immuno path Flashcards
liver macrophage is …
kupffer cell
kidney macrophage is…
mesangial cell
spleen macrophage is…
sinusoidal-lining cell
bone macrophage is….
osteoclast
lung macrophage is…
alveolar macrophage
CNS macrophage is….
microglia
skin macrophage is….
langerhans cell
connective tissue macrophage is..
histiocyte
what types of T cell recognise what type of HLA ??
- CD8+ T cells recognise peptide presented by HLA class I molecules
- CD4+ T cells recognise peptide presented by HLA class II molecules
CD4+ T cells help B cell differentiation – requires what ligand receptor interaction?
CD40L:CD40 interaction
what is the mantoux test and outline its basic principles ..
- Inject 0.1 ml of 5 tuberculin (=purified protein derivative) units intradermally, examine arm 48-72 hrs after
- A positive result is indicated by induration (swelling that can be felt) of at least 10 mm in diameter (erythema around not measured). This implies previous exposure to tuberculin protein - thus it could represent previous BCG exposure
3 barrier immune deficiencies and outline
- Burns –> keratinsied cells and sebaceous glands –> increased risk of infection since barrier detsroyed
- IgA deficiency –> this is sectreted in mucosal surfaces to defend
- antibiotic use –> detsroys good bacteria and allows other organisms to colonise an undefended niche (e.g. candida, C Difficile )
give an overview of how you would break down the phagocyte deficiencies (in the topic of immuno deficiency)
go through every stage of a phagocyte
- production - reticular dysgenisis (Failure of production of: Neutrophils, Lymphocytes, Monocyte/macrophages, Platelets)
- maturation - Kostman syndrome (Autosomal recessive severe congenital neutropenia) / cyclic neutropenia (Autosomal dominant episodic neutropenia every 4-6 weeks)
- migration to site of infection - Leukocyte adhesion deficiency (nuetrophils dont have adhesion molecules so can’t bind to vessel wall endothelium and escape the circulation )
- oxidative killing - chronic granulomatous disease (absent respiratory burst - deficient in NADPH oxidase so can’t make superoxide therefore impaired killing of microorganisms)
- cytokine production - Deficiency of IL-12 and IFNγ and their receptors (Susceptibility to infection with mycobacteria (TB and atypical), BCG, Salmonella - inabliity to form granulomas)
give an overview of how you would break down the lymphocyte deficiencies (in the topic of immuno deficiency)
- Production in Bone Marrow
Reticular dysgenisis
Severe combined immune deficiency (Effect on different lymphocyte subsets (T, B, NK) depend on exact mutation e.g. X-linked SCID .. Very low or absent T cell + NK cell numbers, Normal or increased B cell numbers)
Adenosine Deaminase deficiency - can’t respond to cytokines –> * Very low or absent T cell and NK cell numbers + Very low or absent B cell numbers - Thymus (maturation and selection)
DiGeorge - Normal numbers of B cells and reduced numbers of T cells cause thymus is fucked
Bare lymphocyte syndrom - defect in regulatory genes, absent HLA class II, there reduced CD4+ T cells - Cytokine release problem
Deficiency of IL-2 and IFNy
Wiskott-Aldrich Syndrome (WAS) - problem with Tb cell - APC interaction - B cell maturation -
Bruton’s X-linked hypogamma globulinaemia -
Common variable immune deficiency - class switching
Hyper IgM syndrome - failure to express CD40L so cant do class switch. due to a T cell defect
Selective IgA Deficiency
how does leukocyte adhesion defieicny present ?
A rare autosomal recessive immunodeficiency.
Neutrophils are unable to adhere to vascular endothelial - hence they cannot transmigrate into tissues to fight infection.
This leads to a high level of neutrophils in the blood (neutrophilia). As a result, there is no abscess formation or pus.
The neutrophils function normally (so will be be normal in the NBT test) but simply cannot get to where they are needed.
Clinically, this may present with delayed umbilical cord sloughing as neutrophils are involved in this process.
There is often infections of the skin (particularly omphalitis, infection of the umbilical cord), pneumonia or gums. The only curative therapy is haematopoietic stem cell transplantation.
how does common variable immunodeficiency present ?
Common Variable Immunodeficiency (CVID) is a diagnosis of exclusion in patients greater than 4 years old. The diagnostic criteria are:
- Decrease in serum IgG and a decrease in one of IgM or IgA.
- There is a lack of antibody response to antigens or immunisation
-more than 4 years old.
Patients will have increased infections with bacteria such as Haemophilus, Strep (usually immunized against) and Staph. There is an increased rate of autoimmune conditions and malignancies. Treatment is with normal human IVIg for life.
Bruton’s Agammaglobulinaemia - how does it present ?
Blood tests reveal a low lymphocyte count, with very low B cells but normal T cell levels.
There as very low levels of IgM, IgA and IgG.
how does Nitroblue-tetrazolium (NBT) or dihydrorhodamine (DHR) tests work??
In CGD, these tests are negative. In the NBT or DHR tests, the presence of reactive oxygen species will cause a colour change. A positive (normal) NBT test will stain neutrophils blue. A negative (abnormal) test will remain colourless
test for chronic granulomatous disease
which organisms are you suseptible to if you have chronic granulomatous disease ?
Catalase positive organisms express catalase and therefore are resistant to some methods of hydrogen peroxide based killing. Examples include:
E coli
Staphylococcus Aureus
Listeria spp
Klebsiella spp
Serratia marcescens
Candida spp
They are a common cause of infections in patients with chronic granulomatous disease.
features of rheumatoid artrhitisi
- Symmetrical polyarthritis
- DIP sparing
- Hand deformities:
o Swann neck, Boutinnier’s, Z-thumb and ulnar deviation - Extra articular
o Fibrosis
o Pericardial effusions
o Rheumatoid nodules
Sjogren’s
- Dryness and rash
- Schirmer’s test
features of SLE
- SOAP BRAIN MD:
o Serositis
o Oral ulcers
o Arthritis
o Photosensitivity
o Bloods (pancytopenia)
o Renal
o ANA
o Immunological
o Neurological
o Malar rash
o Discoid rash - Titre antibodies to measure disease severity and progression
- Complement can also be used for above (SLE causes complement consumption)
o Inactive = normal C3 and 4
o Active = lowered C4 normal C3
o Severe = both depleted
features of Dermatomyositis
- Proximal myopathy
- Rash (heliotrope rash around eyes), gottron’s papules on dorsum of hand and macular rash on back
- Investigation: CK and muscle biopsy
featuers of Polymyositis
- Diffuse myopathy
- Respiratory weakness and GI dysphagia
- Investigation: CK and muscle biopsy
features of CREST
- Calcinosis
- Raynaud’s
- Oesophageal dysmotility
- Sclerodactyly
- Telangiectasia
- Does not pass forearms
- Speckled pattern on immunofluorescence
- Pulmonary hypertension in elderly
features of Diffuse CREST
- CREST + greater resp and GI involvement
- Involves trunk as well
- Nucleolar pattern on immunofluorescence
- Pulmonary fibrosis
features of Granulomatosis with Polyangiitis
(Wegner’s)
- URT (nosebleeds)
- LRT (haemoptysis)
- Renal (rapidly progressive glomerulonephritis)
Eosinophilic Granulomatosis with Polyangiitis (Churg Strauss)
- Allergic asthma
features of Microscopic Polyangiitis
- LRT (haemoptysis)
- Renal (rapidly progressive glomerulonephritis)
give examples of Live attenuated vaccine
Live pathogen Modified to limit pathogenesis
‘MMR-VBOY’
* MMR
* VZV
* BCG
* Oral – polio (Sabin), typhoid
* Yellow fever
* Influenza (Fluenz tetra) – 2-17yo
give examples of inactivated vaccines
Inactivated:
Influenza (quadrivalent), Polio (Salk), Cholera, Bubonic plague, Hep A, Rabies, Pertussis, Anthrax?
give examples of component/subunit vaccines
Component/subunit:
Hep B [HbS antigen], HPV [Capsid], Influenza recombinant quadrivalent) [haemagglutinin, neuraminidase],
give examples of Conjugate Polysaccharide vaccine
NHS’
* N meningitidis
* H influenzae
* Strep pneumonia (Prevenar)
* Tetanus
give examples of DNA / RNA vaccine ?
Pathogen’s genetic material (DNA/RNA) delivered to host cells via viral vector/ lipid complex.
Host cells produce + express protein immune response
- mRNA: SARS-CoV-2
- Adenoviral vector: AstraZeneca (ChAdOx1-S), Sputnik (Adenovirus types 26, 5)
- Ongoing research into other uses
what vaccines cAN HIV Patients receieve ?
HIV positive patients can receive MMR but not BCG or Yellow fever.
what is an adjuvant in terms of vaccines …
‘increase the immune response without altering its specificity’
Adjuvants are used in vaccines to further boost the immune response.
2 Main Types of Adjuvants
1. Depot Adjuvant
* Slow down the release of the antigen increasing time immune system is exposed to antigen prolonged immune response
* Most used = ALUM
- Stimulatory Adjuvant
* Mimic the action of PAMPs on TLR and PRRs -> increasing receptor activation -> boosted immune response
* Most used= CpG
how to treat SCID?
Haematopoietic SCT
how to treat Bruton’s X linked agammaglobulinemia
Human Normal Immunoglobulin (IVIG)
Antibody replacement
preformed IgG to wide range of unspecified organisms
how to treat X linked hyper IgM syndrome
Human Normal Immunoglobulin (IVIG)
Antibody replacement
preformed IgG to wide range of unspecified organisms
how to treat Common variable immune deficiency
Human Normal Immunoglobulin (IVIG)
Antibody replacement
preformed IgG to wide range of unspecified organisms
steroids mode of action in immune modulation
- Prostaglandins: Inhibits phospholipase A2 no breakdown of phospholipids to arachidonic acid prostaglandin synthesis blocked = reduced inflammation
- Phagocytes: inhibits phagocyte trafficking, phagocytosis & release of proteolytic enzymes. NOTE: causes transient increase neutrophil count
- Lymphocytes: lymphopenia (sequestered in lymphoid tissue), blocks cytokine gene expression, Ab production, promotes apoptosis.
examples of anti-proliferative agents in immune modulation and mechanisms
inhibit DNA synthesis, cells with rapid turnover most sensitive
- methotreaxte = anti-folate. inhibits dihydrofolate reductase (DHFR) therefore decreases DNA synthesis
- Azathioprine = anti metabolite. metabolised by liver to 6 mercaptopurine, blocks de novo purine (eg adenine, guanine) synthesis – prevents replication of DNA, preferentially inhibits T cell activation & proliferation > B cell
others are… Cyclophosphamide and mycophenolate/mofetil
what is Rituximab used for and what surface anitgen does target?
Lymphoma, rheumatoid arthritis, SLE
Anti-CD20, depletes mature B cells (not plasma cells)
Isograft –
transplant from a twin
Allograft –
from the same species
Xenograft –
from different species
Split graft –
shared by two recipients e.g., liver
what is order of importance for HLA mismatch in transplantation ?
Human leucocyte antigens (HLA) mismatch - most important DR>B>A, coded by MHC complex on Chr 6, cell surface proteins, present foreign antigens to T cells activation
transplatn rejection in minutes/hours what is it /….
hyperacute
Preformed Ab which activates complement
Thrombosis and Necrosis
Prevention: Crossmatch
(ABO groups)
HLA-matching
post organ transplant you get rash, D&V, jaundice - what type of rejection is this ? what time frame would you expect ?
Graft vs Host disease
days- weeks
donor cells attacking host
list all different types of organ transplant rejection
hyperacute (mins/hours)
acute-cellular (< 6mo) - cellular infiltrate
acute antibody mediated (<6 mo) - vascultiis
chronic (> 6 mo) - fibrosis, glomerulopathy, vasculoptahy
Graft vs Host disease (days-weeks) - rash/ gastro/ jaudnice
after xenograft this rejection takes place 4-6 days after - what is it?
acute vascular rejection
what type of rejection do you get with Haematopoietic stem-cell transplantation (HSCT)
– graft-versus-host disease
o Occurs in Allogeneic HSCT - donor lymphocytes recognise + attack host HLA
o Related to degree of HLA-incompatibility
o Symptoms: skin desquamation, rash, GI disturbance (nausea, vomiting, abdominal pain, diarrhoea, bloody stool), liver failure (jaundice), BM failure
HIV pos person is classified as having AIDS when….
AIDS <200cells/µL blood - CD4+ t cell count
