Immunology basics Flashcards
What is immunodeficiency?
Immunodeficiency is when the immune system is unable to defend the body from micropathogens.
When the thyroid tissue is subject to an autoimmune attack, what is it called?
Thyroiditis
When the RBCs are subject to an autoimmune attack, what is the term?
Autoimmune haemolytic anaemia
When the joints are subject to an autoimmune attack, what is the term?
Rheumatoid arthritis
What system do the most common autoimmune conditions affect?
Musculoskeletal
Give 2 examples of autoimmune connective tissue diseases.
Rheumatoid arthritis
Systemic Lupus erythematous
Important tests for connective tissue disease?
Rheumatoid factor (found in 80% of those with rheumatoid arthritis) Antinuclear antibodies (SLE) WCC, ESR, CRP may also be helpful. Creatine kinase may be raised in polymyositis and dermatomyositis.
How is immunodeficiency demonstrated in the laboratory?
Reduced levels/ absence of antibodies.
What is clinical allergy?
Interaction of allergens with IgE on basophils causing the release of histamines, creating allergy sx.
How can you investigate allergy?
Allergen specific IgE testing.
What is hypersensitivity?
An over-reactive response to a stimulus/ allergen. Present in 10% population.
What are the 3 phases of immune response to a transplanted graft?
Phase 1: recognition of foreign antigens
Phase 2: Activation of antigen specific lymphocytes
Phase 3: Effector phase of graft rejection
What are the most relevant protein variations in clinical transplantation?
1) ABO blood group - can transplant between incompatible people though - as can remove Ab against A or B
2) HLA (human leukocyte antigens)
Some other determinants are also important such as minor histocompatibility genes
What are the 2 main components in transplant rejection?
1) T cell-mediated rejection
2) Antibody-mediated rejection
What cells express HLA class 1 (A,B,C)?
All cells
What cells express HLA class 2 (DR, DQ, DP)?
APCs, can be upregulated in other cells under stress
What does this picture show?
MHC class 1
What does a 2:1:0 mismatch mean in organ transplantation?
This is a type of tissue typing investigation done before a transplant to look at the difference between the patient and donor HLA molecules. It looks specifically at the HLA-A, B and DR locuses of each person.
It shows that there are 2 mismatches at the HLA-A locus, 1 mismatch at the HLA-B locus and 0 mismatches at the HLA-DR locus. This means there is a total mismatch of 3 out of a possible total of 6. This means that there is a medium risk of rejection in this patient as some locuses match, but others don’t, so the patient may recognise the donor’s tissue as foreign and reject it (mount an immune response against it).
What is the gold-standard for tissue typing now-a-days?
PCR-based DNA sequence analysis for all HLA alleles (i.e. not just A, B and DR) to determine the individual’s genotype and then compare the donor and patient HLA alleles to determine mismatches.
What does this picture show?
Graft biopsy of acute T cell mediated rejection
Shows interstitial inflammation and tubulitis (tubules have also been infiltrated by T cells)
What does this picture show?
T cell mediated acute graft rejection
Arteritis
Invasion of arterial wall with T cells
How do mycophenolate mofetil and azathioprine work in transplant patients?
Work downstream of mTOR activation - preventing T cell cycle (proliferation - Azathioprine) and Nucelotide synthesis (Mycophenolate mofetil).
How does Alemtuzumab work in tranplant patients?
Anti-CD52 - depletes T cells in transplant patients. Reducing strength and longevity of T cell reaction.
What are the 3 phases of antibody-mediated rejection of transplants?
1) B cells recognise foreign HLA
2) Proliferation and maturation of B cells with anti0HLA Ab production
3) Effector phase - Ab bind to graft endotheliu -> intra-vascular disease
What does this picture show?
Ab-mediated kidney transplant rejection
Inflammatory cells within the lumens of the capillary loops (GLOMERULITIS)
Purely vascular
Cells have been recruited by Ab laid down on the vascular endothelium
In the capillaries between the tubules this also happens (see on left) - we call this capiliritis.
Apart from inflammation, what would also stain positive in a sample of graft that the recipient had rejected via Ab mediated transplant rejection?
Complement fragments such as C4d would stain positive on vascular endothelium of the graft.
Other than rejection what other things do we see in transplant patient’s biopsies?
Drug toxicity i.e. calcineurin toxicity - tx: reduce immunosuppressive drugs (may also present with increased creatinine)
Viral infections i.e. latent infections Poliomavirus, BK nephropathy tx: reduce immunosuppressive drugs
Vascular disease small lumen and larger arterial wall - collagen and elastin - HTN and drug-induced - tx: BP control and vascular stent may be neeeded if larger arteries are affected
Post transplant lymphoproliferative disease - tx: reduce immunosuppressive drugs +/- chemotherapy
Recurrent glomerulonephritis/ issues that they had before depends on the nature of the problem
The most imporant antigenic determinant for rejection in current clinical practice of kidney transplantation is…
HLA/MHC
The main effector cells in T-cell mediated transplant rejection are…
T cells and monocyte/macrophages
A patient has an episode of acute T-cell mediated rejection 2 months post transplantation. What additional drug would most commonly be administered?
Methylprednisolone (CORTICOSTEROID) - 3 pulses given given 3 days in a row followed by an oral steroid taper.
Which cell is injured in the effector phase of Ab-mediated rejection?
Vascular endothelial cells
What is SCID?
Severe combined ImmunoDeficiency affecting multiple aspects of the immune response
What are the characteristics of CD8+ T cells?
Specialised cytotoxic cells
Recognise peptides derived from intracellular proteins in association with HLA class 1 - HLA-A, HLA-B, HLA-C
Kill cells directly (perforin, granzymes, fas-ligand)
Secrete cytokines i.e. IFN-y and TNFa
Particularly important in defence against viral infections and tumours
What clinical features might you see in a patient with Di George’s syndrome?
High forehead
Low set, abnormally folded ears, cleft palate, small mouth and jaw
Hypocalcaemia
Oesophageal atresia
Under developed thymus
Thyroid abnormalities
Complex congenital heart disease
A 1 year old boy has recurrent bacterial infections. His CD4 and CD8 T cells are present. B cells are absent
X-linked agammaglobulinaemia
Severe recurrent infections from 3 months. T cells are absent, B cells are present. Igs are low. No NK cells. Normal facial features. Normal cardiac echo.
Which is most likely?
a) 22q11.2 deletion syndrome
b) Bare lymphocyte syndrome type 2
c) X-linked SCID
d) IFN-y receptor deficiency
c) X-linked SCID
Recurrent childhood infections. Abnormal facial features, congenital heart disease. Normal B cells. REduced T cells. Low IgA, low IgG.
Which is most likely?
a) 22q 11.2 deletion syndrome
b) Bare lymphocyte syndrome type 2
c) X-linked SCID
d) IFN-y receptor deficiency
a) 22q 11.2 deletion syndrome AKA Di George’s
A young adult has a chronic infection with Mycobacterium marinum.
Which is most likely?
a) Bare lymphocyte syndrome type 2
b) X-linked SCID
c) 22q 11.2 deletion syndrome
d) IFN-y receptor deficiency
d) IFN-y receptor deficiency - the others would typically present a lot earlier
A 6 month baby with 2 recent serious bacterial infections. T cells are present - but only the CD8+ subset. B cells are present. IgM present but IgG is low.
What is most likely?
Bare lymphocyte syndrome type 2
A 1 year old boy has recurrent bacterial infections. CD4 and CD8 T cells are present. B cells are absent. IgG, IgA and IgM are all absent.
Which is most likely?
a) Bruton’s x-linked hypoglobulinaemia
b) Common variable immunodeficiency
c) IgA deficiency
d) X-linked Hyper IgM syndrome due to CD40L mutation
a) Bruton’s x-linked hypoglobulinaemia
Recurrent bacterial infections in a child. Episode of pneumocystic pneumonia, high IgM, absent IgA and IgG.
What is most likely?
X-linked Hyper IgM syndrome due to CD40L mutation
Adult with bronchiectasis, recurrent sinusitis and development of atypical SLE.
What is most likely?
Common variable immune deficiency (airway disease common, alongisde recurrent bacterial sinusitis and development of autoimmune disease)
Define immunopathology
Damage to the host caused by the immune response
What is auto-inflammatory disease?
Immunopathology in the absence of an infection. This is caused by an innate immune response. Can be monogenic (rarer) or polygenic (more common).
What is auto-immune disease?
Immunopathology in the absence of infection. Caused by an adaptive immune response. Can be monogenic (rarer) or polygenic (more common).
What are the different factors affecting protein/gene expression?
Mutations - germline or somatic
Epigenetics
MiRNA