• dechallenge- disease improvement after agent removal
• rechallenge- disease recurrence after agent re-exposure

diseases that are the result of genetic or congenital defects in the components of immune system or its products

result from environmental agents influence on a previously functional immune system

Group based on part of immune system affected

• B cell (Ab) deficiencies
• T cell deficiencies
• combined B and T cell deficiencies
• phagocyte defects
• complement system defects

• many of the syndromes are X linked inheritance
• 70% affected are males

• never receive live virus vaccines
  • oral polio
  • measles
  • chicken pox
• avoid contact with anyone with an infection or contagious disorder
• any febrile illness/infection needs aggressive treatment

• Bruton's agammaglobinemia
• isolated IgA deficiency
• hyper IgM immunodeficiency
• common variable immunodeficiency aka acquired agammaglobinemia

• recurrent pyogenic infections
• viruses handled normally except enteroviruses (IgA found in gut)

• genetics
  • congenital X linked
  • Bruton's tyrosine kinase (Btk) gene defect at Xq22
• pathophysiology- genetic defect prevent differentiation of pre B lymphocytes
  • leads to very low/absent B cells in peripheral blood
• signs/symptoms
  • recurrent pyogenic infections usually by 5-6 months of age (stopping breast feeding) 
    • Pneumococcus, haemophilus, streptococcus
• Ig levels
  • IgE less than 200
  • absent/very low IgM, IgA, IgD, IgE
• treatment- Ig replacement (allows children to now live to adulthood but may still develop autoimmune disorders)

• genetics- most cases sporadic, but there are familial cases
• prevalance- most common and mildest form of isolated immunodef.
• Ig levels- absent are marked reduction of serum IgA with normal levels of other Ig's and intact cellular immunity
• pathophysiology- block in differentiation of IgA line of B lymphocytes
  • exposure to penicillamine, phenytoin, other drugs
  • familial and sporadic
• signs
  • recurrent respiratory infections
  • chronic diarrhea
  • allergy/dermatitis
  • autoimmune disease
• treatment- some dont need, but others need continuous antibiotics
  • if they ever need transfusion, there can be no IgA in the blood

• genetics- congenital, usually X linked
  • variable neutropenia in X linked form
  • cellular immunity impaired
• Ig levels
  • low IgG and IgA
  • normal, high IgM
  • POOR AB FUNCTION
• treatment- IV Ig's

• recurrent pyogenic infections
• otitis media
• pneumonia
• septicemia
• pneumocystitis carinii pneumonia is frequent initial infection
• some recurrent neutropenia, hemolytic anemia, aploastic anemia
• adults- sclerosing cholangitis
• hepatitis
• hepatoma

• allergic/hypersensitivity rxns
• transplantation rejection
• autoimmune disorders
• immunodeficiency states

• clinical manifestation
  • recurrent pyogenic infection at any age, but usually onset on 2nd and 3rd decade of life
    • resp. infections (S. pneumoniae, H influenzae, S. aureus)
• B and T cell number
  • B cell number usually normal
  • T cell number/immunity normal
  • no plasma cells
  • total Ig's low (less than 300)
  • IgG low (less than 250)
• treatment
  • lifelong IV Ig required
  • antibiotic should treat each infection
• genetics
  • heterogeneous disease (mix of genetic, familial, other factors)
  • equal sex distribution
• see increased incidence of autoimmune disorders and cancer
  • can see with other immunodeficiencies like IgA def. and ataxia telangiestasia

• less than 50% disease concordance in monozygotic twins
• seasonality in birth dates in disease onset
• biological plausability from in vitro data and animal studies
• epidemiologic associations between specific exposures and certain diseases

• in infancy, we see more severe forms
• later, we see less severe forms

• absent, depressed, or defective immune component

increased susceptibility to viruses and fungi

• DiGeorge's syndrome
• chronic mucocutaneous candidiasis

• genetics- deletion at 22q11
• clinical associations
  • recurrent viral and fungal infections
  • fish shaped mouth
  • low set ears
  • associated hypoparathyroidism
• pathophysiology- rudimentary thymus leading to T lymphocyte deficiency
  • hypoplastic T dependent areas in lymph nodes and spleens
• B cell numbers near normal

• pathophys.- selective defect in T cell immunity with normal B cells resulting in susceptibility to chronic candidal infection
  • negative delayed hypersensitivity skin test to Candida Ag despite infection
• T and B cell numbers
  • T cell- intact T cell immunity to most Ag
  • normal Ab response to Candidia
• genetics- affects both males and females, some familial cases

• clinical manifestation
  • infections in first year of life
    • recurrent etiology- bacterial, viral, fungal
    • persistent despite routine treatment
    • severe including sepsis, meningitis
    • opportunistic pathogens such as PCP pneumonia
• T cells decreased or absent (poor prolif. to in vitro mitogens
• B cells absent or nonfunctional
  • low IgGs after maternal IgG wanes (no specific Ab responses)
• treatment- fatal without bone marrow reconstruction

• cause deep abscesses
• unusually frequent or severe
• respond poorly to standard antbiotics

• pathophysiology- deficient NADPH oxidase, so no respiratory burst for WBC's
• genetics- X linked recessive (also autosomal recessive)
• clinical presentation
  • early childhood in most
  • widespread granulomatous lesion of skin, lung, lymph nodtes
  • IgG high, anemia, leukocytosis
  • defective killing of certain bacteria or fungi
• treatment
  • intermitent continous antibiotic use
  • bone marrow transplant
  • possibly IFN therapy (under study)

• ADA def.
• PNP def.
• X linked SCID/Y chain def.
• autosomal SCID (DNA repair defect)

• host factors- age, severe stress, splenectomy, thymectomy, disease states, including neoplasia
• environmental factors- malnutrition, infections, drugs, radiation

• infects mainly CD4 T cells, but also macrophages
• when immune system weakened, it cannot protect from serious infection, AIDS is present
• latency from HIV to AIDS (2-10 yrs)

• clinical manifestations
  • susceptible to resp. infection, viral disease, gastroenteritis
  • infections increase metabolic requirments and decrease appetite, leading to more malnutrition and immunodeficiency
• T cell immunodef. w/ cutaneous anergy
  • low T cell levels
  • poor prolif. response to mitogens and Ag
  • deficiencies in lymphokines (IFN) and cytotoxic activity
• degree of immune impairment depends on:
  • degree and duration of malnutrition and any underlying illness
• tx- nutritional rehab leads to immune defect reversal rapidly

• clinical manifestation
  • increase susceptibility to H. influenza, E coli, pneumococci, streptococci
• tx
  • continuous prophylactic Ab's for first 2-3 yrs of life
    • thereafter, antibiotics at onset of each fiebrile episode and with surgery
  • receive Haemophilis, pneumococcal, meningococcal vacines

• amorphis and eosinophilic staining on H E
• fibrillar electron micrograph appearance
• beta pleated sheet pattern on X ray diffraction
• apple green birefringence on Congo red stain
• soluble in water
• buffers of low conc.

• prognosis- poor
• diagnosis
  • rectal, gingival biopsy
  • congo red stain

• amyloidosis- immunocyte dyscrasias with amyloidosis aka primary amyloidosis
• diseases- multiple myeloma and other monoclonal B cell prolif.
• precursor- Ig light chain, mainly gamma

• reactive systemic amyloidosis (secondary amyloidosis) OR familial mediterranian fever
• disease- chronic inflammatory conditions (only in secondary amyloidosis)
• precursor- SAA 

• hemodialysis associated amyloidosis AND hereditary amyloidosis
• assoc. disease- chronic renal failure
• precursor- β₂ microglobulin

• systemic senile amyloidosis and familial amyloidotic neuropathies
• precursor- transthyretin

• senile cerebral localized amyloidosis
• associated with Alziemer's disease
• precursor- APP