Immunodeficiencies Flashcards
What are the 2 types of immunodefiency disease?
Primary (congenital) immunodeficienies
Secondary Immuno deficiencies
What is primary immunodeficieny?
A condition resulting from a genetic or developmental defect abbreviated as PID
What is secondary immunodeficiency?
Originates from result of malnutrition, cancer drug treatment or infection
What is immunodeficiency?
Defects in one of more components of immune system leading to diseases
What is the most common cause of secondary immunodeficiency?
AIDS?
What causes PID?
Defect present from birth usually inherited
What are the clinical features of primary immunodeficiencies?
- Recurrent infections
- Severe infections of unusual pathogens in unusual sites
What are the 10 warning signs of PID?
copy past later
What part of the immune system does PID affect?
Can affect either innate or adaptive
Innate if defect causied by phagocytic or complement system
Adaptive if lymphoid cell disorders (affect B and T cells)
Can affeect both innate and adaptive = SEVER IMMUNODEFICIENCIES
What other condition to patients with immunodeficiences also present with and why?
Autoimmunity because cells that regulate own cells are not present
How does severity of PID change in diff individuals?
Depends which stage of haemotopoesis the defect is at, earlier on can affect entire immune system (more components and types involved)
- defects later of show less pathology
name a few adaptive immunodeficiencies?
XLA, selective IgA ID, SCID, DiGeorge, WAS
How are cells affected by PID in adaptive systems?
B cells, T cells or both
T cell defects impair antibody production
Defects in lymphocyte development and activation
Name a few major B cell PID disorders?
X linked agammaglobulinaemia (Bruton’s disease)
Selective IgA deficiency
What cause X linked agammaglobulinaemia (Bruton’s disease?
Defect in BTK gene - found on X chromosome
Why does mutation in BTK cause affect B cells in Bruton’s disease?
BTK codes for bruton’s tyrosine kinase without which there is a block in B cell development (halts at pre-B cell)
What are the effects/symptoms of Bruton’s disease?
Recuurent sever bacterial infections
2nd half of first year (affecting lung, ears, GI)
Autoimmine diseases in many patients
What are pre-B cells?
Bone marrow lymphoid cells that lack surface Igs but have intraplasmic regions of IgM heavy chains
How do you diagnose X linked agammaglobulinaemia?
B cells are absent / low despite and plasma cells completely absent
Immunoglobulin levels are low
T cells and T cell response all normal
- seen on flow cytometry
What is the treatment for X linked agammaglobulinaemia?
DO NOT GIVE LIVE ATTENTUATE VACCINES
Intravenous administration of exogenous antibodies
Prompt antibiotic therapy
What is IgA important for?
Important mucosal antibody
What is the presentation of selective IgA deficiency?
Most are asymptomatic but have infections of respiratory, urogenital ot gastrointestinal tract
Low levels of secretory IgA
Sometimes increased incidence of allergic disease
Name a combined immunodeficiency (PID)?
Sever immunocombined immunodeficiency (SCID)
What are the causes of SCID? and what cells does each one effects !!!
1) Defects in cytokines receptor in gamma chain!!!!!!. Cytokines needed for survival of T cell precursors without which T cells are defective and in turn don’t stimulate B cells - not T cell or antibodies but B cells present
2) defects in rag-1 or Rag-2 - no T or B cells
- ADA (adenosine deaminase deficiency) - not T cells
What is ADA and why does it cause SCID?
Adenosine deaminase deficiency - accumulation of deoxyadenosine which is toxic for rapidly dividing thymocytes
What is a sign of SCID?
Total low lymphocyte counting (NK, T and B cells)
Pattern of lymphocytes - low T cell, normal or absent B cells
No immunoglobulins
- all seen in flow cytometry
What is the treatment for SCID?
Isolation to prevent further infections and DO NOT GIVE LIVE VACCINES
Ig replacement intravenously (IV)
Bone marrow.haemotpoeitic stem cell transplant
gene therapy for ADA and gamma chain genes)
What is the outcome of SCID even with treatment?
Higher survival is early diagnosis and good donor match without infections previously
Lower survival if later diagnosis and already has chronic infections and poorly matched donors
Name a few combined immunodeficiencies affecting predominantly T cells?
DiGeorge Syndrome
Wiskott-Aldrich syndrome
Ataxia-telagiectasia
Name a few combined immunodeficiencies affecting predominantly T cells?
DiGeorge Syndrome
Wiskott-Aldrich syndrome
Ataxia-telagiectasia
What causes DiGeorge syndrome?
Thymic hypoplasia due to 22q11 deletion
What are the visible physical effects of deletion of 22q11 in DiGeorge syndrome?
Failure of development of 3+4th pharyngeal pouches
many developmental defects including cleft palate, low set ears, fish shaped mouth
What are the visible physical effects of deletion of 22q11 in DiGeorge syndrome?
Cardiac abnormalities, hypocalcaemia
How does DiGeorge syndrome vary?
Thymic incomplete resulting in either absent or partial T cell development
How do you treat DiGeorge syndrome ?
Partial transplantation of thymus
What causes Wiskott-Aldrich syndrome?
X linked with defect i WASP
What is WASP?
Protein involved in actin polymerisation. T cells remodel cytoskeleton for correct signalling without which T cells are defected
What are the consequences + symptoms of wiskott-aldrich syndrome?
Thrombocytopenia, Eczema, infections
Progressive immunodeficiency ( due to T cell loss as cell die since they cannot remodel properly)
Low antibody production due to low T cell count
Name a few innate system immunodeficiencs?
Chronic granulomatous disease
Chediak Higashi syndrome
Leukocyte Adhesion deficiency
Which are the defects in PID of innate immunity?
Phagocyte defects (quantitative - low levels, qualitative, altered function) Recruitment defects Transmigration defects Complement defects
What is chronic granulomatous disease?
Phagocyte defects
Defect in oxidative killing of phagocytosed microbes due to mutation in phagocyte oxidase components (NADPH) - content in phagolysosome not destroyed
How does CGD present?
Formation of granulomas - immune cells (macrophages) surround areas without being able to get rid of content inside
How do you diagnose CGD?
Nitro blue tetrazolium reduction test Dihydrorhodamine assay (no shift on flow cytometry for affected patients when stimulated)
What causes chediak higashi syndrome?
Defect in LYST gene (regulate lysosome traffic
- rare genetic disease
What does having a defected LYST gene result in?
Nuetrophils defective in phagocytosis
- symptom of repetitive and severe infections
How do you diagnose chediak higashi syndrome?
Decreased number of NEUTROPHILS and neutrohils have large granules
Why is leukocyte adhesion deficiencya problem?
LAD - luekocytes normally migrate from blood flow to are of infection via adhesins - deficiency = they can’t migrate
What are the mechanisms of LAD’?
Defect in beta 2 integrins
Defect in a ligand
Delayed umbilical cord spearation
How does LAD present?
Skin, GIT infections and perianal ulcers
How do you diagnose LAD?
Low neutrophil chemotaxis and low integrin expression on pahgocytes
- seen through flow cytometry
What are the general rules for treatment of PID?
Prevent infeciton - cant give live vaccine, antibiotics, can isolate them
Minimise infection
Nutrition
Replace defective.absent component of immune system e.g. bone marrow or thymus transplant
gene therapy (the defected gene causing the disease)
What is gene therpay?
Modify stem cells from patient and return to patient to resolve the genetic cause of problem
What cells does HIv affect causing secondary immunodeficiency?
T cells
What is a major cause in death of AIDS?
infections caused by other parasites, intracellular bacteria, fungi and viruses not HIV itself
What are the treatment option for HIV?
Highly active antiviral therpay
HAART!!! and PrEP (drugs that prevent transmission of virus)
What are the 2 ways to get PID? - congenital primary
Either inherited or acquired 9through malnutrion/infection)
