Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Immunology > Week 16 > Flashcards

Week 16 Flashcards

1
Q

How is EAE induced in murine models?

A

This disease is produced in experimental
animals by injecting them with isolated spinal cord homogenized in complete Freund’s adjuvant.

One of the autoantigens identified in the spinal cord homogenate is myelin basic protein (MBP)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Example of epitope spreading in SLE

A

B cells with BCRs specific for DNA can also internalize histones and present them to histone-specific T cells via MHC II. These histone-specific T cells can then additionally provide help to histone-specific BCRs, leading to the production of histone-specific antibodies.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

autoimmune hemolytic anemia

A

antibodies against self antigens on red blood cells trigger destruction of the cells, leading to anemia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

autoimmune thrombocytopenic purpura

A

autoantibodies against the GpIIb:IIIa fibrinogen receptor or other platelet-specific surface antigens can cause thrombocytopenia (a depletion of platelets), which can in turn cause hemorrhage.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Flt3l–/– mice

A

deficient in dendritic cells (DCs)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Batf3–/–

A

lack cross-presenting DCs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

autoimmune surveillance of hypersecreting mutants (ASHM) theory

A

Postulates that autoimmunity to endocrine and exocrine organs comes from the targeting of hypersecreting parenchymal cells of these organs by the immune system - this typically keeps these organ in proliferative balance, but a shift towards hypersecretion would engender a responding increase in immune reactivity, that could lead to autoimmunity in that organ.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Requirement of autoimmune disease (definition)

A
  1. Involve some sort of component of the adaptive immune system (autoantibodies, T cells)
  2. This leads to an attack on tissue
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Causal/associated factors of autoimmune diseases

A

genetics
physiologic processes
environment

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

genetic factors influencing autoimmune disease

A

sex chromosomes
HLA alleles / SNPs
monogenic (rare)
somatic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

physiologic factors influencing autoimmune disease

A

child development/puberty
pregnancy/menopause
stress/depression/cancer
aging/degeneration

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Environmental factors influencing autoimmune disease

A

microorganisms (microbiome)
UV light / food
toxins (carcinogens)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

6 mechanisms causing/attributed to autoimmune disease

A
  • loss of tolerance
  • alteration of self
  • molecular mimicry
  • B cell epitope spread
  • exposure of a ‘sequestered’ tissue-specific antigen
  • overexuberant self-directed turnover
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are general and specific examples of a loss of tolerance in autoimmune disease?

A

General - loss of Tregs

Specific - escape of TCR clone with high self-reactivity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What are examples of alteration of self that might contribute to autoimmune disease?

A

neo-antigens from mutations/altered splicing

post-translation modifications

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

How is B cell reactivity against the placental/trophoblast antigens prevented?

A

B cells specific for a model trophoblast antigen are strongly suppressed through CD22-Lyn inhibitory signaling, which in turn implicates the sialylated glycans of the antigen as key suppressive determinants.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What might be another role for self-reactive TCRs?

A

Some T cell subsets have been shown to engage in normality sensing in the skin, wherein they engage in clusters that recognize Skint1 on keratinocytes during homeostasis, which primes them for reactivity if this signaling is disrupted.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Concepts to consider in etiology of autoimmune disease

A

Is it single-factor (monomeric, one autoAb, etc) or multi-factoral?

Is X a casual driver versus an amplifier (not sufficient alone) versus a response to a pathological event

Is it adaptive cell intrinsic or extrinsic?

Does it promote a specific reaction or a general risk of autoimmunity?

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

How can genetic association studies assist with the study of the underlying biology of autoimmune disease?

A

While monogenic associations are rare, they are incredibly helpful for delineating specific pathways.

SNPs can associate either with a generalizable loss of tolerance (many autoimmune disease associations) or one specific autoimmune disease, which can implicate that genetic product as being specific for that single autoimmune disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What are the two broad impacts of biological sex on autoimmune disease?

A

system wide amplifiers (sex hormones such as estrogen)

cell-intrinsic impacts (X-linked expression of immune genes)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

How might the X chromosome contribute to autoimmune disease?

A

The X chromosome harbors the highest number of immune-related genes of any chromosome.

X-chromosome inactivation is unique in lymphocytes and pDCs: for example, TLR7 gene escapes X-linked inactivation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

GPR174

A

GPR174 is an X-chromosome-linked G-protein coupled receptor and is thus differentially expressed between males and females.

It interacts with CCL21 in the germinal center - antigen-activated male B cells do not position themselves as efficiently s female B cells in the GC and spend less time in the GC

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What are the strongest gene-associations in autoimmune disease?

A

HLA alleles impose the strongest gene-associations in autoimmunity

Although many HLA alleles are assocaited with heightened risk for autoimmunity, some HLA alleles can even confer protection against autoimmune disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Which HLA isotypes are the most variable?

A

HLA-A, HLA-B, and HLA-C of MHCI are all highly polymorphic

For MHCII, HLA-DR Beta chain is also highly polymorphic and associated with many autoimmune diseases

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What are the mechanisms of HLA impact on autoimmune risk/protection?

A
  1. enhances binding to a self antigen: promotes a T cell response to self
  2. widespread TCR repertoire shaping
  3. HLA locus acts as a transcriptional hub for immune genes (SNPs in this locus than impact expression of immune system genes)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Shared Epitope Theory for RA

A

5 amino acid stretch found in HLA-DRB1 alleles that confer high risk of RA.

This sequence is within the peptide binding pocket and it is hypothesized to promote self-antigen response to citrullinated peptides (post-translationally modified) and promote anti-CCPantibodies, leading to RA.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Do monozygotic twins share TCR repertoires?

A

No, it is still a fundamentally stochastic process that will differ significantly between even identical twins - hence, different autoimmune penetrance between twins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Mechanism of Rheumatic Fever

A

Group A streptococcus infection has molecular mimicry against myosin/laminin and the immune system subsequently attacks the cardiac helical proteins with epitope spreading

Associated with HLA-DR7

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

6 Rheumatic autoimmune disorders

A 
Rheumatoid Arthritis
psoriasis
lupus
myositis
scleroderma
ankylosing spondylitis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Target of rheumatic arthritis disease

A

Synovial joint lining of articular joints (macrophages and fibroblasts that produce synovial fluid)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

Rheumatoid Factor (RF)

A

antibodies against Fc portion of IgG
Most often is an IgM
binds immune complexes, generates larger immune complexes
Present in RA and other autoimmune diseases

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

anti-citrullinated protein antibodies (ACPA)

A

antibodies against citrullinated proteins (fibrinogen, vimentin)
highly specific diagnostic (if you have these, 90% change you will have RA)
marker of bone-erosive disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

Collagen-induced arthritis (CIA)

A

an experimental model of RA, in which an inflammatory articular condition is induced in mice by injecting them with an emulsion of complete Freund’s adjuvant and type II collagen

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

IPEX

A

Immune dysregulation, polyendocrinopathy, enteropathy, X-linked.

caused my missense mutations in Foxp3.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

autoimmune lymphoproliferative syndrome (ALPS)

A

a systemic autoimmune syndrome caused by mutations in the gene encoding Fas

lead to a massive accumulation of lymphocytes, especially T cells, and in mice, to the production of large quantities of pathogenic autoan- tibodies and a disease that resembles SLE

36
Q

NOD2

A

an intracellular receptor for the muramyl dipeptide derived from bacterial peptidoglycan, and its stimulation activates the transcription fac- tor NF􏰝B and the expression of genes encoding pro-inflammatory cytokines and chemokines

Mutations in NOD2 are highly assocaited with CD, as NOD2 ligation in paneth cells leads to AMP production and the sequestering of commensals to the lumen of the intestine.

37
Q

Type I hypersensitivity reactions

A

represent immediate-type allergic reactions mediated by IgE antibodies, with mast-cell activation the major final effector mechanism

38
Q

Type II or III hypersensitivity reactions

A

driven by antigen-specific IgG antibodies, the final effector mechanism being complement (type II) or FcR-bearing cellular effectors (type III)

39
Q

Type IV hypersensitivity reactions

A

depicted as being driven by cellular effec- tors, including lymphocytes and a variety of myeloid cell types

40
Q

atopic march

A

progression of allergic responses in some individuals from atopic eczema in childhood to allergic rhinitis and eventually to asthma in later life

41
Q

Der p 1

A

cysteine protease that is present in the feces of the house dust mite. Cleaves occludin present in the tight junctions of airway epithelial cells, leading to a loss of TJ integrity and abnormal access to underlying APCs

42
Q

Netherton’s syndrome

A

characterized by high levels of IgE and multiple allergies.

caused by a mutation in serine protease inhibitor LEKTI, expressed in the most differentiated viable layer of the skin. Absence of LEKTI in Netherton’s syndrome results in overly active epidermal kallikreins, proteases that can cleave desmosomes in the skin, leading to keratinocyte shedding and disturbed skin barrier function.

43
Q

kallikreins

A

proteases that can cleave desmosomes in the skin. Inhibited by LEKTI.

44
Q

Environmental factors that correlate with a decrease in allergic disease

A

Frequent person:person contact
Natural delivery
breastfeeding
Farming (dust)

45
Q

How does the ‘protective’ lifestyle contribute to decrease in allergic disease?

A

Immune system is exposed to allergens without the damage of the epithelial barrier, which leads to a lack of IL-33 / GM-CSF / TSLP (alarmins) in the context of sensitization. This leads to tolerogenic DCs that lead to Th1 or Tregs, which induce IgG or IgA as opposed to IgE

46
Q

Three columns of allergic sensitization

A

Epithelia, microbiota, and immune cells.

47
Q

What factors may contribute to the atopic march?

A

skin barrier damage (increased TSLP and IL-33)
alterations in the microbiome
genetic predisposition
epigenetic factors

48
Q

Mechanisms of atopic march

A

There is barrier damage in the context of allergen exposure that leads to the activation of innate cells (eosinophils, basophils, etc.), which then recirculate to other environments in the body (i.e. lung) and re-activate upon re-exposure.

49
Q

Genes associated with allergic disease

A

Genes expressed in airway epithelial cells (Chemokines / AMPs/ TJ integrity)

Genes regulating CD4 T cell function and. ILC2 differentiation
(trans factors / cytokines (receptors) / PRRs)

Genes with other functions
(proteinases / signaling proteins / etc.)

50
Q

How is immediate hypersensitivity set up, using HDM as an example?

A

House dust mite contains the enzyme Der p 1, which cleaves occludin in the tight junctions of the epithelial barrier. DCs recognize this enzyme and present it in the LN to T cells in the context of Th2 polarizing signals. These Th2 cells induce B cellsto undergo IgE switching, and this IgE is displayed on FcERI on mast cells back at the mucosal barrier.

51
Q

Enzymes released by mast cells in allergic responses

A

Tryptase, chymase, cathespin G, carboxypeptidase

These degrade the connective tissue

52
Q

Toxic mediators released by mast cells in allergic responses

A

Histamine and herapin

These increase vascular permeability and cause smooth muscle contraction

53
Q

Cytokines released by activated mast cells in allergic response

A

Th2-polarizing cytokines (IL-4, IL-13, IL-33)

Eosinophil-activating cytokines (IL-3, IL-5, GM-CSF)

inflammatory cytokines such as TNFa

54
Q

Chemokine released by activated mast cells in allergic responses

A

CCL3, which attracts monocytes, macrophages, and neutrophils

55
Q

Lipid mediators released by activated mast cells in allergic responses

A

Prostaglandins D2 / E2
Leukotrienes C4, D4, and E4
Platelet activating factor

56
Q

Enzymes released by eosinophils in allergic responses

A

Eosinophil peroxidase
Eosinophil collagenase
Matrix metalloproteinase-9

57
Q

How does epithelial barrier damage lead to allergen sensitization?

A

Epithelial damage leads to the production of IL-25, IL-33, and TSLP, all of which promote ILC2 and DC activation towards Th2 polarization. Further, the translocation of the microbiota further provides an inflammatory context for these reactions.

58
Q

omalizumab

A

anti-IgE biologic for allergy

59
Q

Three stages of allergen desensitization immunotherapy

A

Allergen is introduced to the patient either through oral (OIT) or epicutaneous (ECIT - through a patch) in increasing dose escalation under medical observance. This then enters a plateaued maintenance dosing wherein the same dosage is used overa period of months to years. This is then followed by an avoidance phase - the goal is not to completely abrogate the allergic reaction (impossible), but to raise the threshold so that anaphylaxis is less likely following an accidental exposure.

60
Q

Which receptors on mast cells are responsible for non-IgE mediated allergic responses?

A

FcgRIII binds to immune complexes formed by IgG and allergens, and leads to degranulation, inflammation, etc.

61
Q

Delayed type vs immediate type of allergen hypersensitivity

A

Immediate hypersensitivity is mediated by IgE and mast cells, delayed type hypersensitivity is mediated by Th1 cells.

62
Q

CD23

A

FceRII, low-affinity IgE receptor present on many cells that may have a role for IgE I:C capture by APCs.

63
Q

major factors for mast cell growth and differentiation

A

stem-cell factor (ligand for Kit), IL-3, IL-4, and IL-9.

64
Q

Through which adaptor does FcERI signal?

A

Syk

65
Q

arachidonic acid

A

cleaved from membrane phospholipids by phospholipase A2 during cell activation. Its derivative include eicosanoids such as prostaglandins and leukotrienes.

66
Q

Prostaglandin D2

A

Major prostaglandin produced by mast cells, recruits Th2, eosinophils and basophils.

Ibuprofin and aspirin work by inhibiting its synthesis.

67
Q

How do activated eosino[hils regulate Th1 cells?

A

eosinophils secrete TH2-type cytokines and in vitro can promote the apoptosis of TH1 cells by their expression of IDO and consequent production of kynurenine, which acts on the TH1 cells.

68
Q

eotaxins

A

specificity for eosinophils: CCL11 (eotaxin 1), CCL24 (eotaxin 2), and CCL26 (eotaxin 3)

69
Q

eotaxin receptor on eosinopphils

A

CCR3, is quite promiscuous and binds other CC chemokines, including CCL5, CCL7, and CCL13, which also induce eosinophil chemotaxis and activation

70
Q

major basic protein

A

released in eosinophil degranulation and causes the degranulation of mast cells and basophils

71
Q

Immediate allergic reaction mediators

A

IgE-mediated mast-cell activation, leading to the release of histamine, prostaglandins, and others.

This leads to rapid increase in vascular permeability, edema, reddening, and airway narrowing due to smooth muscle contraction.

72
Q

How does the route off administration of allergen determine the type of IgE-mediated allergic response?

A

Mast cells assocaited with connective tissue and those associated with mucosa have slightly different reactions to FcERI cross-linking.

Systemic allergen activates connective tissue Mast cells, which leads to systemic release of histamine and other mediators.

mucosa-assocaited mast cells release less histamine, and are chracterized more by smooth muscle contraction and mucus- promotion

73
Q

How does epinephrine resolve anaphylactic shock?

A

Epinephrine stimulates B-adrenergic receptors, which causes relaxation of airway smooth muscles, and a-adrenergic receptors, which reverses the cardiovascular effects.

74
Q

Why is penicillin a common allergen?

A

Penicillin acts as a hapten, as it is a small molecule with a highly reactive B-lactam ring that can react with amino groups on host proteins to form covalent conjugates.

75
Q

What happens within chronic exposure of allergen to asthmatic individuals?

A

This leads to chronic inflammation of the airways, characterized by increased numbers of pathologic lymphocytes and other luekocytes, airway hyperreactivity and tissue remodeling - a thickening of the airways walls due to hyperplasia and hypertrophy of the smooth muscle layer. Also, fibrosis.

76
Q

Phenotype of mice lacking the transcription factor T-bet

A

These mice are lacking most Th1 responses, and thus largely polarize towards Th2 responses. They show spontaneous development of asthma-like disease, with airway inflammation and basophils and eosinophils, as well as increased collagen deposition and airway remodeling.

77
Q

What is one of the main causes of hospitalizations for asthmatics?

A

rhinovirus infection, which can augment the asthmatic response

78
Q

Which cells are the most important for transplantation rejection?

A

T cells are essential for graft rejection. Very few T cells are sufficient for graft rejection.

79
Q

Hyperacute rejection of solid organs

A

graft loss within the first 48h of transplant. This is mediated by preformed Abs within the host against transplant endothelial cells. There can also be high-affinity IgG against HLA antigens.

80
Q

Acute rejection in solid organ transplants

A

Occurs within 5-90 days after transplant. Driven by CD8 and CD8s, as well as Mqs. Increased expression of IL-2, IFNg, and TGFB.

81
Q

5 mechanisms of T cell tolerance

A

Central tolerance in the thymus
Peripheral tolerance: apoptosis post-activation
Anergy induced by TCR stim in absence of co-stim
Suppression by Tregs
Ignorance or physical separation from antigen

82
Q

Do foreign peptides or foreign MHCs contribute to alloreactivity in transplantation?

A

It seems likely that both contribute somewhat

83
Q

HSCT

A

Haematopoietic stem cell transplant

84
Q

Direct allorejection

A

Occurs after donor-derived APCs (passenger leukocytes) migrate to the SLO via the circulation and present their donor-derived peptides to the host immune system. Since the central tolerance of the host may not have presented the same peptides, this can lead to activation of T alloreactive T cell, which in turn migrate to and attack the transplant.

85
Q

Indirect allorejection

A

Occurs after recipient APCs present donor antigen to T cells, thus activating them.

86
Q

Why is direct allorejection often quicker than indirect allorejection?

A

Direct allorejection is typically via MHC I (since they are cell-derived proteins), and thus activates CD8 T cells.

Indirect involves the uptake of extracellular antigen by APCs and thus is typically MHC II mediated, thus activating primarily CD4s, although these can in turn activate macrophages and other cells that induce cell damage. Cross-presentation can also directly activate CD8s via this route.

87
Q

Why does hyperacute graft rejection happen so quickly?

A

This is often due to preexisting alloantibodies in the recipient that are specific for ABO antigens that are present in the endothelium. Complement deposition on the endothelium of the graft results in clotting and destruction of the vasculature, leading to deoxygenation and necrosis of the graft.

Immunology (17 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions