Immunodeficiencies Flashcards
Primary immunodeficiency
Results from genetic or developmental defect in immune system
Secondary immunodeficiency
Acquired as a result of other disease or condition (malnutrition, drug treatments, etc.)
Can be reversed
What branches of immune system can primary immunodeficiencies affect??
Adaptive (T and/or B cells)
Innate (phagocytes, complement)
Consequences of primary immunodeficiencies depends on what two factors?
Number of immune system components involved
Type of immune system components involved
Defects occurring at what period during hematopoietic development affect the entire immune system?
Early stages of hematopoietic developmental scheme
Defects in more highly differentiated components of immune system have what kinds of consequences?
More specific, less severe
Deficiencies in humoral immunity leave patients susceptible to what kinds of infections?
Extracellular bacterial infections
X-linked agammaglobulinemia
Deficiency in humoral immunity
Caused by defect in B cell maturation and VDJ rearrangement
Low levels of mature B cells and antibodies
Transient immunodeficiency
Babies are born with low levels of IgG- production doesn’t begin until about 6 months of age
IgG levels are low around 6 months- maternal antibodies wear off, IgG is just starting to be made
Hyper IgM syndrome
Humoral immune deficiency Defect in class switching: T helper cells don't express CD40 (co-stimulatory molecule needed for B cell activation) Recurrent, chronic bacterial infections
Selective IgA deficiency
Humoral immune deficiency
Decreased IgA, but normal IgG and IgM
Defect in differentiation of B cells to plasma cells
Patients are generally asymptomatic, but some have a higher incidence of respiratory and GI infections
Deficiencies in cell-mediated immunity would lead to an increased susceptibility to what kinds of infections?
Viral, protozoan, fungal
How are cell-mediated immunodeficiencies diagnosed?
Decreased T cell numbers
Decreased proliferative responses of T cells
Deficient delayed-type hypersensitivity response
DiGeorge syndrome
Cell mediated immunodeficiency
Lack of T cell maturation
Susceptible to viral and bacterial infections
Heart disease, behavioral problems, etc.
Severe combined immunodeficiency syndrome
Cell mediated immunodeficiency
Defects in T and B cell production
Susceptible to any infection (bubble boy)
Most common cause of severe combined immunodeficiency syndrome
Recombination activating genes (RAG 1 and 2) are defective: no synthesis of T or B cell receptors
Phagocytic deficiencies result in susceptibility to what types of infections?
Bacterial, fungal
Leukocyte-adhesion deficiency
Phagocytic deficiency
Defect of integrin adhesion molecules: neutrophils can’t get into tissues
Susceptible to bacterial infections
Chronic granulomatous disease
Phagocytic deficiency
Defect in intracellular killing of ingested bacteria (decreased hydrogen peroxide by cytochrome b): bacteria are carried to organs by phagocytes, where they give rise to lesions
Patients with this disease die in childhood due to septicemia
Most common immunodeficiencies occur at what two points in life cycle?
Young
Old
Treatments for immunodeficiency
Replacement of missing protein (e.g. antibodies)
Replacement of missing cell type or lineage (bone marrow, etc.)
Gene therapy
Most common cause of secondary immunodeficiency
Malnutrition
Ways that HIV can be transmitted
Sexual contact Pregnancy, childbirth, breast feeding Injection drug use Occupational exposure Blood transfusion/organ transplant
How HIV affects the immune system
Attacks CD4 T cells: uses them to replicate, then destroys them
Without T helper cells, body becomes unable to fight infections: AIDS
HIV treatment targets
Chemokine receptor antagonists (prevent HIV binding to cell)
Inhibit viral fusion (virus entering cell)
Inhibit reverse transcription (viral RNA made into DNA)
Inhibit integrase (enables integration of DNA into cellular genome)
Inhibit protease (cleavage of viral proteins that can then be assembled)
Why HIV vaccines can’t be made
HIV infection can remain latent for long periods
HIV mutates at a rapid pace
Killed HIV doesn’t retain antigenicity and live vaccine raises safety issues
