Immunology Flashcards

1
Q

What are the hallmarks of immune deficiency?

A
SPUR
Serious infections
Persistent infections
Unusual infections
Recurrent infections
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2
Q

What is a primary immunodeficiency disorder?

A

A disorder characterised by the absence of one or more parts of the immune system.

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3
Q

Which primary immunodeficiencies are most associated with sinusitis and otitis media?

A

Primary antibody deficiency

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4
Q

Give examples of primary antibody deficiency.

A

Selective IgA deficiency
Common variable immunodeficiency
Specific antibody deficiency
X-linked agammaglobulinemia

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5
Q

What type of conditions should be considered in patients with laryngeal angioedema?

A

Complement system disorders

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6
Q

Give an example of a complement system disorder

A

Hereditary angioedema

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7
Q

What is the most common pulmonary symptom of many primary immune deficiencies?

A

Pneumonia

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8
Q

True or false? All people suffering from a primary immune deficiency disorder are registered.

A

True

The united kingdom primary immune deficiency registry (UKPID) serves to track these conditions

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9
Q

What types of pathogens are people suffering from congenital neutropenia more susceptible too?

A

Bacteria

Fungi

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10
Q

What is Kostmann syndrome?

A

A severe congenital neutropenia

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11
Q

What are the clinical manifestations of Kostmann syndrome?

A

Severe chronic neutropenia from birth
Accumulation of precursor cells in the bone marrow
Recurrent bacterial and fungal infections with no pus

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12
Q

What is the treatment for severe congenital neutropenia?

A

Recombinant G-CSF

A haemopoietic growth factor

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13
Q

What is a recurrent infection with no pus suggestive of?

A

Severe neutropenia (most likely congenital)

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14
Q

What is Leukocyte adhesion deficiency?

A

An autosomal recessive immunodeficiency

Causes failure of neutrophil adhesion and migration

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15
Q

What is the clinical picture of leukocyte adhesion deficiency?

A

Marked leukocytosis and localized bacterial infections

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16
Q

What is Chronic granulomatous disease?

A

A condition causing the absence of the respiratory burst in phagocytes
Commonly by effecting the NADPH oxidase complex

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17
Q

What are the clinical features of chronic granulomatous disease?

A

Recurrent deep bacterial infections and recurrent fungal infections
Failure to thrive
Lymphadenopathy and hepatosplenomegaly
Granuloma formation

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18
Q

Briefly explain the IL-12: IFN-gamma network

A

A mechanism to improve action against intracellular pathogens
Infected macrophages produce IL-12
IL-12 stimulates NK cells and Th1 cells to secrete IFN-gamma
IFN-gamma stimulates macrophages and neutrophils to produce TNF-alpha which stimulates activation of the NADPH oxidase complex

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19
Q

What are the treatments for phagocyte deficiencies?

A

Immunoglobulin replacement therapy (IVIg)
Aggressive management of infection (PO/IV antibiotics or antifungals, surgical abscess drainage)
Definitive therapy is by a haematopoietic stem cell transplant

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20
Q

Where do mature B cells come from?

A

The bone marrow (B for Bone)

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21
Q

Where do mature T cells come from?

A

The thymus (T for Thymus)

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22
Q

What is the normal function of an antibody?

A

To aid the identification of pathogens by opsonisation
To recruit/activate other aspects of the immune response (e.g complement, phagocytes, NK cells)
Neutralisation of toxins

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23
Q

What is the main group of pathogens antibodies act against?

A

Bacterias

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24
Q

How are macrophages stimulated?

A

TH1 cells costimulation with pathogen-derived peptide

IFN-gamma

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25
How are TH0 cells stimulated?
By IL-2 released from TH0 cells | Stimulation of CD4+ T cells through MHC-II presented antigen to T-cell receptors cause differentiation of TH0 cells
26
How are CD8+ T cells stimulated to cytotoxic T lymphocytes?
MHC-I costimulation by antigen presenting cells leads to differentiation IL-2 from TH0 cells contributes to this
27
How are B cells stimulated?
Cytokines + Costimulation from TFH cells along with stimulation of B-cell receptors and opsonin receptors by opsinosided pathogens
28
What is reticular dysgenesis?
Failure of production of all lymphocytes | Fatal without a haematopoietic stem cell transplant
29
What is severe combined immunodeficiency?
The failure in the production of lymphocytes
30
Give the clinical phenotype of combined immunodeficiency.
``` Unwell by 3 months of age Persistent diarrhoea Failure to thrive All types of infections Unusual skin disease (Graft versus host disease) Family history of early infant death ```
31
What is the most common genetic defect in severe combined immunodeficiency?
Common gamma chain (X-linked)
32
What is the commonest form of severe combined immunodeficiency?
X-linked SCID | 45% of all SCIDs
33
Explain X-linked SCID
Mutation of the IL-2Rgammac gene (A common element of many cytokine receptors) Results in the inability to respond to cytokines
34
Give the clinical phenotype of X-linked SCID
Very low or absent T cells Normal or increased B cells Poorly developed lymphoid tissue and thymus
35
Give the treatment of severe combined immunodeficiency
Prophylactic: Avoid infections (prophylactic antibiotics/antifungals) aggressive treatment of existing infections, antibody replacement therapy Definitive treatment: Haemopoietic stem cell transplant
36
What is DiGeorge syndrome?
A failure in production of CD4+ and CD8+ T cells.
37
Give the phenotype of DiGeorge syndrome.
Development defect of the 3rd/4th pharyngeal pouch Low set abnormally folded ears, high forehead, cleft palate, small mouth and jaw Hypocalcaemia Oesophageal atresia (Incomplete oesophagus) T cell lymphopenia Complex congenital heart disease
38
What type of infection is mostly associated with DiGeorge syndrome?
Viral due to lack of CD4+ and CD8+ T cells | All due to lack of CD4+ T cells
39
Give the management of DiGeorge syndrome.
Correct metabolic/anatomic abnormalities Prophylactic antibiotics Early and aggressive treatment of infections The possible need for IV immunoglobulin replacement
40
In DiGeorge syndrome does T cell function improve or worsen with age?
Improve | Suggestive of extra-thymic maturation site of T-cells
41
What is X-linked agammaglobulinaemia?
An absense of B cells due to a defect in Bruton tyrosine kinase
42
What is the typical presentation of X-linked agammaglobulinaemia?
Lower and upper respiratory infections, diarrhoea, cellulitis, meningitis and sepsis Usually due to Gram-positive highly pathogenic encapsulated organism (Strep.pneumonia, H.influenzae)
43
Which 2 pathogens are particaully associated with X-linked agammaglobulinaemia?
Streptococci pneumonia | Haemophilus infleunzae
44
What is Hyper IgM syndrome?
A defect in class-switch recombination resulting in only/effectively only IgM being produced A severe reduction in serum IgG and IgA Normal/elevated IgM Normal B cell numbers
45
What is meant by class switch recombination?
The change of B-cell differentiation to plasma IgM to another type of Ig
46
What is Selective IgA deficiency?
A defect in class-switch recombination resulting in a lack of IgA plasma cells (and thus a lack of IgA)
47
What type of infections are seen in B cell deficiencies?
Recurrent bacterial infection often by very common organisms
48
What is a hypersensitivity reaction?
The immune response that results in bystander damage to the self Usually an exaggeration of normal immune mechanisms (Includes allergies and autoimmunity)
49
Explain the Gel and Coomb's classification.
Type I: Immediate hypersensitivity (IgE) Type II: Direct cell effect Type III: Immune complex-mediated Type IV: Delayed-type
50
What is a Type I hypersensitivity?
An IgE mediated antibody response to an external antigen (AKA allergen)
51
Give the theory behind the increase in allergic-type hypersensitivity reactions.
The hygiene hypothesis The hygiene hypothesis poses that an overclean childhood promotes differentiation to Th2 cells leading to the allergic response
52
What causes stimulation of B-cells to class switch to IgE plasma cells.
IL-4, IL-5, IL-13 from TH2 cells
53
Explain the mechanism of an allergic reaction.
Sensitisation stage: Mast cells and eosinophils express Fc receptors for IgE antibodies, on the first allergen exposure IgE binds to these Fc receptors and the allergen is cleared. Allergic stage: When an allergen is re-encountered the allergen binds to the IgE coats causing the release of pre-formed pro-inflammatory mediators
54
Explain the MoA of a mast cell.
Resident in tissues (especially at the external environment interface) Produce vasoactive inflammatory substance (Histamine, tryptase, heparin. leukotrienes, prostaglandins and pro-inflammatory cytokines)
55
What type of pathogen are mast cells particularly useful in?
Mast cells
56
What are the clinical features of a type I hypersensitivity reaction?
Muscle spasm (e.g bronchoconstriction) Mucosal inflammation Inflammatory cell infiltrate Oedema (Anaphylaxis)
57
What is a type II hypersensitivity?
A direct cell effect reaction involving IgM or IgG antibodies to the cell surface antigens.
58
What is the mechanism of a type II hypersensitivity reaction?
Self-reactive antibodies cause: Activation of the complement Opsonisation and phagocytosis Antibody-dependent cellular cytotoxicity via NK cells Anti-receptor antibodies disturb the normal function of cell surface receptor
59
Explain Goodpasture's syndrome
Autoreactive antibodies against the basement membrane [anti-GBM] (TypeII hypersensitivity) Effects the alveoli and glomeruli Due to exposure to environmental insult
60
What is the treatment of Goodpasture's syndrome
Corticosteroids Plasmapheresis Smoking cessation
61
What is a type III hypersensitivity?
Immune complex-mediated The presence of immune complexes activated complement and attracts inflammatory cells such as neutrophils Enzymes from inflammatory cells cause local damage (often at the basement membrane)
62
Explain the immunology of acute hypersensitivity pneumonitis.
A type III hypersensitivity reaction | Leukocyte accumulation and inflammation within the alveoli
63
What is the clinical picture of acute hypersensitivity pneumonitis?
Wheeze and malaise 4-8hours post antigen exposure Possible associated dry cough, pyrexia and breathlessness O/E often normal
64
What is the management of type III hypersensitivity reactions?
Avoidance of the causative antigen Corticosteroids, decrease the inflammation Immunosuppression, decrease the production of antibodies
65
Explain type IV hypersensitivity reactions.
Activation of CD4+ T cells and Th1 cells along with macrophages cause damage to tissues. This is due to antigen exposure directly to cells.
66
What type of hypersensitivity is sarcoidosis?
Type IV?
67
Explain the pathogenesis of sarcoidosis.
Inhalation of an antigen stimulates alveolar macrophages along with T cells, this fails to clear leading to persistent immune activation damage and fibrosis.
68
What is the management of sarcoidosis?
Watching and waiting often goes into spontaneous remission NSAIDs for acute onset Systemic corticosteroids to block T cell and macrophage activation
69
What is autoimmunity?
The presence of immune responses against self-tissue/cells | This can be harmful if the titres of autoreactive antibodies or T cells is high, can also be harmless
70
What 3 states can T and B cells be when generated in primary lymphoid tissue
Not expressing an antigen-specific receptor Expressing a non-self antigen-specific receptor (These are good B&T cells) Expressing a self antigen-specific receptor (These can cause a problem)
71
Explain central tolerance.
The deletion of self-reactive lymphocytes in primary lymphoid tissues.
72
Explain peripheral tolerance.
The inactivation of self-reactive lymphocytes in peripheral tissues that escape the central tolerance
73
What are the major cells of peripheral tolerance
Regulatory T cells (Treg cells)
74
What are the 2 major cytokines produced by Treg cells?
TGF-beta, IL-10
75
Explain briefly the pathogenesis of autoimmune disease.
Genetic susceptibility is present Initiating event leads to break down of immune tolerance to self-antigen This leads to an autoimmune phenomenon or an autoimmune disease
76
What is IPEX syndrome?
An X-linked genetic autoimmune disease Presents in early childhood Characterised by overwhelming systemic autoimmunity
77
What are the symptoms of IPEX syndrome?
``` Severe infections Intractable diarrhoea Eczema Very early onset diabetes mellitus Autoimmune manifestations ```
78
What is the treatment of IPEX syndrome?
Hematopoietic stem cell transplantation | Supportive care: immunosuppressive drugs + parenteral nutrition
79
What are MHC/HLA molecules?
Proteins which express peptides T cells can only be stimulated by peptides expressed on these molecules Can be class I or class II
80
Why are MHC molecules polymorphic?
Allows maintenance of diversity in antigen responsiveness at the population level and at the level of the individual.
81
Are autoimmune conditions more common in men or women?
Mostly in women | Diabetes mellitus is more common in men
82
What is a superantigen?
A molecule that can cause MHC receptor stimulation without the presence of an antigen
83
What is Grave's disease?
A odd type II hypersensitivity disease A leading cause of hyperthyroidism Auto-antibodies are generated that bind to the thyroid stimulating hormone receptor
84
What type of hypersensitivity is SLE?
type III
85
What type of hypersensitivity is rheumatoid arthritis?
type IV