Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

Unit 9 > Diseases of the Immune System 1 > Flashcards

Diseases of the Immune System 1 Flashcards

1
Q

Features of acute inflammation

A

Physical- trauma, heat and cold uv, radiation
irritant and corrosive substances
microbial infections
immune mediated hypersensitivity
tissue necrosis

-predominantly tissue residents cells and influx of neutrophils

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

Features of chronic irritation

A

Arises when the causative agent cannot be eliminated
- endogenous foreign objects eg gout
- phagocytosis resistance organisms eg TB
-autoimmune conditions

-predominantly T cells, plasma cells, macrophages
-causes tissue damage but also ongoing repair

-tissue injury form oxygen radicals and proteases
-revasculariation due to angiogenic factors
-fibrosis due to GF and fibrogenic cytokines
- continued T cell activity

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

What Is central tolerance

A

Thymus
- education and selection of T cells
Bone marrow
-production of selection of B cells

during development of lymphocytes we have mechanisms to prevent the generation of cells which may recognise self antigens

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

What is peripheral tolerance

A

Preventing aberrant activation of the immune response in the periphery

additional mechanisms to reduce the chance of mature cells being activated

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

B cell receptor development

A
  1. CLP stem cells
  2. Early Pro-B cell
    -heavy chain rearrangement D-J
  3. Late Pro-B cell
    -Heavy chain rearrangement V-DJ
  4. Large Pre-B cell
    -VDJ rearrangement and pre-b celll receptor expressed
    -rearrangement of functional heavy light chain initiates light chain gene rearrangement
    -light chain can undergo successive rearrangements until a functional receptor is formed
  5. Small Pre-B cell
    -V-J light chain rearrangement begins
  6. Immature B cell
    -Light chain rearrangement finished and IgM expressed on surface
  7. Mature B cell
    -immunoglobulin genes rearranged and B cell starts to produce IgD
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

B cell testing for auto reactivity- NO SELF REACTION

A

B cell migrates to periphery expressing surface IgD

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

B cell testing for auto reactivity- multivalent self molecule

A

Either

receptor editing -> release of mature B cell
clonal depletion-> apoptosis

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

B cell testing for auto reactivity- Soluble self molecule

A

B cell migrates to periphery-> anergic in periphery die relatively quickly

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

B cell testing for auto reactivity - low affinity no crosslinking

A

B cell migrates to periphery-> affinity for self but doesn’t react in normal conditions

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

Where does T cell receptor development happen

A

Thymus

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

Process of T cell receptor development

A
  1. CLP stem cell
  2. Thymocytes undergo proliferation
  3. Double negative thymocyte CD3-4-8-
  4. Double positive thymocyte CD3+4+8+
  5. Single positive CD4+ export to periphery and single positive CD8+ export to periphery
  6. Double negative export to periphery
    - those which develop in early life and populate in the epidermis. Later in life they become more established in the epithelium and lymphoid organs
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

How does a double negative thymocyte become a double positive?

A
  1. Double negative thymocyte
  2. Start to rearrange beta chain D-J
  3. Continue rearrange B chain V-DJ. Express pre-TCR with surrogate alpha. If cell fails to make a successful beta- death
  4. Stop rearrangement and start to proliferate
  5. Double positive- start rearrangement of alpha chain
    - life Spain of 3-4 days before either selected or apoptosed.

T cell can continue successive rearrangement of alpha until a functioning receptor is produced

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

What can happen in positive selection of T cell?

A

Does the TCR recognise self MHC and peptide?

YES- MHC1= CD8+
YES- MHC11= CD4+
NO- apoptosis

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

What can happen In negative selection of T cell?

A

Does the TCR bind with a strong affinity to self peptide?

CD8+
YES- apoptosis
NO- released into periphery

CD4+
YES- apoptosis
NO- released into periphery
LOW AFFINITY- natural T reg CD4+CD25+ (anti inflam)

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

What is AIRE gene and what does it do

A

Expressed in the nucleus of medullary stromatolites cells- a subset of thymocyte cortical epithelium

it is s transcriptional regulator which induces expression of self proteins in the thymus

  • teaches T cells about antigens in the body
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What happens if we loose AIRE

A

Can lead to destruction of tissues
-slow and doesn’t necessarily affect all of them

17
Q

Describe antigen segregation (peripheral tolerance)

A

Physical Barrier to the lymphoid system preventing self antigen access
- these tissues often produce TGF-B in homeostatic conditions down regulating any inflammatory responses

18
Q

Describe activation induced cell death ( peripheral tolerance)

A

Persistent high levels of activation and IL-2 leads to the up regulation of FAS and FASL proteins on T cells
- binding of FAS and FASL induced cell death

19
Q

Describe peripheral anergy (peripheral tolerance)

A

T cell require costimulatory molecule expression in order to become activated
- when they are presented antigen without this- they become anergic

20
Q

Describe regulatory T cells (peripheral tolerance)

A

Regulatory T cells suppress the activation of other leukocytes and provide a source of anti-inflammatory cytokines
- they either develop during T cell selection (nTreg) or induced in the periphery by anti-inflammatory cytokines (iTreg)

21
Q

What do natural T regulatory cell do

A

Act to prevent an immune response developing to self antigens

22
Q

receptors of natural T reg cells

A

T cell receptor
CD4
CD25
CTLA4

transcription factor- FOXP3

23
Q

4 ways in which natural T reg cells work

A

COMPETITION
- T cell receptor and CTLA-4 bind to expressed antigen and inhibit activation

CYTOKINE SECRETION
- nTreg secretes IL-10 to alter the phenotype of T helper cell
- stops polarisation of SR T cell

CELL KILLING
- nTregs can release performing and granzymes

IL-2 DEPLETION
- CD-25 has high affinity for IL-2
-preventing SR T cell proliferation

24
Q

How to induce Tregs

A

In the absence of pathogens and IL-6
TGF-B produced in tissues
T cell produces TGF-B and IL-10

In gut
-CD103+ dendritic cells in the gut produce TGF-B and retinoids acid to promote FOXP3 expression
- iTregs are present In large numbers and control the population of effector T cells

25
What happens if there is disregulation of TH17 and Tregs in inflammatory diseases
Th17 cells are associated with several diseases - rheumatoid arthritis - lupus -MS -IBS chronic inflammation and tissue damage with continue to promote the expansion of TH17 cells ( IL-6 and Il-1) IL-17 promotes the release of more pro-inflammatory mediators and MMPs - disruption of this is a target for treatment of inflammatory diseases tocilizumab is humanised anti-Il-6 receptor antibody -disrupts Th17
26
What is immunosuppression?
Reduction in the activity or efficacy of the immune response
27
5 ways in which immunosuppression can occur
AVOID OR RESIST RECOGNITION- herpes - Down regulate or remove immune mechanisms needed to see the pathogen -eg reducing MHC1, block complement cascade DESTROY/INHIBIT HOST RESPONSES- TB,Epstein Barr - inhibit phagosome formation and resides in macrophages. -EB can block adhesion of lymphocytes to infected cells ANTIGENIC VARIATION- influenza -pathogen has many genes to switch its surface antigens or different strains have very different antigens PERSIST AT UNDETECTABLE LEVELS- herpes -virus hides inside host cells and replicates at levels too low to detect. Only re-emerges when host response is low or absent. PREVENT CYTOKINE EXPRESSION- Epstein Barr - produce homologous of cytokine eg IL-10 to prevent adaptive immune response
28
Definition of immunodeficiency
Failure of the immune system to protect the body adequately from infection due to the absence or insufficiency of some component process or substance
29
Features of primary immunodeficiency
Inherited mutations INNATE - deficiencies in complement - susceptibility to extra cellular bacteria particularly Neisseria -problems with phagocytosis -susceptibility to bacteria and fungi -TLR signalling ADAPTIVE - compromised T/B cells -general increased susceptibility - antibodies -No IgA causes susceptibility to respiratory infections
30
Features of secondary innumodeficiency
acquired from external factors DISEASE - cancer, AIDS, pathogens ENVIRONMENTAL FACTORS -starvation, radiation, diabetes MEDICAL INTERVENTION - chemo
31
WHAT IS SCID
Severe combined immunodeficiency - cannot make T cell dependent antibody responses
32
What is ADA (SCID)
Enzyme needed for purine metabolism CLP cannot become thymocyte CLP cannot become Pro B cell
33
What is Yc (XSCID)
Common gamma chain for Il receptors -2,4,7,9,5,21 Thymocyte cannot become Pro T cell
34
Treatments for X linked SCID
Prophylactic treatment -sterile environment, antibiotics, immunoglobulin Bone marrow transplant -relies on close HLA match and successful reconstitution Gene therapy -ADA replaced the gene in peripheral T cells which survived for decade
35
Process for gene therapy for SCID
1. Patients bone marrow is harvested 2. Stem cells are extracted from the harvested bone marrow 3. Missing gene is transfected into viral vector 4. Transformed virus is introduced to cells 5. Transformed stem cells are cryopreserved until needed 6. Patients bone marrow is depleted to make room for new cells 7. Patient receives cells which repopulate the bone marrow and produce the missing protein
36
What does HIV target?
CD4 and uses CCR5 and CXCR4 as co-receptor -infects mucosal CD4+ cells and spread to lymph nodes as T cells enriched with CCR5
37
Disease progression of AIDS
ACUTE PHASE -influenza like symptoms -dec circulating CD4 -activation of CD8 -Virus killing and antibody production CLINICAL LATENCY -persistent replication of virus -dec CD4 -virus mutates rapidly -avoids CD8 cells and antibody responses AIDS -6-20 year latency CD4 cell numbers are at critical level -patients lose cell mediated immunity -lose resistance to opportunistic pathogens -oral candida species are early indicator
38
What is CART-T cells therapy and what are the benefits with HIV
Genetically engineered for their receptor to recognise a disease specific epitope and induce a cytotoxic response. Benefits in HIV treatment - remain active for 6 months (target reactivating HIV) -independent of MHCI which HIV suppresses -can access CNS
39
What are CRISPR and how is it used for HIV
Uses RNA molecules which bind to and target an endonuclease and cause double stranded DNA breaks in the genome -scan be designed to recognise HIV sequences in the genome 1.adeno-associated virus is engineered to deliver the guide RNA and enzymes into cells 2. Complementary guide RNA binds at the inserted HIV sequence and the endonuclease cuts the DNA 3.segment is excised and DNA repairs

Unit 9 (6 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions