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EMS: MoD > Lecture 3- immunodeficiency and autoimmunity > Flashcards

Lecture 3- immunodeficiency and autoimmunity Flashcards

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1
Q

what are the general principles of the immune system?

A

-multi-layer defense
-network of pathogen recognition
effective inter-cellular communication
-many mechanisms for pathogen clearance
-adaptive response to changing pathogens
-self-regulation
-limitation of host damage

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2
Q

self-regulation of immune system

A

important in terms of causing disease. when self-regulation is not correct, disease results

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3
Q

innate immune system

A

neutrophils, macrophages produce simple chemicals that kill bacteria

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4
Q

adaptive immune system

A

more precise and potent but this needs regulation

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5
Q

what are PRR?

A

pattern recognition receptor. they recognise components of the microorganism

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6
Q

what are the different barrier components of the immune system

A

SKIN
tears
saliver

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7
Q

name the different mechanisms of the immune system

A
  • barrier and chemical mechanism
  • PRR
  • cellular-such as phagocytes/natural killer cells
  • humoral
  • cellular
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8
Q

where are the cells of immune system produced?

A

bone marrow from precursors

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9
Q

which precursors do innate immune cells come from

A

myeloid precursors

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10
Q

where do dendritic cells, macrophages, and neutrophils arise from?

A

common stem cell

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11
Q

what do lymphoid precursors divide into?

A

B and T cells

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12
Q

where do B cells mature?

A

initially mature in the bone marrow

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13
Q

where do T cells mature?

A

mature in the thymus.

when released into the periphery, it matures further into specialised TH1 and TH2 cells

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14
Q

autoimmune disease

A

range of conditions where own immune system attacks target or systemic autoimmunity.

has distinct clinical entities

breakdown of self-tolerance

environmental factors acting on favourable genetic background

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15
Q

requirements for autoimmune disease to develop

A

genetic predisposition
environment
immune regulation

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16
Q

what is HLA

A

human leukocyte antigen

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17
Q

where are HLA molecules found?

A

found at the surface of antigen presenting cells and can attach to variety of proteins

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18
Q

what causes rheumatoid arthritis?

A

shared epitopes, several HLA alleles that can present certain proteins in ways to cause the disease.

these are proteins that can be citronated and cause disease chain reaction

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19
Q

what are the risk factors of rheumatoid arthritis?

A

smoking –> cause citronisation more rapidly, leading to damaged proteins and initiate autoimmune response

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20
Q

what is HLA-DRB1?

A

The HLA-DRB1 gene provides instructions for making a protein that plays a critical role in the immune system. The HLA-DRB1 gene is part of a family of genes called the human leukocyte antigen (HLA) complex.

The protein produced from the HLA-DRB1 gene, called the beta chain, attaches (binds) to another protein called the alpha chain, which is produced from the HLA-DRA gene. Together, they form a functional protein complex called the HLA-DR antigen-binding heterodimer. This complex displays foreign peptides to the immune system to trigger the body’s immune response

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21
Q

which HLA-DRB1 is associated with tye 1 diabetes?

A

DR3,DR4

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22
Q

which HLA-DRB1 is associated with graves disease?

A

DR3

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23
Q

which HLA-DRB1 is associated with multiple sclerosis?

A

DR2

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24
Q

which HLA-DRB1 is associated with systemic lupus erythematosus (SLE)?

A

DR2,DR3

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25
Rheumatoid arthritis
DR1, DR4
26
which genetic defect is linked with autoimmune polyendocrine sydrome type 1?
AIRE
27
what is the mode of inheritance for autoimmune polyendocrine syndrome type 1?
Autosomal recessive
28
what is the mechanism of disease for autoimmune polyendocrine syndrome type 1?
adaptive immunity affected | defective thymic expression of self antigen
29
which genetic defect is linked with immune dysregulation, polyendocrinopathy, enteropathy
FOXP3
30
which genetic defect is linked with type 1 diabetes?
insulin gene
31
which genetic defect is linked with type 1 diabetes, rheumatoid arthritis, autoimmune thyroid disease?
PTPN22
32
which genetic defect is linked with type 1 diabetes, autoimmune thyroid disease, rheumatoid arthritis
CTLA4
33
which genetic defect is linked with SLE, type 1 diabetes, rheumatoid arthritis?
PD1
34
which genetic defect is linked with autoimmune polyendocrine syndrome type 2?
unknown
35
which genetic defect is linked with SLE?
IRF5 | complement deficiencies C1Q, C2, C4
36
what is the mode of inheritance for diseases caused by FOXP3 gene?
X-linked recessive
37
what is the mechanism of disease for diseases caused by FOXP3 gene?
- adaptive immunity affected | - defective production of regulatory T cells
38
what is the mechanism of disease for type 1 diabetes caused by deficiency in insulin gene?
- adaptive immunity affected - reduced thymic expression of insulin - reduced negative selection of T cells
39
what is the mechanism of disease for diseases caused by deficiency in PTPN22 gene?
- adaptive immunity affected - reduced thymocyte responsiveness to negative selection - reduced regulatory T cell function
40
what is the mechanism of disease for diseases caused by deficiency in CTLA4?
- adaptive immunity affected - reduced regulatory T cell function - inadequade negative signalling in effector T cells
41
what is the mechanism of disease for diseases caused by deficiency in PD1?
- adaptive immunity affected | - inadequate negative signalling in effector T cells
42
what is the mechanism of disease for autoimmune polyendocrine syndrome type 2
- adaptive and innate immunity affected | - reduced regulatory T cells function
43
what is the mechanism of disease for SLE caused by deficiency in IRF5 gene?
- innate immunity affected | - altered signalling thresholds in TLR(toll-like-receptor) pathway
44
what is the mechanism of disease for SLE caused by deficiency in complement C1Q, C2, C4?
- adaptive and innate immunity affected - altered pathogen recognition - altered effector functions (immune complex clearance)
45
what happens if the thymus doesnt have AIR gene?
it cannot remove potentially self-reactive T cells
46
what are FOXP3 genes important in?
development of T regulatory cells, which is produced centrally in thymus
47
what are other causative associations of autoimmune disease?
- sex --> hormonal influence. woman >> men - age --> more common in elderly - environmental triggers --> infection, trauma-tissue damage, smoking
48
autoreactive B cells and autoantibodies are...
- directly cytotoxic - activation of complement - interfere with normal physiological function
49
autoreactive T cells are...
- directly cytotoxic | - inflammatory cytokine production
50
what is organ specific autoimmune disease?
- affect a single organ - autoimmunity restricted to autoantigens if that organ - overlap with other organ specific diseases - autoimmune thyroid diseases is typical
51
what is systemic autoimmune diseases?
- affect several organs simultaneously - autoimmunity associated with autoantigens found in most cells body - overlap with other non-organ specific diseases - connective tissue diseases are typical
52
what is hashimotos thyroiditis?
- destruction of thyroid follicles by autoimmune process - associated with auto-antibodies to thyroglobulin and thyriod peroxidase - leads to hypothyrodism
53
what is Grave's disease?
inappropriate stimulation of thyroid gland by anti-TSH-auto-antibody -leads to hyperthyrodism
54
list connective tissue autoimmune diseases
- SLE - scleroderma - polymyositis - sjogrens syndrome
55
name a non-specific diagnostic test used for auto-immune disease
inflammatory markers
56
name a disease specific diagnostic test used for auto-immune disease
- auto-antibody testing | - HLA typing
57
why measure autoantibdies
- diagnostic - early diagnosis - pathogenic - subtyping of patients - mointoring of exacerbation/remission - exclusion of diagnosis - cost of treatment
58
what is immunosupression?
a natural or artificial process which turns off the immune respnse, partially or fully, accidentally or on purpose -can result in immunodeficiency
59
what is immunodeficiency?
the lack of an efficient immune system-susceptibility to infections
60
what are the causes of immunodeficiency?
- infection --> the result of transient immunodeficiency -secondary to effects of external factors -primary immunodeficiency --> caused by genetic defects in individual components of immune system -
61
what the causes of secondary or acquired immunodeficiencies?
- stress - surgery/burns - malnutrition - cancer --> esp. lymphoproliferative disease - immunosupressive effect of drugs inc. cancer therapy - irradiation (clinical or other) - AIDS - other infection e.g. measles, TB
62
when are primary immunodeficiency often diagnosed?
childhood - recurrent infection often suggests immunological problem
63
what does SCID stand for?
severe combined immunodeficiency syndrome
64
what happens if there is a defect in both B and T cells?
- SCID - combined immunodeficiency syndrome - bone marrow transplantation curative - gene therapy
65
what are symptoms of defects in T cells?
recurrent infection with opportunistic infection, bacteria, viruses, fungi (candida), protozoa (pneimocystis)
66
why are defects in T cells more severe than defects in just B cells?
because T cells are needed for normal functioning of B cells

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