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Immunologic and inflammatory disorders/ T cell development Flashcards

1
Q

——————- :a variety of proliferative disorders ‘macrophages’ (= over-production of white blood cells = histiocytes)

A

Histocytosis

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2
Q

Histiocytes can lead to ———- and ———–formation

A

Histiocytes can lead to organ damage and tumour formation

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3
Q

Is Langerhans cell histocytosis a sytemic disease?

A

Yes

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4
Q

What are langerhans cells?

A

type of WBCs that help the body fight infections (provide immunity)

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5
Q

bulidup of langerhans cells in certain body parts will lead to?

A

tumours or organ damage

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6
Q

LCH in children vs Adults

A

children –> acute disseminated multisytem disease
Adults –> Indolent Single organ disease

* indolnet –> slowly growing

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7
Q

Piutuitary invlovlement in LCH in adults is assocaited w?

A

Diabetes Insipidus

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8
Q

Calssification of langerhans cell Histocytosis

A

1) Acute disseminated LCH (Letterer - Siwe ds)
2) Multifocal LCH- multifocal eosinophillic granuloma ( Hand-Schuller-Christian disease)
3) Unifocal LCH - Unifocal Eosinophilic granuloma

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9
Q

CF of Acute disseminated LCH (Lettere- Siwe disease)

A
  • mainly occur before the age of 2
    1) Cutaneous abnormalities are present in almost 80% of patients (trunk and scalp)
    2) hepatosplenomegaly
    3) lyphadenopathy
    4) lung involvement
    5) destructive osteolytic bone lesions
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10
Q

In Acute disseminated LCH (Letterer - Siwe disease), when extensive BM involvement occurs pateints present w?

A

1) anemia, thrombocytopenia
2) recurrent infection (otitis media, mastoiditis)
3) if untreated can rapidly be fatal
(with intensive chemotherapy 50%, 5 year survival)

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11
Q

where are Langerhan cells found

A

Skin, spleen, lungs, bone marrow, liver, lymph nodes, skull

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12
Q

in Chronic Unifocal LCH bony lesions may cause ———?

A

Otitis media

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13
Q

CF/Epi of Multifocal LCH (Multiple Eosinophilic granuloma)

A

Classic HSC triad : Calvarian bone defects , exophthalmus , DI

  • Epi : 2-4 yrs

* Calvarian bone : skull

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14
Q

CF/Epi of Unifocal LCH - unifocal eosinophilic granuloma

A
  • Epi: age 5-15 years

1) Solitary clavarial lesions - solitary lesion of skull / vertebra /rib / mandible/ femur / ilium / scapula
2) Asymptomatic/ tenderness
3) an indolent disease (relatively benign)

* if clavarial lesion extend to the nervous system theyll cause neuro sx

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15
Q

which type of Histocytosis is associated w/ Tobacco smoking

A

Pulmonary LCH X
(Uncommon intersitital lung disease)

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16
Q

Epi of Pulmonary LCH X

A
  • intersitial lung disease ass. w/ Smoking (tobacco)
  • Affects young adults
  • benign, RARE
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17
Q

CF of Pulmonary LCH X

A

1) Nonproductive cough (56-70%)
2) Dyspnea (40%)
3) Fatigue (30%)
4) Weight loss (20-30%)
5) Chest pain (21%)
6) Spontaneous pneumothorax, which may be recurrent, is a classic presentation found in 10-20% of patients
7) Fever (15%)
8) Cystic bone lesions (4-20%): These may be painful and may predispose the patient to pathologic fracture

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18
Q

what makes up a granuloma?

A

collection of Organized macrophages (ask Histocytes)

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19
Q

most common cause of lung granulomas?

A

fungal infections that primarily affect the lungs

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20
Q

Granulomas are most often the result of an ——— and most frequently occur in the ————, but can occur in other parts of the body as well

A

Granulomas are most often the result of an infection and most frequently occur in the
lungs, but can occur in other parts of the body as well

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21
Q

Apart from infections, ——- conditions can also cause granulomas

A

Autoimmune systemic conditions

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22
Q

Examples of Autoimmune systemic conditions

A

SLE, rheumatid arthritis, scelroderma

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23
Q

chracteristics of a granuloma

A

1) inflammation
2) fungal infections in the lungs
3) Autoimmune systemic conditions

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24
Q

macrophages in granulomas are often referred to as ”————-“

A

macrophages in granulomas are often referred to as “epithelioid”

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25
**TURE/FALSE** Loosely dispersed macrophages are not considered to be granulomas
**True** they must be organized
26
infections that are characterised by granulomas
1) **TB** 2) leprosy, 3) histoplasmosis, cryptococcosis, coccidioidomycosis, blastomycosis and cat scratch disease
27
Non-infectious Granulomatous diseases
1) **sarcoidosis,** 2) **Chron's disease**, 3) berylliosis, 4) **granulomatosis with polyangiitis**, 5) eosinophilic granulomatosis with polyangiitis, 6) pulmonary rheumatoid nodules 7) **Wegener granulomatosis**
28
-----------: multisystem inflammatory disease, that manifests as **non-caseating granulomas**, predominantly in the lungs and intra-thoracic lymph nodes
Sarcoidosis
29
CF of Sarcoidosis
1) **Lupus pernio** (painful skin sores on face) 2) Lesion on back, arms, neck, face and scalp 3) **Enlarges lymph nodes** (in chest near wind pipe adn lungs) 4) **Scarring and granulomas in lung** 5) **Spleen enlargment** 6) **Heart complications (rare)** 7) **Conjuctival lesions and scleral plaques** 8) **Anterior/ posterior granulomatous uveitis (most frequent)** 9) crackel sounds in the lungs 10) **Erythema nodosum** 11) **Violaceous rash on the cheeks or nose (common)**
30
One of the main featurs of Wegner's granulomatosis (GPA) | * GPA - granulomatosis w/ polyngiitis
**Vasculitis**
31
CF of Granulomatosis w/ polyngiitis (Wegner's ganulomatosis)
1) recurrent respiratory infection in **Adults** 2) upper and lower respiratory tract problems in **children** 3) Fevers, night sweats 4) Fatigue, lethargy 5) Loss of appetite 6) Weight loss
32
CF: * Typical **Saddle nose damage** * **Sclerokeratitis** * **Vasculitis** are features of?
**Wegener's Granulomatosis** = GPA granulomatosis w/ polyangiitis
33
cell mediated vs Humoral immune respose
* **Cell mediated immunity (T cells)**--> does not produce Ag specific Abs * **Humoral response (B cells)** --> produces Ag-specific Abs
34
where does the development of T cells take palce
* produced in the Bone marrow * mature in the thymus
35
Mature T cells leaving the thymus, are diverse in their specificities and are both **----------------**and restricted to **-------------**
Mature T cells leaving the thymus, are diverse in their specificities and are both **tolerant to self** and restricted to **self-MHC**
36
T cells undergo development in the **---------** and migrate to the **---------------**, where they are activated by foreign antigens
T cells undergo development in the **thymus** and migrate to the **peripheral lymphoid organs**, where they are activated by foreign antigens
37
developing T cells are called **----------**
**Thymocytes**
38
the 2 events of T-cell development
1) Early thymocyte development --> T-cell receptor independent 2) Selection events --> T-cell receptor dependent
39
VERY early thymocyte development occurs in the **-----------**
Bone marrow
40
The 3 stages pf Thymocyte Development
1) Early thymocyte development 2) Positive and negative selection 3) Lineage commitment
41
Immature T-cells (progenitor cells) migrating from the BM to the Thymus **[Express/ do not Express]** Ag receptors/ CD4 or CD8 or CD3
**Do not Express**
42
In Early thymocyte development Cells go through a series of different stages, what are they?
1) Double negative **(DN)** no CD4 or CD8 expression CD4-CD8 2) Double positive **(DP)**—both CD4 and CD8 (TCR expressing 3) Recombination of TCR gene segments occurs in the DN stages
43
What is lineage commitment?
Its when selceted thymocytes mature to become **SP** (single positive) , Where thye either become CD4+ or CD8+ T cells * Note: this happens after positive and negative selection (so Thymocytes that have passed the +ve selection will undergo Lineage commitment) | * First DN --> DP --> SP
44
Selected thymocytes mature to become single positive (SP), where only CD4 or CD8 are expressed, this is known as?
**Lineage Commitment**
45
Exaplin what happnes during the selection events of Thymocyte development
Positive/ Negative selection satges : **1) Postive selection** --> selection for those cells whose TCR respond to self-MHC **2) Negative selection** --> selection against those cells whose TCR reacts strongly to self-peptide/MHC combinations 3) **selected thymocytes** (the ones passing positive selection) --> are **realeased into the peripheral bloodstream**
46
# T-cell development in the cortex 1) **DN:** once they encounter the thymic environment they **-----------** 2) **DN**: **-------------** begins to rearrange 3) **DN:** those that have successfully rearranged β-chain form **------------** , they proliferate and mature to **---------** 4) **DP:** initiation of **-----------** chain, if successful then **---------** is expressed and cells are ready for the second stage of T cell development (**----------**)
1) **DN:** once they encounter the thymic environment they **proliferate** 2) **DN**: **β-chain** begins to rearrange 3) **DN:** those that have successfully rearranged β-chain form **pre-TCR** , they proliferate and mature to **DP** 4) **DP:** initiation of **TCRα chain**, if successful then **TCR** is expressed and cells are ready for the second stage of T cell development (**selection**)
47
**--------------** ensures only one β-and α-chain are expressed per cell during the early thymocyte development
**Allelic exclusion**
48
Surface molecules expressed during development of T-cells (during the DN and DP stage)
**RAG1/RAG2 and TdT**
49
why is thymic selection necessary?
**Randomly generated TCRs can recognize all possible MHC/peptide combinations--> dangerous (they will attack "self")** * note: i.e. recognize foreign MHC/peptides – not useful i.e. recognize self MHC/self peptides – dangerous!!!! i.e. recognize **self-MHC forgein-peptide- useful**
50
Positive selection ensures **-------------**
**MHC restriction**
51
how does positive selection ensure MHC restriction?
Selects thymocytes bearing T cell receptors (TCR) capable of binding **self-MHC molecules**, allowing the creation of a self-MHC restricted T cell repertoire | * repertoire : store/ collection
52
Negative selection ensures **------------**
**Self-tolerance** (Central tolerance)
53
**Negative selection** happens in the **------------** and the **--------** of the thymus and eliminates T cells that bind too strongly to self-MHC+ self peptide **(---------------------)**
Negative selection happens in the **cortex** and the **medula** of the thymus and eliminates T cells that bind too strongly to self-MHC+ self peptide **(central tolerance)**
54
cells involved in the +ve/-ve selection of thymocyte development
Cortical and medullary thymic **epi cells, macrophages and DCs**
55
Funtion of cortical and medullary thymic epi cells, macrophages and DCs?
1) Express MHC I and II 2) developing T cells interact w/ these cells through TCR-CD3
56
Cortical and medullary thymic epi cells, macrophages and DCs play important roles in the selection * These cells **express MHC I and II** and developing T cells interact with them through their **-------------**
**TCR-CD3**
57
Developing T cells that can bind MHCs shift from ------ to -------
**DP --> SP** * If the TCR can bind to an MHC class II molecule, it becomes a CD4+ cells * The opposite happens if the TCR binds to an MHC class I molecule, it becomes a CD8+ cell
58
How are developing T cells checked against self- antigens that are not expressed in the thymus?
The thymus expresses and presents proteins from all the body, those are presented to ---> **AIRE**, expressed by medullary thymic epithelial cells (**mTECs**), which **eliminate autoreactive T cells** --> preventing them from being released into the peripheral bloodstream
59
Maturation of T cells happens in the Thymus, in which part does final maturation occur **1) Thymic medulla or 2) Thymic cortex ?**
**Medulla**
60
While most self-reactive T cells will be deleted in the thymus, a small population of these T cells will instead differentiate into **------------**
**TREG cells**
61
T regulatory cells (Tregs) belong to a subset of **CD4+ T cells** charcaterized by constitutive expression of **--------, ------ and ---------** transcription factor
They belong to a subset of CD4+ T cells characterized by constitutive expression of **CD4, CD25 and FoxP3** transcription factor
62
What cytokines are secreted by Tregs?
IL-10 and TGF-β
63
fx of IL-10 and TGF-β
anti-inflammatory Cytokines released by Tregs (inhibit inflammation)
64
How do Tregs serve in peripheral tolerance?
when they leave the thymus they inhibit the fxn of escaping autoreactive T cells

immunlogy (18 decks)

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