Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Immunology > Basic immunology > Flashcards

Basic immunology Flashcards

1
Q

Purpose of eosinophils

A

Kill pathogens too large to be ingested by a macrophage

Release granules that are toxic

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

Functions of complement

A

1) Opsonisation
2) Cytolysis
3) Inflammation via anaphylatoxins (C3a, C5a >C4a)
4) Immune complex clearing

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

Why is C1 esterase inhibitor important?

A

Prevents activation of classical pathway and coagulation patyway

In C1-INH deficiency
= Activates classical pathway + activates coagulation pathway (makes bradykinin)
= Bradykinin –> increased capillary permeability –> oedema
= Hereditary angioedema

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

What happens to C4, C2, and C3 in hereditary angioedema?

A

C1 esterase inhibitor deficiency

Low C4, C2, normal C3 (C4 binding protein binds to C4 and prevents activation of distal pathway including C3)

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

Hereditary angioedema clinical features

A

Recurrent attacks of oedema

  • Non-pruritic
  • No urticaria although atypical skin rashes associated - - Painless

Cutaneous angioedema
Laryngeal oedema
Bowel wall oedema –> abdo pain, fluid loss

Usually resoles within 72h

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What precipitates Hereditary angioedema?

A 
ACEI
Estrogens
Trauma
Surgery
Concurrent illness
Emotional stress
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Types of Hereditary angioedema

A

Type 1 (majority) - reduced level of C1-INH

Type 2 - dysfunctional C1-INH (normal or increased)

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

Who can get acquired C1 inhibitor deficiency?

A 
B cell lymphoma, MGUS (consumes C1-INH)
Autoimmune disease (generate ab against C1-INH)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

How to diagnose/confirm Hereditary angioedema ?

A

Reduced C4, normal C3 (do this first)

C1-INH level

  • Reduced in type 1 HAE
  • Normal in type 2 HAE

Functional C1-INH assay (do it in those with normal C1-INH level)

C1q reduced

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

Acute treatment of Hereditary angioedema

A

1) Icatibant (bradykinin receptor inhibitor)
- Can reverse HAE
- Patients can do it themselves at home if they feel at attack is coming

2) Replacement of Purified C1-INH protein

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

Prevention of Hereditary angioedema

A

Anabolic steroids e.g. danazol (androgen)

Tranexamic acid (acts on fibrionlytic pathway… blocks plasminogen and lowers release of bradykinin)

C1-INH (regular infusions)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What infection do you get in C5, C6, C7, C8, C9 deficiency?

A

Neisseria infection

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

What diseases do you get in C3 deficiency?

A

C3 is the start of the common pathway

Recurrent pyogenic infections

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

Causes of low C3, C4

A

C4 deficiency

  • Consumption - Immune disorders - SLE (reflects disease activity), serum sickness (Ag Ab complexing in the blood, depositing in the tissue and activating complement and consuming it), mesangiocapillary GN (C3), post-infectious GN (C3), cryoglobulinemia (C4), C1-INH (C4), Chronic infections e.g. IE
  • Reduce production - malnutrition, liver disease
  • Increased loss - Nephrotic syndrome, burns
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Eculizumab MOA

A

C5 inhibitor (common pathway)

Inhibit MAC (C5, C6, C7, C8) so cells don’t lyse

Role in PNH, atypical HUS

Risk of neisseria (vaccinate pre treatment)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What are the classical pathway components?

A

C1q, C1r, C1s, C2, C4, C3

Similar to lectin pathway
Replace C1q, C1r, C1s with MBL + MASP 1 + MASP 2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What are the alternate pathway components?

A

C3, B, D, properdin (stabilises complex)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What are the MAC components?

A

C5, C6, C7, C8 makes MAC

Attracts C9 = cytolysis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What are the anaphylatoxins made in the complement pathways?

A

C3a, C5a (stronger)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Regarding Hereditary angioedema, its inheritance follows an ……. pattern

A

AD

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q 
Which of the following doesn't function as a pattern recognition receptor?
A) C1q
B) CRP
C) Alpha 1 antitrypsin
D) Mannose binding protein
A

Alpha-1 antitrypsin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Anakinra MOA

A

IL1 blocker

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Tociluzumab MOA

A

IL6 blocker

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

The innate immune system involves recognition of PAMPs and DAMPs by PRRs. What do the following PRRs do?

1) C-type leptin receptors (CLR)
2) Toll like receptors (TLR)
3) Nod-like receptors (NLR)
4) Rig-like receptors (RLR)
5) AIM2/cGAS

A

1) C-type leptin receptors (CLR) - “glue” to stick to pathogens, recognises CHO patterns on microorganisms, phagocytosis
2) Toll like receptors (TLR) - exist on cell surface and intracellularly (endocystic vesicles), “cell activators” = activate NFKB and release of antimicrobial peptides and cytokines
3) Nod-like receptors (NLR) - exist intracellularly; activate “inflammasomes” via IL1
4) Rig-like receptors (RLR) - exist intracellularly in the cytoplasm; sense RNA (should not be there) –> release IFN type 1
5) AIM2/cGAS - exist intracellularly in the cytoplasm; sense DNA (should not be there) –> release IFN type 1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

When do interferons get released?

A

Released from many cell types in response to viral infection
Interfere with viral infection

Important in fighting COVID
Defects may be responsible for severe COVID

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Example of an inflammasome mediated disease

A

Gout

Urate crystals –> activates NLRP3 (inflammasome component) –> inflammasome gets assembled –> activates caspase 1 –> IL1b production –> inflammation

Hence IL1 blockers could be helpful

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Lack of neutrophils result in

A

High grade bacterial infections - staph aureus, gram neg bacteria (ecoli, pseudomonas, P. mirabilis, serratia)

Invasive candiasis/aspergillus

Chronic granulomatous disease (defect in NADPH oxidase –> lack of oxidative burst –> neutrophils can’t kill intracellular organisms that it phagocytoses)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What’s NETosis? (neutrophils)

A

When neutrophils die –> it throws all its DNA into the surrounding like a net, lined with antimicrobial peptides –> traps passing bacteria

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

What’s the main difference between conventional dendritic cells vs plasmacytoid dendritic cells?

A

cDCs lurk in tissues as sentinels then initiate immune response by capturing the antigen and presenting it to T and B cells in spleen, LNs, MALT. Produce IL6, IL12, TNF.

pDCs respond to viral infections by releasing lots of type 1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

What are innate-lymphoid cells?

A

Similar to T helper cells of the adaptive immune system

They contain no specific antigen receptors
They sense ‘distress’ signals from DCs, macrophages activated by PAMPS/DAMPS, and respond by producing cytokines.

ILCs are grouped into 3 groups based on the cytokines they produce.

  • Group 1 ILCs are like Th1 cells, make IFN-y. E.g. NK cells
  • Group 2 ILCs are like Th2 cells, involved in allergic disease and helminths. Activated by TSLP.
  • Group 3 ILCs are like Th17 cells
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

HIV and CCR5 mutation

What’s the significance?

A

CCR5 is a chemokine receptor that HIV uses to enter CD4 cells

With time/late infection, the CCR5 receptor mutates to CCR4X which allows increased expression on cells, and increased entry of HIV virion into cells = more aggressive

Fun fact - if you lack CCR5, HIV can’t enter CD4 cells and you can’t get HIV!

32
Q

What do NK cells do?

A

Kill virus infected cells and tumour cells

33
Q

Which 3 molecules are involved in the adhesion cascade (getting leukocytes into tissues)?

A

1) Selectin (epithelial cell)
2) Integrin (leukocyte)
3) Cell adhesion molecule (CAM) (epithelial cell)

34
Q

Steps in adhesion cascade (getting leukocytes into tissues)

A

1) Rolling
- Leukocytes are rolling across epithelium

2) Integrin activation
- Leukocyte interacts with chemokines
- Activates integrin (on leukocyte) from inactive to active state

3) Firm adhesion
- Integrin activates with CAM

4) Diapedesis
- Leukocyte moves through the epithelium

35
Q

2 examples of integrin blockers being used in Crohn’s and MS

A

1) Vedolizumab
- Blocks alpha-4-beta-7 integrin
- Prevents T cells from entering gut epithelium by blocking integrin (adhesion cascade)
- Used in IBD (CD, UC)

2) Natalizumab
- Blocks alpha-4 integrin
- Prevents T cells from entering gut epithelium and into brain
- Used in Crohn’s and MS
- Risk of JC virus (T cells no longer monitor pathogens in the brain)

36
Q

What’s the difference between MHC/HLA class I and II?

A

Class I

  • Bind peptides derived from degraded intracellular proteins
  • Can be self proteins, intracellular bacteria, viruses, tumour antigens
  • Expressed on most cells
  • Present to CD8 T cells

Class II

  • Bind peptides derived from degraded extracellular proteins
  • Expressed only on specialised APCs
  • To present to CD4 T cells
37
Q

Why do all cells express MHC class I?

A

So they can signal when they’ve been infected

38
Q

HLAB27 is associated with

A

AS

39
Q

HLADR4 is associated with

A

RA

40
Q

What test must we do before prescribing abacavir to avoid drug hypersensitivity?

A

HLAB5701

41
Q

What test must we do before prescribing carbamazepine to avoid drug hypersensitivity?

A

HLAB1502

42
Q

MOA of TRALI

A

HLA antibodies from blood donor (patients who have had previous transfusions and subsequent reactions, mothers who have had children reacting to paternal HLA) bind to HLA proteins of the recipient

43
Q

MOA of platelet transfusion refractoriness

A 
Platelets express HLA class I proteins 
Some patients develop anti-HLA antibodies to foreign HLA proteins and become refractory to platelet transfusions
44
Q

Hyperacute rejection MOA

A

Ab mediated rejection
Recipient ab bind proteins on donor graft cells –> complement activation + platelet accumulation leading to thrombosis and tissue necrosis

Driven by

  • Anti-ABO antibodies (natural IgM ab that develop early in life)
  • Anti-HLA antibodies (rare these days as recipients are screened these days for ab). Can develop from previous exposure to foreign HLA proteins e.g. pregnancy (paternal HLA in foetus), transfusion (platelet/RBC with contaminating WCs which contain HLA proteins on their cell surface), previous transplants
45
Q

How soon does hyperacute rejection occur?

A

Within minutes of reperfusion of transplanted organ –> graft destruction

46
Q

Is hyperacute rejection common?

A

No
Due to antibody screening and better donor-recipient matching

Transplant is not performed if anti-donor HLA antibodies are detected

47
Q

Acute rejection MOA

A 
Direct pathway
1) HLA class I on donor tissue cells activate recipient cytotoxic T cells --> kills graft cells

2) HLA class II on donor DCs (carried with the graft) activate recipient cytotoxic T cells
- Foreign HLA molecule mistaken by T cell as ‘self HLA + foreign peptide’

48
Q

Chronic rejection MOA

A

Indirect pathway
- Recipient DCs infiltrate the graft –> replace donor APCs –> process and present graft antigens with self HLA –> activate recipient T cells (Th cells) –> ab response

Both T cell and ab mediated (ab can be existing or be de novo)

49
Q

Major cause of renal graft failure after the first year

A

Chronic rejection

50
Q

How do we choose donors for solid organ transplant?

A

1) HLA typing (HLA- A, B, C, DR, DQ, DP)
- Determines level of mismatch

2) Screen for anti-HLA antibodies (donor specific ab)

3) HLA crossmatch
- Positive crossX means the patient has ab against the donor HLA = hyperacute rejection = contraindicated
- In vitro crossX (mix donor lymphocytes with recipient serum and see if any of the recipient antibodies bind to the donor lymphocytes) OR virtual crossX (done on computer; compare recipient anti-HLA antibodies with the HLA type of the potential donor and predict likelihood of reaction)

51
Q

Which organ transplant do we not do HLA matching?

A

Heart and Lung

  • Small patient/donor pool
  • Usually fairly urgent

Donor selection is based on

  • Negative HLA cross X
  • Absence of donor specific ab

Liver
- No HLA matching/ab testing/crossmatching unless its combined with renal transplant (liver absorbs some anti HLA antibodies)

52
Q

Which organ transplants have the best prognosis?

A

Kidney > heart > liver > pancreas > lung > heart/lung

53
Q

Can organ transplants be done with ABO incompatibility?

A

Yes but not ideal

Will need to remove antibodies first with plasmaphareis, rituximab, IVIG

54
Q

Most common cause of death with a functioning kidney graft

1) First year
2) After first year

A

1) Infection, also cardiovascular

2) cancer

55
Q

How does allogeneic haematopoietic stem cell transplant happen?

A

2 ways

1) Bone marrow harvest
2) Donor receives G-CSF –> stimulates BM to produce stem cells and release them into the bloodstream –> peripheral blood collection (more common)

Recipients are given pre-transplant conditioning (chemo and radiotherapy) to wipe out their immune system before receiving HSC infusion

56
Q

Common indications for autologous hematopoietic stem cell transplant

A

In order of prevalence
Myeloma
NHL
HL

57
Q

Common indications for autogeneic hematopoietic stem cell transplant

A

In order of prevalence

AML
ALL
MDS
NHL
CML
58
Q

MOA of haematopoietic stem cell transplants

A

1) Antibody mediated rejection
- Donor specific anti-HLA antibodies present pre-transplant
- If no other options, can give plasmapharesis + rituximab pre transplant but its difficult to reduce ab to a low level

2) T cell mediated rejection
- If there are residual T cells after pre-transplant conditioning

59
Q

MOA GVHD

A

Gut epithelium is damaged by by pre-transplant conditioning which can activate cytokines and APCs to present to donor T cells (carried across with the transplant organ) –> activated donor cytotoxic T cells and NK cells attack the patient’s organs and tissues (skin, liver, gut) –> more tissue damage and more APCs and more cytotoxic T cells activated (vicious cycle)

60
Q

Which organs does GVHD typically affect?

A

Lymphocyte rich organs

Hematopoietic stem cell transplant (peripheral transplant > BM transplant)
Liver
Blood product transfusions (need to be irradiated or leucocyte depleted)

61
Q

When does acute and chronic GVHD occur?

A

Acute: 6-100 days
Chronic: >100 days

However there is overlap in reality

62
Q

How does acute and chronic GVHD typically present?

A

Acute
- Dermatitis, hepatitis, enteritis

Chronic
- More diverse and extensive symptoms e.g. skin, liver, eyes, mouth, lungs, GIT

63
Q

Most common cause of death in the 1st year post allogeneic hematopoetic stem cell transplant

A

Disease relapse > Infection > GVHD

64
Q

What’s graft vs leukaemia?

A

This is good

Graft T cells wipe out residual leukemic cells not removed during pre-transplant conditioning

Mild GVHD can be good for the graft vs leukemia effect (Depleting T cells from the donor marrow is good to prevent GVHD, but this means less graft vs leukemia reaction and increases relapse rates. Its a fine balance!)

65
Q

How to prevent GVHD?

A

1) Reduce intensity of pre-transplant conditioning
2) Manipulate gut microbiota
3) Block inflammatory cytokines
4) T cell depletion of donor marrow

66
Q

What’s a haploidentical donor for hematopoietic stem cell transplants?

A

A haploidentical, or half-matched, donor is usually your mom, your dad or your child. Parents are always a half-match for their children. Siblings (brothers or sisters) have a 50% chance of being a half-match for each other, and 25% of being a full match.

HLA mismatch can be overcome with cyclophosphamide

67
Q

MOA fingolimod

A

Inhibits SIP-1 molecule and stops lymphocytes from leaving lymph node

Produces significant lymphopenia but short t1/2, so if you stop the drug, cells will go back to normal within 24h (does not increase sepsis susceptibility)

68
Q

Which complement pathway is activated by immune complexes?

A

Classical pathway

69
Q

Defects in the classical pathway results in

A

Autoimmunity e.g. SLE

70
Q

Which complement pathway is activated by activated microbial cell wall products?

A

Alternative pathway

71
Q

Defects in the alternative pathway results in

A

Infections e.g. Neisseria

72
Q

Which organisms are susceptible to complement?

A

Encapsulated organisms - they need opsonisation and phagocytosis

E.g. Neisseria

73
Q

Whats CTLA4?

A

Inhibitory molecule

APC binds to T cell via

  • MHC —— TCR
  • B7 ——- CD28

When CTLA4 is expressed on T cell

  • B7 ——- CTLA4 instead (instead of CD28)
  • This inhibits T cell
74
Q

How does ipilimumab work?

A

Binds to CTLA4 (T cell) so B7 (APC) can bind to CD28 (T cell) = activate T cell

75
Q

How does abatacept work?

A

Binds to B7 (CD80/86) on APC so it can’t bind to CD28 on T cell

Loss of costimulation = loss of T cell activation

Immunology (6 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions