Immunology 1 - Immunodeficiency Flashcards
define primary immune deficiency
Primary immunodeficiencies are disorders in which part of the body’s immune system is missing or does not function normally. To be considered a primary immunodeficiency (PID), the immune deficiency must be inborn, not caused by secondary factors such as other disease, drug treatment, or environmental exposure to toxins.
define secondary immune deficiency
Secondary immunodeficiency (SID) is a condition where the immune system is weakened by external factors, making it harder to fight off infections.
explain the classification of primary immune deficiency disorders
Primary i.e. intrinsic defect:
- can be innate involving phagocytes, complement, pattern recognition receptors or
- can be adaptive involving antibody deficiency, combined deficiency
- congenital or late onset presentation
give examples of primary immunodeficiency disorders of T cell function
- DiGeorge syndrome (congenital thymic aplasia)
- Hyper-IgM syndrome
- Chronic Mucocutaneous Candidasis
- Interleukin-12 receptor deficiency
give an example of a primary immunodeficiency disorder leading to B-cell deficiency
- X-linked (Bruton) Agammaglobulinemia
Primary immunodeficiencies leading to both T-cell and B-cell deficiency include:
- severe combined immunodeficiency disease (SCID)
- Wiskott-Aldrich sundrome
- immunodeficiency with ataxia-telangiectasia
- major histocompatibiy complex deficiency
Primary immunodeficiencies leading to complement deficiency include:
- hereditary angiodema
- deficiency of C3
- deficiency of membrane attack complex
- C2 or C4 deficiency secondary to autoimmunity
Primary immunodeficiencies leading to phagocyte deficiency include:
- chronic granulomatosis disease
- leukocyte adhesion deficiency syndrome
what are the functions of B cells?
- differentiates into plasma cells producing antibodies
- opsonization
- complement activation
- toxin neutralisation
what are the functions of T cell?
- helper T cells provide B cells with signals necessary for antibody production
- cytotoxic T cells destroy virally infected cells and tumour cells
- T regulatory cells suppress auto-reactive T cells
what are the functions of a phagocyte?
- engulfs and destroys microbes
- antigen presentation
what are the functions of complement proteins?
- opsonization (C3b)
- terminal components create the membrane attack complex
what is the function of natural killer cells?
- destroys virally infected cells and tumour cells
when should you suspect primary immunodeficiency?
- family history
- recurrent or chronic infection
- infections with unusual organisms e.g. PJP or NTM
- early-onset eczematous skin rashes
- early-onset autoimmunity
- failure to thrive
Primary immunodeficiency management: overview
- antimicrobial: prophylactic can be tailored to sensitivities, aggressive treatment of clinical infection
- immunoglobulin replacement therapy in antibody deficiency or dysfunction
- haematopoietic stem cell transplant (HSCT): definititive treatment for all types of SCID and the preferred treatment for many monogenic primary immunodeficiencies that present in childhood
what is the most common form of primary immune deficiency?
primary antibody deficiency
primary antibody deficiency clues from presentation
- recurrent sinus/chest infection - history of repeated ENT surgery, early bronchiectasis
- a second system usually involved e.g. skin sepsis (boils, abscesses), gut infections, meningitis
- fungal and viral infections are uncommon
- infections are due to common bacteria e.g. S.pneumoniae and H.influenzae
- non-infectious features are common e.g. immune thrombocytopenic purpura (ITP)
primary antibody deficiency management
- replace IgG, intravenous or subcutaneous
- antibiotics
- immunisation
- look after lungs e.g. regular physio and exercise
- treat cause
- monitor
- support
describe transient hypogammaglobulinaemia
normal infant slow to synthesis IgG
- so when maternally acquired antibodies fall, the infant becomes susceptible to recurrent pyogenic infections
describe XLA-Bruton’s disease presentation, cause, and management
- presentation: X-linked > young boys, recurrent pyogenic infection
- failure of pre-B lymphocyte to differentiate further > no B-lymphocytes, no plasma cells, no antibodies
- mutation in BTK gene
- management: immunoglobulin replacement and antibiotics
what is Hyper IgM syndromes? and what are the two forms?
- severe antibody deficiency
- BUT normal numbers of B cells and normal or raised serum IgM levels at presentation
- X-linked: due to CD40 ligand deficiency on T cells
- pure B- cell form: deficiency of enzyme AID
describe common variable immunodeficiency, its distinguishing features and treatment
- heterogenous group of disorders
- most common primary antibody deficiency
- low serum levels of IgG and IgA with normal or reduced IgM and normal or low numbers of B cells.
- management: replacement immunoglobulin + treat complications ad hoc
features of selective IgA deficiency
- commonly picked up as an incidental finding as young adults
- undetectable or very low serum IgA levels, with normal concentration of IgG and IgM and production of normal antibodies to pathogens: most individuals are healthy and do not suffer from recurrent infections
- clinical relevance: associated with development of coeliac disease, anaphylaxis risk with blood products
Di George Syndrome clinical features
CATCH 22
- Cardiac defects
- Abnormal faces
- Thymic aplasia > CD3 cells low
- Cleft palate
- Hypoparathyroidism
- 22q11 deletion
