immunology Flashcards
1
Q
What is the hallmark of immune deficiency?
A
Recurrent infections
2
Q
What is SPUR and what does it indicate?
A
- indicates immune deficiency
- Serious infections
- Persistant infections
- Unusual Infections
- Recurrent infections
3
Q
What are some signs and symptoms suggestive of primary immunodeficiency?
A
- weight loss or failure to thrive
- severe skin rash
- chronic diarrhoea
- mouth ulceration
- unusual autoimmune disease
- lymphoproliferative disorders
- cancer
- family history
4
Q
What are some of the conditions associated with secondary immune deficiency?
A
- physiological immune deficiency: ageing, prematurity
- Infection: HIV, measles
- treatment interventions: immunosuppressive therapy
- malignancy: cancer of the immune system
- biochemical and nutritional disorders: malnutrition
5
Q
What are some of the upper respiratory complications of PIDs
A
- sinusitis
- otitis media
- laryngeal angiodema
6
Q
What are some of the lower respiratory complications associated with PIDs?
A
- malignancies
- interstitial lung disease
- pneumonia
- bronchitis, bronchiectasis
7
Q
What is the most frequent PID associated with sinusitis and otitis media?
A
- primary antibody deficiency:
- selective IgA deficiency
- common variable immunodeficiency
- specific antibody deficiency
- X lined agammaglobulinemia
8
Q
what PID is associated with laryngeal angioedema?
A
- complement system disorders: hereditary angioedema
9
Q
Give examples of PIDs associated with pneumonia?
A
- primary antibody deficiency
- complement system disorders
- congenital phagocytosis deficiency
- combined immunodeficiency
10
Q
What is severe congenital neutropenia?
A
- failure to produce neutrophils
- G- CSF is not produced so allow differentiation past progenitor stage
11
Q
What is Kostmann syndrome?
A
- severe congenital neutropenia
- rare genetic disorder: mutation in ELANE gene
12
Q
What are the symptoms of Kostmann syndrome?
A
- low neutrophil count
- accumulation of precursor cells in bone marrow
- recurrent bacterial/fungal infections with no pus
- can be treated with recombinant G - CSF
13
Q
What happens in defects in neutrophil trans - endothelial migration?
A
- phagocytes are unable to bind to endothelial adhesion molecules
- failure to recognise activation markers expressed on endothelial cells
- neutrophils are mobilised but cannot exit the blood stream
14
Q
What are the symptoms of defects in neutrophils trans endothelial migration?
A
- recurrent bacterial and fungal infections
- very high blood neutrophil count
- infection in deep tissues but no pus
15
Q
What is leukocyte adhesion deficiency?
A
- rare autosomal recessive PID
- caused by genetic defect in CD18 intern gene
- failure of neutrophil adhesion and migration
- characterised by marked leukocytosis and localised bacterial infections
16
Q
What is chronic granulomatous disease?
A
- deficiency of killing mechanism of phagocytes
- deficiency of p47phox gene which is a component of the NADPH oxidase complex
- inability to generate ROS
- impaired killing of microorganism
17
Q
What are the symptoms of chronic granulomatous disease?
A
- recurrent deep bacterial infections
- recurrent fungal infections
- failure to thrive
- lymphadenopathy and hepatosplenomegaly
- granuloma formation
18
Q
how are phagocyte deficiencies treated?
A
- immunoglobulin replacement therapy
- aggressive management of infection
- definitive therapy: stem cell transplant, gene therapy
19
Q
What is SCID?
A
- failure of the production of T and B lymphocytes
20
Q
What are the symptoms of SCID?
A
- unwell by 3 months of age
- persistant diarrhoea
- failure to thrive
- many types of infection
- unusual skin disease
- family history of early infant death
21
Q
What type of infections would a patient with SCID get?
A
- recurrent viral infection
- recurrent bacterial infections
- frequent fungal infections
22
Q
what is the cause of SCID?
A
- more than 20 possible pathways identified
- presence of different lymphocyte subsets depend on exact mutation
23
Q
What is X-lined SCID?
A
- caused by a mutation of a component of the IL-2 receptor
- failure of T cell and NK cell development
- production of immature B cells
24
Q
describe the clinical phenotype of x-lined SCID?
A
- very low or absent T cells
- because IL2 is so important for T cell development
- normal or increased B cells
- poorly developed lymphoid tissue and thymus
25
How can SCID be treated?
- prophylactic treatment: avoid infections, aggressive treatment of existing infection, antibody replacement
- definitive treatment: stem cell transplant
- gene therapy
26
What is Brutons x-lined hypogammaglobulinaemia?
- no circulating B cells
- No plasma cells
- no circulating antibody after the first 6 months
27
What are hypersensitivity reactions?
- immune response that results in bystander damage to self
28
What are type 1 hypersensitivity reactions?
IgE mediated antibody response to external antigen
29
Give examples of type 1 hypersensitivity reactions?
- asthma
- hay fever
- urticaria
- angiodema
- atopic eczema
- allergies
30
Why is the prevalence of allergy increasing?
- the 'hygiene hypothesis'
| - changes in microbial stimuli influences the maturation of the immune response
31
According to the hygiene hypothesis what may influence increased production of Th2 in a hypersensitivity reaction?
- being an only child
- widespread use of ABX
- urban environment with allergen sensitisation
32
Describe the sensitisation stage of an allergic reaction?
- on first encounter with allergen B cells produce antigen specific IgE
- allergen is cleared
- residual IgE antibodies bind to circling mast cells via Ice receptors
- no great consequence
33
describe the allergic stage of an allergic reaction?
- re encounter the allergen
- allergen binds to IgE coated mast cells and disrupts cell membrane
- immediate release go vasoactive mediators (histamine, tryptase)
- also increased expression of pro-inflammatory cytokines and leukotrienes
34
What are the clinical features of allergic disease?
- muscle spasms
- mucosal inflammation
- inflammatory cell infiltrate
35
Describe the management of IgE mediated allergic disorders?
- avoidance of allergen
- block mast cell activation
- prevent effects of mast cell activation
- anti-inflammatory agents
- management of anaphylaxis
- immunotherapy
36
What are type II hypersensitivity reactions?
antibody mediated process in which IgG and IgM are directed against antigens on cells leading to cell lysis
37
What are some of the mechanisms that type II hypersensitivity reactions can occur through?
1. Immunological mechanisms
- complement system activation
- opsonisation and phagocytosis
- ADVV via NK cells or eosinophils
2. other mechanisms
- Anti-receptor antibodies disturb the normal function of cell surface receptor
38
give examples of type II hypersensitivity?
- Goodpastures syndrome
| - graves disease
39
What is good pastures syndrome?
- autoimmune disease that affects the lungs and kidneys
- defined by presence of auto reactive antibodies to the a3 chain of type IV collagen
- thought to result from an environmental insult in a person with genetic susceptibility
40
What is the treatment for good pastures syndrome?
- corticosteroids, cyclophosphamide
- plasmapheresis
- stop smoking
41
What is plasmapheresis?
- the removal of plasma from the blood
- rapidly removes circulating antibodies
- stops further production of antibodies
- removes offending agents that may have initiated antibody production
42
What are type III hypersensitivity reactions?
- an accumulation of antibodies (blood vessels, joints and glomeruli) results in:
- activation of complement
- opsonisation
- infiltration and activation of neutrophils and macrophages
43
Give an example of type III hypersensitivity
- Acute hypersensitivity pneumonitis (farmers lung ect)
44
How are type III hypersensitivity disorders managed?
- avoidance
- decrease inflammation with corticosteroids
- decrease production of antibody (immunosuppression)
45
What is type IV hypersensitivity?
- delayed immune response that occurs when CD4+Th1 cells recognise foreign antigen in a complex with MHC class II molecules
46
Describe the mechanism of type IV hypersensitivity?
- foreign antigen encountered by CD4+Th1 and MHC class II
- CD4+T cells secrete IL2 and IFNgamma which mediates the immune response
- Activated CD8 cells destroy the antigen on contact
47
What are the autoimmune diseases associated with type IV hypersensitivity?
- type 1 diabetes
- psoriasis
- rheumatoid arthritis
48
What are the non autoimmune diseases associated with type IV hypersensitivity?
- contact dermatitis
- TB
- leprosy
- sarcoidosis
- cellular rejection of organ transplant
49
What is autoimmunity?
- the presence of immune responses against self tissues and cells
50
How does the immune system deal with the presence of autoreactive T and B cells?
specific tolerance mechanisms are required
1. deletion of self reactive lymphocytes in primary lymphoid tissues
2. inactivation of self reactive lymphocytes in peripheral tissues that escape central tolerance
51
What is the role of Treg cells?
- suppress hyper-reactive or auto-reactive T cells via the production of anti-inflammatory cytokines
52
describe the pathogenesis of autoimmune disease?
- genetic susceptibility
- initiating event
- breakdown of immune tolerance to self antigens
- autoimmune phenomena or autoimmune disease
53
what is IPEX syndrome?
- rare genetic disorder of immune dysregulation
- presents early
- characterised by overwhelming systemic autoimmunity
54
What is the treatment for IPEX syndrome?
- hematopoetic stem cell transplant (cure)
| - supportive care - immunosuppressive drugs ect
55
Describe the genetic features of IPEX syndrome?
- X linked (only males affected)
- mutation in FOXP3 gene
- failure of peripheral tolerance mechanisms due to defective/absent T cells (Tregs)
56
which type of cells express class I MHC molecules?
- all nucleated cells
57
Which type of cells express class II MHC molecules?
- specialised antigen presenting cells
58
Why are all HLA (MHC) molecules highly polymorphic?
- maintenance of diversity in antigen responsiveness at the population level and at the level of the individual
- proteins are processed into many different component peptides
- different HLA molecules bind to different subsets of peptides
- to maximise the net availability to bind to all antigenic peptides
59
How does sex influence autoimmune disease?
- sex bias in predisposing genetic factors
- different hormonal influences on lymphocyte function
- alteration of the course of some autoimmune disease during pregnancy
60
What are the factors that contribute to autoimmune disease?
- genes
- immune regulation
- environment
61
How are genetics associated with autoimmune disease?
- via HLA genes
| - autoimmune diseases share genetic associations within other gene loci
62
How is the environment associated with autoimmune disease?
- infection: cross reactivity between antigens expressed by pathogen and self
- self antigens altered in some way
- super antigens
- tissue damage
63
How is immune regulation associated with autoimmune disease?
- importance of immune regulation in maintaining self tolerance
64
How can autoimmune diseases be classified?
1. clinical classification
- organ specific disease
- non organ specific or multi-system disease
2. pathological classification
- gel and coombs classification
65
What is graves disease?
- leading cause of hyperthyroidism
- auto-antibodies are generated that bind to the thyroid stimulating hormone receptor
- unusual type II hypersensitivity disease
66
What is systemic lupus erythematous?
- prototypic multi-system autoimmune disease
- rare type III hypersensitivity disease
- increased risk of cardiovascular disease
- high female preponderance
strong genetic predisposition
67
describe the pathogenesis of systemic lupus erythematous?
- increased apoptosis; defective clearance of apoptotic material and dysregulation of neutrophil NETS
68
What is the function of Th17 cells?
- associated with defence against extracellular bacteria and fungi as well as the development of autoimmune diseases
- they are highly pro-inflammatory
