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Year 5 MEDICINE Pathology > Immunology > Flashcards

Immunology Flashcards

1
Q

monogenic auto-inflammatory diseases?

and autoimmune diseases?
Mechanisms?

A

autoinflammatory
1. Familial mediterranean fever(IL 1). Treat with colchicine. Long term risk of AA amyloidosis -> deposits in Kidney -> nephrotic syndrome
2. TRAPs

autoimmune -
1. ALPS = autoimmune lymphoproliferative syndrome. FAS mutation!! Lymphocytes don’t undergo apoptosis = high lymphocyte numbers!! LYMPHOMA, CYTOPENIA

2. IPEX = mutation in foxP3. 3DS diabetes, dermatitis and diarrhoea. symptoms. Failure of treg cells to bring about peripheral tolerance.

3. Autoimmune polyendocrine syndrome type 1. APSI. Mutation in AIRE!! Failure of central tolerance. Many autoimmune conditions. Also known as APACED.
Without Aire your body will CHAR = chronic mucocutaneous candidiasis, hypoparathyroidism, adrenal insufficiency, recurrent Candida infections) hypothyroidism

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2
Q

Familial mediterreanean fever

pathology?


presentation

complications


investigation

management

A

Autosomal recessive condition
Mutation in MEFV gene
MEFV gene encodes pyrin-marenostrin
Pyrin-marenostrin expressed mainly in neutrophils
Failure to regulate cryopyrin driven activation of neutrophils

Periodic fevers lasting 48-96 hours associated with:
Abdominal pain due to peritonitis
Chest pain due to pleurisy and pericarditis
Arthritis
Rash

AA amyloidosis -> nephrotic syndrome


high CRP, high serum AA
genetic test

colchicine

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3
Q

Immune dysregulation, polyendocrinopathy, enteropathy, X- linked syndromeIPEX pathology? presentation?

A

Mutations in Foxp3 (Forkhead box p3) which is required for development of CD25+Treg cells

Failure to negatively regulate T cell responses
Autoreactive B cells
limited repertoire of autoreactive B cells


Autoimmune diseases
Diabetes Mellitus
Hypothyroidism

Enteropathy
Eczem

‘Diarrhoea, diabetes and dermatitis’

genetic test

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4
Q

Auto-immune lymphoproliferative syndromeALPS pathology? presentation?

A

Mutations within FAS pathway
Eg mutations in TNFRSF6 which encodes FAS
Disease is heterogeneous depending on the mutation

Defect in apoptosis of lymphocytes
Failure of tolerance
Failure of lymphocyte ‘homeostasis’

High lymphocyte numbers with large spleen and lymph nodes

Auto-immune disease
commonly auto-immune cytopenias

Lymphoma

genetic test - look for mutations in FAS pathway

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5
Q

polygenic auto-inflammatory disease examples


mutations identified in chrons?

A

chrons - IBD1, NOD2

ulcerative colitis

osteoarthritis

giant cell arthritis

Takayasus arteritis

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6
Q

Polygenic autoimmune disease examples

A

Rheumatoid arthritis Systemic lupus erythematosus
Myaesthenia Gravis Primary biliary cholangitis
Pernicious anaemia
Addison disease

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7
Q

examples of mixed pattern diseases

A

Axial spondyloarthritis
Psoriatic arthritis
Behcet’s syndrome

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8
Q

Axial spondyloarthritis
presentation?
gene associations?
treatment?

A

pain in sacroiliac joints, in entheses
Low back pain and stiffness
Enthesitis
Large joint arthritis

associated with HLAB27 mostly
but also IL23R, IL32

Treatment
Non-steroidal anti-inflammatory drugs
Immunosuppression
Anti-TNF alpha
Anti-IL17

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9
Q

Hypersensitivity types/groups

A

Type I: Anaphylactic hypersensitivity
- Immediate hypersensitivity which is IgE mediated – rarely self antigen

Type II: Cytotoxic hypersensitivity
- Antibody reacts with cellular antigen

Type III: Immune complex hypersensitivity
- Antibody reacts with soluble antigen to form an immune complex

Type IV: Delayed type hypersensitivity
- T-cell mediated response

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10
Q

conditions with Type 2 hypersensitivity

A

goodpastures disease
pemphigus vulgaris
graves disease
myasthenia gravis

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11
Q

conditions with type 3 hypersensitivity

A

SLE

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12
Q

conditions with type 4 hypersensitivity

A

insulin dependent diabetes mellitus

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13
Q

antibodies seen in hashimotos thyroiditis?

A

anti thyroid peroxidase
anti thyroglobulin

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14
Q

Investigation of Connective Tissue DiseaseSLE, Sjogrens, Systemic sclerosis, Idiopathic inflammatory myopathy


they are all ANA+ve

A

ENA+ve:
1. Ro, La, Sm, RNP - SLE, sjogrens
2. SCL70 - diffuse cutaneous systemic sclerosis
3. Centromere - crest

cytoplasmic:
t-RNA synthetase (Jo1) - myositis

dsDNA+ve:
SLE

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15
Q

state the 3 small vessel vasculitis that are associated with ANCA

A

1. microscopic polyangitis - P-ANCA
2. granulomatosis with polyangitis - C-ANCA
3. eosinophilic granulomatosis with polyangitis - P-ANCA

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16
Q

p-anca vs c-anca

A

p anca = antimyloperoxidase

c anca = antiproteinase 3

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17
Q

TH2 immune response

A

IL4, IL5, IL13

mast cells cross link IgE -> release of histamines and leukotrienes -> worm and allergen expulsion

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18
Q

increased secretion of pro-inflammatory innate cytokines by PBMC following exposure to environmental microbial product may protect against development of asthma

A

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19
Q

most appropriate initial test for food allergy with urticaria and angioedema?

A

skin prick test

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20
Q

anaphylaxis treatment

A

adrenaline

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21
Q

60 year old with hypotension and rash during surgery, what test will you use to diagnose anaphylaxis?

A

serial mast cell tryptase -> quick turnaround

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22
Q

two types of immune response to infection

A

cell death or extensive damage -> microbial PAMP and host DAMP -> type 1 and 3 immune responses

cell stress or tissue pertubation -> host DAMP >>> microbial PAMP -> type 2 immune response

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23
Q

type 1 immune response is directed against? how does it work?

A

Intracellular pathogens!!!
CD4 TH1 cell activation -> secretion of interferon gamma which activates macrophages and CD8 T cells and CD4 also interacts with b cell using IL21 and interferon gamma to secrete antibodies, IgG>IgA

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24
Q

type 3 immune response is directed against? how does it work?

A

Extracellular bacteria and fungi!!!!!!
CD4 TH17 -> IL17 -> neutrophil
CD4 -> IL22 -> maintain epithelial cell integrity

igA>IgG

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25
Q

type 2 immune response is directed against? how does it work?

A

Extracellular parasites!!!!!
CD4 TH2 -> IL 4, 5 AND 13 -> mast cells, basophils, eosinophils

b cell -> IgE

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26
Q

Features of marginal zone b cells?

A

T cell independent
protect against encapsulated organisms
found in spleen

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27
Q

features of extrafollicular b cells

A

rapid response
respond to protein
t cell dependent and independent
memory
short lived plasma cells

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28
Q

features of germinal centre b cells

A

t cell dependent
respond to protein
memory
long lived plasma cells

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29
Q

structure of immuniglobulins and function of each part.

A

2 fab units
1 fc unit -> isotype class switching, ig subclasses, modification of hinge region, glycosylation

Fcr binding causes complement release, phagocytosis etc

30
Q

what is the most common cause of inborn errors of immunity?

A

antibody deficiency syndromes
thus, b cells must important cellular component

31
Q

causes of genetic succeptibility to Tuberculosis

A

1. one cause is Variant in TYK2 -> signalling protein involved in Type 1 immune response
impairs IL23
80% chance of TB disease if homozygous

2. mutation in IL12

32
Q

causes of genetic succeptibility to covid19?

A

defects in type 1 interferon
some patients have antibodies that inhibit type 1 interferon

33
Q

what conditions are associated with inborn errors of immunity?

A

inborn errors of metabolism and autoimmune dieases are often linked, especially autoimmune diseases seen in children -> cytopenias

autoinflammatory diseases eg familial mediterranean fever

allergic disease eg eczema, eosinophilia and IgE may be a sign of inborn errors of immunity, eg sever atopy + susceptibility to infection

early onset viral cancers may be a sign of inborn errors of immunity eg EBV succeptibility in combined immune deficiency syndromes


in history ask about immune deficiency and consanguity

34
Q

most common inborn error of immunity?

A

selective IgA deficiency

35
Q

first line blood tests for inborn errors of immunity?

A

FISH

Full blood count -> look at neutrophil and lymphocyte count

Serum Immunoglobulins

Serum complement

Hiv test

others:
measure concentration of vaccine antibodies - failure to respond to vaccination is a sign

36
Q

name inborn errors involving the innate immune system

A

neutrophil:
1. neutropenia syndromes:
- chronic benign neutropenia (asymptomatic, no treatment needed)
- severe congenital neutropenias

2. defects in neutrophil function:
- leukocyte adhesion deficiency syndrome (defect in binding to endothelium)
- Chronic granulomatous disease (defect in generation of reactive oxygen speicies)


complement:
1. C1-C4-2
- SLE in C1Q deficiency 90% of time
- succeptibility to encapsulated bacteria infections -> hib, strep pneumoniae

2. Alternative pathway
- neisseria meningitis (properidin)

3. C3
- C3 glomerulopathy

4, Terminal complement pathway deficiency
- neisseria meningitis
- disseminated gonoccocal infection

5. MBL deficiency
up to 30%. of population, not significant

6. C1 INHIBITOR deficiency
- recurrent episodes of angioedema of skin, abdomen, larynx
- Low C4, normal C3
- treat with C1 inhibitor NOT adrenaline

vaccination and prohylactic antibiotics to people with complement deficiencies

37
Q

Leukocyte adhesion deficiency
pathology?
clinical features?
management?

A

deficient CD18 expression on neutrophils, so not enough to bind to ICAM1. neutrophils cant exit blood stream to tissues

- delayed separation of umbilical cord
- very high neutrophil counts
- absence of pus formation

stem cell transplant

38
Q

Chronic granulomatous disease
pathology?
clinical features?
management?

A

NADPH oxidase deficiency. oxygen free radicals cant be generated which combine with MPO to form HCl/bleach which kills pathogens

bacterial, fungal infections, increased risk of TB. skin lymph nodes, liver, bone, chest. gastrointestinal and genitourinary inflammatory disease

cotrimoxazole and itroconazole prophylaxis
ifn gamma, stem cell and gene therapy

39
Q

name inborn errors involving lymphoid precursors

A

T and B cell progenitors:
1. SCID


T cell progenitors:
1. Di George

40
Q

SCID
pathology?
clinical features?
management?

which organism is NOT associated with SCID?

A

Defects in generation of lymphoid precursors in bone marrow. absent or dysfunctional t cells, affecting humoral response

multiple recurrent infections and opportunistic infections
usually unwell by 3 months of age

low lymphocyte count = diagnostic
low cd3
low serum immuniglobulins

stem cell transplantation

influenza A not associated

41
Q

22q11.2 deletion syndrome
pathology?
clinical features?
management?

A

defect in t cell maturation/selection in thymus
most common chromosomal deletion syndrome

failure of pharyngeal arch to develop;
- craniofacial structures
- thymus
- parathyroid glands, aortic arch
- cardiac outflow tract

classic triad of immune deficiency, hypoparathyroidism, congenital heart disease. but can present differently

5% reduced tcell numbers which resolve

42
Q

state antibody deficiency syndromes

A

selective IgA deficiency
CVID
XLA

43
Q

Selective IgA deficiency
pathology?
clinical features?
management?

A

most common

- allergic diseases
- Sinopulmonary and enteric diseases
- Gi cancers
- autoimmune disease

44
Q

CVID
pathology?
clinical features?



diagnosis?


management

A

adult onset -> median age 35
most common antibody deficiency in adults

- recurrent sinopulmonary infection with encapsulated bacteria. otitis media and hib conjuctivitis
- repeated chest and sinus infections -> bronchiectasis, recurrent sinusitis

- enteric, skin infections
- autoimmune disease
- granulomatous disease!!! - not just chronic granulomatous disease
- lymphoproliferative disease

diagnosis?
1. over 4 years
2. reduction in IgG and IgA or M
3. poor vaccine response
4. exclude other causes of antibody deficiency - b cell cancers, drugs

lung disease treatment
IgG replacement

45
Q

XLApathology?
clinical features?
management?

A

mutation in BTK - Bruton Tyrosine Kinase

succeptibility to disseminated enteroviral infection if not on IgG replacement

neutropenia can be a feature

chronic/acute lung disease = most common cause of death

46
Q

describe 4 ways to boost the immune response

A

1. vaccination
2. replacement of missing components - BMT, antibody/immunoglobulin replacement for primary antibody deficiencies or secondary eg in hematological malignancies or after BMT
3. blocking immune checkpoints
4. cytokine therapy - eg interferon alpha in hepatitis, interleukin 2 in renal cell cancer, interferon gamma in chronic granulomatous disease

47
Q

name some live attenuated vaccines
*learn as you cant give to immunosuppressed

A

MMR - VBOY

MMR
Varicella
BCG!!!
Oral polio (Sabin), Oral typhoid
Yellow fever

Influenza (Fluenz tetra for children 2-17 years)

48
Q

name some inactivated vaccines

A

Influenza (inactivated quadrivalent), Cholera, Bubonic plague, Polio (Salk- injected)!!!, Hepatitis A, Pertussis, Rabies

49
Q

name some component/subunit vaccines

A

Hepatitis B (HbS antigen), HPV (capsid), Influenza (recombinant quadrivalent - less commonly used)

50
Q

name a condition that immunoglobulin replacement therapy can be used in

A

x linked hyper IgM

51
Q

Nivolumab and Pembroluzimab

mechanism?

indication?

A

antibodies that bind to PD1. blocks immune checkpoint, cause T cell activation

indicated in:
advanced melanoma
metastatic renal cell cancer

52
Q

ipilimumab mechanism?
indication?

A

antibody binding to CTLA4 blocks immune checkpoint, cause T cell activation

indicated in advanced melanoma

53
Q

Describe ways of suppressing immune response

A

1. Steroids
2. Anti-proliferative agents (inhibit DNA synthesis)- eg cyclophosphamide, mycophenolate, azathioprine
3. Plasmapheresis - removal of pathogenic antibodies
4. Inhibitors of cell signalling - MTOR, JAK, PDE, and Calcineurin inhibitors
5. Agents directed at cell surface antigens - eg rituximab/anti-cd20
6. Agents directed at cytokines and their receptors - eg anti tnf alpha

54
Q

side effects of anti proliferative agents?

A

Bone marrow suppression
Infection
Malignancy
Teratogenic

55
Q

Cyclophosphamide key side effects?

A

Bone marrow suppression
Hair loss
Sterility (male>>female)

Haemorrhagic cystitis

Malignancy - Bladder, Haematological, Non-melanoma skin cancer

Infection - Pneumocystis jiroveci

56
Q

Azathioprine key side effects?

A

bone marrow suppression
hepatotoxicity
infection

57
Q

Mcophenalate motil key side effects?

A

1. Bone marrow suppression Infection

2. Infection:
- Particular risk of herpes virus reactivation
- Progressive multifocal leukoencephalopathy (JC virus)

58
Q

indications for plasmapheresis?

A

Severe antibody-mediated disease:
- Goodpasture syndrome - Anti-glomerular basement membrane antibodies
- Severe acute myasthenia gravis- Anti-acetyl choline receptor antibodies
- Antibody mediated transplant rejection/ABO incompatible

59
Q

name different drugs that inhibit cell signalling
and use

A

1. Calcineurin inhibitors - ciclosporin, tacrolimus - used in transplantation, sle, psoriatic arthritis
2.MTOR inhibitors - Rapamycin, sirolimus - transplantation
3. PDE 4 inhibitors - ampremilast used in psoriasis and psoriatic arthritis
4. JAK inhibitors

60
Q

name agents directed at cell surface antigens

A

directed at T cells:
- Rabbit anti-thymocyte globulin - used in allograft rejection
- Basiliximab – anti-CD25 - allograft rejection, transplants
- Abatacept – CTLA4-Ig - rheumatoid arthritis

directed at B cells:
Rituximab – anti-CD20 - lymphoma, rheumatoid arthritis, SLE

Targeting lymphocyte migration:
- Vedolizumab – anti-a4b7 integrin - used in IBD

61
Q

name agents targeting cytokines and their receptors?




antibodies in asthma/eczema?

A

anti-TNF alpha antibodies - infliximab, adalimumab, certolizumab, golimumab

TNF alpha antagonist - etanercept

anti-IL6 antibodies - tocolizumab,!! sarilumab!! - IL6 targeting important for rheumatoid arthritis!!!

antibody against IL23 - guselkumab or antibodies against IL17 secukinumab- psoriasis, psoriatic arthritis

anti-rank ligand antibody eg denosumab - osteoporosis

IL 4, 5, and 13 in asthma - target them

62
Q

side effects of immunosuprression with drugs?

A

infection
malignancy
autoimmunity

63
Q

IL1 drives what conditions?

IL6 drives what conditions?

IL 17/23 pathway drives what conditions?


IL 4/5/13 drive what conditions?

RANK pathway drives what condition?


TNF alpha can be targeted for what diseases?

*not really expected to know drug names for exam

A

IL1 = gout, familial mediterranean fever, adult onset stills disease

IL6 - rheumatoid arthritis!

IL17/23 pathway - axial spondyloarthritis, psoriasis! , psoriatic arthritis.(essentially drive spondylarthritis group "PAIR") IBD is IL23 only. (note, Not effective for RA)

IL 4/5/13 - asthma, eczema,

RANK L = osteoporosis

TNF Alpha = rheumatoid arthritis,! psoriasis!, psoriatic arthritis, spondyloarthritis, IBD, familial mediterannean fever

64
Q

antibody mediated transplant rejection options

A

eculizimab
velclade - proteosome inhibitor
rituximab
intravenous Ig

plasma echange

65
Q

1,1,0 Mismatch means what?

A

1A, 1B, 0 DR

66
Q

which cells mediate damage in effector phase of t cell organ transplant?

A

T cells and monocytes/macrorophages

67
Q

what drug is administered after acute t cell mediated organ rejection

A

methylprednisolone!!!

high dose, 3 days in a row

68
Q

main cell type injured in effector phase of antibody mediated rejection?

A

endothelial cells

69
Q

hla match rate in parent to child

A

3/6

70
Q

A

Year 5 MEDICINE Pathology (11 decks)

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