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RACP Immunology 2020 > Immunology concept > Flashcards

Immunology concept Flashcards

1
Q

Component of the innate immune system and its function

A

Cells:

  • macrophage
  • dendritic cells
  • natural killer cells
  • neutrophils
  • eosinophils
  • mast cells and basophils
  • epithelial cells

Molecules:

  • locally active: cytokines and chemokines
  • circulating: complement, coagulation protein, acute-phase protein.
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2
Q

Function of macrophage

A

Innate: phagocytose + kill bacteria, produce antimicrobial peptide, bind LPS, produce cytokines

Adaptive:

  • IL1 + TNFa to attract antigen specific lymphocyte
  • IL12 to recruit Th1 cells
  • upregulate costimulatory molecule (B71 and B72) needed for T cell activation
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3
Q

Function of dendritic cells

A

Innate: make IFNa (antitumour + antiviral)

Adaptive: IFNa activate macrophage and become APCs

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4
Q

Function Natural Killer cells

A

Innate: kill foreign + host cells w/ low MHC+ self peptides

Adaptive: produce TNFa and IFN gamma to help recruit Th1 cells

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5
Q

Function of neutrophils

A

Innate: phagocytose and kill bacteria

Adaptive: produce Nitric oxide -> inhibit apoptosis, so prolong adaptive immune system for longer

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6
Q

Function of eosinophils

A

Kill invading parasites, associate with chronic allergic response

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7
Q

Mast cells and basophils

A

make TNFa, IL6 and IFN gamma in respone to PAMPs

Produce IL4 which recruit Th2 and reruit Ig1 + IgE.

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8
Q

What are adhesion molecules?

A

Facilitate leukocytes movement from intravascular region to the tissue.

e.g. selectins, integrin, immunoglobulin.

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9
Q

4 components of complement pathway

A
  1. classical (antigen/antibody complex)
    - C1q, C1R, C1S, C4, C2
  2. MB lectin pathway -
    (microbes w/ terminal mannose group)
    - MBL, MASP1 + 2, C4, C2
  3. Alternative pathway (microbial cell wall + tumour cells)
    - C3, B and D
  4. Terminal pathway
    C5, C6, C7, C8, poly C9
    - membrane attack complex
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10
Q

Defect of classical complement pathway

A

autoimmunity (SLE)

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11
Q

Deficiency in C1 esterase inhibitor

A

Hereditary angiodema

MOA: C1 inh inhibit kallikrein. Its absence releases bradykinin leading to angiodema.

Affects skin and mucosa. Gets abdominal pain, cutaneous swelling, airway swelling.

consider in isolated angiodema, young, + family hx.

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12
Q

Defect in late complement pathway

A

Propensity for Neisseria infection because dysfunctional membrane attack complex.

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13
Q

Defects in complement regulators can cause

A

Regulators are present in the blood, much more than complement themselves.

aHUS/glomerulonephritis

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14
Q

Toll like Receptors

A

single-pass membrane-spanning receptors expressed on cells such as macrophages and dendritic cells. Recognise PAMPs (Pathogen associated molecular pattern) or DAMPs (Damage ascoiated molecular pattern)

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15
Q

Extracellular TLR

A

Recognise different types of extracellular pathogenic material.

TLR 1/6, TLR 2, TLR 4, TLR 5

Activate MyD88 and IRAK4 -> produces cytokines IL6, 12, TNF -> inflammation

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16
Q

Intracellular TLR

A

Recognise viral products

TLR 7/8, TLR9, TLR 3.

Activate TRIF -> make Type 1 IFN -> inflammation

17
Q

How does inflammasome work?

A

triggered by DAMP/PAMP

Need 2 signals: PAMP/DAMP and IL1-beta (produced on activation of TLR).

Once activated, caspase 1 activated and cleave proIL1B to IL1B leading to inflammation.

often assoc. w/ neurodegenerative disease/metabolic syndrome

18
Q

What happens when there are defects in inflammasome? What is the treatment?

A

Autoinflammation

Treat with:

  • anakinra (IL 1 blocker)
  • NSAIDs
  • anti-TNFa
  • anti-IL18
19
Q

Where do T cells developed?

A

in the Thymus.

There, self antigens are presented to double positive lymphocytes by cortical thymic epithelial cells facilitated by AIRE.

20
Q

MHC Class 1

A
  • In human, encoded for by HLA A, B, C
  • present in all nucleated cells
  • antigen presented are cytosolic proteins (e.g. virus, etc)
  • acts with CD8+ cytotoxic cells
21
Q

MHC class II

A
  • in human, necoded for by HLA-DP, DM, DOA, DOB, DQ, DR.
  • present in APCs (DC, B-cells)
  • antigen presented are phagocytosed extracellular protein
  • acts with naive CD4+ cells
22
Q

During T cell development - what is positive and negative selection?

A

Cells binding self-antigens with high affinity die (negatively selected). Cells with low affinity survive (positively selected).
cells with intermediate affinity become T-regs

23
Q

3 signals needed for T-cell differentiation

A

1) antigen presentation, 2) cytokines (driven by innate immune system) and
3) costimulation at the site of immunological synapse (CD28/B7-1 or B7-2 and CD40/CD40L)

24
Q

What are immune check points?

A

regulatory costimulation of T cell to allow self tolerance. Defect in this will cause autoimmunity.

e.g. CTLA-4, PD1

25
Q

Mechanism of action of CTLA4 inhibitor

A

Normally: CTLA4 is expressed on Tcell post activation and binds to CD80/CD86 (B7-1 or B7-2) to “stop” T cell activation.

Cytotoxic T cells can recognise tumour cells, but can be inhibited by CTLA4. So by inhibiting this, allows T cells to kill tumour cells (concept of check point inhibitor)

26
Q

Mechanism of action of PD1/PDL1 inhibitor

A

Coinhibitory receptor expressed on T cell, B cell and NK following activation.

2 ligands (PDL1 and PDL2). Binding to this inhibits T cell receptor signalling and downregulate immune response. Thus preventing tissue damage and promote peripheral tolerance and balance.

Tumours upregulate PDL1 causing downregulation of T cell activity. Thus inhibiting PD1/PDL1 binding will cause on going immune response.

27
Q

B cell class switching recombination

A

Draw the diagram

28
Q

Function of Th1 cells

A

Activated by: IFN gamma and IL12

Produce IFN gamma, IL2 and TNF beta:

  • anti viral/microbial immunity
  • cell mediated immunity
  • inflammation
29
Q

Function of Th2 cells

A

Activated by: IL4, IL10

Produce IL4, IL5, IL10 and IL13 for AB production, eosinophil activation, inhibition of macrophage and provide phagocyte independent responses.

30
Q

Function of Th17 cells

A

Activated by: IL-1b, IL6, IL23

Produce: IL21, 22, 24, 26, IL17A, IL17F

Function: recruit neutrophils and macrophages to infected tissues

31
Q

Function of T regulatory cells

A

Down play immune response.

Produce immunosuppresive cytokines (TGFb, IL10, IL35)

Also has CTLA-4 (CD152) and GITR (glucocorticoid induced TNF receptor) which have inhibitory effect.

RACP Immunology 2020 (5 decks)

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