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Flashcards in Immunology Deck (131)
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1

What is complement?

A soluble danger recognition and effector mechanism. It is a proteolytic cascade.

2

What are the three pathways of complement?

Classical, alternative and lectin.

3

How is the classical pathway activated?

The C1 complex, this occurs when C1q binds to IgM or IgG complexed with antigens. It is also activated when C1q binds directly to the surface of a pathogen.

4

How is the alternative pathway activated?

It is continuously activated at low levels however it amplifies if it is stabilised. Binding to pathogens activates the alternative pathway, it relies on pathogen carbohydrates.

5

How is the lectin pathway activated?

It is activated by mannose-binding lectin and ficolins instead of C1q.

6

What are the clinical indications of complement disorders?

Recurrent infections in children (especially pulmonary).
Swelling in the hands/face.
Fatigue, butterfly rash, cold sensitivity in the extremities.
Fever and tachycardia after a blood transfusion.
Recurrent infection in end-stage liver disease.
Morning urine colour.

7

Name some examples of complement disorders.

Paroxysmal nocturnal haemoglobinuria, atypical haemolytic uraemic syndrome, hereditary angioedema, SLE.

8

What is the effect of complement on pathogens?

Stimulates phagocytes to clear foreign and damaged material, proxy inflammation to attract additional phagocytes, activation of the membrane attack complex leading to cell lysis.

9

What are the two regions of antibodies and what do they bind to?

Fab - specifically bind to different antigens
Fc - binds to complement, Fc receptors on phagocytes or NK cells

10

What are the 5 classes of immunoglobulins?

IgG, IgM, IgA, IgD and IgE

11

What does IgM do?

It is important in the primary response.

12

What does IgA do?

It is found in secretions and protects mucosal surfaces.

13

What does IgD do?

Function is unknown.

14

What does IgE do?

It is associated with allergic reactions and defence against parasites.

15

What does IgG do?

It is the main type of antibody found in blood and extracellular fluid, it binds many pathogens and protects the body from infection.

16

How do antibodies protect against infection?

Specific binding e.g. neutralise toxins, immobilise motile microbes, prevent binding to and infection of host cells, form complexes.
Enhance innate mechanisms e.g. activate complement, bind Fc receptors on phagocytes, mast cells and NK cells.

17

What do T helper cells do?

They help B cells make antibodies, activate macrophages and NK cells and they help the development of cytotoxic T cells.

18

What do cytotoxic T cells do?

Recognise and kill infected host cells via apoptosis.

19

What do T regulatory cells do?

Suppress immune responses

20

How do T cells recognise antigens?

When they are cell-associated processed antigens.

21

What is the major histocompatibility complex?

It is a set of cell surface proteins. It is important in graft rejections, is very polymorphic and has a major role in initiating T cell responses.

22

On what cells is MHC I expressed on?

It is expressed on all nucleated cells and it displays antigens to CD8+ T cells

23

On what cells in MHC II expressed on?

It is expressed on macrophages, dendritic cells and B cells. It displays antigens to CD4+ T cells.

24

What is the function of interferons?

To limit the spread of viral infection.

25

What is the function of interleukins?

They can be pro- or anti-inflammatory. The function of the immune system depends in a large part on interleukins.

26

What are chemokines?

They direct the movement of leukocytes and other cells from the blood.

27

What does colony stimulating factor do?

They are involved in directing the division and differentiation of bone marrow stem cells.

28

What does tumour necrosis factor do?

They mediate inflammation and cytotoxic reactions.

29

What is the characteristic cell of acute inflammation?

Neutrophil polymorph.

30

What are the initial steps of acute inflammation?

Initial reaction of tissue to injury, dilatation of blood vessels, vascular leakage of protein-rich fluid.

31

What are the possible outcomes of acute inflammation?

Resolution, suppuration, organisation or chronic inflammation.

32

What are the possible causes of acute inflammation?

Microbial infections, hypersensitivity reactions, physical agents e.g. trauma, heat, chemicals e.g. acids, alkalis, bacterial toxins and tissue necrosis e.g. infarction.

33

What is the macroscopic appearance of inflammation?

Redness, heat (systemic and local), swelling, pain and loss of function.

34

What are the early stages of acute inflammation?

Oedema, fluid, fibrin and neutrophil polymorphs accumulate in the extracellular spaces of the damaged tissue.

35

What are the immediate transient causes of increased vascular permeability in acute inflammation?

Chemical mediators e.g. histamine, bradykinin, NO, C5a, leukotriene B4, platelet activating factor.

36

What are the immediate sustained causes of increased vascular permeability in acute inflammation?

Severe, direct vascular injury e.g. trauma.

37

What are the delayed prolonged causes of increased vascular permeability in acute inflammation?

Endothelial cell injury e.g. X-rays or bacterial toxins.

38

What are the chemical mediators of acute inflammation from cells?

Histamine, lysosomal compounds, eicosanoids, serotonin, chemokines.

39

What are the effects of acute inflammation?

Destruction of invading bacteria/microorganisms, empyema, digestion of normal tissues, swelling, inappropriate inflammatory response.

40

What are the systemic effects of inflammation?

Pyrexia, constitutional symptoms, weight loss, reactive hyperplasia of the reticulo-endothelial system, haematological changes, amyloidosis.

41

What are the causes of chronic inflammation?

Primary chronic inflammation, transplant rejection, progression from acute inflammation, recurrent episodes of acute inflammation.

42

What are some examples of primary chronic inflammation?

Infective agent e.g. TB, leprosy
Endogenous e.g. bone, uric acid crystals
Exogenous e.g. silica, asbestos, sutures
Autoimmune e.g. Hashimoto's thyroiditis, rheumatoid arthritis
Primary granulomatous diseases e.g. Crohn's, sarcoidosis

43

What are the macroscopic appearances of chronic inflammation?

Chronic ulcer, chronic abscess cavity, thickening of the wall of a hollow viscus, granulomatous inflammation, fibrosis.

44

What are the microscopic features of chronic inflammation?

Cellular infiltrate consists of plasma cells, lymphocytes and macrophages.
Eosinophil polymorphs may be present.
Macrophages may form giant cells.
May be production of new fibrous tissue from granulation tissue.
May be evidence of continuing destruction of tissue as well as tissue regeneration and repair.
Tissue necrosis may be a prominent feature.

45

What is a granuloma?

An aggregate of epithelioid histiocytes, it may also contain lymphocytes and histiocytic giant cells.

46

What are epithelioid histiocytes?

They have a vague histological appearance to epithelial cells. They have large vesicular nuclei, plentiful eosinophilic cytoplasm and often elongated. They secrete ACE and have little phagocytic activity.

47

What are histiocytic giant cells?

They tend to form where particulate matter is indigestible by macrophages, may contain >100 nuclei, thought to form by accident. They have little phagocytic activity and no known function.

48

Name three types of histiocytic giant cells.

Langhans' giant cells, foreign body giant cells, Touton giant cells.

49

What is the development of immunological memory?

Vaccination/exposure ->
Antigen presentation to T cells ->
Production of IgM ->
Establishment of high specificity IgG ->
Production of lots of IgG

50

What are the different types of patterns the body can recognise?

Gram positive vs. Gram negative
DNA content of viruses e.g. dsDNA
CpG motifs - unmethylated is likely to be bacterial

51

What are Toll-like receptors?

Cell-associated pattern recognition receptors

52

What do Toll-like receptors recognise?

dsRNA, ssRNA, flagelin, viral proteins

53

What is the purpose of Toll-like receptors?

They drive cytokine production by antigen-presenting cells and can increase the likelihood of successful T cell activation.

54

Name some other pattern recognition receptors.

Mannose receptors on macrophages - fungi
Dectin-1 on phagocytes - betoglucans in fungal walls
Scavenger receptors on macrophages

55

What do NOD-like receptors detect?

Intracellular microbial pathogens, peptidoglycan and muramyl dipeptide.

56

What do rig-like receptors detect?

Intracellular double stranded viral DNA and RNA.

57

What response to rig-like receptors enable?

Enable an anti-viral response.

58

What is the ultimate goal of tumour immunology?

To induce clinically effective anti-tumour immune responses that would discriminate between tumour cells and self cells.

59

What is cancer immunosurveillance?

Where the immune system can recognise and destroy nascent, transformed cells.

60

What is cancer immunoediting?

Where the immune system can kill and also induce changes in the tumour resulting in tumour escape and recurrence.

61

What are tumour-specific antigens?

They are only found on tumours and are as a result of point mutations or gene arrangement. They're derived from viral antigens e.g. HPV.

62

What are tumour-associated antigens?

They are found on both normal cells and tumour cells but overexpressed on cancer cells.

63

What is the evidence for tumour immunity?

Spontaneous regression, regression of mets after the primary tumour is removed, infiltration of tumours by lymphocytes and macrophages, lymphocyte proliferation in draining lymph nodes, a higher incidence of cancer in the immunosuppressed.

64

What is tumour escape?

Where the immune responses change tumours so that tumours will no longer be "seen" by the immune system.

65

What is immune evasion?

When tumours change the immune responses by promoting immune suppressor cells.

66

What are privileged site tumours?

Tumours that grown in nodules surrounded by physical barriers such as collagen and fibrin. Sites such as the eye and brain lack an immune response due to the blood brain barrier.

67

What are the mechanisms by which tumours avoid immune recognition?

Low immunogenicity, tumour is treated as a self-antigen, antigenic modulation, tumour-induced immune suppression, tumour-induced privileged site.

68

What is active immunotherapy against cancer?

It WOULD be a vaccination of an augmentation of the host immunity to tumours with cytokines and co-stimulators. It could be: killed tumour vaccines, purified tumour antigen vaccines, APC-based vaccines, cytokine and co-stimulator-enhanced vaccines.

69

What is passive immunotherapy against cancer?

Anti-tumour antibodies.

70

What are tumour macrophages?

They accumulate in hypoxic areas (HIF-1 and vWF involved).

71

What are the three classes of HLA?

Class I: HLA-A, HLA-B, HLA-C
Class II: HLA-DR, HLA-DP, HLA-DQ
Class III: HLA C4A, C4B, C2, TNF alpha, TNF beta, HSP 70

72

What cells are Class I HLA complexes expressed on?

All nucleated cells and platelets; they interact with CD8+ T cells.

73

What cells are Class II HLA complexes expressed on?

B cells, monocytes, dendritic cells and macrophages; they interact with CD4+ T helper cells.

74

What are the events of ischaemia-reperfusion injury in transplantation?

Precipitation traumatic event e.g. CVA, head injury, hypoxia
Resuscitation
Brain death process
Removal of organ
Cold storage of the organ
Transplantation

75

What is the basis of hyperacute organ rejection?

It is due to preformed antibodies and complement-mediated endothelial injury. It happens within minutes of transplantation.

76

What is the basis of acute organ rejection?

It can be T lymphocyte mediated against donor HLA or antibody-mediated.

77

What are the symptoms of acute organ rejection?

Fever, graft tenderness and declining organ function.

78

What is the treatment for cellular rejection?

Methylprednisolone, OKT3, ATG

79

What is the treatment for antibody rejection?

Plasmapheresis, IVIG and rituximab

80

When does chronic organ rejection occur?

>6 months post-transplant

81

In what patients can sensitisation occur?

In patients who are pregnant, blood transfusions, failed renal transplants, viral and bacterial infections.

82

What desensitisation treatments can live donors have?

Plasmapheresis, IGIV, rituximab, tacrolimus, mycophenolate mofetil (MMF), prednisolone.

83

List some immunosuppressive agents.

Steroids: prednisolone
Antiproliferative: azathioprine, mycophenolate mofetil, mycophenolate sodium
Calcineurin inhibitors: ciclosporin, tacrolimus
mTOR inhibitors: sirolimus

84

What is active immunisation?

Manipulating the immune system to generate a persistent protective response against pathogens.

85

What does immunisation with a vaccine do?

Trigger an immune response
Safely mimic the natural infection
Mobilises appropriate arms of the immune system
Generates immunological memory

86

What is passive immunisation?

The transfer of pre-formed antibodies to the circulation

87

Give examples of natural and artificial passive immunisation.

Natural: maternal antibodies passing to the foetus, crossing the placenta
Artificial: IVIG

88

What are the indications of artificial passive immunisation?

Individuals with agammaglobulinaemias
Exposure to disease that causes complications
No time for active immunisation e.g. short incubation time
Acute danger of infection

89

What toxoids are used in vaccines?

Tetanus, botulism, diphtheria

90

What are the aims of a perfect vaccine?

To achieve long term protection
To stimulate B and T cells
To induce memory B and T cells
To stimulate protective high affinity IgG production

91

What are the different types of vaccines?

Whole organism: live, attenuated e.g. BCG, measles
killed, inactivated e.g. anthrax
Subunit: toxoids, antigenic extracts, recombinant proteins
Peptides
DNA vaccines
Engineered virus

92

What are adjuvants?

Any substance that is added to a vaccine to stimulate the immune system, they accentuate the immune response.

93

What should the ideal vaccine be?

Safe
Induce a suitable immune response
Generates T and B cell memory
Should be stable and easy to transport
Not require repeated boosting

94

What are the elements in host defence?

Physical barriers: skin, mucosal surfaces, ciliary function
Humoral factors: complement, collectins, beta-defensins
Phagocytes: macrophages, neutrophils, non-professional phagocyte cells
B cells and antibody production
T cells and cell mediated immunity

95

What infections are associated with HIV?

Viruses: Herpes, CMV, HSV, VZ, HHV-8
Bacteria: mycobacteria, salmonella, listeria, rocardia, S. pneumoniae
Fungi: yeasts candida spp. cryptococcus neoformans, pneumocystis jirovecii
Parasites: spore forming cryptosporidia, toxoplasma gondi, leishmania spp.
Malignancies: EBV-associated lymphoma, CIN

96

What organisms are associated with B cell depletion?

Bacteria: S. pneumoniae, H. influenzae
Enteric: salmonella, shigella, campylobacter, rotaviruses
Parasites: giardia lamblia

97

What is chronic granulomatous disease?

An autosomal recessive or X-linked deficiency of components of the NADPH complex

98

What are the characteristic organisms of chronic granulomatous disease?

S. aureus, S. marcessens, Aspergillus fumigatus

99

How is the diagnosis of chronic granulomatous disease?

Nitroblue tetrazolium test, flow cytometry and genetics

100

What is the treatment of chronic granulomatous disease?

Antibiotics, IFN-gamma, TMP-SMX, itraconazole

101

What is hyperIgM syndrome?

A (mostly) X-linked syndrome where patients lack the CD40 ligand so patients can't switch switch antibodies.

102

What infections do patients with hyperIgM syndrome most commonly get?

Respiratory and intestinal infections.

103

What causes IgA deficiency?

An autoimmune phenomena.

104

What are the symptoms of IgA deficiency?

Sometimes recurrent respiratory and intestinal infections, an increase in allergic phenomena.

105

What causes T-cell deficiency?

Congenital thymic aplasia, it is an autosomal dominant disease where there is a development failure of the 3rd and 4th pharyngeal pouch.

106

What are the other congenital defects associated with T-cell deficiency?

Absent parathyroid gland, congenital heart disease, oesophageal fistulae and a cleft life and/or palate.

107

What is SCID?

Severe combined immunodeficiency disease, it is a serious of heterogenous defects. Patients have graft vs host disease with the mothers T cells.

108

What treatment do patients with SCID require?

Stem cell transplants.

109

What is Wiskott-Aldrich syndrome?

An X-linked condition where patients lack WS protein which regulates the actin cytoskeleton.

110

What infections are patients with Wiskott-Aldrich syndrome prone to?

S. aureus, PCP and molluscum contagiosum.

111

What conditions are patients with Wiskott-Aldrich syndrome prone to?

Thrombocytopenia, bleeding, allergic manifestations, autoimmune features and malignancy, especially of B cells.

112

What is ataxia telangiectasia?

An autosomal dominant condition where patients have a defect in a S/T kinase needed for DNA repair.

113

What conditions can patients with ataxia telangiectasia have?

Lymphopenia, decreased IgA/IgE +/- IgG, sinopulmonary infections, neurologic defects, skin and eye problems, malignancies and progeric effects.

114

What are tests to assess immune function?

Neutrophils: numbers, morphology, flow cytometry
B cells: Ig subsets, numbers and markers, response to vaccines
T cells: subsets, response to T cell dependent vaccines, Genetic testing or detection of particular proteins.

115

What is the basis of immunodeficiency in patients with cancer?

It is a multifactorial immunodeficiency but a major factor is a decrease in neutrophils due to chemotherapy. Sometimes it can be due to the malignancy.

116

What is the basis of immunodeficiency in HIV?

Acquired CD4+ T cell deficiency. There are other immune defects of B cells, CD8+ T cells and macrophages.

117

What are the clinical indications of allergy?

Epithelial - eczema, itching
Excessive mucus production
Airway constriction
Abdominal bloating, vomiting, diarrhoea
Anaphylaxis

118

What is an allergy?

An abnormal response to harmful foreign material e.g. pollen

119

What is atopy?

A tendency to develop allergies.

120

What are the cells involved in allergy?

Mast cells
Eosinophils
Lymphocytes
Dendritic cells
Smooth muscle
Fibroblasts
Epithelial cells

121

What are CD23 proteins?

Low affinity IgE receptors

122

Where are CD23 proteins expressed?

B cells, T cells, monocytes, eosinophils, platelets and neutrophils

123

What does CD23 do?

Regulate IgE synthesis, the triggering of cytokine release by monocytes and antigen presentation by cells.

124

What do mast cells do?

The have a primary role in innate and acquired immunity, they have granules with preformed contents?

125

What are the preformed compounds found in mast cell granules?

Histamine
Chemotactic factors e.g. IL4
Proteases e.g. chymase, tryptase
Proteoglycans

126

What are the lipid-derived mediators found in mast cell granules?

Leukotrienes
Prostaglandin D2
Platelet activating factor

127

What do mast cell chemotactic factors do?

Lead to eosinophil attraction and activation

128

What do mast cell derived cytokines do?

Promote a Th2 response, can lead to B cell class switching.

129

What happens in anaphylaxis?

It occurs in minutes and relies on mast cell and/or basophil activation. It is associated with IgE or direct activation. Serum tryptase and histamine are usually elevated in the blood.

130

What are the systemic effects of anaphylaxis?

CV: vasodilation, increased vascular permeability, decreased BP
Respiratory: bronchial smooth muscle contraction, mucus
Skin: rash, swelling
GI: pain, vomiting

131

What are the treatment strategies for allergens?

Avoid allergens
Desensitise to allergens
Prevent IgE production
Prevent IgE interaction with its receptor
Prevent mast cell activation
Inhibit mast cell products