T4 - L2 Autoimmune diseases Flashcards
1
Q
list features of the innate immune system
A
- inflammation in target tissues
- Pattern recognition against broad classes of antigen
- present from birth
- no memory
- no amplification
- little regulation
- fast response (hours-days)
- short duration
- macrophages, dendritic cells, mast cells, neutrophils, complement system
2
Q
list features of the adaptive immune system
A
- learned response in immune organs
- high specific (due to T and B cell receptors)
- strong memory
- strong amplification
- slow response (days to weeks for initial exposure)
- T and B cells
3
Q
what does the adaptive immune system require the innate immune system to do?
A
- present antigen to T cells (dendritic cells)
- T cell cytokines and B cell antibodies activate innate cells to cause inflammation
4
Q
what are some components of innate immune system inflammation?
A
- phagocytic cells e.g. neutrophils, macrophages, dendritic cells
- histamine producing cells e.g. mast cells, basophils, eosinophils
- complement proteins system
- cytokines
- chemokine
5
Q
how do phagocytic cells play a part in innate immune system inflammation?
A
Neutrophils: eat and destroy pathogens
Macrophages: produce chemokines to attract other immune cells
Dendritic cells: also present antigen to adaptive immune system
6
Q
how do cytokines play a part in innate immune system inflammation?
A
Signal between different immune cells (e.g. innate to adaptive, adaptive to innate)
7
Q
how do chemokines play a part in innate immune system inflammation?
A
Attract other immune cells to sites of inflammation
8
Q
what is autoimmunity?
A
the adaptive immune system recognises and targets the body’s own
molecules, cells and tissues
NB: Many cells of the immune system have capacity for autoimmune functions and overlap with normal immune functions e.g. anti-tumour immunity
9
Q
autoimmunity occurs as a result of the innate or adaptive immune system?
A
adaptive immune system
10
Q
how to T cells play a role in autoimmunity?
A
T cells that recognise self antigens
11
Q
how to B cells play a role in autoimmunity?
A
B cells and plasma cells that make autoantibodies
12
Q
inflammation is due to the innate or adaptive immune system?
A
innate immune system
NB: adaptive immune system/T cells and B cells rely on innate immune cells to cause inflammation
13
Q
what is autoinflammation?
A
When innate immune cells become activated, due to dysregulated secretion of pro-inflammatory cytokines and consequent damage to host tissues, it is termed Autoinflammation
14
Q
what are the main characteristics of auto inflammation?
A
- spontaneous attacks of systemic inflammation
- no demonstrable source of infection as cause
- absence of autoantibodies and auto reactive T cells
- no evidence of auto-antigenic exposure
15
Q
autoinflammation occurs as a result of the innate or adaptive immune system?
A
innate immunity
16
Q
what is the main cellular involvement in auto inflammation?
A
neutrophils, macrophages
17
Q
what is the main cellular involvement in autoimmunity?
A
B and T cells
18
Q
what is the main antibody involvement in auto inflammation?
A
few/no antibodies
19
Q
what is the main antibody involvement in autoimmunity?
A
autoantibodies
20
Q
what is the main clinical features of auto inflammation?
A
- recurrent
- unprovoked attacks
21
Q
what is the main clinical features of autoimmunity?
A
continuous progression
22
Q
list some examples of auto inflammatory diseases.
A
- monogenic hereditary periodic fevers e.g. TRAPS
- polygenic Crohn’s disease
- spondylarthropathies
23
Q
list some examples of autoimmune diseases.
A
- monogenic ALPS
- IPEX
- Polygenic RA
- SLE
24
Q
autoimmune diseases all have what in common?
A
breakdown of self-tolerance
25
what 3 things need to happen for autoimmune disease?
- genetic susceptibility
- environmental trigger
- an aspect of immune regulation to not be working
26
where are lymphocytes produced?
bone marrow
27
where do T-cells develop?
originate in bone marrow
mature in thymus
28
what is an autoreactive lymphocyte?
they recognise self
29
where do B-cells develop?
bone marrow
30
what is a thymocyte?
a lymphocyte(t-cell) developing within the thymus gland.
31
describe what is meant but "central tolerance" in the thymus
- pre-cursor T cells enter the thymus
- T-cells are randomly generated different receptors as part of their maturation
- T-cells experience different body antigens in the thymus, those that match - auto reactive T cell get deleted (negative selection)
- T-cells that don't match body antigens get released into the periphery - positive selection
32
what is meant by "negative selection" in central tolerance of the thymus?
T-cells that match self-antigens being deleted
33
what is meant by "positive selection" in central tolerance of the thymus?
T-cells that do not match self-antigens are released into the periphery
34
In central tolerance, carried out by the thymus, what happens to T-cells that have an intermediate level of recognition of self-antigens? (50/50 self/foreign)
turned into
| regulatory T-cells then released into circulation (Tregs)
35
What do Treg cells do?
Tregs are T cells that recognise cells as self and suppress activation of the immune system for that cell to prevent pathological self-reactivity/autotimmune diseases.
36
which MHC class is found on all nucleated cells in the body?
MHC class I
NB: also found on platelets
37
which MHC class is found on all platelet cells in the body?
MHC class I
38
which MHC class is found on antigen presenting cells in the body?
MHC class II
39
which MHC class is found on macrophages in the body?
MHC class II
40
which MHC class is found on dendritic cells in the body?
MHC class II
41
which MHC class is found on B lymphocytes in the body?
MHC class II
42
which MHC class interacts with CD8+ T cells?
MHC class I
43
which MHC class interacts with CD4+ T cells?
MHC class II
44
which genes encode for MHC class I?
HLA-A
HLA-B
HLA-C
45
which genes encode for MHC class II?
HLA-DP
HLA-DQ
HLA-DR
46
You can't inherit T-cells, so why can we inherit immune diseases?
- inherit MHC classes from parents
- some MHC classes favour binding of some antigens rather than other antigens
-
47
which MHC class presents self-antigens?
MHC class I
48
what is the two main roles MHC class I has?
MHC class I presents self-antigens (any antigens from within the cell) useful for:
- Cancer cells - present malignancy on the surface
- Viruses - present virus inside the cell on the surface
49
which MHC class would present malignancy antigens on the surface of cancer cells?
MHC class I
present self-antigens (any antigen from within the cell)
50
which MHC class would present virus antigens on the surface cells?
MHC class I
present self-antigens (any antigen from within the cell)
51
which MHC class would present pathogen/allergen antigens on the surface cells?
MHC class II
- found on the surface of antigen presenting cells e.g. macrophages, dendritic cells etc
52
what happens if the gene FOXP3 is mutated?
Mutations of FOXP3 cause failure to develop regulatory T-cells
Causing severe autoimmunity
53
what happens if the gene PTPN22 is mutated?
Mutations of PTPN22 cause T-cells to be activated more easily
Causing stronger immune response in general
54
are autoimmune diseases more common in female or males?
more common in women
- thought to be a hormonal influence
55
what is the associated between age and autoimmunity?
autoimmunity more common in elderly
- inc with age due to inc exposure to the environment
56
what is a sequestered antigen?
certain sequestered antigens are isolated from the circulation of the blood and the lymph and therefore do not contact the cells of the immune system
e.g. brain, lens of the eye, spermatozoa
57
what is the sequestered antigen hypothesis for autoimmunity?
the immune system doesn't usually see these antigens (e.g. lens of the eye) and so if it comes into contact with them it recognises them as foreign
58
how can the immune system come into contact with sequestered antigens?
environmental triggers:
- infection
- trauma-tissue damage
- smoking
59
what is meant by Molecular mimicry?
possibility that similarities between foreign and self-peptides are sufficient enough to result in the cross-activation of autoreactive T or B cells by pathogen-derived peptides.
60
give an example of molecular mimicry
in rheumatic fever, antibodies against M protein of Streptococcus also react
against the glycoproteins of the heart
[causing heart disease and damage to heart valves]
61
Changes in amount or nature or autoantigens may cause autoimmunity, explain.
After self-antigens are made, sometimes they change.
e. g:
- citrullination of proteins
- tissue transglutamase
- failure to clear apoptotic debris
62
how can citrullination of proteins make them more immunogenic and cause autoimmunity?
- Citrulline is an extra amino acid but not encoded by the DNA
- Citrullination = Citrulline starts appearing within the proteins in the body
- Once proteins become citrullinated, the immune system starts recognising it as foreign = immune response
63
how does citrulline gain access to the human body?
- diet
| - smoking
64
what is Tissue transglutamase, and what is its role in coeliac disease?
Tissue transglutamase alters gluten to help it bind to HLA-DQ
- the subsequent MHC type doesn't recognise normal gluten
- it recognises gluten if it has this alteration to the protein
- People with celiac disease often make antibodies that attack this enzyme. These are called anti-tissue transglutaminase antibodies.
65
citrullination is a type of post-translational modification, what does this involve?
conversion of the amino acid arginine in a protein into the amino acid citrulline.
66
People with celiac disease often make antibodies that attack which enzyme?
Tissue transglutamase
67
how does failure to clear apoptotic debris result in a predisposition for autoimmunity?
increases availability of sequestered antigens inside the cell
e. g. SLE
- antigens in nucleus aren't usually exposed and so not recognised
- cell damage occurs and isn't properly cleaned up antigens in the nucleus are seen by immune system
68
how do auto reactive T cells cause inflammation?
- differentiate into Th1: to make cytokines and stimulates macrophages to produce
more cytokines → inflammation
- differentiate into Th2: help B-cells (also detects antigens) to become antibody
producing plasma cells, which can make autoantibodies → inflammation
69
how do auto reactive B cells cause inflammation?
- directly cytotoxic
- activation of complement
- interferences with normal physiological function
70
features of organ specific autoimmune disease?
- affect a single organ
- autoimmunity restricted to auto antigens of the organ
- overlap with other organ specific diseases
- autoimmune thyroid disease is typical
71
features of systemic autoimmune disease?
- affects several organs simultaneously
- autoimmunity associated with auto antigens found in most cells of the body (e.g. nuclei)
- overlap with other non-organ specific diseases
- connective tissue diseases are typical
72
are connective tissue diseases typical of systemic or organ specific autoimmune disease?
systemic
73
what are some general clinical features of autoimmune disease?
- can affect any organ of the body
- onset: middle age/old age
- more common in elderly
- more common in women
- lifelong-chronic condition
- characteristic exacerbation and remission
- divided into organ specific or systemic
- common for diseases to overlap
74
what type of autoimmune disease is Hashimotos thyroiditis?
organ specific
75
what is Hashimotos thyroiditis?
- Destruction of thyroid follicles by autoimmune process
| - Associated with autoantibodies to thyroglobulin and to thyroid peroxidase
76
does Hashimotos thyroiditis lead to hypothyroidism or hyperthyroidism?
hypothyroidism
77
what are autoantibodies?
an antibody produced by in response to a constituent of its own tissues
78
Hashimotos thyroiditis is associated with autoantibodies that attack what?
thyroglobulin
thyroid peroxidase
79
does Grave's disease lead to hypothyroidism or hyperthyroidism?
hyperthyroidism
80
what is grave's disease?
Inappropriate stimulation of thyroid gland by anti-TSH-autoantibody
- mimics the function of TSH = excess TSH
81
what is myasthenia gravis?
- anti-ACh-autoantibody is bound into the acetylcholine receptor, blocking the binding of ACh preventing the signal to get through.
causing:
- muscle weakness, especially of the eye
82
what type of autoimmune disease is vitiligo?
organ specific
