Immunology Flashcards
What are the signs and symptoms of anaphylaxis?
Airway and breathing- bronchospasm, wheezing, tongue swelling, stridor, hoarse voice
Circulation- vasodilation, tachycardia, hypotension, cardiac arrest
Neurological- feeling faint, decreased cerebral blood flow, confusion, light headedness, feeling of impending doom
GI- pain, vomitting, diarrhoea, smooth muscle contraction.
Skin-Itching due to histamine and bradykinin release.
Name some common allergens.
Pollen Food Medications Blood donations Latex Anaesthetics
What are the mediators of Type 1 hypersensitivity reactions?
IgE, mast cell degranulation
What are the mediators of Type 2 hypersensitivity reactions?
IgG, IgM, complement
What are the mediators of Type 3 hypersensitivity reactions?
IgG, complement
What are the mediators of Type 4 hypersensitivity reactions?
T cells
Give examples of Type 1 hypersensitivity reactions.
Asthma Atopy- dermatitis/ eczema Anaphylaxis Allergic rhinitis Food allergy
Give examples of Type 2 hypersensitivity reactions.
Grave’s disease
Incompatible transfusions
Autoimmune hemolytic anaemia
TTP
Give examples of Type 3 hypersensitivity reactions.
Arthus reaction
Serum sickness
SLE
RA
Give examples of Type 4 hypersensitivity reactions.
Contact dermatitis
Mantoux test
Coeliac
TB
What are the 4 key antibiotics given in Tuberculosis infections?
Rifampicin
Isoniazid
Pyrazinamide
Ethambutol
What are the side effects of the 4 antibiotics used in TB?
Rifampacin- Dark urine, hepatotoxicity, decreased effectiveness of the oral contraceptive pill
Isoniazid- Peripheral neuropathy- Vit B6 given alongside, clumsiness/ unsteadiness
Pyrazinamide- Gout
Ethambutol- Eye damage- colour blindness and vision loss
Which components of the immune system are involved in response to viral infections?
INF alpha and beta
Cytotoxic T cells
Natural killer cells
Which type of T helper cell is involved in Autoimmunity, inflammation, intracellular pathogens?
Th1
What is released from mast cells?
Histamine
Prostaglandins
Leukotreines
Tryptase
What are the effects of mast cell mediators?
Vasodilation and tachycardia
Increased vessel permeability
Gland secretion
Bronchoconstriction
Which allergy usually appears first in life?
Rhinitis
Asthma
Dermatitis and food allergy
Dermatitis and food allergy
What genetic defect may there be for atopic dermatitis to occur?
Filaggrin defect= membrane disruption
What are the signs and symptoms of immediate (<1 hour) drug reactions?
Vomit and diarrhoea Tachycardia, hypotension Wheeze, stridor Urticaria (hives), angioedema Loss of consciousness
What are the signs and symptoms of delayed (>1 hour) drug reactions?
Myalgia and arthralgia
Fever
GI upset
Itching and rash
How can a suspected Penicillin allergy be investigated?
Blood tests: look for eosinophils, plateles, haemolytic anaemia
Measure Tryptase: after 2 hours (peak) and 24 hours- this represents mast cell degranulation
What is Chronic Spontaneous Urticaria?
NOT anaphylaxis or allergy
Itching and rash, slow to resolve
Can have panic attack and angioedema
What is a biphasic anaphylaxis reaction?
2 episodes 1-8 hours apart
Mast cells refill and degranulate again
How soon after exposure does anaphylaxis usually occur?
Within 60 minutes
Later onset = less severe
What are the potential differential diagnoses for anaphylaxis?
Vocal cord dysfunction
Chronic urticaria
Hypotension due to shock, sepsis, blood loss, MI
Syncope. faint- but would appear white not blue
How is anaphylaxis managed?
ABCDE
Adrenalin IM 0.5mls (1:1000) repeat after 5 mins if no improvement
High flow oxygen
Fluid challenge (500-1000mls) for hypotension
Bronchodilator
Supportive management to prevent a biphasic reaction eg. Corticosteroids, anti histamines
In mastocytosis, which blood test level is always raised?
Tryptase
What is positive selection and where does it occur?
In the thymic cortex, imposed by cortical epithelial cells.
Developing T cells which recognise self peptide on MCH can continue maturing.
What is negative selection and where does it occur?
In the cortico-medullary junction of the thymus.
Developing T cells which have autoreactive TCRs are removed via apoptosis.
What are 2 examples of peripheral tolerance?
- Immune privelege- physical barries eg BBB, cells in testes express Fas which induces apoptosis in any T cells.
- TReg cells- downregulate immune responses
How can loss of tolerance occur (3 methods)?
- Immune priveledge lost eg. penetrating eye injury
- Failure of TReg cells
- Molecular mimicry- eg. Rheumatic fever may follow infection with Haemolytic strep
What can predispose to autoimmunity?
Female sex
Autoantibodies
HLA class DQ2 and DQ8
Which HLA classes are associated with coeliac disease?
HLA DQ2 in 95%
HLA DQ8
When should coeliac disease be suspected?
Diarrhoea, weight loss, anaemia
What are the key histological features of coeliac disease?
Villous atrophy
Crypt hyperplasia
Raised intra epithelial WBCs
What are the risk factors for rheumatoid arthritis?
Smoking Female HLA DR4 CCP autoantibodies Lung infections
What blood results/ antibodies will be found in rheumatoid arthritis?
CRP Raised
RF Raised
CCP autoantibodies
C3 and C4 Raised
NO dsDNA antibodies, ANA low
What are the key features of rheumatoid arthritis?
Symmetrical polyarthritis
Synovial joints of hands and feet
Morning stiffness
What systemic features may be present in rheumatoid arthritis?
Necrotising granulomas
Vasculitis
Atherosclerosis
How does rheumatoid arthritis appear on Xray?
Loss of joint space
Soft tissue swelling
Joint deformity
What is the treatment for Rheumatoid Arthritis?
Immunosuppression: Steroids
NSAIDs
Anti TNFalpha eg. Infliximab
What will be found on a urine dip in a patient with SLE?
Protein and blood
SLE can lead to nephrotic syndrome, due to kidneys being blocked with immune complexes
What blood results/antibodies will be found in a patient with SLE?
ANA high
dsDNA high
ENA (extractable nuclear antigens) Sm and RNP
CRP normal/ low
C3 and C4 low (no acute phase response)
What is the treatment for SLE?
Immunosuppression- NSAIDs, hydroxychloroquinine, Azathiaprine, Methotrexate
Anti B cells (Rituximab/Belimumab)
What are some of the key clinical features of SLE?
Malar rash Discoid rash Malaise Fatigue Alopecia Raynaud's Oral/ nasal ulcers Synovitis Serositis
What blood results/ antibodies will be found in vasculitis?
CRP high
ESR high
ANCA antibodies (pANCA in Microscopic Polyarteritis, cANCA in Wegener’s Granulomatosus)
What is vasculitis?
Autoimmune condition
Autoantibodies against neutrophil enzymes, leads to neutrophil activation and damage to small blood vessels, and acute renal syndromes.
What is the treatment for vasculitis?
Steroids
Cyclophosphamide
Anti B cell (Rituximab, Belimumab)
What is Antiphospholipid Syndrome?
Where antiphospholipid antibodies cause: Recurrent abortions Arterial or venous thrombi Pre-eclampsia Migraine Stroke
Is associated with SLE or can present alone
Which autoantibodies are found in antiphospholipid syndrome?
Anti-Cardiolipin
Which autoantibodies are found in SLE?
ANA
Anti dsDNA
Which autoantibodies are found in Primary Biliary Cholangitis?
AMA
Which autoantibodies are found in Goodpastures disease?
Anti GBM
Which autoantibodies are found in Rheumatoid arthritis?
Anti CCP
What does scleroderma result in?
Skin, blood vessel and muscle changes
Collagen deposition
What is CREST?
A syndrome due to Scleroderma:
C-Calcium deposition R- Raynaud's E-Oesophageal reflux S- Sclerodactyly (skin thickening) T- Telangiectasia (spider veins)
What are the main types of innate immunodeficiency?
- Neutrophil defect
- Complement defects
- NK defects
- Cytokine/ TLR defects
- Splenectomy
What are the main types of adaptive immunideficiency?
- B cell/ antibody defects
2. T cell defects
How do neutrophil defects present?
Neutropenic sepsis; bacterial or fungal infection WITHOUT pus
What are the causes of neutrophil defect?
Drugs- chemo
Leukaemia
Adhesion defect eg. LFA-1 deficiency
Respiratory burst defect eg. Chronic Granulomatous Disease
What treatments are used for neutrophil defect?
G-CSF
Antifungals, Antibiotics
How do patients with a splenectomy usually present?
Septicaemia
Infection with pneumococcus, meningococcus and malaria
Which Ig in the spleen normally opsonises encapsulated bacteria?
IgM
What is the treatment for patients who have had a splenectomy?
Penicillin prophylaxis
Vaccination: Meningococcus C, Haem B and Pneumococcal
How do patients with NK defects present?
Viral infections eg. CMV, Herpes Zoster
How do patients with complement (C3) defects present?
Pyogenic infections
How do patients with complement (C5-9) defects present?
Neisseria or meningitis infections
How do patients with complement (C1,2,4) defects present?
Immune complex diseases
How do patients with Cytokine/TLR defects present?
Recurrent intracellular bacterial infections eg. Atypical mycobacterium avium
How do patients with B cell/ Antibody defects present?
- Pneumonia, sinusitis, otitis
- Campylobacter (diarrhoea), Strep pneumonia, Haem influenza
- Pyogenic infections from encapsulated and non encapsulated bacteria
- Diarrhoea and malabsoprtion
- Aged 4 or 5 months
What are the causes of B cell defects?
- Genetic (present >6 months of age) in males
- BTK deficiency
- B cell malignancy eg. CLL
- HIV
- Immunosuppression
How can B cell defects be diagnosed?
Serum Igs and electrophoresis
Paraprotein?
Lymphocyte count will be normal (as B cells only count for 10%)
Give vaccines- eg. HIb and Meningitis and look for immune response
How can B cell defects be treated?
Replace Igs
Antibiotics
When does a T cell defect present in a patient?
Presents from birth- with failure to thrive, and opportunistic infections.
What is Di Georg’es Syndrome?
A type of T cell defect; due to defective thymus.
Presents with opportunistic infections: Candida, EBV, P.Carini
What are the features of Di George’s syndrome?
Small jaw
Abnormal ears
Cleft palate
Lymphopenia
What is the commonest cause of CD4 cell deficiency?
HIV
Which infections do HIV patients get?
- Intracellular: TB, Salmonella, Pneumocystis
- Viruses: Kaposi’s sarcoma, CMV, EBV
- Encapsulated bacteria- pneumonia
- Fungi and yeast- Candida, cryptococcus
- Protozoa- Pneumocystis, cryptosporidiosis, toxoplasmosis
What is a likely cause of a chest infection in a HIV patient?
Pneumocystis (fungi)
Which type of T helper cell is involved in secreting regulatory cytokines and restricting co-stimulatory availability for other T cells?
Treg
Which type of T helper cell is involved in protection against extracellular helminths, promoting B cell class switching to IgE and involved in allergy and asthma?
Th2
Which type of T helper cell is involved in protection against fungi, extracellular bacteria, autoimmunity and epithelial barriers?
Th17
Which interferons are most important for protection against viruses?
IFN aplha and beta
Which interferons are most important for protection against intracellular (non viral) infections?
IFN gamma
Which cytokines are important in protection against parasitic infections?
Il 4 and Il5
Secreted frorm Th2 cells
Which cells are the main phagocytes for extracellular bacteria?
Neutrophils
What is the most common antibody deficiency?
IgA deficiency
In Hyper IgM syndrome, there are low levels of which 2 antibody classes?
Low IgG and IgA
Presents with Pneumocystis and Crptosporidiosis
BTK deficiency presents around what age?
6 months
The autoantigen 21 hydroxylase is found in which condition?
Addison’s
What % of RA patients have both RF and anti CCP in their serum?
70%
Which antibody is most useful for predicting SLE disease severity?
Anti dsDNA
60-70% patients with CREST have which antibodies?
Anti centromere
Sjogrens syndrome patients usually have dry what?
Dry eyes
Dry mouth
Which autoantibodies are present in Sjorgens syndrome?
ENA Ro and La
Which cytokine is linked with IgE production?
Interleukin 4
What are the effects of histamine?
Increased blood flow
Increased permeability
Itching due to nerve stimulation
Smooth muscle contraction
Eosinophils are attracted to which cytokine?
Interleukin 5
Asthma, hayfever and eczema are associated with which subset of T helper cells?
Th2
Give an example of a H1 receptor antagonist drug.
Loratidine
Cetirizine
