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Immunology Monica xxx > Immunology > Flashcards

Immunology Flashcards

1
Q

What does the immune system do?

A

identify + eliminate

  • microorganisms
  • other harmful substances -abnormal cancer cells
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2
Q

How does the immune system identify and eliminate?

A

-Distinguish what is ‘self’ from ‘non-self’ molecules
-Identify ‘danger’ signals
Or combination

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3
Q

what must the immune system strike a difficult balance between?

A
  • Clearing the pathogen

- Cause accidental damage to the host

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4
Q

What does a balanced immune system lead to?

A

Optimal effectiveness

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5
Q

What can animmune system under-reaction lead to?

A
  • Cancer (HCV, HIV, EBV)

- Infection (Viruses, bacteria, fungi, parasites)

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6
Q

What is the internal threat of an immune over reaction?

A

Autoimmune problem (type 1 diabetes, rheumatoid arthritis, psoriasis, multiple sclerosis, lupus, IDB)

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7
Q

What is the external threat of an immune over-reaction?

A

Allergic reaction (hay fever, eczema, asthma, sinusitis)

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8
Q

List 5 problems associated with the immune system going wrong

A

-Recurrent infections
-Allergy
-Autoimmune disease
-Cancer
T-ransplant rejection

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9
Q

Only some multicellular organisms have some form of immune system (T/F)

A

False - all multicellular organisms have some sort of immune system

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10
Q

What has been the basis for many major advances in human health?

A

Modulating the immune system

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11
Q

Vaccinations are…

A

One of the most important scientific accomplishments of the past century

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12
Q

List key achievements of vaccinations

A
  • Eradication of smallpox
  • 100% decrease in poliomyelitis in North and South America
  • 99% decrease in diphtheria, measles, mumps, rubella
  • 97% decrease in whooping cough
  • Dramatic decline in HiB infections in UK
  • Promising early data: HPV infection and cervical cancer
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13
Q

What is immune suppression essential for?

A

Treatment of autoimmune disease, allergic diseases + transplantation

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14
Q

What does cancer immunotherapy enable the immune system to do?

A

-Recognise target
-Eliminate cancer cells
(Making it a universal answer to cancer)

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15
Q

List pathogens points of entry

A
  • Digestive system
  • Respiratory system
  • Urogenital system
  • Break in skin
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16
Q

List pathogen routes of attack

A
  • Circulatory system

- Lymphatic system

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17
Q

Each pathogen routes have what kind of barriers to infection?

A

Specific constitutive barriers

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18
Q

What happens if defences = breached?

A

Immune system = activated

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19
Q

List the constitutive barriers to infection

A
  • Skin
  • Mucous
  • Commensal bacteria
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20
Q

Skin is the least important barrier to infection (T/F)

A

False - most important

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21
Q

Skin as a physical barrier composed of what?

A

Tightly packed, highly keratinised multi-layered cells

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22
Q

What does the skin constantly undergo?

A

Renewal and replacemnt

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23
Q

What is the pH of skin?

A

low ph = 5.5 = acidic

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24
Q

Skin = low oxygen tension (T/F)

A

True

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25
Q

Outline characteristics of sebaceous glands

A
  • Secrete hydrophobic cells
  • Lysozyme
  • Ammonia
  • Antimicrobial peptides
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26
Q

Secreted mucous membranes line all body cavities that come into contact with which environments?

A
  • Respiratory
  • Gastrointestinal
  • Urogenital tract
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27
Q

What is the role of mucus?

A
  • Traps bacteria

- Subsequently removed by ciliated cells

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28
Q

What’s the role of secretory IgA?

A

Prevent bacteria + viruses attaching to + penetrating epithelial cells

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29
Q

Mucous contains enzymes. Name these and their role

A

Lysozyme
Defensins
Antimicrobial peptides
Directly kill invading pathogens

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30
Q

What does lactoferrin do?

A

Starve invading bacteria of iron

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31
Q

Outline the role of cilia

A

Traps pathogen directly

Contributes to mucous removal

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32
Q

What is cilia assisted by?

A

Physical manoeuvres e.g. sneezing + coughing

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33
Q

What do 100 trillion bacteria normally do?

A

Reside at epithelial surfaces

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34
Q

How many different microbial species exist?

A

> 500

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35
Q

Commensal bacteria exhibit a ______ relationship with the host

A

Symbiotic

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36
Q

List 5 key features of commensal bacteria

A
  • Produces bactericidins - influence other bacteria
  • Reduce pH of large bowel
  • Compete for essential nutrients
  • Synthesis of vitamins - vitamin K, B12
  • Produce anti-microbial short chain fatty acids
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37
Q

How can commensal bacteria be affected?

A
  • Alterations in homeostasis
  • Malnutrition
  • Intercurrent infection
  • Age
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38
Q

Examples of commensal bacteria importance

A
  • Oral candidiasis after oral antibiotics
  • Vaginal candidiasis after oral antibiotics
  • Clostridium difficile infection after intravenous antibiotics
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39
Q

What does eradication of the normal flora with broad-spectrum antibiotics commonly result in?

A

-Opportunistic infections

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40
Q

Explain opportunistic infections

A

Organisms rapidly colonise an undefended ecological niche

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41
Q

Constitutive barriers = _________ effective

A

Highly

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42
Q

If an external defence = breached what is activated?

A

Immune system

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43
Q

How are external defences breached?

A

By a wound or organism

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44
Q

How are constitutive barriers breached during provision of health care?

A
  • Insertion of hardware e.g. intravenous lines
  • Antibiotics
  • Other therapeutics e.g. anti-acid medication, nasal decongestants, anti-bacterial wipes
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45
Q

What are unfavourable pH’s which can act as natural barriers?

A
  • Stomach acid
  • Sweat
  • Saliva
  • Urine
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46
Q

Where are lysozyme enzymes found?

A
  • Tears

- Aweat

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47
Q

What is the purpose of lysozyme enzymes?

A

Digests bacterial cell walls

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48
Q

What are phagocytic white blood cells?

A

Leukocytes

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49
Q

Macrophages, neutrophils and natural killer cells are?

A

Leukocytes

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50
Q

List the innate/natural immune responses

A
  • Natural barrier
  • Soluble components
  • Cellular components
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51
Q

List the acquired immune response

A
  • Humoral (B cells/ antibody)

- Cell-mediated T cells

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52
Q

Innate/Natural response is adaptive

A

False - non-adaptive

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53
Q

Is acquired response adaptive or non-adaptive?

A

Adaptive

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54
Q

Define innate imunity

A
  • Present continuously

- Defence mechanism present from birth

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55
Q

Define adaptive immunity

A

-Immunity is induced by presence of foreign material

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56
Q

Is innate or adaptive immunity specific?

A

Adaptive

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57
Q

What hours does the rapid innate first response to infection take place?

A

0-96hrs

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58
Q

Does innate immune response have immunological memory?

A

No

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59
Q

Acquired response occurs when?

A

96hrs+

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60
Q

Acquired immunity has immunological memory. Explain what this means

A

-Subsequent responses are faster + more powerful

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61
Q

What is immunological memory the basis of?

A

-Protective vaccination against infectious diseases

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62
Q

Acquired immunity is specific for each antigen encountered

A

True

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63
Q

T cells allow what?

A

-Self regulating function

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64
Q

What can acquired immunity distinguish between?

A

SELF from NON-SELF

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65
Q

Adaptive immunity should act against self molecules

A

False - should act against non-self molecules

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66
Q

Immune System is compromised of 2 arms. What are both are responsible for?

A

Detecting and destroying the pathogen

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67
Q

Both arms of immune response are not essential

A

False - both essential for maximal protection but work in different ways

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68
Q

What is the result when physical barriers = breached?

A
  • Soluble components

- Cellular components

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69
Q

Leukocytes include

A
  • Phagocytic white blood cells
  • Macrophages
  • Neutrophils
  • NK cells
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70
Q

What is the complement system?

A

Proteins that destroy cells

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71
Q

What is the effect of the inflammatory response?

A
  • Increases body temp
  • Increases capillary permeability
  • Attracts macrophages
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72
Q

Finish the sentence

Physical barriers breached

A
  • Pathogens invade

- Innate Immune Response Initiated

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73
Q

What do tissue-resident innate immune cells recognise pathogens as?

A
  • ‘non-self’

- Dangerous

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74
Q

What are Phagocytic cells?

A

Macrophages + Dendritic cells

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75
Q

What are killer cells?

A

Natural killer cells

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76
Q

Name another type of cells

A

Mast cells

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77
Q

Where do macrophages reside and what in?

A

In - exposed epithelial cells

At - common sites where pathogens invade

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78
Q

Macrophages are fast acting. What are they the first line of defence against?

A

Invading pathogens

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79
Q

What are pathogens important in defending against?

A
  • Bacteria

- Fungi

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80
Q

List the 5 functions of macrophages

A

-Ingest and kill existing pathogens
-Role in antigen presentation
-Induce pro and anti
inflammatory responses
-Clear debris from dead/dying tissue cells
-Promote tissue repair and wound healing

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81
Q

What are macrophages called in the liver?

A

Kupffer cells

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82
Q

What are macrophages called in the lungs?

A

Alveolar macrophages

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83
Q

What are macrophages called in the kidney?

A

Mesangial cells

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84
Q

What are macrophages called in the nervous system?

A

Microglial cells

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85
Q

Where are dendritic cells located?

A

In peripheral tissues

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86
Q

What kind of state are dendritic cells in when they are located in the peripheral tissue?

A

Immature state

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87
Q

What do dendritic cells phagocytose?

A
  • Antigens
  • Cell debris
  • Particles
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88
Q

Explain what dendritic cells do?

A

Process + present materials on the cells via MHC molecules

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89
Q

What is the purpose of processing and presenting these proteins?

A

Initiate T cell immune response + adaptive immunity

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90
Q

Natural killer cells are _____ _______ cells

A

Large granular

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91
Q

What do NK cells specifically kill?

A
  • Infected cells

- Abnormal cancer cell

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92
Q

What else can NK cells kill?

A
  • Antibody-bound cells

- Pathogens

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93
Q

Mast cells have a _____ nucleus which is _____ granular

A

Single

Highly

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94
Q

Where do mast cells reside in?

A

Tissues

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95
Q

What kind of surfaces do mast cells protect?

A

Mucosal

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96
Q

What kind of parasites do mast cells protect against/

A

Large anti-body coated parasites (those that cannot be phagocytosed e.g. worm)

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97
Q

What do mast cells play a key role in?

A

Mediating allergic responses

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98
Q

What happens to mast cells upon activation?

A

-Release chemicals e.g. histamine, heparin + pro-inflammatory cytokines

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99
Q

What do tissue-resident innate immune cells recognise pathogens as?

A
  • ‘Non-self’

- Dangerous

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100
Q

What kind of molecules do pathogens express?

A

‘Signature’ molecules

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101
Q

Are signature molecules found on/in human cells?

A

No

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102
Q

Pathogens are recognised by tissue-resident innate immune cells by

A

Pathogen associated molecular patterns (PAMP)

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103
Q

Pathogen associate molecular patterns are not common to many different pathogens

A

False - they are common

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104
Q

What do innate immune cells express?

A

Partner receptors to pathogen associate molecular patterns (PAMP)

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105
Q

Where are innate immune cells found?

A
  • Cell surfaces

- Intracellularly for detecting extra + intra cellular pathogens

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106
Q

Extracellular bacterial pathogens invade cells

A

False - do not invade cells

-proliferate extracellular environment instead

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107
Q

What is the extracellular enriched with?

A

Body fluids

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108
Q

What is ingested by macrophages?

A
  • Extracellular bacteria

- Fungi

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109
Q

List the modes of ingestion by macrophages

A
  • Pinocytosis
  • Receptor-mediated endocytosis
  • Phagocytosis
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110
Q

Describe pinoocytosis

A

Ingestion of fluid surrounding cells

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111
Q

Explain receptor-mediated endocytosis

A

Membrane receptor bound molecules = internalized

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112
Q

Receptor mediate endocytosis is an important step in the generation of what kind of immunity?

A

Adaptive

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113
Q

Phagocytosis is key for macrophages. How are intact particles internalised?

A

Whole

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114
Q

Intact particles are internalized whole, but what are they facilitated by?

A

Opsonisation

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115
Q

Phagocytosis is a specific form of what?

A

Endocytosis

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116
Q

Phagocytosis internalise what?

A

Solid matter

Including apoptotic cells + microbial pathogens

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117
Q

Most cells are capable of phagocytosis

A

True

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118
Q

What truly excels in phagocytosis?

A
  • Professional phagocyte of the immune system
  • Macrophages
  • Neutrophils
  • Immature dendritic cells
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119
Q

Outline the 1st stage of phagocytosis

A

Specific PAMPs expressed on the surface of any different extracellular pathogens are recognised by macrophages

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120
Q

The 2nd stage of phagocytosis begins with macrophages rearranging their cytoskeleton. What happens next?

A

Cell membrane = extend around target
Eventually envelopes it
Pinching off occurs
Form phagosome

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121
Q

During the 3rd stage of phagocytosis the vesicle can mature and acidify through fusion with…

A

Late endosomes + lysosomes

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122
Q

What does the fusion of late endosomes + lysosomes form?

A

Phagolysososme

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123
Q

Forming a phagolysosome results in what?

A

Degradation + digestion of cargo

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124
Q

Why does killing occur as a result of phagolysosomes?

A

Phagolysosomes contain

  • Hydrolytic enzymes
  • Proteases
  • Highly acidic pH
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125
Q

What is the final step of phagocytosis?

A

Cellular debris in form of small soluble molecules = released

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126
Q

What also happens in conjunction with the final step?

A

Pro- inflammatory mediators e.g. TNF alpha = secreted
Promotes acute inflammation
Peptides derived from pathogen = expressed on special cell surface receptors

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127
Q

Single phagocytes can ingest more than 1 cellular corpse. This is essential for…

A

Secretion of pro-inflammatory cytokines

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128
Q

Define opsonisation

A

Coating of pathogens by soluble factors (opsonins)

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129
Q

What does opsonisation enhance?

A

Phagocytosis

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130
Q

Give 3 examples of opsonins

A
  • C3b
  • C-reactive protein
  • IgG/IgM
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131
Q

Virally infected cells produce + release small proteins. What are these called?

A

Intereferons

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132
Q

What do interferons play a vita role in?

A

Immune protection against viruses

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133
Q

Why does a virus invade the cells when it infects a person?

A

To survive + replicate

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134
Q

Interferons are host and virus specific

A

False - host specific but not virus specific

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135
Q

Interferons have what kind of general protection?

A

Anti-viral

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136
Q

How do interferons prevent replication of viruses?

A

Directly interfere with ability to replicate within an infected cell

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137
Q

What protects the cell from viral infection?

A

Cell signals produce anti-viral factors —> interfere with viral multiplication

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138
Q

What else to interferons act as?

A

Signalling molecules

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139
Q

What does interferons acting as signalling molecules allow?

A

Infected cells to warn nearby cells or viral presence

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140
Q

What advantage does warning nearby cells of viral presence give?

A

Neighbouring cells = increase MHC class 1 molecules upon surfaces increase

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141
Q

What does increasing the number of MHC class 1 molecules allow?

A

T cells surveying the area can identify + eliminate viral infection

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142
Q

Outline the 4 steps undertaken by NK cells

A
  • Release perforin protein
  • Insert into membrane of target cell
  • Form pores = fluid can move in/out of cell
  • Cell ruptures (lysis) —> apoptosis = cell death
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143
Q

Natural killer cells are lymphocyres

A

True

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144
Q

What can NK cells recognise and destroy?

A

Viral or cancerous cells

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145
Q

When NK cells come into contact with abnormal cells what happens?

A

They release cytotoxic molecules

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146
Q

What do cytotoxic molecules cause?

A

Abnormal cells to undergo apoptosis

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147
Q

What do NK cells respond to?

A

Levels of class 1 MHC molecules on cell surface

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148
Q

Reduced levels of MHC class 1 leads to killing in what kind of cells?

A

Virally infected cells

Cancerous cells

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149
Q

Mast cells play a role in degranulation explain

A

Pre-formed pro-inflammatory substances released

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150
Q

Mast cells play a role in gene expression explain

A

New pro-inflammatory substances produced.

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151
Q

Communication between _____ and _____ enhances killing

A

NK cells

Macrophages

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152
Q

What is macrophage activation enhanced by?

A

Inflammatory mediators e.g. IFNy

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153
Q

List bacteria that can evade phagolysosome killing

A
  • Salmonella
  • Straph. aureus
  • Mycobacteria
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154
Q

What is macrophage activation enhanced by?

A

Pro-inflammatory mediators e.g. IFN gamma

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155
Q

What does macrophage activation lead to?

A
  • Increased MCH-II expression
  • Produces toxic reactive
  • Oxygen and Nitrogen species
  • Increase intracellular bacteria killing
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156
Q

List the clinical features of acute inflammation

A
  • Fever
  • Liver - Increased synthesis of acute phase proteins
  • Bone marrow - Increased production + metabolism of neutrophilia
  • Local cellulitis
  • Pain
  • Redness
  • Swelling
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157
Q

What is neutrophilia?

A

A hallmark of acute inflammation

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158
Q

What are regarded as innate immune system late events?

A
  • Production of pro-inflammatory mediators

- Production of chemokines

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159
Q

Give examples of pro-inflammatory mediators

A
  • Histamnine
  • Leukotrienes
  • TNFalpha
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160
Q

Chemokines are small insoluble molecules

A

False - small soluble molecules

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161
Q

What do chemokines promote?

A

Direct movement of cells

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162
Q

What do cells normall travel down?

A

Chemokine gradient

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163
Q

Where do cells that normally travel down a chemokine gradient travel to?

A

Source of chemokine

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164
Q

What else do hemokines promote other than directed movement of cells?

A

-Adhesion of neutrophils + other leukocytes to endothelial cels in infected/ inflamed tissues

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165
Q

What are neutrophils critically involved in?

A

Initiation + maintenance of inflammation

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166
Q

Where must neutrophils be able to get to?

A

Site of injury/ tissue damage from their usual bloody location

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167
Q

Why do specific neutrophil mechanisms exist?

A

Recruit + direct cells to appropriate places

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168
Q

Explain the term transendothelial migration

A

Neutrophil movemnet from blood to tissues through blood vessel wall

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169
Q

What is transendothelial migration triggered by?

A

Pro-inflammatory mediators - alter local vasculature

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170
Q

Where do neutrophils circulate?

A

In bloodstream

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171
Q

Where do neutrophils migrate?

A

Into infected and/or inflamed tissues

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172
Q

What kind of nucleus do neutrophils possess?

A

A multi-loved nucleus

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173
Q

Neutrophils have a pink cytoplasm

A

True

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174
Q

What percentage of circulating leukocytes do neutrophils compromise?

A

50-70%

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175
Q

Neutrophils are short lived cells and have a half life of?

A

6 hours

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176
Q

How many neutrophils are released into circulation?

A

60x10^6/minute

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177
Q

When does the number of neutrophils released into circulation increase dramatically?

A

During inflammation

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178
Q

What is the main function of neutrophils?

A
  • Kill pathogen

- Promote inflammation

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179
Q

Do healthy cells have inflammatory mediators?

A

No

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180
Q

Healthy tissue have abnormal vasculature

A

False - normal

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181
Q

Healthy tissues have circulating neutrophils

A

True

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182
Q

What does inflammation promote?

A
  • Vascular changes

- Recruitment + activation of neutrophils

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183
Q

What are the 4 changes to the local vasculature in infected/damaged tissues

A
  • Loss of tight junctions in endothelial cells
  • Post capillary venules dilated
  • Specific adhesion molecules on endothelial cell surface expressed
  • Adhesion molecule receptors on circulating neutrophils activated
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184
Q

What does loss of tight junctions between endothelial cells lead to?

A

Increased vascular permeability

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185
Q

List the steps of transendothelial migration

A

Step 1 - NEED TO DO REVISIT SLIDE !! 11

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186
Q

In infected tissues, pathogens release _____ sthat attracts _______

A

Chemokine-like signals

Neutrophils

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187
Q

WHat do neutrophils use to bind to and phagocytose pathogens?

A

Pattern Recognition Receptors

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188
Q

Name the 2 distinct mechanisms used to kill internalised pathogens

A
  • Phagolysosomal killing

- ROS-mediated killing

189
Q

Do neutrophils require extra stimulation to kill via ROS-dependent mechanism

A

NO - already possess ability

190
Q

What do lysozymes do?

A

Degrade cell wall of some gram +ve bacteria

191
Q

Acidification in phagolysosomal killing

A

Bactericidal or bacteriostatic

192
Q

Lactoferrin in phagolysosomal killing

A

Fe binding protein (competitor)

193
Q

Acid hydrolyases in phagolysosomal killing

A

Further digests bacteria

194
Q

What happens during degranulation?

A

Anti-bacterial proteins from neutrophil granules released

Directly into extracellular millieu

195
Q

DEgranulation results in direct killing of what?

A

Extracellular pathogens - bacteria + fungi

196
Q

Degranulation can result in _____ damage and _____ inflammation

A

Tissue

(potentially) systemic

197
Q

How can the tissue damage and systemic inflammation become limited?

A

By increasing expression of proteinase inhibitors

198
Q

What is the 3rd neutrophil killing mechanism?

A

NETs

199
Q

What does NETs stand for/

A

Neutrophil Extracellular Traps

200
Q

What do neutrophils release?

A

Intracellular structures into extracellular enviroment

201
Q

How do NETs immobilise pathogens?

A
  • Prevent spreading

- Facilitate phagocytosis

202
Q

What do neutrophils minimise?

A

Damage to host cells

203
Q

NET formation can be induced by what?

A

Extracellular bacteria + Hyphal fungi forms

204
Q

NET formation is a form of suicide carried out in order to…

A

Trap + kill pathogens

205
Q

How do NETs prevent them from from spreading?

A

Immobilize pathogens

206
Q

What do NETS facilitate subsequent phagocytosis of?

A

Trapped microorganisms

207
Q

What are NETS composed of?

A
  • Genomic DNA
  • Histones
  • Granular proteins
  • Enzymes
208
Q

Name the granular proteins

A
  • Lactoferrin

- Cathepsins

209
Q

Name the enzymes

A

Neutrophil elastase

210
Q

What is PUS made of?

A
  • Neutrophils
  • NETS
  • Dead bacteria
  • Cellular debris
211
Q

What is an abscess?

A
  • Collection of pus

- Surrounded by membrane of sprouting capillaries, neutrophils + occasional fibroblasts

212
Q

What is responsible for inducing a fever?

A

-Activated macrophages releasing Pro- inflammatory mediators

213
Q

What type of response is the accute phase response?

A

Systemic

214
Q

What does an inflammation response result in?

A

Changes in plasma conc. of specific proteins

215
Q

Activated macrophages release what?

A

Pro - inflammatory mediators

216
Q

The acute phase response os mediated by liver hepatocytes. What do these produce a variety of?

A

Acute phase proteins

217
Q

List the roles of C reactive protein?

A
  • Prime certain bacteria - destruction by complement system

- Prognostic role

218
Q

What kind of protein is a C reactive protein in humans?

A
  • Major

- Acute

219
Q

What kind of protein is used as a marker for inflammation?

A

C reactive protein

220
Q

When does CRP increase rapidly?

A

During inflammation

221
Q

CRP possesses a very short half life. What is the result of this characteristic?

A

CRP rapidly disappears once inflammation = resolved

222
Q

Name 2 complement system proteins

A
  • MBL

- C3

223
Q

The complement system is made up of approx how many proteins?

A

30

224
Q

Where are the proteins of the complement system produced?

A

In the liver

225
Q

Where do the proteins of the complement system circulate?

A

In the blood (constitute 10% serum proteins)

226
Q

The complement system enters _______ and ______ tissues

A

Infected

Inflamed

227
Q

How are pathogens activated?

A

Directly or indirectly

228
Q

What happens when the complement system is triggered?

A

Specific complement proteins = enzymatically activate other complement proteins

229
Q

How do specific complement proteins enzymatically activate other complementary proteins when triggered?

A

Cascade type reaction

230
Q

How can this be referred to as a very powerful system?

A
  • Rapid amplification

- 1 upstream molecule activates many downstream molecules

231
Q

Pro-inflammatory cytokines + histamine stimulate what?

A

Increased

  • vascular permeability
  • leakage of plasma proteins —-> tissues
232
Q

What are complement proteins made up of?

A
  • Kinins
  • Coagulation factors
  • Fibrinolytic system
233
Q

An activated complement system creates a cascade of chemical reactions. What does this promote?

A
  • Opsonisation
  • Chemotaxis
  • Agulation
  • MAC production
234
Q

What does the kinin system generate?

A
  • Proteins capable of sustaining vasodilation

- Physical inflammatory effects

235
Q

What does the coagulation system/ clotting cascade form?

A

Protective protein mesh over injury site

236
Q

What acts in opposition to the coagulation system?

A

Fibrinolysis system

237
Q

What is the purpose of the fibrinolysis system?

A

Counterbalance clotting

Generate inflammatory mediators

238
Q

What does activation of downstream complement proteins lead to?

A
  • Pathogen killing
  • Pathogen opsonisation
  • Leukocyte recruitment + inflammation
  • Immune complexes removal
239
Q

Name an acute phase protein

A

Mannose-binding lectin

240
Q

Mannose expression is applicable to human cells

A

False - not expressed on human cells

241
Q

Why do selective activation arise?

A

mannose expression = unique to certain pathogens

242
Q

What stops C3b being unstable and rapidly degradable?

A

Binding to cell surfaces

243
Q

Human cells express inhibitory proteins. What do they prevent?

A

C3b activating downstream events

244
Q

Pathogens express inhibitory proteins

A

False - do not express these inhibitory proteins

245
Q

What do the last 5 proteins in a complement cascade do?

A

Self associate - form membrane-attack complex

246
Q

What inserts into pathogen membranes?

A

Membrane Attack Complex

247
Q

What do MACs allow?

A

Extracellular salts + water to enter —–> Microbe swells + bursts

248
Q

What is C3a and C5a AKA?

A

Anaphylatoxins

249
Q

What do anaphylatoxins promote?

A
  • Vasculature changes
  • Acute inflammation
  • Leukocyte recruitment
250
Q

How do amphylatoxins promote

  • vasculature changes
  • acute inflammation
  • leukocyte recruitment
A
  1. Activating mast cells - degranulate- release histamine + pro-inflammatory mediators
  2. Act on local blood vessels directly
251
Q

Name 2 types of lymphocytes

A

B cells

T cells

252
Q

Antibodies are AKA

A

Immunoglobins

253
Q

What do lymphocytes + antibodies respond to?

A

Antigens

254
Q

How many and where abouts do Individual B and T cells express antigen receptors?

A

1 type of antigen receptor

On cell surface

255
Q

Individual B and T cells express only 1 type of antigen receptor what does this mean for each individual cell?

A

They can only respond to 1 specific antigen

256
Q

There are plenty of each antigen specific cell within the human body

A

False - limited number

257
Q

What does he limited number of each antigen-specific cell result in?

A

Few antigenic specific cells = not sufficient 2 kill + eliminate antigen-carrying pathogen

258
Q

What does each pathogen will express?

A

Many thousands of different antigens

259
Q

Many thousands of different antigens are expressed. What is the effect of this?

A

Many 1000’s of diff B and T cells can respond to any 1 pathogen

260
Q

Where do B cells mature?

A

In the bone marrow

261
Q

What are B cells responsible for?

A

Humoral immune responses

262
Q

What do humoral immune responses produce?

A

Antibodies that attack pathogens circulating blood and lymph

263
Q

Where do T cells mature?

A

In the thymus

264
Q

What are T cells responsible for?

A

Cellular immune responses

265
Q

What do t cells play a key role in?

A

Defence against intracellular pathogens

266
Q

What are CD4+ T cells regulators for?

A

ENTIRE immune system

267
Q

What do CD8+ T cells kill?

A

Virally infected body cells

268
Q

What do B and T cells learn as they develop?

A

Distinguish self + non-self cells

269
Q

How are B and T cells destroyed?

A

Reacting to self-antigens

270
Q

What do antigens induce?

A

Adaptive immune responses

271
Q

Define an antigen

A

Any substance that causes an adaptive immune response by activating B and T cells

272
Q

Define an antibody

A

Protein . that bonds to 1 specific antigenic epitope

273
Q

Individual cells/pathogens contain how_____ ______ antigens

A

Many different

274
Q

What can individual antigens contain?

A

Many different antigenic epitopes

275
Q

What can each specific antibody bind to?

A

Only 1 specific antigenic epitope

276
Q

Antibodies are made of a complex of what?

A

4 polypeptide chains

277
Q

How many heavy and light chains make up the polypeptide chain?

A
  • 2 Light

- 2 Heavy

278
Q

Each antibody has a unique variable region… WWHat does this bind to?

A

1 specific antigen

279
Q

What are millions of diff antibodies able to respond to?

A

Millions of diff antigens

280
Q

What type of glycoproteins fo antibodies have?

A

Large

Globular

281
Q

Discuss the structure of antibodies

A
  • Y shaped
  • 4 polypeptides
  • Held together by disulfide bridges
  • 2 identical heavy chains
  • 2 identical light chains
  • Flexibility at hinge region
282
Q

Where are antibodies normally expressed?

A

On B cell surface

283
Q

Apart from on B cell surfaces, where else can antibodies be secreted?

A

As soluble proteins into extracellular fluids

284
Q

What do antibodies provide defence against?

A

Circulating pathogens

Bacterial toxins

285
Q

Antibody deficiency diseases are never life threatening?

A

False - they can be

286
Q

Name 2 B cell antigen receptors

A
  • IgM

- IgD

287
Q

Why do B cells use membrane bound antibodies?

A

To recognise antigens

288
Q

1 B cel expresses how many copies of 1 specific antibody?

A

50,000

289
Q

Diff B cells express diff antibodies

A

True

290
Q

What forms can antibodies take?

A

Membrane bound form

Soluble form

291
Q

What kind of number of PAMPS do non-specific mechanisms have?

A

Limited

292
Q

What id the effect of non-specific recognition having a limited number of PAMPs?

A

Common to many diff pathogen

293
Q

In non-specific recognition only a small number of different PRRs are required to stimulate what?

A

Innate Immune Cell

294
Q

Specific recognition has millions of different antigens. These are _____ to individual pathogenic species

A

Unique

295
Q

Individual T and B cells of specific recognition express how many specific antigen receptors?

A

1

296
Q

What do Specific antigen receptors bind to?

A

1 specific antgenic epitope

297
Q

Where fo antigen-specific T and B cells develop?

A

Primary lymphoid tissues

298
Q

Name 2 primary lymphoid tissues where antigen specific T and B cells develop

A
  • Bone marrow

- Spleen

299
Q

Lymphocytes develop initially in the…

A

Bone marrow

300
Q

Where do lymphocyes mature

A
  • Bone marrow (B cells)

- Thymus (T cells)

301
Q

Where do t and B cells constantly recirculate between?

A
  • Blood
  • Secondary lymphoid tissues
  • Lymphatic vessels
302
Q

Where are T and B cells activated?

A

Secondary Lymphoid Tissues

303
Q

What are T and B cells activated by?

A

Antigers

304
Q

What are lymph nodes important for?

A

Monitoring tissue infections

305
Q

What is the spleen important for?

A

Monitoring blood-borne infections

306
Q

What is mucosal?

A

Associated lymphoid tissues

307
Q

What is mucosal important for?

A

Monitoring throat/gastrointestinal tract infections

308
Q

Where does lymph flow and through what vessel?

A

Through lymph nodes

Through afferent Lymphatic Vessels

309
Q

Where do B and T cells enter lymph nodes through?

A

High endothelial venules

310
Q

B cells go through HEV and then immediately go where?

A

Lymhoid foilicle

311
Q

After T cells go through HEV, where do they stay?

A

T cell area of lymph nodes

312
Q

What do T cells interact with in the T cell area of the lymph node?

A

Dendritic cells

313
Q

Where do dendritic cells come through?

A

The afferent lymph

314
Q

How do lymph and lymphocytes leave the lymph node?

A

First through medullary sinus

Then through efferent lymphatic vessels

315
Q

Efferent lymph eventually flows where?

A

Into blood circulation

via subclavian vein

316
Q

Where is lymph derived from?

A

Plasma in tissues

317
Q

How does lymph move?

A

Via valves

Movement of smooth muscles in lymphatic vessel walls

318
Q

Where are lymph nodes positioned?

A

Along lymph vessels

319
Q

What do lymph nodes monitor and why?

A

Lymph for signs of infection

320
Q

What is lymph formed from?

A

Fluid that filters out the blood circulation

321
Q

Why is fluid filtered out the blood?

A
  • Nourish cells

- Remove waste products

322
Q

How is fluid returned to the blood circulation?

A
  • Through venous capillaries

- Through force of osmosis in the venous blood

323
Q

Why must a portion of fluid containing proteins, cellular debris, bacteria etc. be returned through the lymphatic collection?

A

Maintain tissue fluid balance

324
Q

REVISE SLIDE 21

A

LECTURE 4

325
Q

B cells produce specific antibodies in response to what?

A

Specific antigens

326
Q

What is used to bind to pathogenic antigens?

A

Membrane bound, antigen-specific IgM

327
Q

B cells _____ _________ and ______ into different types of effector cells upon activation

A

Proliferate

Differentiate

328
Q

Nme 2 types of effector cells

A

Plasma Cells

Memory B cells

329
Q

What is the role of plasma cells?

A

Produce + secrete soluble, antigen specific antibodies

330
Q

Explain Memory B cells?

A

Long lived cells

circulate round the body continually

331
Q

How do b cells encounter antigens?

A

Specialised cells within B zone can ‘trap’ opsonised antigens

332
Q

B cells need to receive 2 signals to become fully activated + clonally proliferate. Name them:

A

Antigen

Helper signals from T cells

333
Q

What do B cells express?

A

BCRs

334
Q

What do the BCRs expressed all have in common?

A

The same specificity as the parent B cell

335
Q

Where do highly proliferative cells form a secondary follicle?

A

Within B cell zone (AKA Germinal Centre)

336
Q

What do B cells differentiate into?

A

Plasma cell

337
Q

Differentiation into plasma cells results in an expanded population of cells. They now have sufficient numbers to be able to deal with what?

A

Any pathogen that expresses specific antigen on their surface

338
Q

What happens once B cells stop proliferating?

A

Differentiate into anti-body screening plasma cells

339
Q

What are IgM antibodies?

A

Initial antibody class that B cells secrete

340
Q

What do secreted antibodies recognise?

A

Same specific antigen as original parent B cell

341
Q

Initially, low affinity antigen specific IgM antibodies are secreted into what?

A

Short lived plasma cells

342
Q

What do T cells help the production and secretion of and in what reaction?

A

‘Better’ antibodies

Germinal Centre

343
Q

What do T cells stimulate?

A

Production of antigen specific memory B cells

344
Q

Where do long-lived plasma cells migrate to?

A

Bone marrow

345
Q

Why are the antibodies produced with the help of T cells considered better?

A

High affinity antibodies

346
Q

Antibodies kill/inactivate pathogens through

A

Recognition function

Effector function

347
Q

Recognition function involves?

A

Binding to antigen

348
Q

What is recognition factor mediated by?

A

Variable region sites

349
Q

Explain the effector function

A

Clearance mechanism

mediated interaction of heavy chain constant region with effector molecules

350
Q

What are the effector molecules of the effector function?

A

Complement

Fc receptors

351
Q

What kind of microbes do antibodies provide immunological defence against?

A

Extracellular

E.g. bacteria/virus

352
Q

How do antibodies provide immunological defence against extracelullar microbes?

A

Recognise microbe as foreign

Inactivate/Eliminate microbe

353
Q

What can antibodies bind to?

A
  • Soluble antigens
  • Membrane-bound antigens expressed on surface of microbes
  • Other immune cells
354
Q

In membrane bound form IgM serves as…

A

B cell cell antigen receptor

355
Q

What is the function of IgM as a B cell antigen receptor?

A

B cell activation

356
Q

When is the first Ig type produced + secreted?

A

During a humoral (adaptive) immune system

357
Q

Where is IgM present?

A

In plasma + secretory fluids

358
Q

Why does IgM not enter tissues?

A

It’s too large

359
Q

What is the IgM monomer?

A

BCR

360
Q

What is IgM secreted from?

A

A pentamer

361
Q

What are the functions of IgM present in plasma + secretory fluids?

A

Agglutination (immune complex formation)

Complement system activation

362
Q

Why is IgM good at agglutinating antigens?

A

Has 10 antigen binding sites

363
Q

What is the term for immune complex formation?

A

Agglutination

364
Q

What is agglutination mediated by?

A

Specific antigen binding to IgM and IgG antibodies

365
Q

What does agglutionincrease?

A

The efficacy of pathogen elimination

366
Q

How does agglutination increase the efficacy of pathogen elimination?

A

Enhances phagocytosis

367
Q

What do phagocytic cells express?

A

Fc receptors

368
Q

What can agglutination prevent?

A

Viruses binding to + infecting host cells

-AKA ‘neutralisation’

369
Q

Define aggulation

A
  • Particles clumping together

- result of antibodies binding to antigens on surface of 2 adjacent cells/particles etc.

370
Q

Why is phagocytosis an advantage?

A

Large clumps of bacteria = eliminated in 1 pass

371
Q

What is the classical complement pathway activated by?

A

Fc antibody region

372
Q

What must each C1 molecule bind to via its globular heads?

A

AT least 2 Fc sites for a stable interaction

373
Q

When a C1 molecule binds what is the result?

A

A conformational change within the Fc region of the antibody

374
Q

What is exposed when the C1 molecule changes conformation?

A

AC1q

375
Q

What is C1q?

A

Initiating factor of classical complement pathwats

376
Q

C1q binds to antibody Fc regions. What does this activate + lead to?

A

Activates - classical compliment cascade

Leads- C3 cleavage + downstream events

377
Q

How does a single IgM pentamer activate Classic pathway?

A

Binds multiple antigen at once

378
Q

What must several different IgG antibodies bind?

A

Closely located antigens

379
Q

Why must several different IgG antibodies bind closely located antigens?

A

To recruit + activate C1 complex

380
Q

What is the most abundant antobody in normal human serum?

A

IgG

381
Q

What is the function of IgG?

A 
Agglutination
Complement System Activation
Foetal Immune Protection
Neutralisation
Opsonisation
Natural Killer cell activation
382
Q

What kind of half life does IgG possess?

A

Longest (20-24 days)

383
Q

List the 4 human subclasses of IgG

A

IgG1, IgG2, IgG3, IgG4

384
Q

What do the 4 human subclasses contain?

A

A different heavy chain

385
Q

What are highly homologous?

A

FIND ANDWER SLIDE ££ PP 4

386
Q

What do ______ differ in (FIND MISSING WORD ON SLIDE 33 PP 4)

A
  • Hinge region

- Activatte host immune system extent

387
Q

During pregnancy IgG from maternal circulation is transported across what and where to?

A
  • Transported across placenta

- Directly into foetal blood circulation

388
Q

What is the only antibody that can cross the placenta?

A

IgG

389
Q

What is IgG uniquely mediated by?

A

Fc region of IgG antibodies

390
Q

What increases over the course of pregnancy?

A

IgG levels of maternal origin in foetal circulation

391
Q

What indicates the placenta develops an active transport mechanism for IgG molecules?

A

End of gestation - foetal IgG levels exceed those in maternal circulation

392
Q

AT birth what do babies have high levels of?

A

Circulating maternal IgG antibodies

393
Q

What are IgG antibodeis collectively able to recognise?

A

Range of different antigen specificities

394
Q

Why are the high levels of IgG molecules present at birth essential?

A

Helps protect neonate against many diff pathogens until full adaptive immune system develops

395
Q

What is transient hypogammaglobulinaemia>

A

A type of immunodeficiency

396
Q

Why does maternally derived IgG wane over time?

A

Due to natural half-life of IgG proteins

397
Q

What is neutralisation mediated by?

A

Antigen binding sites of antibodies

398
Q

How can antibodies neutralise viral infectivity?

A
  • interfere with virus binding to receptor
  • block uptake into cells
  • prevent uncoating of genomes in endosomes
  • cause aggregation of virus particles
399
Q

What is opsonisation initiated by?

A

Specific antigen binding

400
Q

What do phagocytes express and what do they specifically bind to?

A

Express Fc receptors

Bind - constant regions of Ig heavy chain of IgG

401
Q

Opsonisation enhances phagocytosis what is this especially important for?

A

Encapsulating bacterial species

402
Q

Define phagocytosis

A

Coating of pathogens by immune proteins to enhance phagocytosis

403
Q

What is the most effective opsonins?

A

IgG type antibodies

404
Q

What is opsonisation mediated by?

A

Fc region of IgG

405
Q

What mediates the activation of NK cells?

A

Fc region of IgG

406
Q

What are good activators of NK cells?

A

IgG antibodies

407
Q

IgA is the 2nd most abundant Ig type (T/F)

A

True

408
Q

Where is IgA monomeric form present in?

A

Serum

409
Q

What is the function of the IgA in monomeric form?

A

Neutralisation

410
Q

Where is the IgA dimeric form present in?

A

Secretory fluids

411
Q

What are the functions of secretory IgA?

A

Neonatal defence

Neutralisation (@ mucosal site)

412
Q

Why is most IgA present in secreted form?

A
  • Stability to neutralise invading pathogens
  • Binds to antigens on pathogen surface
  • Prevents attaching to + infecting host
413
Q

What is IgA actively transported across?

A

Epithelial surfaces

Into secretions

414
Q

IgA is a primary defence mechanism at what type of surface?

A

Mucosal

415
Q

IgA is a neutralising antibody. What does this prevent?

A

Invading pathogens attaching + penetrating epithelial suraces

416
Q

Virus Neutralisation by secretory IgA plays an important role in what?

A

Protecting mucosal tissues

417
Q

Viruses that spread in the blood are dealth with by what antibodies?

A

IgG and IgM

418
Q

What antibody types can be secreted across epithelial surfaces?

A

slgA

419
Q

What are sIgA antibodies transported into to protect GI tract of neonates?

A
  • Colostrum

- Breast milk

420
Q

What is colostrum?

A
  • Milk Form
  • Produced by mammary glands of mammals
  • Late pregnancy
  • Just prior to giving birth
421
Q

What does colostrum contain?

A
  • Antibodies

- Help protect newborn against disease

422
Q

Protein concn. in colostrum is substantially higher than in milk (T/F)

A

True

423
Q

SIgA in breast milk can help protect during periods of what?

A

Transient hypogammaglobulineaemia

424
Q

What serves as the B cell antigen receptor?

A

IgD

-In menbrane bound form

425
Q

WHat is the function of IgD?

A

B cell activation

426
Q

IgD has what kind of concentrations in blood?

A

Extremely low

427
Q

What can IgE antibodies trigger?

A

Allergic responses

428
Q

List 3 allergic responses

A

Allergy
Asthma
Anaphylaxis

429
Q

What do B cells not require to recognise+ respond to antigens?

A
  • MHC cells

- Dendritic cells

430
Q

What type pf pathogens do cell - mediated T cells play a key role in defending against?

A

Intracellular pathogens

431
Q

What’s the result of CD4+ T cells?

A

Key regulators of entire immune system

432
Q

What’s the result of CD8+ T cells?

A

Kill virally infected body cells

433
Q

T cells - _____, _____ & ____ pathogens hiding in infected cells

A

Attack
Learn
Remember

434
Q

What do T cells recognise?

A

Antigen fragments

435
Q

T cells defend against what?

A

‘Non-self’ body cells

436
Q

Give 2 examples of’non self’ body cells

A
  • Cancer cells

- Transplant cells

437
Q

Give 3 types of T cells?

A
  • Helper T cells
  • Killer T cells
  • Memory T cels
438
Q

What is the purpose of helper T cells?

A

Alerts rest of immune system

439
Q

What is the purpose of killer (cytotoxic) T cells?

A

Attack infected body cells

440
Q

What is the purpose of memory T cells?

A

Long term immunity

441
Q

T cells only recognise peptide antigens presented to their what?

A
  • TCR molecules

- MHC molecules

442
Q

B cells require involvement of MHC molecules to ‘see’ antigen (T/F)

A

False

443
Q

MHC is the abbreviation for what?

A

Major Histocompatibility Complex

444
Q

What do MHC molecules display?

A

Peptide antigens to T cells

445
Q

What are MHC molecules also refererred to as?

A

Human Leukocyte Antigens

446
Q

MHC molecules can present what?

A

Different peptides

447
Q

What are MHC molecules encoded by?

A

Highly polymorphic genes

448
Q

Where are MHC molecules first identified?

A

Early transplantation procedures

449
Q

T cells only recognise what kind of antigen?

A

Peptide antigens

450
Q

WHat does a single T cell express?

A

1000’s single antigen receptors

451
Q

A hypervariable region formed by tips of alpha/beta TCR is involved in what?

A

Antigen binding

452
Q

Hypervariable region is unique to each individual T cell. Hence what does each T cell express?

A

Unique TCR that binds to only 1 specific peptide antigen

453
Q

How many classes of MHC molecules exist?

A

2

454
Q

Where is class 1 MHC expressed?

A

On all nucleated cells

455
Q

What does Class 1 MHC molecules present peptide antigens to?

A

CD8+ T cellls

456
Q

What does Class 2 MHC express?

A

Only professional antigen presenting cels

457
Q

Name antigen presenting cells

A

Dendritic cells

Macrophages, B cells

458
Q

What do Class 2 MHC molecules present peptide antigens to?

A

CD4+ T cells

459
Q

What is the first stage of T cell activation?

A

Particles + antigens derived from pathogens are released by phagocytes

460
Q

What is the main function of dendritic cells?

A

-Process + present antigens on their cell surface to T cells

461
Q

Where are dendritic cells present in large numbers?

A
  • Tissues in contact with external environment e.g. skin

- Other epithelial tissues

462
Q

What are dendritic cells called inskin?

A

Langerhans cells

463
Q

Give an example of epithelial tissue

A
  • Respiratory tract

- Gut

464
Q

What is the 2nd stage of T cell activation?

A

Dendritic cells phagocytose pathogen-derived particles + antigens

465
Q

What is the 3rd stage of T cell activation?

A

Pro-inflammatory TNFalpha stimulates immature tissue-resident dendritic cells = increase co-stimulatory molecule expression

466
Q

What can infected/inflamed tissues cells recognise + phagocytose?

A

Dendritic cells

467
Q

What do Dendritic cells do in the presence of pro-inflammatory mediators e.g. TNFalpha?

A

Mature + increase expression of key co-stimulatory surface molecules

468
Q

What is the 4th stage of T cell activation?

A

Dendritic cells ingest proteins + display small proteins derived from these on their cell surface on complex with MHC proteins

469
Q

What happens after phagocytosing the pathogenic antigens?

A
  • Dendritic cells break proteins down into short peptides

- Loaded MHC molecules transported to cell surface

Immunology Monica xxx (1 decks)

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