Brainscape's Knowledge GenomeTM

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


See full index

Pathology > Immunology > Flashcards

Immunology Flashcards

1
Q

Define the terms ‘allergen’ and ‘allergic disorder’

A

An allergen is a foreign protein that stimulates an IgE-mediated immune response
An allergic disorder is an immunological response that occurs after exposure to an allergen, with reproducibility

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

Describe the pathogenesis of allergic disorder

A
  • Allergens can cause epithelial stress -> cytokines released including TSLP, IL-25 +33
  • Cytokines act primarily on Th2 cells (+Th9, ILC2) to cause more cytokine release (IL 4, 5, 13) which recruit eosinophils and basophils
  • Also stimulate Tfh2 cells to produce IL-4 which recruits B cells to produce IgE and IgG4

*Key points: allergens cause epithelial cells to release TSLP, which stimulates Th2 cells to recruit eosinophils + basophils, and make B cells produce IgE

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

Describe the role of mast cells in allergic disease

A

Allergens cause IgE crosslinking on mast cells -> release of histamine, leukotrienes and prostaglandins

  • > vasodilation, permeability, smooth muscle contraction, etc
  • > swelling, inflammation, airway obstruction, itching
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

___ exposure is more likely to cause IgE formation and allergy compared to ___ exposure, because of ___ cells

A

Skin/respiratory exposure vs oral exposure because of Treg cells in the GI tract

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

Describe the symptoms and signs of an IgE mediated immune response

A

Occurs minutes-hours after exposure, reproducible

  • Lip + tongue swelling
  • Difficulty breathing, stridor, wheeze
  • Urticaria
  • Nasal congestion + itching
  • Watery red eyes
  • D+V
  • Hypotension
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

How are IgE-mediated allergic disorders diagnosed? Describe the different tests, and positives + negatives

A

-Clinical evidence is essential for diagnosis. IgE adds to diagnosis but alone is not enough
-During an episode: serial mast cell tryptase (suspected anaphylaxis, unclear)
-Skin prick testing: prick skin to inject the allergen. Need a positive control (histamine) and negative control (diluent). Wait 15-20 minutes and measure the wheals (NO antihistamines in this time). 3+ mm over control is positive test for sensitivity. Rapid and easy, good NPV. Need experience, not great PPV, have to stop antihistamines.
-RAST: put patient IgE on solid polymer of allergen to cause binding. Add a fluorescent tagged IgE antibody that is specific to the patient IgE you are looking for (eg. anti-peanut protein IgE). If binds, this is positive for that IgE type. Used if widespread skin disease preventing SPT, can’t stop antihistamines. Expensive.
-Component resolved testing: IgE to single protein. Especially used in peanut allergy where there are 5 major allergens causing different symptoms
-Basophil activation test: looks at if basophils are activated in response to allergens. Activated cells express CD63, CD203 and CD300
GOLD STANDARD for food + drug: challenge test
-Exposed to slowly increasing quantities of allergen in a controlled medical environment w/ resusc ability. Double blind + placebo.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Define anaphylaxis.

A

A life-threatening acute immunological response to allergen exposure. Affects airways and circulation.
Usually IgE mediated, also IgG or complement.

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

Name some conditions that can mimic anaphylaxis

A

ACEi use can cause urticaria and angioedema
C1 inhibitor deficiency can cause throat swelling (hereditary angioedema)
Severe asthma, MI, PE, anxiety, phaeo, systemic mastocytosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Describe the management of anaphylaxis

A
  • Elevate legs and give high flow O2
  • IM adrenaline
  • Inhaled bronchodilators
  • IV fluids
  • IV Hydrocortisone 200mg
  • IV chlorphenamine 10mg

-Refer to allergy clinic for investigation, give written info, EpiPen x2, Medic Alert bracelet. Dietician if food allergy

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

What is the difference between food allergy and food intolerance?

A
  • Allergy: immunological mediated hypersensitivity to specific allergens in food
  • Intolerance: non-immunological hypersensitivity
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is oral allergy syndrome?

A

A type of allergic disorder caused by allergy to pollen causing cross-reactivity with fruits eg. apple. Only if raw.
Oral cavity symptoms: swelling, itching

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

What are some skin barriers to pathogens?

A

Tightly packed cells, low pH, sebaceous glands with oils, lysozymes + ammonias

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

Name some mucous membrane barriers to pathogens

A

Mucin, IgAs, lysozymes, lactoferrin, cilia, commensals

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

ImportedName some components of the innate immune system

A 
Neutrophils, eosinophils, basophils
Monocytes/macrophages
NK cells
Dendritic cells
Complement
Cytokines
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Describe the function of polymorphs in the innate immune response

A

Migrate to sites of injury
Express pattern recognition receptors (PRRs)
Destroy pathogens by phagocytosis, oxidative and non-oxidative killing

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

What is the difference between polymorphs and macrophages?

A

Polymorphs cannot present antigens to T cells

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

Describe oxidative and non-oxidative killing

A

Oxidative: NADPH oxidase creates reactive oxygen species -> damage
Non-oxidative: release of enzymes

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

What is opsonisation?

A

Opsonins (Igs) bind to bacteria and aid in phagocytosis

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

Describe the function of NK cells

A
  • Primarily regulated by Inhibition by normal T cells

- Cytotoxic when no inhibitory signals

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

Describe the function of dendritic cells

A

Phagocytose pathogens

Migrate to lymph nodes to present antigens to lymphocytes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What are the primary lymphoid organs? Secondary?

A

1˚: Bone marrow and thymus

2˚: spleen, lymph nodes

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

What are some differences between the innate and adaptive immune responses?

A

Adaptive has much more pathogen recognition and is not genetically encoded, also has memory

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

Describe the process of T cell maturation

A

T cells created in the bone marrow
Migrate to the thymus
Undergo affinity maturation (a process where they are checked for the correct response to antigens- self-reactive or non-reactive undergo apoptosis)

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

What is the function of CD4+ cells? CD8+?

A 
CD4+: detect foreign antigens presented on HLA class II (DR, DP, DQ). Immune regulatory function eg. activate B cells/CD8
CD8+: detect self antigens presented on HLA class I (A, B, C). Cytotoxic with FasL, perforin, secrete cytokines
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Which cells express foxp3?

A

Treg cells

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

Describe the process of B cell maturation and differentiation

A
  • Created in the bone marrow as pre B cells (IgM)
  • Central tolerance check
  • Can stay as IgM or
  • Undergo reaction in germinal centre to differentiate into IgG, IgA, IgE (somatic hypermutation and isotype switching), with help of primed CD4+ Th cells and CD40L
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Describe the structure of Igs

A

2 heavy chains, 2 light chains
Fc region: binds to receptor/produces effect
Fab region: variable, binds to antigen

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

What are the 3 pathways of complement activation?

A

Classical: C1, 2, 4. Activated by immune complexes
Alternative: C3 binds directly to pathogen cell wall components
Mannose binding pathway: MBL, C2, C4. Binds directly to cell surface.
–> common pathway: C3, C5-9 -> MAC

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

What type of virus is HIV? What is the key enzyme it has?

A

RNA retrovirus. Reverse transcriptase -> inserts into genome.

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

Describe the genetic makeup of HIV

A

9 genes encoding 15 proteins

  • Envelope proteins: gp120 and gp41
  • Gag proteins: p17, 24, 9, 7. 24- capsid
  • Enzymes: RT, protease, IN
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

How is HIV transmitted? Which cells does HIV infect? Describe the process of HIV infection

A

Transmission through blood, sex (damaged mucosal surfaces), vertical.
CD4+ T cells, monocytes, dendritic cells
Uses CD4 and CCR5/CXCR4 to enter cells via gp120 binding.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

Describe the immune response to HIV infection and how HIV persists

A

Innate: macrophage activation, CK release, NK cells
Adaptive:
-Antibodies to gp120, gp41, p24 gag IgG released -> HIV is still infective
-Both HIV infection and CD8+ cell response leads to decreased CD4 count
**Bc CD4 cells low/inactive -> poor CD8 response
-HIV replication is error prone -> lots of mutations -> evade immune defences

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

Describe the life cycle of HIV with relevant proteins/enzymes

A
  1. Binding and entry via gp120 and gp41
  2. RT converts RNA to DNA
  3. Integration into host genome (integrase)
  4. RNA transcription
  5. Protein synthesis
  6. Protein packaging and release (protease)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

Describe the different targets of HIV drugs and name examples

A
  1. Attachment inhibitors (Maraviroc)
  2. RT inhibitors: nucleoside (Zidovudine), non-nucleoside (Efavirenz), nucleotide (Tenofovir)
  3. Integrase inhibitors: raltegrivir
  4. Protease inhibitors: ritonavir
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

What does a typical ART regime consist of?

A

2 NRTIs and PI/NNRTI

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

Describe the clinical course of HIV infection

A
  • Primary infection with seroconversion. Asymptomatic/mild flu-like illness with generalised lymphadenopathy
  • Asymptomatic phase, with slowly declining CD4 and stable viral load
  • AIDS after 8-10 years: rapid decline in CD4 and CD8, increased viral load. Increased susceptibility to infections/disease (AIDS defining illnesses)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

What are some reasons for long term slow progressors with HIV?

A
  • Genetic factors eg. HLA subtypes, CCR5 mutations etc
  • Less severe strains
  • Strong immune response
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

Describe investigations for HIV

A

Screening: ELISA (HIV antibodies)
Confirm: Western blot (antibodies)
Viral load (PCR) and CD4 count (flow cytometry): baseline and monitoring
Resistance testing: phenotypic (basically sensitivity testing), genotypic (sequence for genes assoc w/ resistance). Used in determining treatment.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

Who should be given HAART?

A

All patients should be offered!!!

Old recommendations: when CD <200 or symptomatic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

What are some benefits and limitations of HAART?

A

Benefits: suppresses viral load, improves CD4 count to improve host immunity, delays/prevents AIDS, prevents transmission
Limitations: does not cure infection, must be taken regularly without missing or risk of mutation, toxicity/SE, cost, high pill burden (adherence)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

Which is the most common type of HIV in the world?

A

HIV-1. HIV-2 in parts of Africa

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

What is PEP? PrEP?

A

PEP: Truvada eg. Tenofivir/Emtricitabine + Raltegrivir
PrEP: Truvada

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

Name some examples of secondary immunodeficiency

A

HIV, leukemia, malnutrition, steroids, chemotherapy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

What would make you consider the possibility of immunodeficiency?

A
  • Recurrent minor infections or multiple major infection
  • Unusual organism
  • Unusual site
  • Chronic infection

Primary: Family Hx, young age, poor growth

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

Name some primary immune deficiencies causing phagocyte deficiency and briefly describe the pathophysiology

A
  • Kostmann syndrome: failure of maturation -> neutropenia
  • Cyclic neutropenia: failure of maturation -> episodic neutropenia
  • Reticular dysgenesis: severe SCID. Neutrophils + other cells do not develop. Fatal if no BMT.
  • Leukocyte adhesion deficiency: neutrophils can’t cross blood -> tissues. High levels in blood, no pus.
  • Chronic granulomatous disease: neutrophils can’t do oxidative killing -> build up -> granulomas. Also hepatosplenomegaly.
  • Cytokine deficiency (IL-12, IFNg): deficiencies in the pathway that activates neutrophils/phagocytes when there is Mycobacterium infection.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

How is chronic granulomatous disease diagnosed?

A

Nitro-blue tetrazolium test (NBT): tests for hydrogen peroxide -> blue. Negative in CGD
Dihydrorhodamine (DHR) flow cytometry: turns fluorescent. Negative in CGD
Both of these test for the presence of superoxide species formed by NADPH, which is deficient in CGD

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

What would you expect in a person with primary phagocyte deficiency? What investigations would you do?

A 
Recurrent infections of skin/mouth esp bacterial, TB
Neutrophil count (FBC), CD18, NBT/DHR test, pus
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

Name some types of NK cell deficiency. How would NK deficiency present?

A

-Classical NK deficiency: no NK cells
-Functional NK deficiency: reduced action of NK cells
Increased viral infections (eg recurrent HSV, severe VZV)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

What would you expect to see in someone with complement deficiency?

A

Increased susceptibility to bacterial infections, specifically encapsulated bacteria (N men, Haemophilus, Strep)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

Why is complement deficiency associated with SLE?

A

Complement stimulates the clearing up of immune complexes/dead cells
If deficient -> build up of immune complexes

51
Q

What are some complement deficiencies?

A
  • Classical pathway: C1, 2, 4 deficiency. C2 is most common, almost all have SLE. Can also have 2˚ deficiency due to using up in SLE
  • Mannose binding lectin: common to be heterozygotic, doesn’t really cause issues unless another reason for immunocompromise eg. chemo.
  • Alternative: rare
  • Common pathway: C3 deficiency. Severe.
  • MAC deficiency
52
Q

How are complement deficiencies investigated?

A 
Complement levels (quantitative)
Complement function (qualitative)- CH50 classical + common, AP50 alternative + common
SLE ABs eg. anti-dsDNA, ANA, anti-Sm
53
Q

How does C1q deficiency present?

A

Severe SLE in childhood, normal C3 and C4 levels

54
Q

How does MBL deficiency present?

A

Recurrent infections when new immunocompromise (eg chemo), but previously well

55
Q

What is SCID? What are some types?

A

Severe combined immunodeficiency: a group of ~20 conditions all causing defects in B+T cell immune function (combined)
Reticular dysgenesis: most severe form. Lymphoid + myeloid affected
X-linked SCID: most common (45%). IL2 receptor mutation -> no cytokine response means no development of T cells and immature B cells.
ADA deficiency: poor development of all lymphocytes

56
Q

How do you differentiate the types of SCID?

A

Reticular dysgenesis: low lymphocytes + polymorphs
X-linked: low T/NK cells, normal/high B cells, no Ig
ADA: low levels of T/B/NK cells

57
Q

How does SCID present?

A

Illness from ~3 months old (before this, protected by maternal IgG)

  • Infections
  • Failure to thrive
  • Persistent diarrhoea
  • Skin disease
  • Family Hx
58
Q

Name some types of primary T cell deficiency and briefly describe

A
  • DiGeorge syndrome (22q11 del): thymic aplasia -> low T cell count, normal B cells. Improvement with age
  • Bare lymphocyte syndrome Type II: problems with MHC II expression -> CD4 deficiency -> no IgG/A
  • IL12/IFNg deficiency: causes poor phagocyte + Th cell response.
  • Wiskott-Aldrich syndrome (WAS): low Plts, high IgE (eczema), lymphopenia
59
Q

What are some features of T cell deficiency?

A

Recurrent/severe viral infections eg. CMV
Fungal infections eg. PCP, crypto
Early malignancy

60
Q

How would you investigate suspected T cell deficiency?

A
  • FBC and differential
  • Flow cytometry
  • Ig levels
  • HIV test!!!
61
Q

Which test is a good marker of CD4 cell presence/function? Why?

A

IgG and IgA - the maturation/class switching of pre-B cells into IgG/A plasma cells is dependent on CD4 Th cells

62
Q

T/F. The IgM response is T cell dependent

A

False. IgM does not require T cell support, but IgG/A/E does -> this is the germinal centre reaction/isotype switching

63
Q

Name some primary B cell deficiencies and briefly describe

A
  • Bruton’s X linked hypogamma globulinaemia: tyrosine kinase mutation -> no maturation of pre-B cells into mature B cells -> no Ig
  • Selective IgA deficiency
  • Hyper IgM syndrome: no CD40L on T cells -> no isotype switching -> ONLY IgM, no IgG/A/E
  • Common variable immune deficiency: unknown cause. Low Ig A and G, especially IgG.
64
Q

How do B cell deficiencies present?

A

Typically ~3 months or later (due to loss of maternal Ig)

  • Recurrent infections
  • Especially URTIs in IgA deficiency
  • Autoimmune disease and granulomas in CVID
  • Boys more commonly affected in Bruton’s and Hyper IgM
65
Q

How would you investigate suspected B cell deficiency?

A

FBC and differential
Flow cytometry (lymphocyte subsets)
Ig levels and electrophoresis (gamma peak shows all Ig)
Functional testing eg. vaccination against tetanus/pneumovax -> check IgG levels after few weeks

66
Q

What is the difference between auto-inflammatory and auto-immune disease?

A

Auto-inflammatory: activation of innate immune response -> local inflamamtion
Auto-immune: breakdown of immune tolerance to self (adaptive system) -> systemic/local inflammation

67
Q

What is the basic pathophysiology of monogenic auto-inflammatory conditions? Give 1-2 examples

A

Mutations in the inflammasome complex (eg. pathways from pathogen -> local inflammation thru IL-1, TNF)

  • Familial Mediterranean fever: MEFV mutation. Episodic neutrophil activation -> abdo pain, chest pain, rash, arthritis.
  • TRAPS
68
Q

What is the basic pathophysiology of monogenic auto-immune conditions? Give several examples

A

Mutations leading to breakdown in tolerance eg. Treg cell abnormality, apoptosis

  • APCED: defect in AIRE protein responsible for T cell selection (central tolerance) -> too many self-reactive T cells
  • IPEX: foxp3 mutation -> no Treg cells -> failure of peripheral tolerance
  • ALPS: FAS pathway defect -> no apoptosis of lymphocytes (high lymphocytes, splenic enlargement)
69
Q

Name some common polygenic auto-inflammatory disorders

A
  • Crohn’s
  • UC
  • Ankylosing spondylitis
70
Q

Which HLA is associated with ankylosing spondylitis?

A

HLA-B27

71
Q

T/F. HLA associations are more common in auto-inflammatory conditions, while auto-antibodies are more common in auto-immune conditions

A

False. Both are more common in auto-immune conditions

72
Q

Name some common auto-immune conditions and classify them by Gel and Coombs method

A

Gel and Coombs method is the types of reaction (1-4)
Type II hypersensitivity reactions (AB mediated):
-Grave’s disease
-Sjogren’s syndrome
-Pemphigus

Type III hypersensitivity reactions (immune complex):
-SLE

Type IV hypersensitivity reactions (T cell mediated):

  • Type 1 DM
  • Rheumatoid arthritis
  • MS
73
Q

Which HLA is associated with Type 1 DM?

A

DR 3 + 4

74
Q

What are the seronegative arthropathies? What does this term mean?

A

Psoriatic arthritis, reactive arthritis, ank spon

They are associated with no RF/anti-CCP, but with HLA-B27

75
Q

SLE is associated with which HLA?

A

DR3

76
Q

Rhematoid arthritis is associated with which HLA?

A

DR4

77
Q

What are the Grave’s antibodies? What type of Ig are they?

How about Hashimoto’s?

A

IgG. anti-TSHR

IgG. anti-TPO, anti-thyroglobulin. These are not specific though, and we often do not measure them as they are common.

78
Q

Which antibodies are found in T1DM?

A

anti-islet cell, anti-GAD (glutamic acid dehydrogenase) and anti-IA2 (islet antigen), anti-insulin

79
Q

Which antibodies are found in MG? What is the test used in diagnosis?

A 
anti-nicotinic ACh R 
Tensilon test (edrophonium- cholinesterase inhibitor)
80
Q

Which antibodies are found in RA? Which is the most specific? Sensitive?

A

RF (IgM antibody) and anti-cyclic citrullinated peptide (CCP)
anti-CCP is the most specific (95%)
RF is the most sensitive (85%)

81
Q

Which different immune mechanisms contribute to rheumatoid arthritis?

A

Type II: antibodies eg. RF, anti-CCP
Type III: immune complexes deposited in joints
Type IV: T cell mediated destruction

82
Q

Which antibodies are found in SLE? Which is most sensitive and which is most specific? Which is used for monitoring disease activity?

A

anti-dsDNA (a type of ANA), anti-Sm, anti-Ro, anti-La
dsDNA is the most specific, also quite sensitive. Used for monitoring disease activity (along with complement)
anti-Ro and La not very specific, also found in others

83
Q

Which antibodies are found in antiphospholipid syndrome?

A

Lupus anticoagulant

Anti-cardiolipin

84
Q

Which antibodies are found in the inflammatory myositis?

A

Dermatomyositis: Jo1 and Mi2

85
Q

What are the types of ANCA? What are they antibodies towards?

A

cANCA: Ab to proteinase 3. Cytoplasmic staining
pANCA: Ab to myeloperoxidase. Perinuclear staining

86
Q

What are the stages of immune response to transplanted organ?

A

1) Recognition
2) Activation of adaptive immune response
3) Effector phase (graft rejection)

87
Q

Which are the most important antigens involved in transplant rejection?

A

ABO

HLA molecules: most important are A, B, DR

88
Q

What is HLA matching in transplantation? How is it done?

A

Compare the alleles at A, B and DR
Everyone has 2 alleles x 3 genes = 6 possible mismatches. Matching reduces graft rejection
PCR donor and recipient for HLA type -> maximise matching. Also check for preformed ABs + crossmatch

89
Q

Describe the process of T cell mediated graft rejection

A

Recognition: T cell activation requires HLA molecule presenting an antigen, costimulatory signals and cytokine release
Activation: proliferation of T cells, cytokine rekease, B cell recruitment
Effector phase: lymphocytes migrate thru endothelium into the interstitium and release enzymes, destroy cells via FasL

90
Q

What are the histological characteristics of T cell mediated graft rejection?

A

Interstitial inflammation and tubular epithelial inflamm
Lymphocytic infiltration
Inflammation of *arteries

91
Q

Describe the process of antibody mediated graft rejection

A

Recognition: donor antigen detected + presented by APC
Activation: B cell proliferation (dependent on CD4 Th) after germinal centre reaction
Effector phase: antibodies produced that bind to endothelial surface HLA

92
Q

What are the histological characteristics of antibody mediated graft rejection?

A

ABs on the endothelial surface (immunofluorescence), complement fixing
Capillary endothelial cell inflammation

93
Q

What are some signs of graft rejection?

A 
Rising Cr (kidney)
Abnormal LFTs (liver)
94
Q

What are the different types of graft rejection? What is the mechanism in each?

A

Hyperacute (mins-hours): preformed ABs detect graft and activate complement (usually ABO)
Acute (<6 months): T cell or AB mediated. Usually direct recognition by donor APCs presenting antigen
Chronic (>6 months): T cell or AB mediated. Usually indirect by recipient APCs presenting antigen.

95
Q

What is graft vs host disease? How does it present?

A

Where the donor lymphocytes found in the graft attack the host tissues.
Presents with rash, D+V, bloody stool, jaundice etc

96
Q

Which drugs are used to prevent graft rejection?

A

Want to inhibit the immune response

  • T cell: steroids, calcineurin inhibitors (Tacrolimus), cell cycle inhibitors (Mycofenilate mofetil), monoclonal ABs
  • Antibody: rituximab, proteasome inhibitors, plasma exchange
97
Q

Describe the immunosuppression regime in transplantation

A
  1. Pre-transplant induction: OKT3/anti-CD25
  2. Baseline immunosuppression: steroids, MMF, tacrolimus
  3. Episodic treatment: steroids, OKT3, plasma exchange, IVIG
98
Q

What are some complications of transplantation?

A
  • Graft rejection
  • GVHD
  • Increased opportunistic infections eg. CMV
  • Malignancy eg. Kaposi’s, EBV related, skin cancer
  • Atherosclerosis
99
Q

What are some reasons for declining renal function in someone with a kidney transplant? What tests can be done?

A

-Graft rejection
-Drug toxicity
-Vascular disease
-Recurrence of disease (reason for transplantation)
BP, U+Es, Biopsy!

100
Q

What is immunological memory? Which cells are involved?

A

The ability of the immune system to have an enhanced response to a subsequent infection
Includes both CD8 T cells and IgG B cells

101
Q

Which antibodies are protective against influenza?

A

Antibodies to haemaglutinin (on the surface of influenza)

102
Q

What is the effect of the BCG vaccine?

A

Does not prevent against primary infection

Prevents against active infection (T cell response)

103
Q

What are the different types of vaccines? Give examples of each

A
  • Live attenuated: MMR, BCG, yellow fever, oral typhoid + polio (Sabin), chickenpox.
  • Inactivated: influenza, polio (Salk), rabies, pertussis
  • Component: Hep B, HPV, influenza
  • Conjugate: tetanus, Hib, meningococcus, pneumococcus
  • Toxoid: diphtheria, tetanus
  • mRNA: Pfizer Covid vaccine
104
Q

What are some advantages and disadvantages of live attenuated vaccines?

A

Advantages: longer lasting memory, protects against cross-reactive strains, activates innate + adaptive immune response
Disadvantages: should be used with caution in immunosuppression, harder to store, may revert

105
Q

What are some advantages and disadvantages of inactivated vaccines?

A

Advantages: easy to store, cheaper, safe in immunosuppression, no reversion
Disadvantages: poorer + shorter immunity, need boosters

106
Q

MMR is a type of __ vaccine

A

Live attenuated

107
Q

Meningococcal is a type of __ vaccine

A

Conjugate

108
Q

HBV is a type of __ vaccine

A

Component

109
Q

What is a conjugate vaccine? Name some examples.

A

Protein + polysaccharide. The polysaccharide is from the capsule of the bacteria, but vaccination with only this causes B cell only response.
Protein stimulates a T cell response to boost the B cell response.
eg. Hib, meningococcus, pneumococcus (encapsulated bacteria)

110
Q

What is the purpose of adjuvants in vaccines? Name some examples.

A

Adjuvants increase the immune response without altering the contents of the vaccine. Mimic PAMPs and bind to PRRs on innate immune cells
eg. aluminium, lipids CpG

111
Q

What is passive immunisation?

A

Giving protection to pathogen without stimulating the recipient immune response
-eg. specific Ig for VZV, HBV, rabies

112
Q

What is CAR-T cell therapy?

A

Remove T cells -> insert a vector containing a specifically engineered receptor to target tumour cell (eg CD19 for B cell malignancy) -> T cells express this receptor -> infuse -> T cells detect target cells and proliferate -> destroy malignant cells

113
Q

What is the effect of steroids?

A
  • Inhibit prostglandin formation: inhibit PLA2 (forms arachidonic acid)
  • Inhibit phagocyte function: inhibit migration, phagocytosis
  • Inhibit lymphocyte release + function: cause sequestration, block CK and AB release
114
Q

Name some antiproliferative agents. How do they work?

A

Work by inhibiting DNA synthesis.

  • Cyclophosphamide: alkylating agent -> damages DNA. B > T cell
  • Azathioprine: antimetabolite. Prevents nucleotide synthesis. T > B cells
  • Mycophenolate mofetil: blocks guanine synthesis. T > B cell
  • Methotrexate: folate inhibitor
115
Q

What are some uses and side effects of cyclophosphamide?

A

Uses: not widely used: malignancy, severe vasculitis

Side effects: BM suppression, malignancy, sterility, haemorrhagic cystitis

116
Q

What are some uses and side effects of azathioprine?

A

Uses: widely used in transplantation, auto-immune/inflammatory diseases eg IBD
Side effects: BM suppression, hepatotoxicity, neutropenia
**Severe response in people with TPMT polymorphism

117
Q

What are some uses and side effects of mycophenolate mofetil?

A

Uses: widely used in transplantation. Also auto-immune/inflammatory disease
Side effects: BM suppression, PML (JC virus), HSV, malignancy

118
Q

What is plasmapharesis? When is it used?

A

Remove patients blood, separate plasma from solid components -> reinfuse solid (eg cells)
Plasma is treated to remove Igs and reinfused/replaced with albumin solution (plasma exchange)
Used in severe antibody mediated disease eg anti-GBM

119
Q

Name some cell signalling inhibitors

A

Calcineurin inhibitors eg. Tacrolimus, cyclosporin

JAK inhibitor eg. Tofacitinib

120
Q

How do calcineurin inhibitors work (broadly)? What are some side effects?

A

Inhibit production of IL-2 -> inhibits T cell proliferation

SEs: nephrotoxicity, hypertension, neurotoxicity, DM

121
Q

What is rituximab? What is it used for?

A

Anti-CD20 antibody. Destroys mature B cells (not plasma cells)
Uses: lymphoma, RA, SLE

122
Q

Name some anti-TNFa antibodies. What are their uses? What are some side effects?

A

Infliximab, adalimumab
Uses: RA, ankspon, IBD
SEs: infection (TB, HBV), lupus-like conditions, demyelination

123
Q

What is a monoclonal antibody used in the treatment of osteoporosis?

A

Denosumab

124
Q

Which HLA is associated with coeliac?

A

DQ2

Pathology (6 decks)

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