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Danielle's MD1 > Foundation > Flashcards

Foundation Flashcards

1
Q

What is the smallest distance between 2 points that can be seen my a light microscope?

A

0.2 um

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2
Q

What are the steps that occur before examining material with a microscope?

A 
Fixation
Sectioning 
Paraffin embedding 
Further sectioning 
Staining
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3
Q

What is involved in fixation of a tissue?

A
  • Removal of tissue from body

- addition of fixative i.e formaldehyde

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4
Q

How do fixatives work?

A

They chemically cross link molecules to lock them in place

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5
Q

What is the most commonly used fixative?

A

Formaldehyde aka formalin

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6
Q

What are the properties of formalin?

A
  • antimicrobial

- toughens tissue

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7
Q

Describe what happens in paraffin embedding?

A
  • tissues are dehydrated in alcohol

- alcohol is then replaced with xylene which mixes well with paraffin

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8
Q

What is the result of paraffin embedding?

A

Stiffens tissues so they can be sectioned thinly

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9
Q

Describe the steps involved in sectioning after tissue has been embedded in paraffin?

A
  • paraffin sections are cut via a microtome
  • thickness is 5-15 um
  • sections are rehydrated via solutions of xylene and alcohol
  • sections are put on glass
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10
Q

Describe haematoxylin staining.

A

Blue/purple stain. Binds to acidic or anionic compounds (-ve charge) ie phosphate groups on nucleus acids(RNA, DNA).

Tissues are described as being basophilic

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11
Q

Describe the eosin stain

A

Pink/orange. Binds to cationic components ie binds to positively charged amino groups of proteins(intra or extra cellular).

Tissue components are described as being acidophilic or eosinophilic

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12
Q

What are the functions of blood?

A
  • transport
  • defence
  • haemostasis
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13
Q

Describe some properties of plasma.

A
  • aqueous
  • made up of: water, protein, salts, lipids, sugar
  • in eqm with extracellular fluid
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14
Q

Name the 3 main types of plasma proteins

A
  • coagulation proteins
  • albumin
  • globulins
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15
Q

Haematocrit equals

A

RBC volume/ blood volume

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16
Q

Normal haematocrit.

A

45%

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17
Q

Describe the features of RBCs.

A
  • biconcave disc
  • 7.2um diam
  • NO nucleus
  • NO organelles eg mitochondria
  • contains haemoglobin
  • transports O2 and CO2
  • life span = 120 days
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18
Q

What does the term amphophilic mean?

A

Substances that stain with both acidic and basic dyes. Eg cytoplasm of cells that produce a lot of protein that have lots of RER

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19
Q

What are 3 main staining techniques used in histology?

A
  • H&E
  • special histochemical stains
  • immunochemistry
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20
Q

What are the 4 basic tissue types?

A
  • connective tissue
  • epithelia
  • muscle
  • neural tissue
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21
Q

What does the term parenchyma mean?

A

Functional cell

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22
Q

What goes the term stroma mean?

A

Support tissue

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23
Q

What are the classifications of connective tissue?

A
  • embryonic connective tissue
  • connective tissue proper
  • specialised connective tissue
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24
Q

Connective tissue proper is further classified into what?

A
  • loose CT

- dense CT: regular and irregular

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25
Q

List examples of specialised connective tissue.

A
  • cartilage
  • bone
  • adipose tissue
  • blood
  • haemopoietic tissue
  • lymphatic tissue
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26
Q

What are the components of blood?

A
  • Fluid(plasma)

- cells

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27
Q

What are reticulocytes?

A

Immature RBCs. They are released into the blood in this form.

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28
Q

What are some features of reticulocytes?

A
  • larger than mature RBCs
  • no nucleus
  • still has some organelles and RNA
  • <1% of circulating RBCs
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29
Q

When do reticulocyte numbers increase?

A

Following haemorrhage or haemolysis

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30
Q

What are normoblasts?

A

Immature nucleated RBCs

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31
Q

Describe some features of platelets

A
  • no nucleus
  • 2-4 um in diam
  • cell fragments
  • come from megakaryocytes
  • contain granules which release their contents
  • life span = 8-10 days
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32
Q

How do WBCs leave blood vessels?

A

Via diapedesis

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33
Q

Describe some features of neutrophils.

A
  • Motile
  • 3 diff types of granules (MPO, lysozyme, collagenase)
  • 3-4 joined lobed nucleus
  • phagocytic
  • degranulate
  • life span = several days
  • involved in acute inflamm
  • rarely found in normal tissues
  • contain Barr body in females
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34
Q

What are the prominent features of granulocytes?

A
  • multi lobated nucleus

- granules

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35
Q

Types of granulocytes.

A
  • neutrophils
  • eosinophils
  • basophils
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36
Q

Describe some features of platelets

A
  • no nucleus
  • 2-4 um in diam
  • cell fragments
  • come from megakaryocytes
  • contain granules which release their contents
  • life span = 8-10 days
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37
Q

What are the 2 types of white blood cells?

A
  • granulocytes

- mononuclear leukocytes

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38
Q

What are the types of mononuclear leukocytes?

A
  • lymphocytes

- monocytes

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39
Q

Types of granulocytes.

A
  • neutrophils
  • eosinophils
  • basophils
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40
Q

What is the other name for neutrophils?

A

Polymorphonuclear leukocyte

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41
Q

Describe some features of eosinophils.

A
  • bilobed nucleus
  • large specific granules
  • exocytose granules
  • involved in allergic rxn and rxns against parasites
  • dense eosin stain
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42
Q

Describe some features of basophils.

A
  • bilobed nucleus
  • large granules containing histamine
  • similar to mast cells
  • degranulate
  • least common
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43
Q

Describe some feature of lymphocytes.

A
  • smallest WBC
  • larger than RBC
  • round densely stained nucleus
  • thin rim of cytoplasm
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44
Q

What are the 3 main types of lymphocytes?

A

B cells
T cells
NK cells

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45
Q

Describe some features of monocytes.

A
  • largest WBC
  • oval/bean shaped nucleus
  • pale nucleus
  • more cytoplasm than lymphocytes
  • precursors of macrophages
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46
Q

What are some roles of bone marrow?

A
  • site of haemopoiesis
  • removal of old RBCs
  • Imm function (B cell differentiation)
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47
Q

Red bone marrow is..

A

Active and haemopoietic

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48
Q

Yellow bone marrow is…

A

Not active and is adipose tissue

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49
Q

All cells are generated from one pluripotential progenitor cell called:

A

Haemopoietic stem cell

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50
Q

Haemopoiesis is tightly controlled via

A
  • growth factors

- microenvironment

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51
Q

What does a full/complete blood exam tell us?

A 
Info about
-RBCs 
-haemoglobin conc
-numbers of diff types of cells
-Electrolytes
-proteins 
-enzymes 
Etc
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52
Q

What are prions?

A

Infectious proteins

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53
Q

Do prokaryotes have a nucleus?

A

No

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54
Q

Describe the appearance of a prokaryotic chromosome.

A

Single closed circle of ds DNA

DNA is looped and supercoiled

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55
Q

Do prokaryotic cells have membrane bound organelles?

A

No

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56
Q

Do prokaryotic cells have ribosomes?

A

Yes 70S

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57
Q

Do eukaryotic cells have ribosomes?

A

Yes 80S

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58
Q

How do prokaryotic cells replicate?

A

Via binary fission

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59
Q

The prokaryotic cytoplasmic matrix is packed with what?

A

Water and ribosomes

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60
Q

Can bacteria carry extrachromosomal DNA?

A

Yes they can carry one or more plasmids

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61
Q

Describe a plasmid.

A
  • Circular, supercoiled piece of dsDNA
  • replicates independently of chromosome
  • variable size and copy number
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62
Q

Describe the bacterial genome

A

Single circular ds DNA with plasmids

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63
Q

What is the main characteristic of viruses?

A

DNA or RNA and a protein coat

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64
Q

How does E. coli acquire new genes?

A

Horizontally by

  • plasmids
  • transposons
  • integrons
  • bacteriophages
  • pathogenicity islands
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65
Q

Describe the basic steps in the gram stain procedure.

A
  • stain with blue dye (all bac is blue)
  • decolourise with alcohol (-bac become invisible, +kept blue dye)
  • stain with red dye
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66
Q

Functions of bacterial cell walls

A
  • rigid layer
  • gives cell shape
  • protects against osmotic lysis
  • protects against harmful substances
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67
Q

The shape and strength of bac cell walls comes from what substance?

A

Peptidoglycan

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68
Q

Describe the cell wall of gram + bac

A
  • thick peptidoglycan layer
  • contains lipoteichoic and teichoic acid
  • p membrane
  • retains blue/purple dye
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69
Q

Describe the cell wall of gram ? bac

A
  • Outer lipopolysaccharide layer
  • thin peptidoglycan layer
  • periplasmic space
  • p membrane

Prevents entry of bile salts and some antibacterials

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70
Q

LPS can act as a what?

A

Endotoxin

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71
Q

What type of cell is a bacterial cell?

A

Prokaryotic cell

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72
Q

What type of cell is a fungi?

A

Eukaryotic cell

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73
Q

What are the 2 main types of fungi?

A
  • yeasts (single cell)

- moulds (filamentous)

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74
Q

What type of cell is a parasite?

A

Eukaryotic cell

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75
Q

List the key components of bac.

A
  • cytoplasmic membrane
  • cytoplasmic matrix
  • ribosomes
  • genome
  • cell wall
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76
Q

Do prokaryotes and eukaryotes have an endoplasmic reticulum?

A

Prok no endoplasmic reticulum

Euk have a endoplasmic reticulum

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77
Q

What are the 3 primary layers in the early embryo?

A
  • ectoderm
  • mesoderm
  • endoderm
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78
Q

Where is collagen type I found?

A

Connective tissue proper
Bone
Tendon
Ligament

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79
Q

Where is collagen type II found?

A

Cartilage

Intervertebral disc

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80
Q

Where is collagen type iii found?

A

Forms reticular fibres

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81
Q

Where is collagen type IV found?

A

Basement membrane.

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82
Q

Where is collagen type VII found?

A

Anchoring fibrils linking to the basement membrane

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83
Q

Describe the collagen present in tendons and ligaments.

A

Type I

Highly organised

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84
Q

Describe the function of reticulin fibres.

A

Thin fibres that provide a delicate supporting framework in certain tissues. Eg bone marrow and liver.

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85
Q

Describe the features of elastin.

A
  • branching fibres or sheets
  • provides elasticity
  • central core of elastin with surrounding network of fibrillin micro fibrils.
  • stains black with special dyes
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86
Q

Where is elastin found in high concs?

A

Aorta
Lungs
Skin

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87
Q

What is Marfan syndrome?

A

Inherited disease of fibrillin 1

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88
Q

From what embryonic layer is epithelium derived from?

A

All 3 layers (endoderm, ectoderm, mesoderm)

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89
Q

What is ground substance?

A

Viscous, clear substance that has a high water content. Often not seen on H&E stains.

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90
Q

What are the main components of ground substance?

A
  • glycosaminoglycans (GAGs)

- glycoproteins

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91
Q

What are GAGs?

A

Long unbranched polysaccharides that attracts Na and with it water because of its negative charge.

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92
Q

What are the main GAGs found in ground substance?

A 
Hyaluronic acid (not linked)
Proteoglycans (linked to proteins)
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93
Q

What are glycoproteins?

A

Glycosylated proteins that are involved in the regulation of deposition and orientation of fibres. They are the LINKS between cells and matrix.

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94
Q

Name some glycoproteins present in ground substance.

A

Fibronectin
Fibrillin
Laminin

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95
Q

What are the roles of ECM?

A
  • structural network
  • metabolic regulatory role
  • mechanical support
  • cell growth and differentiation
  • GFs
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96
Q

Connective tissue is derived from what cell in which layer?

A

Derived from multi potent mesenchymal stem cells in the mesoderm

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97
Q

Muscle is derived from what embryonic layer?

A

Mesoderm

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98
Q

Neural tissue is derived from what embryonic layer?

A

Ectoderm

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99
Q

Explain what connective tissue is.

A

Large continuous compartment between and within organs. There are few cells to a large amount of ECM (fibres and ground substance)

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100
Q

What is the function of connective tissue?

A

It functions to provide support, strength, metabolic, defence and space filling.

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101
Q

Connective tissue fibres are produced by what cell?

A

Fibroblasts

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102
Q

What are the 2 main types of fibres in connective tissue?

A
  • elastin

- collagen

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103
Q

Describe collagen fibres.

A
  • most abundant
  • flexible, strong
  • wavy
  • 3 polypeptide alpha chains that form a triple helix
  • requires vitamin c for formation
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104
Q

What are wandering cells?

A

Lymphocytes
Eosinophils
Plasma cells
Basophils

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105
Q

What are the main cell types that make up bone?

A
  • Osteoid (collagenous type I matrix) that becomes mineralised
  • osteoblasts
  • osteocyte
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106
Q

Describe the cell types that make up basement membrane

A

mainly ECM

  • collagen IV
  • heparan sulphate
  • structural glycoproteins (laminins, fibronectin)
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107
Q

What is another name for basement membrane?

A

Basal lamina

External lamina

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108
Q

What are resident cells

A
  • fibroblasts, myofibroblasts
  • macrophages
  • mast cells
  • mesenchymal stem cells
  • adipocytes
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109
Q

What is the function of fibroblasts?

A

Responsible for the synthesis of ECM.

They are elongated cells with nuclei

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110
Q

Describe macrophages

A

Phagocytic cell that cleans up debris.

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111
Q

Describe mast cells

A

They contain granules containing histamine that are released during inflammation

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112
Q

What is the function of connective tissue proper?

A
  • links and supports organs
  • exchange of nutrients
  • tough but flexible
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113
Q

Describe the lipid present in white adipose tissue

A

One main droplet in the cytoplasm

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114
Q

Describe the lipid present in brown adipose tissue

A

Multiple lipid containing vesicles

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115
Q

What are the main cell types present in cartilage?

A
  • mainly proteoglycan ground substance
  • collagen type II
  • chondrocytes
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116
Q

What is the main type of cartilage?

A

Hyaline

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117
Q

Define homeostasis

A

Maintenance of constant internal environment

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118
Q

Fever is characterised by

A
  • Increase in temp set point

- synthesis of PGE2

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119
Q

Explain why chills occur during fever

A

Heating mechanism activated as set point rises (shivering)

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120
Q

Explain why crisis occurs during fever?

A

Cooling mechanism activated as set point falls (sweating)

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121
Q

Control systems normally operate on what time of feedback?

A

Negative feedback

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122
Q

What does the term regulated variable mean?

A

The thing you wish to control

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123
Q

What does the term sensor mean?

A

The means of measuring the regulated variable

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124
Q

What does the term set point mean?

A

The value you’d like the regulated variable to be

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125
Q

What does the term comparator mean?

A

Means of comparing the regulated variable with the set point

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126
Q

What does the term effector mean?

A

Means of restoring the regulated variable to the set point

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127
Q

Name some situations that can change the set point

A
  • circadian variation
  • ageing
  • in response to persistent changes in ambient levels
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128
Q

Where are the central temperature sensors located and what is their function?

A

-hypothalamus
-spinal cord
Detect warmth

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129
Q

Where are the peripheral temperature sensors located and what is their function?

A

-skin
Detect cold and warmth
Good for early warning of changes in ambient temp

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130
Q

What are the characteristics of the innate Imm system

A
  • rapid
  • no memory
  • recognised shared molecular patters (PAMPS, DAMPS)
  • inherited in the genome
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131
Q

Naive T and B cells migrate from the blood to lymph nodes via

A

High endothelial vessels (HEV)

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132
Q

B cells are found in which part of lymph nodes?

A

Cortex

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133
Q

T cells are found in what part of lymph nodes?

A

Paracortex

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134
Q

Naive lymphocytes return to the blood from LN via

A

Efferent lymphatic and the thoracic duct

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135
Q

What cell links the innate and adaptive systems?

A

Dendritic cell

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136
Q

Name some components of the innate system

A
  • physical barriers
  • antimicrobial chemicals
  • complement
  • epithelial cells, phagocytes, NK cells
  • cytokines
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137
Q

What are the characteristics of the adaptive Imm system?

A
  • recognises Ags
  • slow
  • memory
  • requires gene rearrangement
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138
Q

Name some components of the adaptive Imm system

A
  • lymphocytes
  • abs
  • cytokines
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139
Q

Name some examples of PRRs

A

TLR
NLR
RLH

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140
Q

What is a cytokine?

A

A protein secreted by cells that affects the behaviour of nearby cell bearing the appropriate receptors

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141
Q

What is a chemokine?

A

A secreted protein that attracts cells bearing the appropriate receptors

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142
Q

What are the 2 groups of chemokine receptors?

A

CCR

CXCR

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143
Q

Lymph nodes sample Ags from where?

A

Skin and internal tissues

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144
Q

The spleen samples Ags from where?

A

The blood

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145
Q

Describe some characteristics of acid fast bac

A
  • thick waxy walls
  • peptidoglycan base layer
  • layers of arabinogalactan, mycolic acid and lipid
  • resists drying and harsh chemicals and antibiotics
  • slow growth due to slow nutrient uptake
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146
Q

Where can strict aerobes grow?

A

In O2

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147
Q

Where can strict anaerobes grow?

A

In an environment without O2

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148
Q

Where can facultative anaerobes grow?

A

With or without O2

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149
Q

Can aerotolerant anaerobes survive in O2?

A

Yes

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150
Q

Where do microaerophils grow best?

A

In low concs of O2

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151
Q

Describe bacterial flagella

A
  • thin, long, hollow helical filaments
  • flagellin protein
  • locomotion
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152
Q

What is the O Ag?

A

LPS

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153
Q

What is the H Ag?

A

Flagella

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154
Q

Describe bac pili (fimbriae)

A
  • hair like appendages
  • pilin protein
  • attaches to other cells
  • sex pili= plasmid transfer
  • on most gram -ve bac
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155
Q

Describe bac capsules

A

-polysaccharide
-antigenic
can’t be washed off
-makes colonies appear large and shiny
-visualised by -ve staining
-protects against dehydration and phagocytosis

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156
Q

Describe bac endospores

A
  • resistant dormant structures
  • resistant to heat, UV, dedication, chemicals and stains
  • sporulation occurs when there is a lack of nutrients and moisture
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157
Q

The term fermentation means that the final electron acceptor is:

A

An organic compound

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158
Q

The term respiration means that the final electron acceptor is:

A

Oxygen

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159
Q

The term anaerobic respiration means that the final electron acceptor is:

A

Inorganic compound

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160
Q

What are the diff types of epithelial tissue?

A
  • surface epithelium

- glandular epithelium

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161
Q

What is the function of surface epithelium?

A

Lines surfaces and lumina

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162
Q

What is the function of glandular epithelium?

A

Involved in secretion

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163
Q

What are some functions of epithelium?

A
  • protection
  • barrier
  • absorption
  • secretion
  • receptors
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164
Q

List the different types of surface epithelium

A
  • simple squamous
  • simple cuboidal
  • simple columnar
  • pseudostratified columnar
  • stratified squamous
  • stratified cuboidal
  • other stratified
  • transitional/urothelium
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165
Q

Where is simple squamous epithelium found?

A
  • mesothelium
  • endothelium
  • lining of alveoli
  • lining of glomeruli
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166
Q

Where is simple cuboidal epithelium found?

A
  • thyroid follicles

- renal tubules

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167
Q

What is the function of adherens junctions?

A

Forms strong attachments between cells via linking cells cytoskeleton’s

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168
Q

What are some other names for gap junctions?

A

Nexus or communicating junctions

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169
Q

What is a hemidesmosome?

A

A modified desmosome that links epithelium to basement membrane and underlying connective tissue

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170
Q

Where does a surface columnar layer overlie a myoepithelial layer?

A
  • breast
  • sweat glands
  • salivary glands
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171
Q

Where does a surface columnar layer overlie a basal layer?

A

Prostate

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172
Q

Where is transitional/urothelium found?

A
  • renal pelvis
  • ureters
  • bladder
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173
Q

Describe microvilli

A
  • short
  • most epithelia have a few
  • if numerous= striated/brush boarder
  • increases SA
  • contains cytoskeleton elements (actin)
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174
Q

Describe cilia

A

-long, finger like projections
-core of microtubules
-allows movement in waves
Eg respiratory tract, Fallopian tubes

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175
Q

What components hold zonula adheren junctions together?

A
  • cadherin protein links the 2 cells tog

- plaque/anchoring proteins

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176
Q

What components hold hemidesmosomes together?

A

Integrin binds to laminin which then links epithelial cells to underlying connective tissue (collagen VII)

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177
Q

What are the 4 main types of cell adhesion molecules?

A
  • cadherins
  • integrins
  • selectins
  • immunoglobulin superfamily
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178
Q

Where is dense regular CT found?

A
  • tendons
  • ligaments
  • aponeuroses
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179
Q

What does the term mucosa mean?

A

The layer closest to the lumen. It comprises of lamina propria=surface epithelium and underlying CT

And
Muscularis mucosae=layer of smooth muscle

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180
Q

What does the term serosa mean?

A

The layer furthest from the lumen. Aka serous membrane. It comprises of surface mesothelium, basement membrane and underlying CT

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181
Q

Serous cells often form what..

A

An acinus (a secretory unit)

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182
Q

Describe the staining of serous acini

A

Basophilic at base

Acidophilic at apex

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183
Q

What are the 2 types of glandular epithelium?

A

Exocrine

Endocrine

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184
Q

Where do you find simple tubular glandular epithelium?

A

Colon

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185
Q

Where do you find simple coiled glandular epithelium?

A

Sweat glands

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186
Q

Where do you find simple branched tubular glandular epithelium?

A

Stomach

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187
Q

What are the main substances that exocrine glands secrete?

A

Proteins
Lipids
Glycoproteins

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188
Q

What is serous secretions?

A

Protein in aqueous medium

Eg salivary glands

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189
Q

What is mucous secretions?

A

Glycoprotein in aqueous medium.

Eg respiratory, GIT, cervix

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190
Q

What are goblet cells?

A

Mucous secreting cells packed with membrane bound mucous droplets. Note: the nucleus and organelles are displaced basally. Mucous is none staining in H&E

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191
Q

What are the 2 types of glandular epithelium?

A

Exocrine

Endocrine

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192
Q

What is mucous secretions?

A

Glycoprotein in aqueous medium.

Eg respiratory, GIT, cervix

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193
Q

Define: virus

A

Subcellular genetic elements.

Obligate parasites

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194
Q

What type of capsid symmetry do the poxviruses have?

A

Complex symmetry. They also encode their own proteins for replication (which is rare for a virus)

195
Q

What virus has multi shelled capsids?

A

Rotaviruses. It makes they very hardy, and able to survive passage through the GIT

196
Q

Describe the types of viral genomes

A

ss OR ds DNA
ss OR ds RNA

Can be linear, circular or segmented

197
Q

Describe the further types of ssRNA

A

+ve sense (like mRNA)

?ve sense (complementary to mRNA)

198
Q

Describe the different ways to classify viruses

A

By

  • families
  • genera, species, type
199
Q

How are viruses classified into families?

A

Via

  • type of nucleus acid genome
  • strategy of replication
  • virion morphology
200
Q

What is a distinguishing feature of the DNA virus family?

A

There are no helical DNA viruses

201
Q

What is a distinguishing feature of the RNA virus family?

A

All helical RNA viruses have an envelope

202
Q

What are enteric viruses?

A

Viruses acquired by ingestion of material contaminated with faecal that are localised to the intestinal tract.
Eg rotavirus, astrovirus

203
Q

What are respiratory viruses?

A

Viruses acquired by inhalation if droplets that are then localised to the resp tract.
Eg rhinovirus, adenovirus

204
Q

What is a capsid?

A

Protective protein shell surrounding the viral genome.

205
Q

What are arboviruses?

A

Viruses that you acquire be being bitten by an infected insect.
Eg orbivirus, flavivirus

206
Q

What are sexually transmitted viruses?

A

Acquired by sexual activity. They cause genital lesions(papillomavirus, herpesvirus) or systemic disease(HIV).

207
Q

What are hepatitis viruses?

A

Viruses that target the liver. Can be spread by the enteric route or blood or sexually

208
Q

What are some methods of viral detection?

A
  • direct visualisation by EM
  • viral cultivation
  • viral Ag detection
  • host ab detection
  • viral gene detection
209
Q

What is an important source of new viral diseases in humans?

A

Zoonoses (species jumping)

210
Q

How do you make a specific aetiological diagnosis of an infection?

A
  • demonstrate organism/components/products
  • isolate microorganism
  • demonstrate a serological response
211
Q

Name the techniques used to detect viral Ags

A
  • latex agglutination
  • solid phase assay
  • immunohistochemistry
  • capture assay
212
Q

How do you detect viral nucleic acid?

A

Via

  • hybridisation
  • PCR
213
Q

How do you detect other components of viruses?

A
  • whole genome sequencing

- intact cell mass spect (aka MALDI-TOF)

214
Q

Name some techniques used to demonstrate a serological response in a patient.

A
  • tube agglutination (Widal test)
  • solid phase assay
  • immunoblot (Western blot)
215
Q

What are clusters of capsid protein subunits called?

A

Capsomers

216
Q

What indicates a recent or past infection?

A 
Recent = high levels of specific IgM
Past= rising titre (increasing levels if ab)
217
Q

What is a nucleocapsid?

A

A capsid that is closely associated with the viral nucleus acid.

218
Q

What is a viral envelope?

A

Lipid membrane derived from host cell membrane, surrounding the viral capsid.

219
Q

What is the name for a virus without an envelope?

A

Nacked virus

220
Q

What are expressed on the outside of viral particles?

A

Surface glycoproteins

221
Q

What is a viral matrix?

A

A protein layer connecting the capsid and envelope glycoproteins.

222
Q

How can we visualise viruses?

A

Via transmission electron microscopy or X-ray crystallography

223
Q

What are the types of capsid symmetry?

A
  • icosahedral capsid symmetry
  • helical capsid symmetry
  • complex capsid symmetry
224
Q

Define: necrosis

A

Accidental cell death that induces an inflammatory response

225
Q

Define: apoptosis

A

Programmed/regulated cell death that eliminates unwanted/unrepairable cells with minimal host inflamm response b/c apoptotic bodies form.

226
Q

List the aetiology/causes of necrosis

A
  • hypoxia/anoxia
  • microbial infection
  • drug/toxin induced injury
  • physical trauma
227
Q

What is ischaemia?

A

Hypoxia induced by reduced BF, most commonly due to mechanical arterial obstruction.

Death of cells occurs in 20-30mins!

228
Q

What is infarction?

A

Death of tissue due to loss of blood supply most often as a result of arterial occlusion.

229
Q

Injury can be

A
  • sub lethal

- reversible

230
Q

Describe the Pathogenesis of necrosis.

A
  • loss of p membrane integrity (depletion of mitochondrial ATP)
  • leakage of enzymes
  • protein synthesis fails
  • cell swelling, nuclear dissolution, membrane rupture
  • inflamm response triggered (cell debris is removed by enzymatic digestion and macrophages, tissue repair occurs)
231
Q

Describe some mechanisms of cell injury

A
  • mitochondrial damage (decreased ATP and increased ROS)
  • entry of Ca (increased mitochondrial permeability and activation of enzymes eg proteases)
  • membrane damage (via proteases)
  • protein misfolding
  • DNA damage
232
Q

Describe why reperfusion can cause injury

A

Reperfusion causes mitochondria to produce ROS which damage DNA, modify proteins leading to misfolding or breakage, and cause phospholipid damage.

233
Q

Is apoptosis energy dependent or independent?

A

Energy dependent. Ie ATP processes are still preserved.

234
Q

Describe the nuclear changes evident in necrosis

A
  • pyknosis (n shrinkage)
  • karyorrhexis (n fragmentation)
  • dissolution of nucleus
235
Q

Where does coagulative necrosis occur?

A

Enzymatic dissolution of tissue can occur in solid organs (EXCEPT the brain)

236
Q

Where does liquefactive necrosis occur?

A

Digestion of dead cells thereby transforming tissue into a viscous liquid mass or cavity occurs in the brain.

237
Q

Describe caseous necrosis

A
  • seen in necrotising granulomatous inflammation due to tuberculosis
  • cheese like appearance
  • note: tissue dissolution via enzymes is more advanced than coagulative necrosis but not enough to liquefy the tissue
238
Q

Describe the histology of necrosis

A

Increased cytoplasmic eosinophilia b/c of damaged protein and loss or rRNA

239
Q

What are the two pathways of apoptosis?

A
  • intrinsic/ mitochondrial pathway

- extrinsic/ death receptor pathway

240
Q

List the causes of apoptosis

A
  • DNA damage
  • accumulation of misfolded proteins
  • viral infections
  • immunological rxns
241
Q

Describe the general steps in apoptosis

A
  • signalling
  • execution
  • degradation
  • phagocytic
242
Q

Describe the morphology of apoptosis

A

?cells shrink
?nuclear chromatin condenses
?formation of apoptotic bodies
?phagocytosis of apoptotic bodies via macrophages

243
Q

Describe the features/function of skeletal muscle

A
  • aka= voluntary/somatic/striated muscle
  • attaches to bone to allow movement
  • Giant, multinucleated cells
  • note the nuclei is pushed to the periphery of the cell
244
Q

Describe the features/function of cardiac muscle

A
  • only in the heart
  • also striated muscle
  • single cells connected into a network
  • can contract spontaneously
245
Q

Describe the features/function of smooth muscle

A
  • spindle shaped (fusiform)
  • smaller diam than skeletal muscle
  • associated with hollow viscera, vv, hair follicles
  • sustained contractions
  • central nucleus
  • peripheral organelles
  • NO myofibrils or sarcomeres or t tubules
  • has dense bodies
246
Q

Muscle contraction is initiated by what?

A

A neural AP

247
Q

What is the function of desmosomes in cardiac muscle cells?

A

-reinforce joining of myofibrils

248
Q

What is the function of gap junctions in cardiac muscle cells?

A

gap junctions on longitudinal section (runs parallel to myofibrils) electrically couple cells and coordinate AP

249
Q

Describe the contraction of smooth muscle

A
  • dense bodies are scattered throughout each cell and are connected together via actin and myosin overlapping filaments
  • contraction draws dense bodies together
  • cell shortens/shrinks
250
Q

Describe the amounts of muscle regeneration in the different muscle types

A
  • regeneration capacity varies
  • high plasticity of smooth muscles
  • limited regeneration by skeletal muscle via satellite cells
  • no regeneration of cardiac muscle cells
251
Q

Name 3 other contractile cells

A
  • myoepithelial cells
  • myofibroblasts
  • pericytes
252
Q

Describe myoepithelial cells

A

They surround some exocrine glands. When they contract via actin/myosin they squeeze out gland contents

Eg surround mammary glands

253
Q

Describe myofibroblasts

A

Fibroblasts normally make CT. When CT is injured, scar contained activated fibroblasts which become myofibroblasts. Myofibroblasts pull edges of wounds closed.

254
Q

Describe pericytes

A

They extend around capillaries and regulated capillary blood flow

255
Q

Name the 3 layers of CT that surround axons

A

Epineurium
Perineurium
Endoneurium

256
Q

The cytoskeleton of skeletal muscle is organised into what?

A

Myofibrils

note: they are not an organelle b/c they are not membrane bound

257
Q

What does epineurium surround?

A

Wraps the Whole nerve

258
Q

Contrast the features of type I, IIa and IIb skeletal muscle fibres

A

//fce-study.netdna-ssl.com/2/images/upload-flashcards/97/20/75/8972075_m.jpeg

259
Q

What does endoneurium surround?

A

Wraps individual axons

260
Q

What is a Schwann cell?

A
  • type of glial cell
  • helps axons survive
  • myelinates axons (wraps around multiple times)
261
Q

What is a Node of Ranvier?

A

A gap between myelinated sections of an axon. It increases speed of conduction b/c APs jump node to node.

262
Q

What is a ganglia?

A

Collections of neurons outside the CNS. It includes sympathetic (sensory) and parasymp (autonomic motor) dorsal root ganglia. Satellite cells (glial cells) are present too.

263
Q

What are myofibrils made up of?

A

Sacromeres

264
Q

Describe the basic structure of a sarcomere

A

Each sarcomere has overlapping thick (myosin) and thin (actin) filaments. Z discs are also present which anchor the thin filaments and form a boundary with the next sarcomere.

265
Q

What is the sliding filament mechanism?

A
  • sarcomeres shorten (not the thick or thin filaments)

- sarcomeres are in series therefore the whole myofibril shortens overall leading to muscle contraction

266
Q

What specialised organelle do skeletal muscles have?

A

Sarcoplasmic reticulum which wraps around each myofibril and which is rich in Ca2+ ATPases

267
Q

What are T tubules?

A
  • Structures that surround each myofibril.
  • Note there are 2 T tubules for each myofibril.
  • Their function is to conduct the muscle AP down into the muscle cell to the SR because they penetrate down between sarcomeres.
268
Q

What is an important feature of how cardiac muscle cells communicate?

A

?individual cells are joined by intercalated discs

269
Q

What are the components of cardiac muscle intercalated discs?

A
  • fascia adherentes
  • desmosomes
  • gap junctions on longitudinal section
270
Q

What is the function of fascia adherentes in cardiac muscle cells?

A

-Join myofibrils

271
Q

Name the 5 cardinal features of acute inflammation?

A 
Redness
Swelling
Pain
Heat
Loss of function
272
Q

Describe the vascular response that occurs during acute inflammation

A
  • transient arteriolar constriction
  • arteriolar, capillary and venular dilation
  • increased vascular permeability
  • vasocongestion

(All involve endothelial activation)

273
Q

Function of endothelium

A
  • semi permeable barrier
  • cells linked by junctional complexes
  • synthesises basement membrane
  • prevents blood clotting
  • vascular tone
  • resistant to leukocyte adhesion
  • GFs, cytokines
  • replenished by progenitor cells
274
Q

How does the endothelium prevent blood clotting?

A

Via the compounds nitric oxide and prostacyclin

275
Q

How does the endothelium control vascular tone?

A

Via the compounds nitric oxide, prostacyclin, endothelin

276
Q

Integrin on rolling leukocytes binds to what molecules on the activated endothelium?

A

P selectin and E selectin

277
Q

Describe oedema

A

Abnormal increase in interstitial fluid

278
Q

Describe hyperemia?

A

Active process of vasodilation which results in increase of blood in vv. eg in inflammation and exercise

279
Q

Describe vasocongestion

A

Passive process due to reduced outflow of blood from a tissue

280
Q

When does transudate form?

A

With

  • increased hydrostatic P
  • reduced plasma oncotic P

Note vascular permeability is normal

281
Q

When does an exudate form?

A

When there is

  • increased vascular permeability
  • impaired lymphatic drainage
282
Q

What are the diff types of acute inflammatory exudate?

A
  • purulent/suppurative
  • fibrinous
  • serous
283
Q

Name some examples of suppurative/purulent exudate.

A 
(Bac infections)
Lobar pneumonia 
Bacterial meningitis 
Abscess
Perforated diverticulitis
Generalised acute peritonitis
284
Q

Name some examples of fibrinous exudate

A

Fibrinous pleuritis
Fibrinous pericarditis
Acute appendicitis

285
Q

Name some examples of serous exudate

A

Blister

Pleural effusion

286
Q

What are the two main types of inflammation?

A

Acute

Chronic

287
Q

Describe acute inflammation

A
  • earliest response
  • rapid onset
  • non specific
  • short duration

Features: neutrophils, exudate, vasodilation, macrophages, variable necrosis

288
Q

What is the aim of acute inflammation?

A
  • mediate local defenses
  • destroy infective agents
  • remove debris
289
Q

Describe chronic inflammation

A
  • later response
  • long duration weeks to years)

Features: macrophages, lymphocytes, plasma cells, fibrosis/scarring, immune response

290
Q

What are some causes of acute inflammation?

A
  • infections
  • trauma
  • foreign material
  • burns
  • infarction
291
Q

List some non?receptor targets for drugs

A
  • ion channels
  • enzymes
  • carrier molecules
  • DNA
  • osmotic Pressure
  • direct actions
292
Q

Receptors are the sites of actions of what?

A
  • neurotransmitters
  • hormones
  • 2nd messengers
  • drugs
293
Q

Define: receptor

A

a biological macromolecule/complex that binds another molecule and initiates/modulates signalling or effector activity within a cell

294
Q

Define: ligand

A

a molecule that binds to a receptor

295
Q

Define: binding site

A

the site where ligands bind to binding molecules/targets

296
Q

Define: agonist

A

a ligand that binds to a receptor and activates it. It has affinity and efficacy

297
Q

Define: antagonist

A

a ligand that binds to a receptor without activating it. It has affinity but NO efficacy

298
Q

What are the main classifications of receptors?

A
  • Ligand gated ion channel receptors
  • GPCR
  • Kinase linked receptors
  • Nuclear receptors
299
Q

Describe the features of ligand gated ion channels

A
  • agonist binds directly and regulates the opening of an ion channel
  • the opening of the ion channel induces hyperpolarisation or depolarisation
  • time= msec
300
Q

Name an example of a ligand gated ion channel and its features

A

Nicotinic receptors

  • 5 subunits
  • Ach binds to alpha subunit
  • Na channel opens
  • Na entry–> AP

or Ach receptor

301
Q

Describe the features of GPCRs

A
  • 7 TMS
  • alpha helices
  • mostly on cell surface
  • linked to an effector via G proteins
  • most common type
302
Q

Describe the time scale of GPCRs

A

seconds

303
Q

Name 2 examples of GPCRs

A

Muscarinic receptor

ACh receptor

304
Q

Describe the mechanism of GPCR activation

A

ligand binds and activates G proteins. G proteins can be inhibitory or stimulatory. G proteins inhibit/activate effectors which then produce 2nd messengers. These 2nd messengers can cause Ca2+ release or protein phosphorylation

305
Q

Describe kinase linked receptors

A
  • usually tyrosine or serine linked
  • agonist binds to extracellular domain
  • receptor often dimerises
  • this activates enzymatic activity of the cytoplasmic domain
  • auto and protein phosphorylation
  • causes gene transcription
  • ligand is often large peptides
306
Q

Name 2 examples of kinase linked receptors

A

Growth hormone receptor

cytokine receptors

307
Q

Describe nuclear receptors

A
  • often found intracellularly
  • (lipid soluble) ligand enters cell
  • activates intracellular receptor
  • causes gene transcription
308
Q

Describe the time scale of kinase linked receptors

A

hours

309
Q

Name 2 examples of nuclear receptors

A

oestrogen receptor

glucocorticoid receptor

310
Q

Describe the time scale of nuclear receptors

A

hours

311
Q

Define: pharmacokinetics

A

the study of the movement of drugs into, within and out of the body and factors affecting this

312
Q

Define: pharmacodynamics

A

the study of the drugs pharmacological effect/clinical effects

313
Q

Name a drug that has a narrow therapeutic window

A

phenytoin (digitalis)

314
Q

Name a drug that has a relatively wide therapeutic window

A

paracetamol

315
Q

What is the therapeutic window

A

the range in which you can give a drug that will illicit a beneficial effect but not an adverse effect. i.e. it is the window between the minimum effective conc and the minimum toxic conc.

316
Q

What does isoprenaline act as?

A

beta?1 and beta?2 agonist

317
Q

What does prenalterol act as?

A

beta?1 selective agonist

318
Q

Define: affinity

A

the ability of a drug to bind to its target

319
Q

Define: pharmacological efficacy

A

the ability of the drug once bound, to activate the receptor

320
Q

Full agonists have what type of efficacy?

A

high efficacy

321
Q

Partial agonists have what type of efficacy?

A

low efficacy

322
Q

Define: clinical efficacy

A

the strength of the beneficial effect

323
Q

Name some well known partial agonists

A
  • salbutamol (b2-adrenoceptors)
  • buprenorphin (opiate R)
  • sumatriptan (5-HT1 R)
  • pindolol (b-adrenoceptors)
324
Q

Define: potency

A

how much of a drug is required to produce a particular effect. measured by EC50

325
Q

Over stimulation of a receptor by its ligand often causes what

A

receptor desensitisation

326
Q

List the functions of epithelial cells in innate immunity

A
  • physical barrier
  • dry, no moisture
  • fatty acids
  • commensals
  • microbicidal & inhibitory molecules
327
Q

How do commensals protect against infection?

A
  • produce toxic metabolites
  • bacteriocins/antibiotics via PAMPS on commensals (raises threshold for infection)
  • compete for binding sites
  • control the dev of MALT
328
Q

What are the 4 end results of complement activation

A
  • inflammation via increased BF, permeability, mast cell degran
  • chemotaxis
  • opsonisation
  • lysis via MAC
329
Q

Describe the main steps in the general complement cascade

A
  • activation of complement proenzymes
  • proteolysis of C3–> C3a & C3b via C3 convertase
  • C3b covalently attaches to pathogens surface or abs already bound
  • bound C3b interacts with other molecules to form C5 convertase
  • C5 convertase cleaves C5–>C5a & C5b
  • eventual MAC formation and lysis
330
Q

List Kochs Postulates

A
  • organism is found in all patients with the disease
  • distribution corresponds to lesions
  • cultivate outside host for several generations
  • reproduce the disease in other species
  • demonstrate a specific imm response
331
Q

What must pathogens do to infect mucosal surfaces?

A
  • overcome competition from commensals
  • move through mucus
  • resist mucosal defences
  • adhere
332
Q

How do bacteria adhere to host cells?

A

via surface proteins

  • fimbriae
  • non-fimbriate adhesins
333
Q

What do bacteria adhere to on host cells?

A

host cell glycoproteins

334
Q

Describe the evidence for fimbriae in virulence

A
  • experiments testing virulence of fimbriate and non-fimbriate bac. The non?fimbriate bac (eg ETEC) cause a lower amount of infection/disease in piglets than fimbriate bac. Therefore we assume fimbriae is essential for infection and virulence
  • test virulence via giving anti-fimbrial antibodies. If virulence/disease doesn’t occur then we assume fimbraie is essential
335
Q

What are the 2 routes of entry of bacteria into host tissues?

A
  • through cells via pathogen-mediated endocytosis

- between cells

336
Q

What bacterial surface proteins are involved in pathogen?mediated endocytosis?

A

invasins

337
Q

What is an example of a bacteria that uses invasin to penetrate epithelial cells?

A

Yersinia

gram -ve rod

338
Q

List some strategies employed by bacteria to overcome phagocytosis

A
  • direct evasion via leukocidins, anti-inflammatory toxins and enzymes, and surface anti-phagocytic structures e.g. capsules
  • interfering with opsonins
339
Q

How do capsules enhance virulence?

A
  • electrostatic repulsion
  • resemble host components
  • mask underlying structures
340
Q

What are caspules made out of?

A

polysaccharides

341
Q

What is the evidence for capsules in virulence?

A
  • test virulence of capsulated and unencapsulated bacteria e.g. strep pneumonia. Unencapsulated bac is avirulent
  • Anti-capsular antibodies via passive or active immunisation
342
Q

How do antibodies overcome capsules?

A

IgM and IgG binds and then fixes complement (classical complement pathway). Ig coated bac can then bind to C3b receptors and ig receptors on phagocytes

343
Q

Name 2 examples of bacteria with capsules?

A
  • streptococcus pyrogenes

- meningococcus group B

344
Q

List the bacteriocidal mechanisms of phagocytosis

A
  • lysosomal enzymes and defensins
  • ROS
  • reactive nitrogen intermediates (NO)
345
Q

List some strategies used by intracellular pathogens to resist killing by phagocytes

A
  • inhibit respiratory burst
  • prevent phagolysosome formation
  • escape from phagosome
  • resist bactericidal systems e.g. acid fast bac (thick waxy cell wall)
346
Q

List some strategies that enable pathogens to overcome adaptive immunity?

A
  • direct immunosuppression
  • expression of weak Ags
  • Ag diversity
  • Ag modification (changing Ags during infection)
347
Q

List the stages of infection of a host cell by a pathogen

A
  • colonisation
  • invasion
  • multiplication
  • tissue damage
348
Q

List three mechanisms which occur during bacterial infection which result in tissue damage

A
  • direct toxicity by bacterial toxins
  • cytokines
  • immunopathology
349
Q

What are the 2 main types of bacterial toxins?

A
  • exotoxins

- endotoxins

350
Q

Describe the features of bacterial exotoxins

A
  • secreted
  • toxin is a protein
  • variable resistance to heat
  • high antigenicity
  • can be neutralised by Ab
  • toxoids can be made
  • very high potency
  • highly specific mode of action
351
Q

Describe the features of bacterial endotoxins

A
  • produced by dying cells
  • not secreted/part of cell wall
  • toxin is LPS
  • highly heat resistant
  • variable antigenicity
  • no neutralisation by Ab
  • toxoids can be made
  • moderate potency
  • non specific mode of action
352
Q

what does cytotoxic mean in relation to bacterial toxins?

A

Toxin kills the cell

353
Q

what does cytotonic mean in relation to bacterial toxins?

A

Toxin stimulates the cell e.g. lock jaw

354
Q

Name some examples of extracellular acting toxins that act on intact host cells

A
  • haemolysin

- leucocidins

355
Q

Name some examples of extracellular acting toxins that act on the extracellular matrix

A
  • hyaluronidase

- collagenase

356
Q

What are 2 examples of cytotoxic toxins?

A
  • diphtheria toxin

- shiga toxin

357
Q

What are 2 examples of cytotonic toxins?

A
  • cholera enterotoxin

- heat stable enterotoxin

358
Q

What are the 2 main classes of intracellularly acting toxins?

A
  • simple (not very common)

- bi-functional (A?B type)

359
Q

What is the function of the Ig Fc domain?

A
  • mediates effector functions
  • activation of classical complement pathway
  • delivery of Abs through compartments
360
Q

The heavy chain V?region is comprised of what gene segments?

A

V,D,J

361
Q

The light chain V?region is comprised of what gene segments?

A

VJ

362
Q

Which gene segments are joined first in VDJ recombination?

A

DJ first

363
Q

The TCR alpha chain is comprised of what gene segments?

A

VJ

364
Q

The TCR beta chain is comprised of what gene segments?

A

VDJ

365
Q

What are the 4 main processes that generate diversity?

A
  • Variable region splicing
  • junctional diversity
  • combinatorial diversity
  • somatic hypermutation
366
Q

Describe junctional diversity

A
  • inserting or deleting nucleotides at the time of joining the V(D)J segments
  • makes the greatest contribution to diversity
  • can result in insertion of stop codons, frameshifts etc.
  • mediated by the enzymes TdT and exonucleases
367
Q

What are the names for a B cell when it is undergoing development in the bone marrow?

A

early lymphoid progenitor–> common lymphoid progenitor–> pro-B cell–> pre-B cell –> immature B cell

368
Q

What is the role of Flt3L on the bone marrow stromal cells?

A

Binds to Flt3 on early lymphoid progenitors and promotes the expression of IL-7 R

369
Q

SCF on bone marrow stromal cells binds to what on pro?B cells?

A

cKit

370
Q

What stabilises the u chain when it is expressed on pro?B cells?

A

a light chain analogue

371
Q

In what order do antibodies class switch?

A

IgM–> IgG–> IgE–> IgA

372
Q

Where and when does isotype switching occur?

A

in secondary lymphoid tissues after encounter with Ag

373
Q

What determines the isotype produced?

A

the microenvironment (i.e. cytokines produced by CD4T, TFH, NKcells)

374
Q

What cytokine causes B cells to isotype switch to IgA?

A

TGF-beta

375
Q

What cytokine causes B cells to isotype switch to IgE?

A

IL-4

376
Q

What cytokine causes B cells to isotype switch to IgG?

A

IFN-gamma

377
Q

Isotype switching involves changing what part of the Ig?

A

the constant region on the Fc portion

378
Q

Is isotype switching reversable or irreversable?

A

irreversable because it involves looping out intervening C segments

379
Q

Describe the shape of IgA

A

forms a dimer that is linked by a J-chain

380
Q

Describe the shape of IgM

A

forms a pentamer that is linked by a J chain

381
Q

What antibodies are good at neutralisation?

A

IgG, IgA

382
Q

What antibodies are good at opsonisation?

A

IgG, IgA

383
Q

What antibodies are involved in antibody dependent cytotoxicity?

A

IgG

384
Q

What antibodies are involved in degranulation?

A

IgE

385
Q

What antibodies are involved in complement activation?

A

IgM (most potent)

IgG, IgA

386
Q

What is antibody dependent cellular cytotoxicity?

A
  • when an Ab binds to a target cell via its variable region
  • Ab binds to NK cell via Fcgamma receptor
  • crosslinking results in NK cell killing
387
Q

Describe the process involved in active transport of IgA across mucosal surfaces

A
  • secreted IgA binds to poly Ig receptor
  • transport of IgA bound to receptor across cell
  • IgA is secreted into the lumen with part of secretory component from the receptor still attached
  • this secretory component protects the Ab from degradation
388
Q

Describe affinity maturation

A
  • the process where a B cell increases its affinity for a particular Ag as the immune response progresses.
  • it requires T cell help
  • As Ag levels decrease, B cells with mutations that result in high affinity BCRs are selected for
389
Q

Where is MHC class I found?

A

on all nucleated cells

390
Q

Where is MHC class II found?

A

on APCs

391
Q

What are the diff types of MHC I?

A

HLA-A, -B, -C

392
Q

What are the diff types of MHC II?

A

HLA-DR, -DP, -DQ

393
Q

MHC class I presents what sort of Ag?

A
  • short peptides 8-11 aa long
  • cytosolic/intracellular derived peptides
  • peptides are degraded via a prtoeasome and transported to the ER via peptide transporter TAP
394
Q

MHC class II presents what sort of Ag?

A
  • long peptides 10-30 aa long
  • extracellular derived peptides
  • peptides are endocytosed and degraded in an endosome
395
Q

Describe the structure of MHC class I

A

made up of alpha chains (1-3) and beta-2-microglobulin

396
Q

Describe the structure of MHC class II

A

-alpha chains (1-2) and beta chains (1-2)

397
Q

Where are MHC polymorphisms localised to?

A

the antigen binding cleft

398
Q

What chains in MHC class I vary the most?

A

alpha 1 and alpha 2 chains

399
Q

What chains in MHC class II vary the most?

A

alpha 1 and beta 1 chains

400
Q

What type of MHC class needs to be associated with an invariant chain when it is in the ER?

A

MHC class II

401
Q

What is cross presentation?

A

When peptides derived from the class II processing pathway are process and presented to the class I pathway

402
Q

What does a superantigen do?

A
  • can bind to MHC II and one or more Vbeta chains on TCRs
  • they do not rely on the antigen binding site
  • therefore can activate large numbers of T cells and therefore result in large amounts of non-specific activation
403
Q

What MHC classes do naive B cells express?

A

only MHC I

404
Q

What MHC classes do activated B cells express?

A

MHC I and MHC II

405
Q

What happens when a DC is activated in a tissue which causes it to mature and migrate to LNs?

A
  • loss of anchor molecules
  • increased expression of IL-7R
  • upregs MHC II and I
  • increased ag processing
  • increased adhesion molecules
  • secretion of chemokines and cytokines (IL-12, IL-2)
  • loose capacity to capture ag
  • expression of co-stim molecules (CD80/86)
406
Q

What are the 3 signals that are required for T cell activation?

A
  • TCR binding to peptide + MHC
  • Co-stimulatory molecules (CD28 on T cells binds to CD80/86 on DCs)
  • Cytokines (shapes T cell differentiation)
407
Q

What happens to a T cell that lacks the second and third signal?

A

T cell becomes anergic

408
Q

What are the different CD4 T cell subsets?

A
  • Th1
  • Th2
  • Th17
  • TFH
  • Tregs
409
Q

In the presence of IL?12 CD4 T cells differentiate into what?

A

Th1

410
Q

In the presence of IL?4 CD4 T cells differentiate into what?

A

Th2

411
Q

In the presence of IL-6/IL-21/IL-23/ TGF-beta CD4 T cells differentiate into what?

A

Th17

412
Q

In the presence of IL-6 CD4 T cells differentiate into what?

A

TFH

413
Q

In the presence of TGF-beta CD4 T cells differentiate into what?

A

Treg

414
Q

What cytokines do Th1 cells secrete?

A

IFN-gamma

IL-2

415
Q

What cytokines do Th2 cells secrete?

A

IL-4
IL-5
IL-13

416
Q

What cytokines do Th17 cells secrete?

A 
IL-17A
IL-17F
IL-6
IL-21
IL-22
417
Q

What cytokines do TFH cells secrete?

A

IL-21

418
Q

What cytokines do Treg cells secrete?

A

TGF-beta

IL-10

419
Q

Differentiate between T dependent and T independent responses

A

T dependent

  • protein Ags
  • higher order isotypes
  • higher affinity Abs
  • memory

T- independent

  • polysaccharide/lipids/repetitive structures Ags
  • IgM
  • low affinity Abs
  • no memory
420
Q

When a CD4 T cell is activated by a DC via peptide and MHC what does it upregulate?

A

CD40L

421
Q

What marker does Ag specific B cells downregulate in order to leave the LN?

A

CXCR5 (IL-5)

aka homing marker

422
Q

What marker does Ag specific B cells upregulate in order to leave the LN?

A

CCR7 (IL-7)

423
Q

What is a germinal centre?

A

site of intense B cell stimulation (proliferation and affinity maturation) by TFH cells and FDC (which provide a source of Ag for affinity maturation)

424
Q

What are the effector mechanisms of Th1 cells?

A
  • IFN-gamma activates macrophages and enhances their microbial killing
  • IFN-gamma causes B cells to produce complement fixing and neutralising Abs
  • TNF activates neutrophils
425
Q

What are the effector mechanisms of Th2 cells?

A
  • IL-4 causes B cells to produce neutralising IgG Abs and IgE
  • IL-5 activates eosinophils to combate helminth/allergic rxns
  • IL-13 causes macrophages to have an alternative activation involved in tissue repair
426
Q

Do become activated CD8 T cells must interact with what?

A

Ag presented in MHC I on DCs AND activated CD4 T cells

427
Q

List the ways cytotoxic CD8 T cells kill infected cells

A
  • perforin (punches a hole in the cell) and granzyme (activates apoptosis)
  • FasL binding to Fas on target cell which activates apoptosis
428
Q

Activated CD8 T cells express what cytokines?

A
  • IL-2
  • IFN-gamma
  • TNF-alpha
429
Q

For T cells to move out of the circulation they must express what molecules on their cell surface?

A

VLA-4
CCR5
CXCR3

430
Q

What distinguishing feature does the 5’ end of the sugar?phosphate backbone have?

A

a free phosphate group

431
Q

What distinguishing feature does the 3’ end of the sugar?phosphate backbone have?

A

a free OH group

432
Q

The term exon stands for?

A

Expressing regions

433
Q

The term intron stands for?

A

Intervening regions

434
Q

The 5’ promotor sequence of a gene often contains what?

A

TATA box

435
Q

What does it suggest when a gene has multiple promotors?

A

It can make alternative forms of the protein (i.e. diff sizes or expression in diff cell types)

436
Q

What enzymes are involved in DNA replication?

A
  • helicase (unwinds DNA)
  • RNA polymerase (makes short RNA primer)
  • DNA polymerase (extends from primer with DNA
  • DNA ligase joins fragments tog
437
Q

During transcription RNA polymerase uses what strand of DNA to synthesise mRNA?

A

non-coding (anti-sense) strand as a template

438
Q

What are the 2 main sources of variation?

A
  • genetic factors

- environment

439
Q

What are the 2 main causes of variation?

A
  • mutations

- sexual reproduction

440
Q

What is a silent mutation?

A

where there is no change to aa

441
Q

What is a missense mutation?

A

change to aa

442
Q

What is a nonsense mutation?

A

creates a stop codon, usually results in a truncated protein or mRNA degredation

443
Q

What is a polymorphism?

A

when there is at least 2 or more relatively common alleles of a gene in a pop

444
Q

First cousins are what degree relatives?

A

3rd degree relatives

445
Q

What are first cousins once removed and what degree relatives are they?

A

When mums erin or morgan have a kid. The kid would be a 4th degree relative

446
Q

What are second cousins and what degree relatives are they?

A

If I had a kid and erin or morgan had a kid they would be second cousins and they would be 5th degree relatives

447
Q

What is reduced penetrance?

A

Reduced penetrance when some individuals with a particular genotype don’t have the associated phenotype. e.g. inherited BC

448
Q

what is incomplete dominance?

A

a heterozygotes phenotype is intermediate between two homozygotes. eg achondroplasia (short limbed dwarfism)

449
Q

What is variable expressivity?

A

variable expressivity is when some individuals with a particular genotype have a phenotype with varying severity. e.g. polydactyly

450
Q

Name some examples of autosomal dominant disorders

A

Huntingtons disease

Polydactyly

451
Q

Name some examples of autosomal recessive disorders

A 
sickle cell disease
thalasaemia
albinism
phenylketonuria
Tay sachs disease
452
Q

What is genetic heterogeneity?

A

where more than 1 gene can cause the phenotype. ie diff people can have diff geneotypes but still display the same phenotype. e.g. hearing impairment

453
Q

Describe X?linked recessive inheritance

A

females are often carriers. there is no father?son transmission. e.g. Haemophilia A, Duchenne muscular dystrophy

454
Q

What is X linked dominant inheritance?

A
  • less common
  • twice as common in females cf males
  • males are hemizygous
    e. g. rickets
455
Q

Describe mitochondrial inheritance

A

Mitochondrial DNA is passed through the maternal line. Fathers therefore do NOT pass on their mitochondrial genes
e.g. myoclonic epilepsy

456
Q

What is multifactorial/complex mean in relation to genes?

A

the environment and genes plays a role

457
Q

What does polygenic mean?

A 
more than one gene causes the trait
e.g. height 
spina bifida
anencephaly
cleft palate
458
Q

Name some mediators of acute inflammation that cause vasodilation

A
  • histamine
  • prostaglandins
  • NO
459
Q

Name some mediators of acute inflammation that cause increased vascular permeability

A
  • mast cells
  • serotonin (platelets)
  • bradykinin
  • leukotrienes (cell membranes)
460
Q

Name some mediators of acute inflammation that cause endothelial activation

A
  • TNF

- IL-1

461
Q

Name some mediators of acute inflammation that cause chemotaxis

A
  • complement components
  • bac components
  • chemokines
  • leukotriene B4
462
Q

Name some mediators of acute inflammation that cause tissue damage

A
  • neutrophil granule contents
  • ROS
  • NO
463
Q

Name some mediators of acute inflammation that cause pain

A
  • prostaglandins

- bradykinin

464
Q

Name some mediators of acute inflammation that cause fever

A
  • IL1
  • IL6
  • TNF
  • prostaglandins (PGE2)
465
Q

Functions of prostacyclin (PGI2)

A
  • vasodilation

- inhibits platelet aggregation

466
Q

Functions of thromboxane (TXA2)

A
  • vasoconstriction

- promotes platelet aggregation

467
Q

Functions of PGD2 and PGE2

A
  • vasodilation

- increased vascular permeability

468
Q

Functions of leukotrienes

A
  • vasoconstriction
  • bronchospasm
  • increased vascular permeability
469
Q

What are the major components of granulation tissue?

A
  • inflammatory cells
  • new blood vessels
  • fibroblast migration and proliferation
  • deposition of ECM
470
Q

Distinguish between healing by primary intention and healing by secondary intention

A

Healing by primary intention involves narrow closely opposed edges and results in less dead tissue, less granulation tissue and less scarring.

Healing by secondary intention occurs in larger wounds and results in a larger amount of scar tissue and granulation tissue.

471
Q

Define: juxtacrine

A

between adjacent cells that are in contact. it involves gap junctions

472
Q

Define: autocrine

A

signal is released by a cell that acts on the same cell TYPE or the SAME cell

473
Q

Define: paracrine

A

between nearby cells of a DIFFERENT type

474
Q

Define: endocrine

A

signal/hormone goes into the blood as the target is far away

475
Q

What are the 4 main outcomes of acute inflammation

A
  • resolution
  • healing by repair
  • abscess formation
  • chronic inflammation
476
Q

What are some factors that influences healing

A
  • foreign material
  • infection
  • BF
  • extensive necrosis
  • Radiation
  • movement
  • size, location and type of wound
  • nutrition
  • immune impairement
477
Q

What role does CD21 play in the immune system?

A

It’s the complement (C3b) receptor

Aka CR2

It can bind to complement opsonised to a bacteriums surface that has already been bound my the BCR, thereby enhancing the response.

478
Q

How do resident macrophages and epithelial cells combat intercellular pathogens and stop their spread to nearby cells?

A
  • activation of PRRs cause the release of inflammatory cytokines (type I interferons: IFN alpha and beta)
  • these up regulate MHC I expression
  • and block the translation if viral mRNA in nearby cells
479
Q

Do APCs constitutively express high levels of CD80/CD86?

A

No, they express them when they are activated through PAMPS/DAMPS binding to PRR

480
Q

Where is CD40L expressed?

A

On activated T cells only after they have been activated by APCs

481
Q

Why will a polysaccharide vaccine not work for a child under 2?

A

Because they do not have very good T independent B cell mechanisms. Instead you conjugate a protein onto the polysaccharide so the protein can be broken down into peptides which can be presented in MHC II and then presented to T cells.

482
Q

What is a defining feature of macrophages in chronic inflammation?

A

They fuse together and become multinucleated

483
Q

Describe granulomatous inflammation

A

It develops in response to persistent or non degradable Ags. It is characterised by epitheliod macrophages (with elongated, foot shaped nuclei) that fuse together to form multi nucleated giant cells. Lymphocytes, fibroblasts and necrosis can also be present.

Danielle's MD1 (6 decks)

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