be recognized by a T-cell receptor

381
Q

Describe modern transplant HLA testing

A

-involves the use of molecular techniques to determine the MHC types of both donor and recipient
-also, serological testingto detect the presence of antibodies in the recipient targeting the MHC molecules of potential donor

382
Q

What could happen when an individual inherits certain HLA types?

A

May predispose individuals to the development of autoimmunity

383
Q

If an individual suffers from allergies, how does knowing a persons MHC type help?

A

May help predict type of allergens

384
Q

What is ankylosing spondylitis?

A

Inflammation of the vertebrae spine

385
Q

What is the HLA allele for ankylosing spondylitis? And the strength?

A
  • B27
    +++
386
Q

What are symptoms of celiac disease?

A
  • Intolerance to gluten
  • diarrhea
  • weight loss
387
Q

What is the HLA allele for celiac disease? And the strength?

A

-DQ2
-DQ8
++++

388
Q

What is rheumatoid arthritis?

A

Inflammation of multiple joints

389
Q

What is the HLA allele for rheumatoid arthritis ? And the strength?

A

DR4
+

390
Q

Describe type I diabetes

A

Increase in blood glucose because of destruction of insulin- producing cells

391
Q

What is the HLA allele for type I diabetes?

A

-DQ8
-DQ2
++++

392
Q

Why is the class I MHC presentation pathway also referred to as endogenous pathway of antigen presentation?

A

Both the peptides and MHC molecules arise from within the same cell

393
Q

Describe the endogenous peptide antigens presented by class I MHC molecules

A

-class I MHC represents a sampling of the many polypeptide chains that compose the proteins found within the cells
-these peptides derive from host proteins

394
Q

Describe the class I MHC presentation pathway

A

Provides cytotoxic T cells as a means of survelliancing the interiors of cells through out the body, allowing T cells to search for peptides associated with infection or malignancy

395
Q

What are the steps of class I MHC presentation pathway?

A

① endogenous antigen within cytosol is degraded by proteasome
②peptides are transported into endoplasmic reticulum by TAP
③alpha chain of class I MHC binds B2-microglobulin
④alpha chain of class I MHC binds peptides
⑤peptide- class I MHC transported to Golgi complex and then to cell surface
⑥class I MHC peptides binds to CD8+ T cells

396
Q

What is the most important chaperon protein in the class I MHC presentation pathway?

A

Calnexin → stabilizes the alpha chain until it binds to B2- microglobulin

397
Q

Describe the 2 less significant chaperone proteins in the class I MHC presentation pathway

A
  • Calreticulin
  • tapasin
398
Q

What happens once synthesis of class I MHC molecules is complete?

A

-their antigen-binding sites are oriented toward the interior of the endoplasmic reticulum

399
Q

What are two transporters associated with antigen processing ? How are they essential?

A

-TAP1 and TAP2
-essential for shuttle antigen peptides into the lumen of the endoplasmic reticulum, allowing peptides to interact with newly formed class I MHC molecules

400
Q

Describe TAP-driven translocation

A
  • Dependent on ATP
  • most efficient for peptides of 8 to 16 amino acids in length
  • tapasin ,proton that bridges transporter and MHC, so that peptides can be directly loaded
  • once alpha chain has bound the peptide,the class I MHC peptide complex is rapidly transported to the cell surface
401
Q

What does class I MHC presentation pathway generate?

A
  • Thousands of peptidesfrom proteins that have undergone proteasonal digestion, but only small fraction of these will actually become antigens
402
Q

What variables dictate the binding of peptides to class I MHC molecules?

A

①length of peptide chain. Binding groove is closed and can only accommodate peptides no longer than 11 amino acids
②determine by complementary noncovalent interactions between peptide and the amino acids compromising of alpha helices that form
Binding groove
③different class I molecules have slightly different binding affinities, and these small differences determine the particular antigens to which an individualwill respond

403
Q

How many copies estimated to be expressed in a single cell of class I MHC molecules surface?

A

100,000 - 200,000 copies

404
Q

Describe the peptides of a healthy class I MHC molecules ?

A

All class I molecules contain self- peptides that are ignored by patrolling T cells

405
Q

Describe the peptides of a diseased class I MHC molecules?

A

Some of the peptides displayed originate from microbial proteins or proteins associated with cancer

406
Q

What is an immunogen?

A

A substance that reacts with an antibody or sensitized cell but always triggers an immune response

407
Q

Where is the “foreignness” of an immunogen acquired from?

A

From lymphocytes in the primary lymphoid organs

408
Q

What must occur for the MHC molecules of immunogens to be recognized?

A

Must be subject to enzymatic digestion

409
Q

What is an adjuvant?

A

-Substances delivered simultaneously with an antigen to enhance the immune response; used in vaccines
-also prevents antigen from diffusing more immune cells to the injection site of inoculation

410
Q

What does an adjuvant stimulate?

A

Innate immune receptors

411
Q

What does longer response times with adjuvants do?

A

Attracts more immune cells to the injection site and increase protective immunity

412
Q

What is an allele?

A

Alternate forms of a gene that code for a slightly different variety of the same product

413
Q

What allows CD8+ T cells to continuously check the bodies cells for the presence of nonself antigen?

A

The display of thousands of class I molecules complexed to antigen

414
Q

Describe class II MHC molecules

A

presentation of exogenous antigens to T cells, that is, peptide antigens that are derived from proteins found outside of the presenting cell

415
Q

What needs to occur for presentation of exogenous antigens?

A
  • Extracellular proteins accumulate within the lumen of the vesicle, resulting in peptide chains of 13 to 18 amino acids in size
416
Q

Where are class II MHC moleculessynthesized?

A

Rough endoplasmic reticulum

417
Q

What protein is associated with class II MHC molecules?

A

-the invariant chain → a 31-kDa protein present in great excess of the actual number of class II molecules being synthesized

418
Q

What is required during production of class II MHC molecules? Why?

A

-the invariant chain (li)
-to prevent endogenous peptides from binding to class II peptide binding groove

419
Q

Describe the invariant chain

A
  • Serves as placeholder,ensuring that only exogenous peptide antigens will be bound to MHC II molecules
    -aid in bringing alpha and beta chains together
420
Q

What are the steps of class II MHC molecules presentation nothway?

A

① class II MHC binds invariant chain to block binding of endogenous antigen
② MHC complex goes through Golgi complex
③invariant chain is degraded, leaving CLIP fragment
④exogenous antigentaken in and degraded and routed to intracellular vesicle
⑤ CLIP fragment exchanged for antigenic peptide
⑥ class II MHC antigenic peptide is transported to cell surface
⑦ class II MHC peptide complex binds to CD4+ T cell

421
Q

How is the binding groove different between class I and class II?

A

-class I binding groove is closed on both ends
-class II binding groove is open and can accommodated up to 30 amino acids

422
Q

What is the difference between class I and class II peptide binding locations?

A
  • Class I → occurs mostly at the amino and carbonyl terminal ends
    -class II →hydrogen bonding occurs along the length of the captured peptide
423
Q

Describe class II binding groove structure

A
  • Open ends
    -have pockets that can accommodate amino acids with large side chains, giving class II molecule greater flexibility in the variety of peptides that can bound
424
Q

Describe helper T cells

A

-recognize antigen along with class II MHC protein
- Orchestrate the adaptive immune response, influencing activities of other immune cells
-express CD4 receptors

425
Q

Once an antibody response is generated, haptens are capable of reacting with that antibody. Will precipitation or agglutination reactions occurr? why or why not?

A

Precipitation and agglutination will not occur because the complexes formed are too small.

426
Q

What is a key portion of the antigens?

A

Epitope

427
Q

How do adjuvants work?

A

Acts by activating innate immune cells

428
Q

What is the most polymorphic gene system in humans?

A

HLA system

429
Q

What is the function of cytotoxic T cells?

A

To kill cells infected with intracellular pathogens, such as viruses, bacteria, and cancerous cells

430
Q

What is the function of T helper cells?

A
  • Control the immune response through the secretion of cytokines or signaling molecules that allow communication between immune cells
431
Q

What cell is responsible for producing antibodies?

A

B cells

432
Q

What are the roles of antibodies in immunity?

A

① labeling targets for ingestion by phagocytes
② rendering viruses and toxins inert through neutralization
③ blocking adhesion of microbes to body tissues

433
Q

What is the major difference between lymphocytes of adaptive and innate immunity?

A
  • Gene coding for the primary receptors that activate lymphocytes under goes rearrangement during early stages of T cells or B cells development
434
Q

Describe clonal expansion when infection occurs

A

Only lymphocytes responsive to epitopes found on/in the invading pathogens are activated and proliferate

435
Q

Why is it called clonal expansion?

A

Proliferating lymphocytes give rise to populations of cells with genetically receptors that are specific for the same epitopeand these populations therefore represents clones of each other

436
Q

Why is the delay between an initial infection and an effective adaptive response?

A

Because a handful of pathogen- responsive lymphocytes must undergo a massive clonal expansion before reaching the large number of effector cells needed to alter the course of an infection

437
Q

What is mostly generated during clonal expansion between the innate and adaptive response?

A
  • Effector cells
  • a portion of the clones become memory cells
438
Q

What are effector cells?

A
  • Either T cells that secrete cytokines or cytotoxic
    -OR B cells that produce antibodies
439
Q

Describe memory cells

A

-enter quiescent state and become long-lived
-lie in wait for reinfection with same microbe
- when they encounter their specific epitope, they activate rapidly, resulting in faster response of greater magnitude than the primary response

440
Q

Describe lymphocytes differentiation

A
  • Production of lymphocytes by the body
  • begins in early fetal development because basic adaptive immunity must be in place by birth
    -progenitors of t and B cells appear in fetal liver as early as 8 weeks of pregnancy
441
Q

Later in fetal development, what becomes the source of new lymphocytes?

A
  • Bone marrow
    -remains primary producer of hematopoietic cells at birth and through adult life
442
Q

Describe when progenitor cell divides into two

A

One resulting daughter cell begins to take on the characteristics of lymphocytes where as the other dangther cell retains the stem cell

443
Q

What happens once a T cell precursors formation is complete in the bone marrow?

A

Transported to the thymus by circulating blood

444
Q

Describe the thymus’s location

A
  • Located in the upper thorax, roughly between sternum and heart.
445
Q

What are the two histologically distinct regions of the thymus?

A
  • Outer cortex
  • inner medulla
446
Q

What are the T cell precusors called once they are in the thymus?

A

Thymocytes

447
Q

Where do thymocytes enter the thymus?

A

Cortico-medullary junction

448
Q

What do thymocytes do once they enter the thymus?

A

-immediately begin to migrate toward the thymus cortex under the direction of chemokines

449
Q

How long does is take thymocytes to migrate from the cortex? Where do they migrate?

A
  • Over a 3 week period
    -to the medulla of the thymus
450
Q

What processes occur over the 3 week period when thymocytes migrate from the context to the medulla?

A

①rearrangement of the T cell receptors (TCR) genes
②changes in the expression of thymocyte cell surface markers
③the selection of thymocytes with functional receptors
④The deletion of thymocytes with self-reactive potential

451
Q

What is critical for the differentiation processes for Thymocytes?

A

-interaction with stromal cells within the thymus
-includes macrophages, dendritic cells, fibroblasts, and thyme epithelial cells

452
Q

What are the stages of T cell development?

A

-double negative stage
-double positive stage
- mature T cells

453
Q

Describe T-cell receptor structure (TCR)

A
  • Composed of two transmembrane proteins: alpha and beta
  • each chain possess 3 domains and I variable region
454
Q

What are the 3 domains on each chain of TCR BY?

A

-intracellular signaling domain
- membrane spanning domain
- extracellular domain

455
Q

What is the role of variable regions of TCR?

A

Responsible for recognition of antigens and are therefore the only portions of TCR genes that undergo rearrangement.

456
Q

The gene encoding the variable region of the TCR beta chain are divided into 3 large sections. What are they called? What chromosome dues this occur on?

A

-V
-D
-J
- chromosome 7

457
Q

What are early thymocytes called? Why?

A
  • Double negative thymocytes
    -thymocytes lack both CD4 and CD8
458
Q

What do double negative thymocytes do?

A

Aggregate in the outer cortex of thymus, where the actively proliferate of the cytokines, such as IL-7

459
Q

When does rearrangement of gene coding for the TCR begin?

A

During double negative (DN) stage of t cell development

460
Q

Explain the gene coding for the DN stage of T cell development

A
  • Shuffling and altering or TCR genes result in the expression of a unique antigen receptor by each individual thymocyte
461
Q

What happens during rearrangement of the double negative stage?

A

Enzymes activated in DN thymocytes clip genome DNA and begin stitching it back together in a way that randomly aligns one V segment, one D segment, one J segment, and a segment encoding the constant region

462
Q

In case where rearrangement leads to a faulty TCR beta chain, developing T cells employ two strategies aimed at generating functional proteins. What are these strategies?

A

① because T cells are diploids, the beta chain genes on both copies of chromosome 7 simultaneously under go rearrangement, doubling the probability of a functional beta chain being produced
② the enzymes that mediate TCR gene rearrangement continue clipping and stitching variable - region DNA until a functional TCR is generated

463
Q

What happens when the DN thymocytes express a functional beta chain?

A

The pre-TCR provides survival signals to the T cells differentiation, known as double positive stage

464
Q

What dues it mean when gamma and delta chains appear on TCR beta?

A

There was not a productive rearrangement of DNA coding for a beta chain

465
Q

Describe gamma-delta T cells

A

Unique population of T lymphocytes proceeds down an alternative developmental pathway typically remaining negative for both CD4 and CD8

466
Q

What does successful pre-TCR signaling allow?

A

Allows developing thymocytes to cross a developmental threshold, initiating rearrangement of TCR alpha chain

467
Q

What is the alpha chain gene variable regions divided into?

A

-one V segment
-one J segment

468
Q

What happens when there is an appearance of a functional alpha chain on cell surface?

A
  • Sends signal to suppress any further TCR gene rearrangements
  • concurrently, thymocytes become both CD4+ and CD8+
469
Q

Describe the CD3/TCR complex

A

-TCR alpha and beta chains occur in this complex with 6 other molecules common to all T -cells
-6 chain of nonspecific CD3 portion of the complex assist in intracellular signaling when an antigen binds to the TCR

470
Q

The CD3 complex chains occur in 3 pairs. What are the 3 pairs?

A

-delta-epsilon
-gamma - epsilon
-tau-tau

471
Q

What type of antigen is not recognized alone by T cell receptors?

A

Peptide antigens

472
Q

How are peptide antigens recognized by the T cell receptors is they cannot be recognized alone?

A

-peptide antigen must be held in an MHC molecule or “presented” to T cells, a requirement known as MHC restriction
-this property is established during DP stage of thymocyte development

473
Q

Describe thymocytes encounter with stromal cells

A
  • Occurs during DP stage
    -encounter occurs in the thyme cortex that express MHC class I and II proteins
    -these initial interactions determine the thymocytes fate: high affinity MHC molecule will fail to bind and die by apoptosis
474
Q

What CD markers are expressed in the DP stage of thymocytes?

A
  • Both are expressed
    -depending on which class of MHC molecule a positively selected thymocyte recognizes, the expression of the opposite marker begins to decrease sustainability
475
Q

What CD marker is expressed on MHC I?

A

CD8

476
Q

What CD marker is expressed on MHC II?

A

CD4

477
Q

Where does negative selection occur?

A

In the corticomedullary and medulla region of the thymus

478
Q

Describe the stromal cell activity in negative selection

A
  • Express a variety of self-antigens to positively selected thymocytes
    -A strong reaction between TCR and any of the self- peptides presented by stromal cells indicates a high potential for autoreactivity
479
Q

What prevents self reactive T cells from leaving thymus?

A

Thymocytes with strongly binding TCR are negatively selected and undergo apoptosis

480
Q

When is a T cell considered mature?

A

When it exits the thymus

481
Q

What is a “naive” mature T cell?

A
  • Mature T cell that have not yet encountered the specific peptide epitope recognized by their TCR
    -to enhance probability of a mature naïve T cell encountering its specific antigen, these cells recirculate between the blood stream and lymphatics
482
Q

What influence which cytokines are produced by the Th cells?

A

The signals found within the environment where Th cell activation occurs which cytokines are released

483
Q

What are B cells derived from?

A

Hematopoietic stem cell

484
Q

What is antigen- independent phase?

A

-first phase of B cell development in bone marrow that result in mature B- cells that have not been exposed to antigens

485
Q

What are the subpopulations of antigen independent phase?

A
  • Pro-B cells
    -pre-B cells
    -immature B cells
  • mature B cells
486
Q

What is antigen dependent phase?

A
  • if B cells ave stimulated by antigen, it undergoes transformation to a blast stage that forms memory cells and plasma cells
487
Q

Describe pro B cells

A
  • Stage in B -cell development in which rearrangement of the genes that codefor the heavy-chain region of an antibody occurs
    -b-cell progenitors receive signals from bone marrow stromal call to cell contact as well as soluble cytokines (such as IL -7)
488
Q

What is the earliest developmental stage of B cells?

A

Pro B cells

489
Q

What are important transcription factors expressed within pro-B?

A

-E2A
-easy b-cell factor (EBF)
-interferon regulatory factor 8 (IFR8)
- paired box protein 5 (PAX5)

490
Q

What is one of the most important events of the pro B cell phase?

A

Rearrangement of the B- cell receptor (BCR) genes

491
Q

Describe B-call receptors (BCR)¡

A

Simply a cell surface version of an immunoglobulin or antibody molecules

492
Q

What are the similarties of BCR and TCR?

A

①composed of a different chains
②have variable regions which determine their specificity
③ have constant regions, which allow for intracellular signaling activation of the lymphocyte expressing them
④ have similar gene regions (V, D, and J)
⑤use similar mechanisms for gene rearrangement

493
Q

What are the two chains in BCR?

A

Light and heavy

494
Q

What genes in BCR contain multiple V, D, and J segments?

A

Heavy chain genes

495
Q

Like TCR, what occurs once heavy-chain rearrangement is completed successfully on one chromosome?

A
  • Allelic exclusion silences expression of the heavy chain gene on the opposite chromosome
496
Q

What needs to occur for a pro-B cell to progress to the next phase of differentiation?

A

At least one heavy chain gene must undergo successful rearrangement

497
Q

Describe the pre-B cell phase

A

The stage of B cell development where the heavy chain part of the antibody molecule is present

498
Q

How are pre-BCRs formed?

A
  • Some heavy chains travel to cell surface and combine with a surrogate light chain as well as two shorter chains, Ig - alpha and lg- beta, which are signal- transacting subunits to form pre-BCR
499
Q

What happens to pre-B cells before they assemble the pre-BCR?

A

Undergo several rounds of cell division resulting in many clones of original cell, all of which express an identical heavy chain

500
Q

What occurs simultaneously with the appearance of the pre-BCR at the cell surface?

A

Light chain gene rearrangement begin

501
Q

What are the two types of light chains possessed by humans?

A

-kappa
- lambda

502
Q

Similar to TCR alpha genes, the kappa and lambda light chains are composed of what?

A

V and J segments

503
Q

What happens to V segments, J segments and light chain constant region during rearrangement?

A

-these segments are stitched together

504
Q

What occurs once successfully rearranged light chains are expressed?

A

-macromolecular complexes comprised of two light chains and two heavy chains formed
-immunoglobulins are fastened together by disulfide bonds and journey to the cell surface to replace the pre-BCR

505
Q

What is the first immunoglobulin produced?

A

IgM

506
Q

What signifies the pre-B cells entry into the next phase, immature B cells?

A

The appearance of a functional BCR on the b-cell surface

507
Q

What does the appearance of a functional IgM BCR on the cell surface indicate?

A

-rearrangement of the genes encoding the receptors is now complete and that a new B cell exists with the potential to produce antibody for a specific and unique epitope.

508
Q

What determines the antigen specificity of immature B cell and its IgM BCR?

A

The immunoglobulin variable region, found on both the light and heavy chains

509
Q

What happens to prevent BCRs from responding to self- antigens?

A

Negative selection

510
Q

What happen when the B cell reaches maturity?

A

B-cells respond to binding of antigen to the BCR by activation, proliferation, and antibody production

511
Q

What is the reaction of immature B cells when signaled?

A

Halting their development and undergoing apoptosis

512
Q

What is central tolerance?

A
  • Elimination of B cells that bear self -reactive receptors
  • it is estimated that more than 90% of B-cells die in this manner
513
Q

What surface markers begin to make an appearance during the immature B cell phase?

A

-IgM
-CD21
-CD40
- class II MHC molecules

514
Q

Why ave cell surface markers of an immature B cell phase important?

A
  • Useful for laboratory identification of B cells
  • also essential to The function of B cells - especially
    Their role in antigen presentation to CD4+ Th cells
515
Q

Describe the CD21 cell surface marker

A

-acts as a receptor for a breakdown product of the complement component C3 ( known as CD3)
- presence enhances the likelihood of contact between B cells and antigens frequently become coated with complement fragments during the immune response

516
Q

When is a B cell considered mature?

A

Expresses a functional IgM BCR, survives selection by not reacting to self antigens and begins to display certain B cell markers

517
Q

What happens once a b-cell is considered mature?

A
  • Exit the bone marrow and are carried in the blood to the spleen for next stage of development
518
Q

What are the two types of mature B cells that develop in the spleen?

A

-follicular B cells
- marginal-zone B611

519
Q

Where can follicular B cells be found?

A
  • Constantly recirculate between blood and secondary lymphoid organs in search of their specific antigens
520
Q

Where can marginal-zone B cells be found?

A

Remain in spleen to respond quickly to blood- borne pathogens

521
Q

The majority of mature B cells are destined to be what type of B cell?

A

Follicular B cells

522
Q

What does follicular refer to?

A

To the region of the lymph mode where this type of B cell tends to localize

523
Q

Describe lymphoid follicles

A
  • Represent dense clusters of naïve B cells awaiting exposure to their specific antigens
524
Q

Describe follicular B cell activity during antigen recognition

A

Follicular B cells make contact with CD4 + follicular helper cells

525
Q

Why is cooperation between antigen activated B cells and Tfh cells critical?

A

Formation of immunologic memory

526
Q

Where in the spleen are marginal-zone B cells located?

A

Marginal sinus

527
Q

What happens when marginal-zone B cells contact their specific antigen?

A

They differentiate into IgM secreting plasma cells, each producing vast quantities of anti- microbial IgM and only stopping once the invading microbes have been eliminated
-response must begin a new upon each exposure to a particular polysaccharide antigen.

528
Q

What does the presence of both lgM and IgD on the cell membrane signify?

A

A mature B cell

529
Q

What occurs when a BCR binds to its specific antigen?

A

-multiple BCR molecules are brought together, initiating an intracellular signaling cascade
-these signals drive the B cell to enter a proliferative stage where it divides rapidly to produce both antibody- secreting plasma cells and for follicular B cells, memory B cells

530
Q

What are plasma cells role?

A

A differentiated B cell that actively secretes antibodies

531
Q

Where would immunoglobulins be found in plasma cells?

A

-little expressed on cell surface but has abundant cytoplasmic immunoglobulin

532
Q

What do plasma cells have to accommodate translation and post-translational processing the large quantity of antibodies?

A

Possess ample endoplasmic reticulum and a well defined Golgi

533
Q

What is a common resident of bore marrow and the germinal centers of peripheral lymphoid organs?

A

Plasma cells

534
Q

How do plasma cells survive in the bone marrow?

A

-plasma cells survive in bone marrow niches surroundedby stromal cells, which provided stimulation to plasma cells via cytokines
- stromal en support allows plasma pens to being long lived and fosters their continual production of antibodies

535
Q

What is a key surface marker found on plasma calls?

A

CD138

536
Q

What happens when an infection occurs in the body tissues?

A

-APCs such as macrophages and dendritic cells, are among the first immune cells to respond
- APCs engulf pathogens at these distal sites of infection and carry associated antigensto local lymph nodes

537
Q

What happens upon the arrival of APCs at the lymph nodes near the site of infection?

A
  • Antigen- laden APCs encounter naive T cells in the process of patrolling for antigen.
538
Q

What does the continuous recirculation of naive B cells between the blood and lymph nodes greatly increase the chance of?

A

The likelihood of an APC connecting with one or move of the few T cells whose TCRs recognize the antigen carried by the APC

539
Q

What is the primary mode of communication between T cells and APCs?

A

Direct cell to cell contact

540
Q

Describe antigen presentation of APCs?

A
  • Display peptide antigens to T cells via MHC
    -MHC molecules antigenic peptides and allow the TCR to bind along the entire length of the peptide
541
Q

What do class I MHC molecules present in a healthy cells ?

A

Peptide antigens derived from cytoplasmic sources such as endogenous peptides manufactured by healthy cells

542
Q

What do class I MHC molecules present in diseased cells?

A

Peptides associated with intracellular bacteria, viruses, or even proteins associated with cancer

543
Q

What type of cell does class I MHC molecule antigens present to?

A
  • Cytotoxic T cells
544
Q

What T cell population most useful for destroying malignant cells or infected cells?

A

Cytotoxic T cells

545
Q

The interaction between the cytotoxic TCRand class I MHC is stabilized by what?

A

CD8

546
Q

What do class II MHC molecules present in healthy cells ?

A
  • Peptides captured from the extracellular space, such as those derived from extracellular microbes
    -allow APCs to present such extra cellular derived peptide antigens to Th cells
547
Q

What additional protein is required to stabilize the interaction between class II MHC molecule and Th TCR?

A

CD4

548
Q

CD4 is commonly used as a marker to identify what type of cell?

A

Th cell

549
Q

What happee3ns when a naive T cell enters secondary lymphoid tissues and encounters APCs?

A

-multiple contacts occur between the T cells TCR and peptides presented in MHC molecules on the surfaces of APCs
-if TCR recognize one of the many antigens being presented by an APC, an infracellular signaling cascade is initiated within the T cell

550
Q

Will TCR signaling activate a naive T cell?

A
  • No, for activation to occur, the APC must also provide costimulation to the T cell by expressing CD80 and CD86
551
Q

What do CD80 and CD86 legate?

A

-CD28, T cell surface protein

552
Q

What transforms a naive T call to on activated T cell?

A

-The combination of signals that arises when the TCR recognizes its specific peptide and CD28 is ligated

553
Q

Why are Th cells considered the most important cells of the adaptive response?

A
  • Role in driving activities of other immune cons that act directly fight infection
    -when activated by APCs,Th cells travel to infected tissues orchestrate the immune response via the secretions of cytokines
554
Q

What are the most prominent subsets of Th cells?

A

Th1
Th2
Th17

555
Q

What influence the type of Th cell subset that is produced after differentiation?

A

Influenced by the cytokines present during activation

556
Q

Describe role of Th1

A

-produce INF-gamma, IL-2, and TNF-alpha which protect cells against intracellular pathogens by activating cytotoxic lymphocytes and macrophages

557
Q

Describe role of Th2

A

-essential role is to help B cells produce antibodies against extracellular pathogens and to generally regulate B cell activity
-produce a variety of cytokines, including IL-4, IL-5, IL-6, IL-9, IL-10, and IL-13
-also thought to play a role in allergies

558
Q

Describe the role of Th17

A
  • Produce cytokines IL-17 and IL-22, which lead to the recruitment of granulocytes in response to an extracellular bacterial infection damage
559
Q

Why is the Th17 response often associated with pathology?

A

The granulocytes activity can sometimes cause immune-mediated damage

560
Q

Describe T regulatory cells (Treg cells)?

A
  • Subset of T cell
  • possess the CD4 and CD25 antigens
    -play important role in suppressing the immune response to self-antigens and harmless antigens
561
Q

How do Treg cells suppress the immune response to self and harmless antigens?

A

They proliferate of other t-cen populations by secreting inhibitory cytokines

562
Q

Why is the response of Treg cell antigen-specific?t

A

They possess TCRs that recognize antigenic peptide in MHC class II

563
Q

How do T follicular helper cells assist B cellsin antibody production?

A

-remains in lymph nodes and interacts with B cells and plasma cells there
-Tfh cells provide essential signaling to B cells as they undergo processes such as activation immunoglobulin class switching, affinity maturation, and formation of B cells memory

564
Q

What are the two distinct populations created after cell division of Th cells?

A

① most Th cells begin to secrete cytokines and may travel to infected tissues where their activities are most needed.
② A small percentage of Th cells generated after activation will differentiate into memory cells

565
Q

What do memory Th cells du after creation?

A

-enter a quiescent state and await re-exposure to their specific antigen
-if/when contact with antigen occurs again, memory cells respond rapidly by re-entering cell division and immediately secreting appropriate cytokines

566
Q

What are the roles of cytotoxic T cell?

A

-activated cytotoxic T cells migrate to sites of infection and initiate apoptosis in cells infected with intracellular parasites and viruses
-the activity of cytotoxic T cells is driven by TCR recognition and is therefore antigen-specific

567
Q

There are two primary strategies that are cytotoxic T cells use once recognition of peptide antigen on surface of MHC I occurs. What are these strategies?

A

①The release of cytotoxic granules from the T-cell cytoplasm
② ligation of death receptors on a target cell surface
-either Case, the target all rapidly undergoes apoptosis

568
Q

What are the two toxic substances found in cytotoxic T cell granules?

A

-perforins
-granzymes

569
Q

Describe now performs and granzymes work together

A

-TCR recognition of antigen by a cytotoxic T cell cause accumulation of granules in the T cell cytoplasm adjacent to the target cell
-granules are released by the T cell in the direction of the target cell
-almost immediately, perforins begin forming holes in the target cell membrane, through which gránzymes can enter
- once in target cell, granzymes that cleave DNA and disrupts mitochondria. With its genetic material shredded and energy levels dropping, the target cell quietly dies by apoptosis

570
Q

Describe cytotoxic T cells ability to induce apoptosis by ligation of death receptors

A

-TCR recognition of antigen complexed with target- cell MHC leads to expression of the death-inducing protein Fas-ligand (FasL) by the T cell
- when FasL binds to Fas on the target cell membrane, apoptopic pathways similar to those activated by the granzymes are set in motion

571
Q

What is the essential first step in the activation of a mature B cell?

A

Exposure of the IgM BCR to its specific antigenic epitope

572
Q

Antigen recognition by the different types of mature B cells occur in different anatomical regions. What are these regions?

A
  • Lymph nodes
  • spleen
573
Q

How did T-dependent antigens get their name?

A

The follicular B-cell response depends heavily on the activity of Tfh cells to promote an effective antibody response, antigens that provoke this type of response

574
Q

How did T- independent antigens get their name?

A

-marginal-zone B cells don’t require the help of Tfh cells

575
Q

T-dependent antigens are almost always what? Why?

A

-proteins
-proteins are the only type of antigen that can stimulate a T cell response.

576
Q

How do protein antigens reach the lymph nodes?

A
  • May travel suspended or dissolved within lymphatic fluid, or they may be carried by macrophages or dendritic cells
    -regardless, they arrive at the B cell rich follicles in their state
577
Q

Explain what happens once a follicular B cell and its specific antigen are united

A
  • The BCR locates its epitope and binds the antigen securely via surface immunoglobulin
    -BCR antigen recognition initiates a cascade of intracellular signaling within the B cell, driving the cell into an activated state.
578
Q

What is the response of the B cell cytoskeleton to BCR signaling?

A
  • B cell cytoskeleton is mobilized to internalize the bound antigen using endocytosis
    -antigen uptake allows for digestion of the antigen and presentation of its constituents peptides on class II MHC molecules on the B cell surface
579
Q

What do B cells do after activation?

A
  • B cell migrate to the edges of the follicle, where they ‘ begin to interact with Tfh cells
    -in this context, B cells act as APCs, presenting peptide fragments derived from internalized antigen to Tfh cells
    -if TCR binding to antigenic peptides occurs, a T cell- B cell pair is formed, and the T- dependent phase of the B cell response begins
580
Q

How does Tfh cells complement BCR signaling?

A

Tfh cells provide activated B cells with two additional signals that contribute to the B cell response

581
Q

What does the first signal provided by the T cell require?

A

Physical contact between T cells and B cells

582
Q

What does TCR recognition of peptide antigens cause Tfh cells to do?

A

To express CD40 ligand which binds to CD40 on B cells

583
Q

Describe T cells ability to signal B cells through the secretion of cytokines

A

-T cells secrete IL-2, which secrete CD25 expressed on B cells and spurs them to enter a phase of rapid cell division
-each dangther en produced during this replicative explosion will inherit an identical BCR to that of the parent B cell and will therefore recognize the same antigen

584
Q

What are the two possible fates of dangther B cells that are produced during proliferative phase of T dependent response?

A

① some remain in contact with T cells and differentiate into IgM secreting plasma cells
② others form germinal centers within follicles and participate in a series of processes that enhance the antibody response through time

585
Q

What are the 3 overlapping processes of the germinal center reaction?

A

① immunoglobulin isotope switching
② activity maturation
③memory cell generation

586
Q

What does germinal center formation require?

A

-interaction with T cells, specifically the affiliation of CD40 with CD40L and secretion of cytokines

587
Q

What is the most common class of immunoglobulin molecule incorporated into BCRs of marginal- zone B cells and follicular B cells before and at very early times after antigen recognition? BY

A

IgM

588
Q

Describe IgG

A

-predominant form of antibody found in blood
-found in intestines and the body’s secretion
-associated with allergies

589
Q

What is isotype switching?

A

-under the direction of T cells, germinal center B cells can change which class of antibody they express
-also determines the class of antibody secreted once the B cell differentiates into a plasma cell

590
Q

What is affinity maturation?

A
  • Immunologlobulins bind antigen with increasing strength (affinity) through the course of an immune response, resulting in the production of even more effective antibodies
  • this is accomplished through somatic hypermutation
591
Q

What is somatic hypermutations?

A

Appearance of mutations in immunoglobulin gene variable regions

592
Q

What causes dangther cells to be produced with slightly different antigen -binding abilities?

A
  • Somatic hypermutation
593
Q

What happens to daughter cells whose BCR have a greater affinity? What about lesser affinity?

A

-greater affinity for antigen receive survival signals
-lesser affinity for antigen die of apoptosis?

594
Q

For each generation of daughter cells produced within the germinal center, there are 3 basic populations of cells formed. What are these cells?

A

①plasma cells
② memory cells
③ B cells that remain in the seminal center to continue the process of affinity maturation

595
Q

Describe plasma cell activity after being formed

A
  • Plasma cells exit lymph nodes and secrete large quantities of antibody of isotype and affinity achieved during that replicative generation
596
Q

Describe memory cell activity after being formed

A
  • May remain lymph modes or travel to tissues
    -do not require antigen stimulation for survival, allowing them to lie in wait for re-exposure
597
Q

What happens when a memory B cell is re-exposed to antigen?

A

It can rapidly respond with the production of high affinity, class-switched antibody

598
Q

What are the pro-B cell key CD markers?

A

CD10 and CD19

599
Q

What are the pre-B cell key CD markers?

A

CD10, CD19, and CD20

600
Q

What are the immature B cells key CD markers?

A

CD10
CD19
CD20
CD21
CD40

601
Q

What are the mature B cell key CD markers?

A

CD19
CD20
CD21
CD40

602
Q

What are the pro-B cell receptors?

A

None

603
Q

What is the pre-B cell receptor?

A

Pre-BCR: immunoglobulin heavy chain and surrogate light chain

604
Q

What is the immature B cell receptors

A

Functional BCR: IgM heavy chains and kappa or lambda light chains

605
Q

What is the mature B cell receptor?

A

Functional BCR: IgD or IgM heavy chains and kappa and lambda light chains

606
Q

What is the double negative key CD marker?

A

CD3

607
Q

What is the double negative T cell receptors?

A

None

608
Q

What are the double positive key CD markers?

A

CD3
CD4
CD8

609
Q

What are the double positive T cell receptors

A

TCR alpha and TCR beta

610
Q

What are the single positive key CD markers?

A

CD3
CD4
CD8

611
Q

What are the single positive T cell receptors?

A

TCR alpha and TCR beta

612
Q

What is a characteristic of immune response to a T-independent antigen?

A
  • Antigens are often polysaccharides
613
Q

How does humoral immunity produce antibodies?

A

By plasma cells

614
Q

What is negative selection?

A

-Process that takes place among surviving DP T cells in the corticomedullary region and the medulla of the thymus
- strong reactions with self-peptides other than MHC antigens triggers apoptosis

615
Q

What are thymocytes?

A

Lymphocyte precursors in the thymus that are committed to becoming T cells

616
Q

Describe immature B cells

A

A phase in the growth of B cells characterized by the appearance of complete IgM antibody molecules on the cell surface

617
Q

What are variables?

A

-Contained by both alpha and beta chains on TCR
- recognizes specific antigens

618
Q

Describe T-independent antigens

A

T cell help is required in order for B cellsto respond to antigen

619
Q

What is MHC restriction?

A

Selection of thymocytes that will only interact with the MHC antigens found on host cells

620
Q

What is surrogate light chain?

A

Consists of two shout polypeptide chains that are noncovalently associated with each other along with two shorter chains, Ig-alpha and Ig-beta

621
Q

What is allelic exclusion?

A

Selection of an allele on one chromosome only

622
Q

What is a cytotoxic T cell?

A

-Express CD8 receptor
- interact with antigen and class I MHC protein

623
Q

What is clonal deletion?

A

Process of elimination of clones of cells that would be capable of an autoimmune response

624
Q

What are T regulatory cells?

A

-Possess the CD4 antigen as well as CD25
-play important role in suppressing the immune response to self antigens

625
Q

Describe cell flow cytometry

A

Automated system for identifying cells based on the scattering of light as cells flow single file in a stream of fluid by a laser beam

626
Q

What is positive selection?

A

Process that takes place when the CD3-alphabeta receptor complex (TCR) is complete and expressed on cell surface that allows only DP cells with functional TCR receptors to survive.

627
Q

Describe process used by cytotoxic T-cells to kill target cells

A

Producing granzymes that stimulate apoptosis

628
Q

Where do germinal centers occur?

A

Spleen and lymph nodes

629
Q

What is a distinguishing feature of pre-B cells?

A

Mu chains in the cytoplasm

630
Q

What is acute phase reaction that helps to prevent formation of peroxides and free radicals that can cause damage to tissues?

A

Haptoglobin

631
Q

What are the 3 characteristics of acute phase reactants?

A

① rapid increase following infection
② enhancement of phagocytosis
③ nonspecific indicators of inflammation

632
Q

What are 3 characteristics of on immunogen?

A

① large molecular weight
② internal complexity
③ presence of numerous epitopes

633
Q

Where are class II MHC ANTIGENS found?

A

B cells and macrophages

634
Q

Pattern recognition receptor act by what?

A

Recognizing molecules that are unique to pathogens

635
Q

What type of cells would be found in a primary follicle?

A

Unstimulated B cells

MLT immunology (7 decks)

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