Brainscape's Knowledge GenomeTM

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


See full index

Medical immunology > week 21 p2 > Flashcards

week 21 p2 Flashcards

You may prefer our related Brainscape-certified flashcards:
USMLE® Step 1 flashcards
1
Q

What is central dilemma

A

• Distinguishing defence against dangerous pathogens and chemical substances
• AND
Avoiding unwanted activation of the cells of the adaptive immunity, i.e. T-cells and B-cells

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

What is autoimmunity

A

immunological tolerance that prevents us mounting an immune response to our own tissues and cells
• Mounting an immune response to self-antigens
May be caused by an internal dysregulation of the immune system

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

What is Immunological self-tolerance

A

Controlled inability to respond to self, despite having the capability to do so

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

How des TCR RELATE TO AUTIONIMMUNITY

A

• As the T cell is the principal regulator of the immune system and its normal function depends on immune recognition
or self/non-self discrimination, abnormalities of the idiotypic T-cell receptor (TCR) may be one cause of autoimmune disease.

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

Does innate immunity have this

A

• Limited number and diversity of antigen receptors
• Ligands are common repeating
• structures on pathogens
Self-reactivity does NOT occurs; - Inherent tolerance

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

Does adaptive immunity have this

A

• Enormous diversity of antigen receptors
• Ligands are equally diverse;
• unable to discriminate self and non-self
Self-reactivity is a major issue- Tolerance essential

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

What is the mechanism of tolerance

A
  • 2 types
    • Central Tolerance- Occurs in the primary lymphoid organs
    • Peripheral tolerance- t reg cells migrate to of thymus to the periphery
    • CT- DELATIO OF SELF REACTIVE- T CELLS IN THYMUS , b CELLS IN THE BONE MARROW –AIRE GENE IS EXPRESSIONS
    • PT-INDIFFERENT DELETION- ANERGY OF REG T CELLS- T REG CELLS THEN INHIIT SELF REACTIVE CELLS
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is Aire gene expression

A

• encodes an autoimmune regulator
• Transcription factor expressed in the thymic medulla
• Involved as part of the mechanism for eliminating self-reactive T-cells
By exposing the T-cell population to self- antigens, any T-cells that react to them are eliminated

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is APC in thymus

A
  • Role: positively select T cells capable of recognition and interaction with MHC molecules on their surface
    • Thymocytes enter the cortex of Thymus

then acquire CD4 or CD8 molecules and learn to interact with either MHC Class 2 or MHC Class 1 respectively

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

How does APC in the thymus work

A

• They negatively select T-cells that would react with self-antigens
• Bone marrow derived (haematopoietic) that display self-antigens
• obtained from other cells of the body
• They prime T-cells to need additional signals from the pro-inflammatory environment (sensed by DCs through specific pattern recognition receptors, e.g. Toll-like receptors.
Without co-stimulation T-cells are tolerant

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

What happens cells after this

A

• They negatively select thymocytes of strong self-reactivity,
and also mediate positive selection of T-reg cells

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

Where Is B cells develop from

A
  • Stem cells in bone marrow
    • B cells which meet self-antigen in the marrow are anergised
    • i.e. alive but unresponsive, so they are ‘tolerant
    • Healthy people have self-reactive T and B cells!
    • But most people keep them under control
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is the disadvantage of CT

A

• deletion of self-reactive -T cells in the thymus
• this process is NOT 100% efficient
• Some self-reactive T cells escape to the peripheral lymphoid organs
• Self-reactive cells MUST BE controlled
• (or it could lead to an autoimmune disorders)
SELF REACTIVE -produce antibodies that can react against the body’s own substances

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is + selection T cells

A

Important for immature T-cells (thymocytes)

to be committed to be either T-helper cells or Cytotoxic T-cells

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

What is – selection T cells

A

Recognition of self by thymocytes

generally leads to DEATH

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

Why is T cells deletion of self reactive cells sometimes isnt deficient

A

• T cells- does not bind to receptor or binds self peptides strongly/weakly
Causes deletion of t cell

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

What does Mechanisms of Tolerance In the Thymus mean

A
  • ‘tissue’ antigens are promiscuously expressed within thymic medullary epithelial cell
    • Under the control of the AIRE (autoimmune regulator) gene expressed by medullary epithelial cells
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What happens with AIRE mutations?

A

• Natural or induced mutations of the AIRE (autoimmune regulator) gene results in widespread autoimmune diseases
[Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is an inherited condition that affects many body organs]

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

How does mechanisms of tolerance of CT happens

A

• Deletion of self-reactive cells in the thymus

apoptosis

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

How does mechanism of PT happen

A
  • Deletion causes anergy of reg T cells
    • Delaton also known as Also termed “propriocidal” regulation – where mature T-cells undergo apoptosis in the S-phase of the cell cycle
    • apoptosis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

How does tolerence occurs in the thymus

A

• 2 ways can occur
• Apc binds to thymocytes sue to the strong recognition of self antigen in thymus causes apoptosis- negative selection
Apc binds to thymocytes without strong recognition of self antigen in thymus results in regulatory T cells

22
Q

What is indifference in PT

A

• Restricted migration of naïve cells-(naïve T cells stay in the lymph nodes or circulation)
• Restricted migration of naïve cells- (naïve T cells stay in the lymph nodes or circulation)
Naïve T cell TCRs should have low affinity for self-antigen -(Those with high affinity should have been deleted)

23
Q

what is Autoimmune Disorders

A

• Autoimmunity is when the immune system starts to make T cell
• or antibody responses against self-antigens
It is therefore a breakdown in self-tolerance

24
Q

What is factors causing autoimmunity

A

• Gentic
• Infection and environmental exposure
Both causes immune regulation effects

25
Q

What is immunopathology for Autoimmune disorder

A

• Majority of pathology attributed to the adaptive immune response and dominated by either:
• Cell mediated-Inflammatory cytokine production
• Humoral (antibody) mediated-Immune complexes formation and deposition
Mechanisms mirror hypersensitivities (Types II-IV)

26
Q

What is Cytokines

A

• Innate and adaptive cellular communication
• Distinct innate and adaptive cytokines
Inflammatory mediators -Gamma-IFN and TNF- αlpha are two key players

27
Q

what is Natural killer cells (NK cells)

A

Frequently present in target organs during disease progression

28
Q

What can NK deletion cause

A

NK cell depletion enhances: MS, Colitis

29
Q

What is Toll Like Receptors

A

• Widely expressed (DC, NK, Macrophages)
• Endogenous ligands identified
Activation of autoreactive T and B cells

30
Q

What does Spectrum of Disease

A

Depends on nature of response to specific antigen target

31
Q

What is Systemic autoimmunity e.g. SLE

A

• Immunological damage to many organs / tissues
• Self-reactive T and B-cells
• Autoantibody production
• Immune complex-deposition in blood vessels: Splenomegaly, Glomerulonephritis
And Lymphadenopathy

32
Q

What does Organ-specific, e.g. Type 1 Diabetes

A

What does Organ-specific, e.g. Type 1 Diabetes

33
Q

Monozygotic and dizygotic twins effect autoimmunity

A

• 20%concordance for monozygotic vs 5%for dizygotictwins in both SLE and T1D (IDDM)
MHC genes
• Only 20%concordance for MHC non identical siblings, therefore other genes also involved
Non-MHC

34
Q

Non-MHC alleles link to twins

A

Incidence of autoimmune disease is higher in identical twins than in MHC-identical siblings, e.g. Type 1 Diabetes

35
Q

What are there examples of involvement of non-HLA genes in twins

A

Genes affecting different aspects of tolerance, e.g. AIRE
FoxP3 -CD25+ significant regulator of the regulatory pathway involved in regulatory T-cell development and function
CTLA-4: cell-surface protein on lymphocytes with responsibility for down-regulation of immune respons

36
Q

How can Gender effect Autoimmunity

A

• Females mount more vigorous immune responses:
• produce higher antibody titres
• have higher levels of CD4+ T-helper cells
have significantly higher levels of serum IgM

37
Q

What is the reason that Females are at greater risk, e.g. 3:1 for MS; 9:1 SLE

A

• Oestrogen can stimulate autoantibody production in SLE-prone mice: this can be modulated by anti-oestrogen compounds.
• Testosterone may be effective against autoimmune responses against MS, diabetes, and SLE.
• Prolactin skews the immune response to Th-1 responses.
• Pregnancy promotes Th-2 response to avoid anti-inflammatory environment against foetus:
• SLE gets worse whilst RA and MS improves during pregnancy
T-helper 2 cells (Th-2) stimulate B-cells

38
Q

Infections can cause autoimmunity

A

• Epstein Barr Virus (EBV): a successful human herpes virus that stimulates immune responses
• EBV infect B-cells which become reservoir of infection
• EBV polyclonal activator of B-cells
• Reactivation of persisting Epstein-Barr virus (EBV) in B lymphocytes induces the differentiation of host B cells into plasma cells.
Some EBV-infected B cells can then produce autoantibodies.

39
Q

What are other theories of on the mechanism of autoimmunity

A

• Sequestered self-antigen not seen by developing T and B cells, so when encountered they are perceived as foreign, e.g. sperm antibodies post-vasectomy
• Drugs / viruses that adhere to cell surface which then ‘appears’ foreign because host cell caught up in the attack meant for ‘dangerous’ foreigner, -e.g. methyldopa-RBC -> autoimmune haemolytic anaemia
• ‘Friendly-fire’ Autoreactive lymphocyte activated by cytokines intended to activate a specific lymphocyte against a dangerous antigen, i.e. wrong place-wrong time
Cell injury: impaired clearance of intracellular debris (in apoptosis / necrosis) may stimulate autoantibodies, e.g. to mitochondria, DNA.

40
Q

What is autoimmunity disorder- Graves dioease (hyperthroidism)

A

• Autoantibodies mimic TSH and ‘deceive’ the thyroid into producing more hormones than is needed
~75% of people with an overactive thyroid gland have Graves’ disease

41
Q

What is autoimmunity disease- Hashimoto’s thyroiditis

A

• Antibodies and T cells recognise thyroglobulin and thyroid peroxidase as ‘antigens’ and this
• interferes with iodine uptake, and hence, hypothyroidism (decreased production of thyroid hormones).
Thyroid gland infiltration gives rise to goitre-like features.

42
Q

What is autoimmune disease- pernicious anaemia

A

• Intrinsic factor (IF) is required for successful transport and absorption of Vitamin B12 .
• Pernicious anaemia: caused by lack of intrinsic factor:
In this case: autoantibody attack on gastric parietal cells that synthesise IF or the IF molecule itself.

43
Q

How does autoantibodies target RBC and patelets

A

• Autoantibodies against RBC membrane proteins: Autoimmune haemolytic anaemia
• Autoantibodies against platelet membrane proteins: Idiopathic thrombocytopenic purpura
Results in immune complex uptake by phagocytosis or destruction by triggering classical complement pathway

44
Q

What is autoimmunity diease- Goodpasture’s syndrome:

A

• autoantibodies against basement membrane in lungs and kidney
• Rapid onset occurs in which autoantibodies against collagen type IV bind to the basement membranes in kidneys and lungs
and induce tissue damage through neutrophil recruitment and the injury caused by proteases and reactive oxygen species

45
Q

What is autoimmunity disease- rheumatoid arthritis (RA)

A

• RA, primarily characterised by chronic inflammation in the joints, is induced by autoantibodies to
Citrullinated protein antigens
and a group of autoantibodies called Rheumatoid Factors (mostly
IgM recognising Fc portion of IgG).
Immune complex deposition can cause infiltration, complement activation, and subsequent remodelling.

46
Q

How is MS a autoimmune disease

A

• Is a T cell mediated neurologic disease defective immune response against the CNS myelin antigens
• Few lymphocystis cross the BBB which is normally
• However whets not normal is if that barrier breaks down
• Causes activated of CD4 T cells for myelin antigens and express alpha 4 and beta 1 intrigue
• This binds to vascular cell adhesion molecules causing T cells to migrate out of the blood vessels
• They are reencountered their autoantigen presented by MHCV class II molecules on infiltration macrophage
Causing inflammation

47
Q

Susceptibility factors in the evolution of autoimmune diseases

A

Single genes trait and HLA association

48
Q

How does single gene trait effect

A

• Defects in cytokine production or downstream signalling
• Defects in antigen clearance and presentation, lymphocyte signalling,
co-stimulatory molecules, apoptosis

49
Q

How does HLA association effect

A

• Breakdown of tolerance and autoimmunity exaggerated by Inflammation,
• Tissue injury, Deficient apoptotic cell clearance
Why? Cell debris / intracellular organelle detected as ‘foreign’

50
Q

What is Systemic lupus erythematosus – a systemic autoimmune disease

A

• Prevalence of SLE Highest incidence in Black compared with White ethnicity
• fever, weakness, arthritis, kidney dysfunction, and typical butterfly rash;
• autoantibodies to cells/components such as RBC, platelets, leukocytes, DNA, histones
• Pathological consequences are haemolytic anaemia,
Thrombocytopenic purpura, vasculitis and glomerulonephritis due to immune complex deposition and complement activation

51
Q

What are the theistical strategies

A

• B7 blockage for co stimulatory molecules
• Introduction of self antigen specific T reg clones for infection for T reg issues
• Immune complex removal for antigen clearance
• B cell deletion for APC ore autoantibody secretion
• Cytokine treatment for cytokines issue s
Blockade of TNF ALPHA ( soluble receptor) for inflammatory mediators

Medical immunology (5 decks)

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