Immunity - the basics Flashcards

1
Q

What part of the immune system are inflammasomes found?

A

Part of the innate immune system

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2
Q

Outline the immune mechanism associated with gout

A
  • multiprotein complexes in the cytosol of cells
  • respond to microbes or changes associated with cell injury
  • lead to activation of IL-1b and IL-18
  • use the sensor NLRP3 found on PCS (macrophages/neutrophils/keratinocytes) that is stimulated by URIC ACID
  • urate crystals are recognised by inflammasomes and IL-1 beta production
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3
Q

What is the CD4+ T cell response that IFN-gamma is associated with?

A

Th1 responses&raquo_space; key cytokines - IFN-gamma + IL-2

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4
Q

Briefly outline the Th1 response
(a) functions
(b) cytokines
(c) clinical application examples

A
  • key functions - production of opsonising antibodies, induction of cellular toxicity, macrophage activation (key feature)
  • key cytokines: IL-2, IFN-gamma
  • Clinical examples
    > help in the eradication of intracellular micro-organisms such as mycobacteria
    > promote cytotoxic T cell development + delayed type hypersensitivity reactions
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5
Q

Briefly describe the difference between classic and alternative macrophage activation

A
  • Classically activated macrophages are known to have major roles in host defense against various microbial pathogens, including fungi
  • alternatively activated macrophages are instrumental in immune-regulation and wound healing.
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6
Q

Briefly outline the Th2 response
(a) functions
(b) cytokines
(c) clinical application

A
  • functions - Eosinophil + mast cell activation
  • Key cytokines – IL-4, IL-5, IL-13
  • Clinical applications - immune response against parasitic infections, role in development of allergy + asthma, role in collagen deposition
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7
Q

Dupilumab is used in the treatment of Asthma. What is it and list 2 other conditions it may be used for

A
  • IL-4 receptor antagonist (monoclonal antibody)
  • Indications
    > asthma - mod-severe eosinophilic or oral glucocorticoid dependent
    > atopic dermatitis
    > rhinosinusitis, COPD refractory, eosiniphilic esophagitis
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8
Q

Briefly outline the Th17 response
(a) functions
(b) cytokines
(c) clinical application

A

Key functions: production of pro-inflammatory cytokines + chemokines + neutrophil recruitment
Many cytokines
Clinical application
- Early response to numerous extracellular pathogens (including bacteria + fungi)
- Important role in driving chronic inflammatory responses (e.g. chronic infection, allergy, autoimmunity) + neutrophil predominant asthma

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9
Q

What is the main chronic condition IL-17 antagonists are approved for

A

psoriasis

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10
Q

What is the broad role of TNF

A
  • pro-inflammatory cytokine - many roles (induces fever, inflammation, cell death)
  • thought to have dysregulation in conditions such as Alzeihmers disease, IBD, cancer
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11
Q

List one example of a TNF inhibitor and 3 conditions it can be used for

A
  • etanercept (E), infliximab (I), adalimumab (A), certolizumab pegol (C), and golimumab (G), are biologic agents which are FDA-approved
  • Clinical uses - Crohns disease/UC (IBD), Ankylosing spondylitis, psoriasis, uveitis
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12
Q

What are the principal targets of rejection in transplantation?

A

proteins encoded in the MHC

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13
Q

List the 3 types of transplant rejection

A
  • hyperacute
  • acute
  • chronic
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14
Q

Briefly outline the features of hyperacute rejection and the mechansims associated with this

A
  • onset: minutes to hours
  • pre-existing antibodies of the RECIPIENT match foreign antigens of the donor (e.g. HLA antibodies, ABO isoaggutinnins)
  • thrombosis of graft vessels + ischarmic necorosis (immune reaction activates the complement/clotting system) –> endothelial injury + thrombus formation
  • Hypersensitivity Type II (completement/antibody mediated)
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15
Q

In a hyperacute rejection, the donots antibodies attack the graft vessels. What might be the source of how these antibodies were generated?

A
  • previous blood transfusions (therefore importance of cross-matching)
  • previous transplantations
  • multiple pregnancies
    *this is more a situation where there is pre-formed donor specific antibody attacking the graft tissue vs. acute rejection where there is acute cellular rejection (T-cell mediated)
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16
Q

Briefly outline the features of acute rejection + immune mechanism

A
  • Type IV hypersensitivity response (T cell mediated, either CD4 or CD8 response)
  • antibody mediated responses usually contribute to the vascular components of acute rejection
  • classical pathway (complement activation)
    ***important target in immunosuppressive therapy
17
Q

What are the signs of transplant rejection?

A
  • fever
  • increase SCr (serum creatinine)
  • fever
  • oliguria
  • graft pain
18
Q

List 2 drugs commonly used for transplants

A
  • MMF
  • corticosteroids
  • Calcunerurin inhibitors
19
Q

What is the mechanism of tacrolimus?

A
  • MOA – blockage of protein phosphatase calcinerurin
  • This enzyme is required to allow translocation of the transcription factor NFAT to the nucleus; blocking its activity inhibits the transcription of cytokine genes in the T cells
20
Q

What is the mechanism of action of MMF?

A
21
Q

What is the mechanism of corticoteroids in immunosupression with relevance to transplants?

A
22
Q

Briefly describe the mechanism of chronic rejection

A
  • develops over months to years
  • characterised by gradual narrowing of blood vessels (graft aretriosclerosis), fibrosis of graft
  • mechanism: T cells that react against graft alloantigens and secreter cytokines; A foreign (graft) MHC ‘looks like’ a self MHC with an antigen
23
Q

What is graft vs host disease ?

A

Donor T cells proliferate and attack recipient tissue - most common in bone marrow transplant

24
Q

In a few sentences, describe the mechanism of types of hypersensitivity

A
25
Q

In terms of urticaria, what are the three main mechanisms?

A
  • IgE mediated
  • direct mast cell activation (without IgE)
  • pseudoallergic/pharmacologic
26
Q

List the types of causes of urticaria and the mechanism

A
  1. IgE mediated - many causes (e.g. infection, foods, transfusion medications)
  2. Non-IgE mediated - e.g. vancomyin, contrast, opioids
  3. NSAIDs - abnormalities in arachidonic metabolism (usually seen in NSAIDs that block COX1)
27
Q

List two common medications that block COX-1

A
  • iboprufen
  • paracetamol (weak COX-1 inhibitor)
28
Q

What is the mechanism of allergy associated abnormality in arachnoid acid metabolism?

A
  • Cyclooxygenase inhibition blocks the conversion of
    arachidonic acid to prostaglandins and
    thromboxane resulting in a therapeutic
    anti-inflammatory effect.
  • The resultant increase in free arachidonic acid can be
    alternatively converted into cysteinyl
    leukotrienes.
  • These leukotrienes may
    result in clinical features of allergy such as
    angioedema, urticaria and bronchospasm
29
Q

What is the test used to distinguish immune vs. non-immune causes of haemolytic anaemia?

A

DAT test - the DAT is used to determine whether patient RBCs are coated with IgG, complement, or both.

30
Q

What are the key Ix of haemolytic anaemia and would they be high or low?

A
  • LDH (HIGH)
    > because released from RBCs during the haemolytic process
  • bilirubin (unconj - HIGH)
    > product of heme recycling *unconj form
  • haptoglobin (LOW)
    > mops up free Hb
  • reticulocyte count (HIGH due to haemolysis)

Note LDH, haptoglobin, unconj bilirubin are all non-specific

31
Q

Describe the pathogenesis of a type 1 hypersensitivity reaction

A
  • two broad steps - sensitsation then effect (latter = response)
  • activation of Th2 response –> IL4,5,13 00 –> B cells switch to IgE –> secrete as plasma cells –> antibodies bind to mast cells and cross link releasing substances
    *the IgE testing tells you about a sensitisation, NOT an allergy
32
Q

What are the two in vivo methods of allergy testing and which is better (in terms of sensitivity and specificity?

A

*these methods allow detetection of sensitisation
- skin prick - more specific and sensitive
- specific IgE testing (blood test) IS NOT diagnostic (only assesses sensitisation)

33
Q

What is the difference between temporary and sustained tolerance?

A
  • temporary - small doses until target dose achieved (temporary, requires regular use) –> common approach with medication
    *given at 15 min intervals
  • sustained aka immunotherapy - give increasing doses –> evoke a sustained response
34
Q

Why is serum tryptase used and what does it measure?

A
  • can support diagnosis of anaphylaxis (sensitive but not specific)
  • need to repeat to ensure return to baseline range
  • marker of mast cell degranulation
35
Q

What is the most common cause of food dependent, excercise induced anaphylaxis?

A

omega-5-gliadin

36
Q

What is the difference between a type A and B adverse drug reaction?

A
  • Type A - predictable and dose dependent
  • Type B - unrpredictable, immune medicated
37
Q

What is the difference between immediate vs. non-immediate drug allergies?

A

immediate - IgE mediated associated with urticaria, angiooedema, anaphylaxis
non-immediate - T cells, DELAYED, organ involvement, systemic features

38
Q

Explain the different type of testing used for Type 1 vs Type 4 hypersensitivity reactions

A

type 1 - skin prick, intradermal testing
type 4 - IDT, patch tests

39
Q

What is the likely mechanism of penicillin cross reactivity?

A

side chain mediated - usually patients will tolerate the medication (e.g. cephlasporin, when you have a penicillin allergy) because its a side chain (and therefore cross reactivity thought to be low)