Immunology

Question 1

Interleukins

Answer 1

IL1 - fever, shock, innate
IL2 - T cells growth factor
IL3 - promotes lymphoid growth + proliferation via bone marrow
IL4 - switch IgG --> IgE
IL5 - eosinophil activation, switch to IgA
IL6 - acute phase reactant
IL7 - Pre T / Pre B cell development
IL8 - activates neutrophils
IL10 - inhibits IL 12, down regulator
IL12 - inhibits IgE, NK stimulation
IL13 - IgE synthesis. Causes airway hyperreactivity
IL17 - autoimmunity

Th1 cells (intracell) –> IFN gamma, IL1, IL2, TNF
Th2 cells (extracell) –> IL4, IL5, IL6, IL10, IL13
Th17 –> IL17a, IL17b, IL22
B cells - IL6

Question 2

CD

Answer 2

CD45 - all leukocytes
CD3 - all T cells
CD4 - T helper cell
CD8 - cytotoxic T cell
CD19/20 - B cell
CD40 - B cell
CD15, 16, 56 - NK cell

Question 3

MHC

Answer 3

MHC I - CD4 helper
MHC II - CD8 cytotoxic
MHC I - HLA A, B, C (nucleated cells)
MHC II - HLA DR, DQ, DP (B cells, APC)
MHC III - complements and cytokines

Question 4

IFN

Answer 4

INF - disrupts viral replication, activates NK cells
INF A + B on viral cells
INF G on Th1 cells, enhance MHC expression
Give IFN alpha in hepatitis
Give IFN beta in MS
Give IFN gamma in CGD

Question 5

Other things to remember

Answer 5

Anakinra - IL1
Toxilucimab - IL6
TGF beta - down regulator
TNF alpha - proinflammatory

Question 6

Immunoglobulins

Answer 6

IgA - mucosa, breast milk. HL 6 days
IgD - membrane bound. Marker for B cell maturity. JL 3 days
IgE - stimulates hypersensitivity reaction. HL 2 days
IgG - most abundant in blood. Most functions. Only one to cross placenta. PAST infection . Activates classical pathway (fixes complement). HL 3-4 weeks
IgM - first to be expressed by foetus. Activates classical pathway (fixes complement). Pentamer. HL 5 days.

Question 7

Opportunistic infections (T cell problem)

Answer 7

Candida
PJP
Mycobacteria
CMV
EBV
VZV
MMR

Question 8

Encapsulated organisms (B cell/antibody/complement problem)

Answer 8

Please SHINE my SKiS

Pseudomonas aeruginosa
Streptococcus pneumoniae
Haemophilus Influenza B
Neisseria meningitidis
Escherichia coli
Salmonella spp.
Klebsiella penumoniae
Group B Streptococcus

Question 9

Catalase positive infection (neutrophil problem)

Answer 9

Staph Aureus
Norcadia
Serratia
Aspergillus
Candida
Burkholderia
Pseudomonas

Question 10

Neutrophil problem

Answer 10

• Kostmanns: persistent neutropaenia
• Cyclical neutropenia: low for 3-6 days every 21 days. Gingivitis
• Leukocyte adhesion deficiency: poor neutrophil function. No pus. Delayed separation of cord. Dx: neutrophil chemotaxis. Tx. BMT
• Chronic granulomatous disease: NADPH oxidase deficiency. Think if indurated gums, lymphadenopathy, recurrent bacterial/fungal infections. Encapsulated. Staph aureus, Burkholderia, Pseudomonas, Serratia, Norcardia, Aspergillus. Dx. Negative Nitroblue response burst, DHR. Tx. BMT, INFg

Question 11

Complement problem

Answer 11

• C1 deficiency: hereditary angioedema type 1 decreased, type 2 dysfunction. Precipidated by stress. NO urticaria. Low C4/2 acute, low C4 always.
• C3 deficiency: recurrent pyogenic (encapsulated organisms). Also membranoproliferative GN.
• Terminal complement pathway deficiency C5-9: recurrent Neisseria (meningicoccal/gonococcal)
• Properin deficiency - X linked. Recurrent neisserial infections

Question 12

B cell problem

Answer 12

• X linked agammaglobulinaemia - BTK mutation. X linked - boys only. No B cells. No lymphoid tissue. Presents 6-9/12. Recurrent OM, sinusitis, encapsulated organisms. Not virus/fungi. No vaccine response. IVIG.
• Hyper IgM - abnormal B cell CD40L. Failure class switching to IgA/G/E. Pyogenic infections, pnuemocystis, mouth ulcers, sclerosis cholangitis - encapsulated and opportunistic. Normal/high IgM, low IgG/IgA, normal T and B cells, absent CD40L. No vaccine response. Pancytopaenia. IVIg, Bactrim, no live vaccines, BMT.
• Combined Variable Immune Deficiency - similar to XLA but less severe. FTT, chronic diarrhoea, recurrent OM/sinusitis. Opportunistic infections. Lymphoma risk. Low Ig but present, low B cells. Poor vaccine response. IVIg Bactrim, no live vaccines.
• IgA deficiency - 1/500. Anaphylaxis to blood transfusions. Sinopulmonary infections, autoimmune disease. If recurrent infections - prophylactic antibiotics.

Question 13

T cell problem (effect T and B cells)

Answer 13

• Severe Combined Immune Deficiency - absent T cell function +/- B cell, NK cell, X linked recessive. ADA/PNP deficiency, JAK3, RAG 1/2. FTT, diarrhoea, recurrent opportunistic infections, THRUSH, absent LN/tonsils, absent thymus. All Ig low, low T cells, B cells, no vaccine response. No live vaccines, Bactrim, BMT - matched/T cell deplete. Gene therapy
• Omenn - RAG1 SCID. Skin + GOT. (loss of eyebrows, alopecia, hepatomegaly, lymphadenopathy, high IgE)
• DiGeorge - thyme genesis (mild - SCID)
• Hyper IgE - Type 1 Jobs AD STAT3. ECZEMA AND BOILS deep seeded abscesses, bad lungs, pneumatoceles, coarse facies. Failure to lose primary teeth. High IgE, normal T/B cells. Low Th17. Failed vaccine response. IVIg, prophylactic Abs, antifungals. No live vaccines. Type 2 tyrosine kinase DOCK8
• IPEX syndrome - Treg. FOXP3 mutation. Eczema, neonatal diabetes, immune problems, enteropathy
• APACED syndrome - AIRE defect. Chronic mucocutaneous candidiasis + autoimmune disease
• Chronic mucocutaneous candidiasis - recurrent candida. Normal B cells, low T cell response to candida skin prick testing. Tx: antifungals, no live vaccines
• Wiskott Aldrich - T+B cell defect. WAS gene. Eczema, thrombocytopenia (small platelets). Recurrent sinopulmonary infection, opportunistic infection, autoimmune disease. No vaccine response. Tx: prophylactic, no live vaccines, BMT/SCT
• Ataxia telangiectasia - recurrent sinopulmonary infection, developmental regression, ataxia, telangiectasia. IVIg, no live vaccines
• X linked lymphoproliferative - inadequate response to EBV (thrombocytopaenia, liver, encephalitis, HLH) FISH for SAP. Rituximab, HLH - BMT, lymphoma chemo
• HLH - fever, splenomegaly, cytopaenia, triglycerides, haemophagocytosis, ferritin, low/abscent NK. BMT