immuno Flashcards

(49 cards)

1
Q

PD-1 inhibitor

A

work by disrupting the binding of PD-1 on tumour cell

–> T cell programmed cell death

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2
Q

mtor inhibitors

A

prevent autonomous activity of the mtor pathway

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3
Q

ctla4 inhibitors

A

enhance ability if APCs to activate T cell

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4
Q

HIV-2

A
– less virulent
– lower viral load
– lower rates of vertical transmission
– slower progression
– HIV-2 is less virulent.
– Seen mainly in western central Africa and southern and western India.
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5
Q

peripheral neuropathy - HAART

A

Didanosine, Stavudine and Zalcitabine

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6
Q

hypersensitivity types

A

Type 1: Specific IgE on mast cell ie: anaphylactic reaction to penicillin.
Type 2: IgG cytotoxic ie: hemolytic anemia
Type 3: Immune complex ie: serum sickness,GN
Type 4: T cell mediated ie: contact dermatitis

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7
Q

most powerful prediction from HIV to AIDS

A

CD4 count

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8
Q

strongest single predictive marker of disease progression at all stages of HIV

A

CD38 expression by CD8 cells

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9
Q

protease inhibitor s/e

- NAVIR

A
  1. lipodystrophy
    - ritoNAVIR
    - saquinavir
    - nefinavir
  2. increased risk of MI
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10
Q

HAART teratogenic

A

efavirenz

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11
Q

HIV cx

A

CD4 >200
-herpes zoster (CD 4: 200-500)

CD4 <200

  • oral candidiasis
  • HSV
  • hairy leukoplakia
  • crytosporidosis
  • toxoplasmosis
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12
Q

Heterozygosity for CCR Delta 32 in HIV

A

slower disease progression to AIDS by two fold

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13
Q

HLA-B5701

A

abacavir hypersensitivity reaction

- avoid Abacavir

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14
Q

atazanavir

A

indirect hyperbili

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15
Q

Absolute contraindication to Protease inhibitors (CYP 3A4 inhibitor)

A
  • Cisapride- torsades.
  • Lovastatin- rhabdomyolysis ** (metabolised by CYP 3A4) –> can use pravastatin
  • Midazolam-prolonged sedation
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16
Q

abacavir

A

MI (90%)

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17
Q

Immune reconstitution sydrome (IRIS)

A

symptoms include:
-high fever, increase in LN, worsened CNS lesion, worsened pulmonary infiltrate, increased pleural effusion

Rx: NSAIDS for symptom relief.
CONTINUE TB therapy and ART!!

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18
Q

hep b rx in HIV and Hepatitis B co-infection

A

For patient who require HBV treatment:
Not yet on HAART:
Truvada (Emtricitabine + tenofovir) + N-NRTI or PI

If on HAART, 2 options:
1. Lamivudine naive:
– Truvada or Lamivudine + tenofovir.
– Entecavir only if patient has full suppression of HIV

  1. On Lamivudine:
    – Add tenofovir or adefovir
    – Or change to Truvada.
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19
Q

opportunistic infection occurs at all CD4 cell counts

A

Pneumococcal pneumonia and TB

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20
Q

T helper cells

A

Th1 secrete IFN-γ, TNF, Lymphotoxin (Defence against intracellular pathogen)

Th2 secrete IL-4,IL-5,IL-6,IL-10,IL-13,TGF-β (Defence against Helminths)

Th17 secrete IL-17 (Defence against candida and staph)

21
Q

MHC

A

Class I– Intracellular proteins.Presents peptide to CD8 T cell.

Class II- extracellular proteins.Presents peptide to CD4 T cell.

22
Q

Types of T cells

A

Helper
– T- helper cells known as CD4+ T cells because they express the CD4 protein on their surface.
– Activated when presented with peptide antigen by MHC class II expressed on APC.
– Once activated, they divide and secrete cytokines
– Can differentiate into one of several subtypes, including TH1, TH2, TH3, TH17,

Cytotoxic
– Cytotoxic T cells destroy virally infected cells and tumor cells, and implicated in transplant rejection.
– Also known as CD8+ T cells
– Recognize their targets by binding to antigen associated with MHC Class I.

Memory
– Memory T cells are a subset of antigen-specific T cells that persist long-term after an infection has resolved.
– Expands to large numbers of effector T cells upon re-exposure to their cognate antigen.
– Memory T cells comprise two subtypes: central memory T cells (TCM cells) and effector memory T cells (TEM cells).
– Memory cells may be either CD4+ or CD8+.
– Memory T cells typically express the cell surface protein CD45RO.

Regulatory
– Regulatory T cells (Treg cells), formerly known as suppressor T cells, are crucial for the maintenance of immunological tolerance.
– Main role is to shut down T cell-mediated immunity toward the end of an immune reaction and to suppress auto-reactive T cells that escaped the process of negative selection in the thymus.
– Two major classes of CD4+ regulatory T cells have been described, including the naturally occurring Treg cells and the adaptive Treg cells.
– Naturally occurring Treg cells (also known as CD4+CD25+FoxP3+ Treg cells) arise in the thymus,
– Adaptive Treg cells (also known as Tr1 cells or Th3 cells) may originate during a normal immune response. Naturally occurring Treg cells can be distinguished from other T cells by the presence of an intracellular molecule called FoxP3.
– Mutations of the FOXP3 gene can prevent regulatory T cell development, causing the fatal autoimmune disease IPEX.

Natural killer
– NKT cells recognize glycolipid antigen presented by a molecule called CD1d
– Once activated, these cells can perform functions ascribed to both Th and Tc cells (i.e., cytokine production and release of cytolytic/cell killing molecules).
– They are also able to recognize and eliminate some tumor cells and cells infected with herpes viruses.

γδ
– γδ T cells (gamma delta T cells) represent a small subset of T cells that possess a distinct T cell receptor (TCR) on their surface.
– A majority of T cells have a TCR composed of two glycoprotein chains called α- and β- TCR chains. However, in γδ T cells, the TCR is made up of one γ-chain and one δ-chain.
– This group of T cells is much less common (2% of total T cells) than the αβ T cells, but are found at their highest abundance in the gut mucosa, within a population of lymphocytes known as intraepithelial lymphocytes (IELs).
– γδ T cells are not MHC restricted and seem to be able to recognize whole proteins rather than requiring peptides to be presented by MHC molecules on antigen presenting cells.

23
Q

coeliac dis

A

HLA-DQ2 or HLA-DQ8 restricted T-cell immune reaction in the lamina propria as well as an immune reaction in the intestinal epithelium

24
Q

IL 1

A
  • produced by macrophage,monocytes and dendritic cells.
  • critical for inflammatory response against infection.
  • Reset the hypothalamus thermoregulatory center causing fever.
25
IL 2
induces proliferation of T-cells.
26
IL 3
Hematopoietic lymphoid growth and proliferation
27
IL 4
acts on B-cells to promote IgE switching | -Overproduction of IL-4 assoc with allergies
28
IL 5
regulates eosinophil growth and activation
29
IL 6
differentiation of activated B-cells to plasma cells
30
IL 8
Neutrophil chemotaxis
31
IL 11
stimulates megakaryocytopoiesis to produce platelets
32
PAMPs assoc pathogens
``` Bacterial: Peptidoglycan Bacterial DNA Lipoteichoic acids (Gram positive) Lipopolysaccharides (Gram negative) ``` RNA viruses: dsRNA Yeast: Mannans.
33
absence of B cells
X-linked agammaglobulinaemia (Bruton’s disease)
34
T cell immunodeficiencies
1) Idiopathic CD4 lymphopenia 2) Chronic mucocutaneous candidiasis 3) Hyper-IgE syndrome
35
X linked SCID
Deficiency of cytokine receptor γ common chain ``` Autosomal recessive SCID: Jak 3 deficiency IL-7Rα deficiency ZAP 70 defieiency CD3 deficiency RAG-1,2 deficiency Myeloid or reticular dysgenesis. ```
36
Disorders of neutrophil phagocytic function
1) Chronic granulomatous disease 2) Leukocyte adhesion deficiency 3) Chediak-Higashi Syndrome 4) Neutrophil enzyme deficiency-G6PD,MPO
37
NOD-like receptor group responsible for the acute inflammation seen in gout
NALP 3 | -Monosodium urate crystals(MSU) and Calcium pyrophosphate dihydrate(CPPD) activates the NALP3 inflammasome
38
Dendritic cells function
– superb APC – Lurks in tissues as sentinels. – Activates quiescent naive and memory T(Th,Tc) and B cells. – Highly potent activators even with low levels of antigen. – Two distict types: conventional(cDCs) and plasmacytoid(pDC) Plasmacytoid DC expresses TLR7(RNA virus) and TLR9(DNA virus) in endosomes and induces rapid anti-viral state.
39
Hereditary Angioedema
-deficiency of C1 inhibitor leading to continuous activation and consumption of C4 and C2. – C2 is responsible for kinin release that results in vasodilation and increased vascular permeability leading to angioedema. Clinical presentation: – Typically school age. – Recurrent edema that is non pruritic, painless, non whealing and usually resolves within 72 hours. – Edema can be cutaneous,laryngeal and abdominal (mimics acute abdomen-early diagnosis may avoid unnecessary surgery!!) Treatment: - C1-inhibitor concentrate. - Danazol if frequent attacks - Tranexamic acid - ε-aminocaproic acid
40
APC
External antigen: dendritic cell, macrophage, B-cell (express MHC II) Internal antigen: All MHC class I positive cells (express MHC I)
41
serum beta 2 microglobulin
``` component of the HLA class I molecule -Clinically relevant in reflecting cell turnover ``` Prognosis in Multiple myeloma and HIV. -The higher the worse.
42
Serum tryptase
Tyrptase helpful if collected within 3 hours of IgE mediated reaction. Used to distinguish mast cell dependent anaphylaxis from other systemic event. Does NOT differentiate between IgE and non-IgE mediated causes.
43
most specific for the diagnosis of NSAIDs hypersensitivity
Basophil activation test
44
acute phase reaction
-IL-1, IL-6 and IL-8, and TNF-α Positive acute phase proteins (Increase in inflammation): - C-reactive protein, - Mannose-binding protein, - complement factors, - ferritin, - ceruloplasmin, - Serum amyloid A and - haptoglobin. - serpins. - Alpha 2-macroglobulin Negative acute phase protein (decrease in inflammation): mnemonic “ATTTRA”. - albumin, - transferrin - transthyretin - transcortin - retinol-binding protein - antithrombin
45
IgG4-positive multiorgan lymphoproliferative syndrome
Characteristic features of IgG(4)+MOLPS are as follow: 1) Serum IgG4 is prominently elevated, 2) IgG4-positive plasma cells infiltrate in involved tissues 3) various mass-forming lesions with fibrosis develop in a timely and spatial manner 4) good response to corticosteroids. 5) no positivity of anti-SS-A/SS-B antibodies Organ system affected by IgG(4)+MOLPS: 1) autoimmune pancreatitis 2) lacrimal and salivary gland (Mikulicz’s disease) 3) retroperitoneal fibrosis 4) IgG4-associated nephropathy
46
CTLA 4
generates a NEGATIVE signal -Stimulating CTLA4 --> Block the immune response Anti-CTLA4 stimulates the immune response by blocking CTLA4
47
hereditary angioedema mx
Acute management includes: 1) C1-INH concentrate from donor blood 2) FFP if in emergency as FFP contains C1-INH. 3) Kallikrein inhibitor (Ecallantide)- inhibits plasma kallikrein. 4) Bradykinin inhibitor (Icatibant)- inhibits bradykinin B2 receptor. Prophylaxis: 1) Danazol- Androgens increase production of C1-INH in the liver. 2) Tranexamic acid- fibrinolysis inhibitors The condition does NOT respond to antihistamines, corticosteroids, or epinephrine.
48
HLA
HLA Class I: - HLA- A, B, C (E,F,G,H) HLA Class II: - HLA- DR, DP, DQ(DM and DO) HLA-DR alpha chain is invariant (unchanged) while HLA-DR beta chain is very polymorphic. Some disease associations: Ankylosing spondylitis HLA B27 Rheumatoid arthritis HLA DR4 Autoimmune conditions (SLE, Addisons, Type 1DM, Grave’s, Myasthenia) HLA DR3. Transplant and HLA: – Acute graft rejection caused by cross reactivity of T cell receptors for foreign MHC.
49
Types of hypersensitivity
Type I – Anaphylactic * antigen reacts with IgE bound to mast cells * anaphylaxis, atopy Type II – Cell bound * IgG or IgM binds to antigen on cell surface * autoimmune haemolytic anaemia, ITP, Goodpasture’s Type III – Immune complex * free antigen and antibody (IgG, IgA) combine * serum sickness, systemic lupus erythematosus, post-streptococcal glomerulonephritis, extrinsic allergic alveolitis (especially acute phase) Type IV – Delayed hypersensitivity * T cell mediated * tuberculosis, tuberculin skin reaction, graft versus host disease, allergic contact dermatitis, scabies, extrinsic allergic alveolitis (especially chronic phase) In recent times a further category has been added: Type V – Stimulated hypersensitivity * IgG antibodies stimulate cells they are directed against * Graves’, myasthenia gravis