Immunodeficiency Flashcards
What are the 3 types of autoimmune diseases? What is each one dependent upon?
Systemic: Ab-dependent damage
Organ Specific: Ab-dependent damage & T-cell dependent damage.
How does Systemic Ab-dependent damage occur?
Immune complex mediated damage: Immune complexes activate complement + bind to Fc receptors on phagocytes causing inflammation + tissue damage.
Describe the systemic Ab-dependent disease systemic lupus erythematosus (SLE).
Ab-Ag complexes lodge into capillaries bursting the blood vessels creating a “butterfly” like rash mostly in the face.
Describe the systemic Ab-dependent disease Rheumatoid arthritis (RA).
Self Antibodies are made against IgG rheumatoid factor or collagen, creating a reaction against self.
What is a common complication of systemic lupus erythematosus (SLE)?
Glomerular Nephritis: immune complexes (DNA+anti-DNA) get trapped on the kidney endothelium where activated macrophages bind, causing damage to the endothelium and basement membrane causing kidney dysfunction (proteinuria).
In systemic lupus erythematosus (SLE), what do macrophages recognize in order to bind to the immune complex
Either Fc-Fab complex or complement on Fc.
How does organ specific Ab-dependent damage occur?
Ab’s react against organ specific antigens.
Describe Graves disease.
Increase thyroid function - Ab’s stimulate the release of thyroid hormones when they bind to the receptor for thyroid stimulating hormone.
What is Graves disease also known as?
Hyperthyroidism or Thyrotoxcosis
Describe Hashimoto’s thryoiditis.
Decreased thyroid function-Ab’s cause the progressive destruction of the thyroid when they are in contact with Thryoglobulin.
What is Hashimoto’s thryoiditis also know as?
Hypothyroidism
Describe Myasthemia Gravis.
Muscle weakness due to Ab’s binding and thus blocking the acetylcholine receptor which impairs nerve impulses + fixes complement, recruiting phagocytes and causing damage
In Myasthemia Gravis, what does the breakdown of acetylcholine receptors inhibit and what does this lead to macrophysically?
Inhibits Na+ influx –> no muscle contraction –> ocular movement dysfunction
How does Organ specific T cell-dependent damage occur?
T-cell damaged by cytokines, cytotoxicity, inflammation, etc.
Describe Insulin-dependent diabetes mellitus (type I or juvenile-onset diabetes).
T-cells cause the destruction of the insulin producing beta cells in the islets of Langerhans in the pancreas.
Describe Multiple Sclerosis.
T-cells are implicated in the disease featuring damage to the CNS.
What is diabetes linked to?
Specific HLA alleles; 96% of diabetics have either or both HLA DR4 or DR3.
List some ways that immunodeficiency diseases can be acquired.
- Malnutrition
- Immunosuppressant drugs/radiation
- AIDS
List some ways that immunodeficiency diseases can be inherited.
SCID, IgA deficiency
In genetic basis oh inherited immunodeficiency, most disease traits are recessive or dominant? Many or X-linked or Y-linked?
Recessive; X-linked
Deficiencies of Ab, complement or phagocyte function cause an increased risk of infection with what type of bacteria?
Pyogenic (pus forming) bacteria
What is the pathway for bacterial toxins?
Ab’s neutralize toxins –> ingested by macrophage
What is the pathway for bacteria in the extracellular space?
Opsonization of bacteria by Ab’s –> ingested by macrophage
What is the pathway for bacteria in plasma?
Complement activation –> lysis and ingestion
Is deficiency of T-cells or B-cells worse in immunodeficiency?
T-cells deficiency is worse.
What does SCID stand for and what does describe?
“Severe Combined Immunodeficiency Disease” – Lack B and T cells
How are deficiencies of T-cell function presented in individuals?
Increased susceptibility to infection - recurrent/chronic/opportunist
Autoimmune complications – SLE or RA
Gastrointestinal Disease – Chronic diarrhea/malnutrition
Hematologic Disease – Anemia, leucopenia, thrombocytopenia
What types of laboratory diagnosis are there for the evaluation of B and T cell function?
Ig levels/titers, DTH skin tests, FACS analysis with mABs specific for T/B cells, Mitogen responses
What types of laboratory diagnosis are there for the evaluation of phagocyte function?
White blood count/differential. NBT test (oxidative burst). Chemotaxis/phagocytosis/intracellular killing.
What types of laboratory diagnosis are there for the evaluation of the complement system?
Assays for hemolytic complement
How do you treat B cell defects?
Replacement immunoglobulin therapy. Antibiotics.
How do you treat T cell defects?
Bone marrow transplant. Replacement immunoglobulin therapy. Antibiotics.
How do you treat phagocyte defects?
Antibiotics. Anti-fungal drugs.
How do you treat complement defects?
Antibiotics.
How do you treat SCID?
Replacement immunoglobulin therapy. Antibiotics. Bone marrow transplant.
Is deficiency in IgA fatal? How many people are affected by this?
No, has potential association with recurrent respiratory infections, but IgM can reach secretions (substitute for IgA); 1/700 people
What disease is related to IgA deficiency?
Common Variable Hypogammaglobulienemia – increase susceptibility to pyogenic bacteria (symptomatic 15-35 years old).
A defect in what leads to Bruton’s X-linked Agammaglobulinemia (XLA).
Defect in B cell development where very few B cells mature.
The above disease has a defect in what gene?
BTK gene (a tyrosine kinase), which causes a signaling defect and impairs B cell development.
Describe Huper IgM Syndrome.
Defect in a form of costimulation where the absence of CD40 ligand disables T cell help for B cells (IgG, A, E decrease) & T cells are impaired, cannot make germinal centers.
What happens in DiGeorge syndrome? Bare Lymphocyte Syndrome?
No thymus; MHC class II not made (CD4 T cells can’t develop).
Impaired T cell function causes failure in?
Failure to fight viral/fungal infections and failure to help B cells (which can’t make antibody responses and susceptible to bacteria).
Describe X-linked SCID.
Defect in gene encoding a common component of several cytokine receptors (impairs gamma chain, IL-2,4,7,15, B cell function, T cell development).
Name 2 enzyme disorders that cause SCID?
Adenoside deaminase deficiency & nucleoside phosphorylase deficiency.
What do adenoside deaminase deficiency & nucleoside phosphorylase deficiency disorders cause?
An accumulation of dATP which reduces ribonucleotide reductase activity inhibiting DNA synthesis and ↓ #’s of B/T cells.
Describe Chronic Granulomatous Disease (CGD).
Phagocyte defect where inability to generate a respiratory burst due to the defect in genes for NADPH oxidase (normally generate superoxide ions). This causes failure to kill ingested microbes.
Individuals with the Chronic Granulomatous Disease are susceptible to what bacteria?
Staphylococci. Pseudonomas. Aspergillus.
What is the most severe complement deficiency?
C3 deficiency – susceptible to pyogenic bacteria
What is the most common complement deficiency?
C2 deficiency
Which complement deficiency inhibits Membrane Attack Complex (MAC) formation?
C5,6,7,8,9 deficiencies (increased neisserial infections).
