Lecture 13 - Immune Deficiencies Flashcards
What is immune deficiency
- a decrease in function or absence of one or more components of the immune system
What organs and tissues are part of the immune system
- spleen
- thymus
- bone marrow
What cells are part of the immune system
- T
- B
- NK
- Phagocytic cells
What proteins are part of the immune system
- complement
- immunoglobulins
- cell signalling
- receptors
- cytokines
What is primary immunodeficiency
congenital (born with)
What is secondary immunodeficiency
- acquired
- viruses such as HIV, EBV, Congenital infections
- drugs (chemotherapy)
- radiation
- malignancy
- malnutrition
- stress
- chronic conditions
- splenectomy
- blood/stem cell transfusion
- Graft-vs-host disease
What are the general characteristics of immunodeficiency
- recurrent infections
- early age
- failure to thrive
- male predominance
- uncommon infections
- site specific infections
- malignancy
- failure to respond to treatment
- autoimmune features
- variable in severity and clinical presentation
What is DiGeorge Syndrome
- impaired development of thymus, parathyroid gland and heart
- has a variety of clinical presentations: congenital heart disease, hypocalcemia, cleft palate, recurrent infections, learning disabilities, autoimmunity
- treatment: IVIg, prophylatic antibiotics, thymus transplant
What are common features of phagocytic cell disorders
- recurrent bacterial and fungal infections
- skin and soft tissue infections (gingivitis, thrush, hepatitis)
- impaired wound healing
- pneumonia caused by S. pneumoniae, Klebsiella, Serratia marcescens, Aspergillis
What is Chediak Higashi
- autosomal recessive mutation 1q42
- LYST lysosomal trafficking regulator gene
- giant non-functional granules
- impaired intracellular killing by neuts and NK cells
- increased lymphocytes
What is the clinical presentation of Chediak Hegashi
- gingivitis, S aureus, Candida
- progressive neurological dysfunction
- reduced pigmentation
- in the accelerated phase - fever, lymph infiltrates, thrombocytopenia, neutropenia, EBV
What is the treatment for Chediak Higashi
hematopoietic stem cell transplant
What is leukocyte adhesion deficiency
- autosomal recessive mutation
- missing beta-2 integrin subunit (CD18)
- common to LFA-1, Mac-1, gp150/95 (CD11)
What is the clinical presentation of leukocyte adhesion deficiency
- gram pos and neg infections, viral response decreased
- absence of pus at wound site
- high WBC count
- variation in severity and outcomes
What is the treatment for Leukocyte Adhesion deficiency
antibiotic prophylaxis and hematopoietic stem cell transplant
What is chronic granulomatous disease
- X linked or autosomal recessive
- unable to produce NADPH oxidase
- decreased intracellular killing
- inflammation and granulomas
What is the clinical presentation of chronic granulomatous disease
- gingivitis, enlarged lymph nodes, granulomas
- bacterial and fungal infections
What is the treatment for chronic granulomatous disease
- early culture and sensitivity
- antibiotic prophylaxis
What is x-linked agammaglobukinemia
- missing brutons tyrosine kinase (cell signaling)
- no maturation of pre-B to B cells
- decreased IgG levels
- systemic infections
- Strep pneumoniae, H influenzae
- treat with IVIg but poor prognosis
What is x-linked hyper IgM
- no CD40L on T cells
- Low IgG, IgA and IgE
- increased IgM
- neutropenia, thrombocytopenia
- pneumonia early in life
- treatment with IVIg
What is IgA deficiency
- varying levels of IgA
- unknown cause
- associated with increased incidence of ITP, allergies, lupus, arthritis
- increased infections of mucosal surface
- treatment with antibiotics
- prevention is key
What is SCID
- severe combined immunodeficiency syndrome
- low, absent or non-function T cells
- B cells, NK cells may also be affected
- several modes of inheritance
- severe immunodeficiency
- poor prognosis
- rare
What are the symptoms of SCID
- failure to thrive
- recurrent infections
- lymphopenia
- hypothymia
What are common infections for SCID
- Staph, strep, hemophilus, candida
- opportunistic infections: candida, pneumocysistis jirovecii, varicella, adenovirus, RSV, parainfluenza 3, CMV, EBV
What causes SCID
- mutation affecting T cells with or without B and NK involvment
- X linked recessive is most common (T-B+NK-, B cells present but non functional)
What is adenosine deaminase deficiency SCID
- autosomal recessive
- ADA function
- accumulation of deoxyadenosine triphosphate inhibits ribonucleotide reductase leading to no DNA synthesis
- ADA and PEG injections as treatment
What is IL-7R alpha SCID
- rare form
- IL-7R gamma and alpha chain missing
- B and NK cells normal in number
What are other causes of SCID
- JAK3 (impaired signalling during hematopoesis)
- ZAP70 (impaired signalling of TCR)
- RAG1/RAG2 (No TCR or Immune globulin rearrangement)
- CD45 (Impaired T and B cell receptor signal transduction)
How is SCID diagnosed
- newborn metabolic screening
- T-cell receptor excision circles PCR
How is SCID managed
- supportive care
- isolation
- antibiotics
- IVIg
- irradiated blood products
What is the treatment for SCID
- hematopoietic stem cell transplant
- gene therapy
