CASE 6 Flashcards

1
Q

what are the effects of mast cells and basophils in the innate immune system?

A

vascular leak, bronchoconstriction, intestinal hyper mobility, inflammation

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2
Q

what is the effect of eosinophils in the innate immune response?

A

granules contain cytotxic cationic granule proteins (capable of producing tissue damage) and histamine

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3
Q

mast cells vs basophils

A

mast cells — present in relatively high numbers in skin and mucosa, can survive for months or years in situ

basophils — minority population, can only survive a few days in the blood

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4
Q

mast cell responses in the skin

A

increased blood flow and increased permeability — vasoconstriction, endothelial cell activation, cellular recruitment (neutrophils and eosinophils)

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5
Q

mast cells responses in airways

A

decreased diameter and increased mucus — coughing (expulsion), immobilisation of pathogen by mucus and cytoprotection

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6
Q

mast cell responses in GI tract

A

increased fluid secretion and increased peristalsis — expulsion of GIT contents (parasites), immobilisation of pathogen by mucus and cytoprotection

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7
Q

mast cell responses in blood vessels

A

increased blood flow and increased permeability — increased tissue fluid, lymph flow to lymph nodes, cells/protein in tissues

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8
Q

name 2 functions of eosinophils

A
  1. attack multicellular parasites

2. tissue remodelling

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9
Q

what antibody is mainly responsible for the initial immune response after a 1st vaccination?

A

IgM

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10
Q

what antibody is mainly responsible for the initial immune response after the 2nd vaccination?

A

IgG

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11
Q

name 5 actions of T lymphocytes in cell-mediated immunity

A
  1. kill virus-infected cells
  2. resistance against intracellular pathogens
  3. activate macrophages
  4. help antibody respones
  5. immunoregulatory function
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12
Q

T cells cannot see antigen in isolation. what do they need to see it with?

A

need to see antigen in the context of an antigen-presenting cell (eg. dendritic cell) and in the context of MHC

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13
Q

MHC class 1 vs class 2

A
CD8 lymphocytes (cytotoxic T cells and suppressor T cells) — MHC class 1
CD4 (T Helper cells) — MHC class 2
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14
Q

endogenous pathway vs exogenous pathway

A

endogenous pathway (intracellular antigens) — MHC class 1 on outside, viral or intracellular bacteria are fragmented then cross cell membrane by transporter protein. CD8 T cells

exogenous pathway (extracellular antigens) — MHC class 2, endocytosis. CD4 T Helper cells

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15
Q

what is CD3?

A

= part of T cell receptor complex

- all T cells express this

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16
Q

what is CD4+?

A
  • T helper cells
  • MHC Class 2 restricted
  • helps activate Tc cells, activates macrophages (Th1) and helps antibody responses (Th2)
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17
Q

what is CD8+?

A
  • Tc cells

- kill virus infected cells

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18
Q

by what mechanism do T and B cell antigen receptors form?

A

random recombination events and gene rearrangement

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19
Q

how do self-reactive antigen receptors arise and why do we limit the production of them?

A

= random selection of gene segments from a large gene pool generates >10^7 antigen specificities and therefore can generate self-reactive antigen receptors due to the wide range of possibilities.
— we limit the production of self reactive T and B cells to prevent the immune system from making tissue damaging reactions against self proteins

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20
Q

how many rounds of selection to T cells undergo to get rid of unwanted self-reactive T cells and what are the rounds?

A

2 rounds of selection =

  1. positive selection — for host MHC class 1 or 2. at this stage the cells are double positive. if T cell fails to recognise host MHC and self-peptide it is deleted — apoptosis
  2. negative selection — to remove self-reactive T cells. occurs when double positive T cells bind to bone marrow derived antigen presenting cells, macrophages and dendritic cells, expressing class 1 or 2 MHC with self peptides (low affinity cells escape)
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21
Q

what is a double positive T cell?

A

expresses both CD4 and CD8 molecules

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22
Q

what are the 2 populations of T reg cells?

A
  1. natural T regs = produced in thymus

2. inducible T regs = produced in periphery, usually mucosa

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23
Q

what do T reg cells do?

A

produce anti-inflammatory cytokines (inhibit proliferation of nearby cells), IL-10 + TGF-B (control/dampen down immune system responses — prevent allergy and autoimmunity)

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24
Q

what is an autoimmune disease?

A

a disease that develops when a specific immune response develops to self-antigen

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25
Q

what is allergy?

A

inappropriate or excessive immune responses to allergens

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26
Q

what is an allergen?

A

an antigen that triggers allergic respones

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27
Q

what are induction and elicitation?

A
  • induction = 1st exposure — individual is ‘primed’

- elicitation = subsequent exposure to same allergen — sensitised individual shows clinical manifestations

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28
Q

describe the different types of hypersensitivity

A
  • type 1 = immediate hypersensitivity
  • type 2 = cytotoxic reactions
  • type 3 = immune complex disorders
  • type 4 = delayed hypersensitivity
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29
Q

describe type 1 hypersensitivity

A

= acute/immediate — occurs within minutes

  • IgE mediated
  • most allergic reactions (food allergy, asthma, rhinitis, atopic eczema)
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30
Q

how does anaphylactic shock come about after a large load of allergen?

A

large load of allergen —> increases vascular permeability and airway constriction —> can’t supply vital organs and fall in blood pressure —> anaphylactic shock

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31
Q

what is the sensitisation phase of type 1 hypersensitivity?

A
  • the Fc part of IgE binds to mast cells/basophils, exposing its variable region
  • mast cells/basophils are ready to work the next time the pollen appears
  • when the antigen reappears, they will come into contact with sensitised (IgE-loaded) mast cells and stimulate it and cause an initial phase reaction and secondary reaction
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32
Q

how long does IgE loading take?

A

10-15 days

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33
Q

what is the initial phase reaction in type 1 hypersensitivity?

A

upon stimulation, the mast cells undergo degranulation, secreting preformed products (primary mediators)

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34
Q

what are the preformed products (primary mediators)

A

include histamine and proteases

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35
Q

what are the effects of proteases?

A

proteases do further tissue damage, causing the release of more inflammation mediators

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36
Q

what are the effects of histamine?

A
  • vasoconstriction
  • increased vascular permeability leading to partial oedema in the area
  • spasmatogenic: histamine receptor are found on smooth muscle lining of the various tracts. histamine causes them to contract
  • increases glandular secretions = luminal obstruction
  • causes narrowing of the lumen of the tract
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37
Q

what is the secondary reaction of type 1 hypersensitivity?

A

upon stimulation, the mast cells secrete cytokines

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38
Q

what cytokines are secreted by the stimulated mast cells?

A

IL-3, IL-5 and leukotrienes

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39
Q

why are the cytokines termed secondary mediators?

A

because they are not pre-formed

40
Q

what are IL-3 and IL-5?

A

cytokines — they are chemotactic agents for eosinophils

41
Q

what do eosinophils do in the secondary reaction?

A

eosinophils secrete their glandular contents: histaminases (reduce inflammation) and enzymes that destroy leukotrienes (reducing attraction of neutrophils)

42
Q

what is the role of the leukotrienes?

A

attract neutrophils (phagocytic cell)

43
Q

type 1 hypersensitivity reactions effect on the skin

A

increased blood flow and permeability — increased fluid, redness, swelling, rashes

44
Q

type 1 hypersensitivity reactions effect on airways

A

decreased diameter and increased mucus — congestion/blockage of airways (wheezing, coughing, phlegm, swelling/mucus secretion)

45
Q

type 1 hypersensitivity reactions effect on the GI tract

A

increased fluid secretion and peristalsis — expulsion of GI tract contents (diarrhoea, vomiting)

46
Q

type 1 hypersensitivity reactions effect on blood vessels

A

increased blood flow and permeability — increased tissue fluid, lymph flow to lymph nodes, cells/protein in tissues

47
Q

treatment of type 1 hypersensitivity reactions and diagnosis

A

DIAGNOSIS = detection of IgE

  1. antihistamines
  2. mast cell stabilising compounds
  3. topical and systemic corticosteroids
  4. for systemic anaphylaxis: adrenaline (EpiPen)
48
Q

describe a type 2 hypersensitivity reaction

A

= cytotoxic hypersensitivity

  • occurs when IgG or IgM attack intrinsic antigens bound to cell surfaces
  • IgG antibodies against cell/matrix associate antigens causing cell lysis or phagocytosis
  • eg. some drug allergies
49
Q

what is the antigen in a type 2 hypersensitivity reaction?

A

cell/matrix

50
Q

penicillin allergy is a type of what hypersensitivity reaction?

A

type 2

51
Q

describe type 3 hypersensitivity

A

= immune complex hypersensitivity

  • specific immune responses to innocuous antigens resulting in pathology
  • occurs when IgG forms free antigen-antibody complexes i tissue fluids or in circulation that are deposited in different tissues
  • at the sites of deposition, these complexes activate complement and trigger intense inflammation — tissue destruction
  • occurs 9-10 hours after exposure to antigen
  • eg. serum sickness, autoimmune diseases such as acute glomerulonephritis
52
Q

describe type 4 hypersensitivity

A
  • mediated by Th1 cells/ Tc cells
  • signs appear 12-72 hours after exposure
  • antigen presented with MHC2 to a Th1 cell
  • if Th1 cell is primed it will become activated — releases chemokines to recruit macrophages and cytokines (eg. interferon-y) to activate them
  • CD4 cells also secrete IL-2 which activated Tc cells
  • eg. Crohn’s Disease, multiple sclerosis, type 1 diabetes melitus, contact dermatitis
53
Q

what do the activated macrophages do in a type 4 hypersensitivity reaction?

A

release pro-inflammatory factors, leading to local swelling, oedema, warmth and redness

54
Q

diagnosis and treatment of type 4 hypersensitivity reactions

A

DIAGNOSIS — patch testing

treatment: identification of allergen = avoidance, mid to high potency topical corticosteroids, extensive (>20% systemic steroids)

55
Q

what does breastfeeding provide?

A
  1. natural nutrition to newborn and infant
  2. IgG antibodies
  3. secretory IgA antibodies
  4. lysosomes
56
Q

what is the possible consequence of prematurely discontinuing breastfeeding?

A

may facilitate pathogenesis of many chronic diseases later in life eg. autoimmune disorders

57
Q

what is staphylococcus aureus?

A

= gram-positive bacteria

  • round-shaped (cocci-shaped)
  • frequently found in the upper respiratory tract and on the skin
  • common cause of skin infection by breaching the barrier (eg. in dry skin)
58
Q

how do disease associated strains of S. aureus often promote infection?

A

by producing potent protein toxins and expressing cell-surface proteins that bind and inactivate antibodies

59
Q

what is MRSA?

A

methicillin-resistant staphylococcus aureus

60
Q

treatment of a staph infection? problem?

A

penicillin — however penicillin resistance is very common

61
Q

what is eczema?

A

= a chronic inflammation of the skin (“boil over”)

- also referred to as atopic dermatitis (inflammation of the skin)

62
Q

what are the common symptoms of eczema?

A
  • redness
  • skin oedema (swelling)
  • itching and dryness
  • crusting
  • flaking
  • blistering
  • cracking
  • oozing
  • bleeding
63
Q

what are the 2 types of eczema?

A
  1. atopic dermatitis (atopic eczema = type 1 HS)

2. contact dermatitis (type 4 HS)

64
Q

what are the 2 different causes of atopic dermatitis?

A
  1. genetics — inherited mutated gene of filaggrin (ichthyosis vulgaris)
  2. environment — defective barrier function — insufficient filaggrin and immune dysregulation (increases serum IgE 80%)
65
Q

what is filaggrin?

A

involved in keratinocyte adhesion. important in the skin barrier’s function

66
Q

what are the 2 different types of contact dermatitis?

A
  1. allergic: type IV hypersensitivity reaction (delayed)

2. irritant: direct reaction to irritant

67
Q

how can more potent drugs lead to deformation of the skin?

A

a drug of higher potency can have detrimental side effects because steroids work by affecting protein synthesis in the skin and so using a drug of increased potency (or using a drug in the long term) can lead to deformation of the skin

68
Q

what cytokine is responsible for the sensation of an itch?

A

IL-31

69
Q

what are corticosteroids?

A

steroid hormones, either produced by the body or man-made

70
Q

name 2 naturally occurring steroids and where they are produced

A

cortisone and hydrocortisone — produced by the outer portion of the adrenal gland — the cortex

71
Q

name the 2 different types of corticosteroids and what they do

A
  1. GLUCOCORTICOIDS (anti-inflammatory) — suppress inflammation and immunity, and assist the breakdown of fats, carbs, and proteins. increase blood sugar when in stress and inhibit transcription of chemokines (to suppress the immune system)
  2. MINERALOCORTICOIDS (salt-retaining) — regulate the balance of water and salt in the body. promote sodium retention in the kidney
72
Q

in the bloodstream, corticosteroids are bound to transport proteins. what is the name of the proteins?

A

transcortins

73
Q

how to corticosteroids exert their effects?

A

exert their effects by determining which genes are transcribed in the nuclei of their target cells, and at what rates

74
Q

what is the adrenal (suprarenal) gland divided into?

A

divided into 2 parts with separate endocrine functions.

  1. superficial suprarenal cortex
  2. inner suprarenal medulla
75
Q

what is the superficial suprarenal cortex divided into and what are its functions?

A

divided into 3 zones:

  1. outer zona glonerulosa — produces mineralocorticoids (aldosterone)
  2. middle zona fasciculata — produces glucocorticoids (hydrocortisone/cortisol)
  3. inner zona reticularis — produces small quantities of androgens (testosterone)
76
Q

what is the role of the suprarenal medulla?

A

produces epinephrine (andrenaline) and norepinephrine (noradrenaline)

77
Q

what are fever a result of?

A

pyrogens

78
Q

how do viral antigens activate the immune response?

A

presentation with MHC class 1 to CD8 T lymphocytes

79
Q

the clinical manifestations of an immediate hypersensitivity response are triggered when what?

A

mast cells release histamine, serotonin and heparin

80
Q

what is the main function of emollients in the treatment of eczema?

A

to prevent flare ups by preventing the skin from becoming dry

81
Q

what is a characteristic of a gram positive bacteria?

A

airborne mode of spread

82
Q

give a few features of staphylococcus aureus

A
  • gram positive
  • coagulase positive
  • cocci (round) shaped
83
Q

what do aminoglycosides, tetracyclines and macrolides all inhibit in bacteria?

A

protein synthesis

84
Q

how long is the latent stage of HIV?

A

10 yeats

85
Q

T cells which survive selection in the thymus have TCRs specific for which antigens and MHCs?

A

foreign antigenic peptide and self-MHC

86
Q

by the time a keratinocyte reaches the stratum corneum it has been alive for approx how long?

A

35-45 days

87
Q

what primarily causes the swelling in inflammation?

A

increased vasopermeability leads to build-up of fluid in interstitial space

88
Q

what do myeloid precursor cells give rise to?

A

RBCs/erythrocytes, platelets, mast cells, osteoclasts, dendritic cells, monocytes, granulocytes

89
Q

mast cells are the effector cells in which sort of hypersensitivity?

A

type 1

90
Q

which antibiotic is suitable to treat staphylococcus aureus?

A

flucloxacillin (not penicillin, methicillin, amoxicillin)

91
Q

which class of immunoglobulin attaches as an individual molecule to exposed surfaces of basophils and mast cells?

A

IgE

92
Q

what is opsonisation?

A

a coating of antibodies and complement proteins increases the effectiveness of phagocytosis

93
Q

what is the job of Langerhans cells?

A

stimulate an immune response

94
Q

what does the eczema type 1 hypersensitivity reaction involve?

A

IgE cross linking receptors on mast cells causing release of histamine

95
Q

what do natural killer cells do in the innate immune system?

A

recognise abnormalities in cells, such as lack of MHC proteins, and bind to them causing apoptosis