Diseases Flashcards
Chronic Granulomatosus Disease (CGD)
- defect in NADPH oxidase
- phagocytes fail to produce adequate levels of oxygen radicals and hydrogen peroxide upon phagocytosis of microbes
- early onset 2-5 years
- granulomas in the skin, GI tract, and GU tract
Chediak-Higashi Syndrome
- abnormal fusion of phagosomes with lysosomes
- failure to kill ingested microbes due to impaired myeloperoxidase
- pyogenic infections
- abnormal function of platelets leading to bleeding
- hypopigmentation
- progressive neurologic dysfunction
Leukocyte Adhesion Deficiency
- group of disorders where interaction of leukocytes with vascular endothelium is disrupted
- Type 1: defect in LFA-1/CD18 - typically die by age 2
- Type 2: fucosyltransferase mutation resulting in the loss of the carbohydrate ligand for P-selectin and E-selectin in leukocytes - better survival than type 1
Complement System Abnormalities
- most common is C8 deficiency
- increased frequency of Neisseria infection because no formation of MAC
IRAK-4 Deficiency
-defect in a key enzyme in TLR signaling resulting in recurrent bacterial infections (mostly gram +)
TLR polymorphisms
-increased sensitivity to certain infections
C3 Deficiency
- loss of opsonization and MAC is not able to form
- pyogenic infections, especially Staph and Neisseria
C1 Inhibitor (C1INH) deficiency
- lose of C1 and kallikrein regulation; kininogen is cleaved to release bradykinin
- causes Hereditary Angioedema
CD59 deficiency
- no inhibition of MAC
- Hemolysis and thrombosis
- Paroxysmal Nocturnal Hemoglobinuria
C1qrs, C4, C2
- lose classical complement pathway
- Systemic Lupus Erythematosus (SLE)
Factor H and Factor I deficiency
- C3 deficiency
- infections, inflammation, macular degeneration, and atypical Hemolytic Uremia Syndrome (aHUS)
AHUS
- Factor H/Factor I deficiency
- hemolysis of RBCs, thrombosis
- shistocytes
- low hemoglobin
- thrombocytopenia
- abnormal kidney function
- treat with blood transfusions, fluid electrolytes, dialysis, or Eculizimab
Heterozygotes for DQ2 and DQ8
-increased incidence of IDDM
Ankylosing Spondylitis
-HLA allotype B27 has 150 times relative risk
-
Class II MHC deficiency
- congenital deficiency where no MHC II molecules are made
- can also have mutations in transcription factors that block the production of MHC II
Class I MHC deficiency
- tapasin mutation
- TAP mutation
- Beta 2 microglobulin mutations
Celiac Disease
- associated with DQ2 allotype
- transglutaminase of gliadin peptide and activation of gliadin specific T cells
- activation of plasma cells and other lymphocytes gives abdominal discomfort/pain
Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy Syndrome (APECED)
- AIRE mutation; a transcription factor responsible for the expression of many ectopic antigens in the thymic medulla
- Endocrinopathy
- Mucocutaneous candidiasis
- Alopecia and keratinitis
Immune Dysfunction polyendocrinopathy enteropathy X-linked syndrome
- Fox3p mutation; important in the development of Treg helper T cells
- enteropathy (IBD)
- Type 1 diabetes
- Eczema
Hemophagocytuc Lymphohistiocytosis (HLH)
- perforin deficiency
- genetic or acquired
- high serum levels of IFN, TNF, IL-6, IL-10
- Symptoms: fever, splenomegaly, haemophagocytosis, hypertriglyceridemia, and hypofibrinogenemia
- attempt to treat with anti INF monoclonal antibodies
Rheumatoid Arthritis
- inflammation within the synovial membrane leading to infiltration of WBC
- typically due to INF and TNF-alpha
- increased angiogenesis, articular cartilage degradation, and bone erosion
- treat with glucocorticoids to prevent inflammation or anti-INF monoclonal antibodies
Muckle Wells Syndrome
- mutation in NALP3
- moderate low grade fevers/rashes in infancy
- joint pains, significant hearing loss in adolescent, may develop amyloidosis and kidney failure
- triggered by cold, stress, or unknown factors
- one of a group of related diseases, CAPS, cryopyrin associated periodic syndrome
type I hypersensitivity
- IgE mediated mast cell activation
- immediate hypersensitivity upon second exposure to allergen
- Examples: allergic rhinitis, hay fever, food allergies, bronchial asthma, anaphylaxis
Type II Hypersensitivity
- IgM/IgG mediated antibody against cell surface or extracellular matrix proteins
- Glomerulonephritis in Goodpasture Syndrome
- Pemphigus Vulgaris
Type III Hypersensitivity
- Immune complex mediated
- Immune complex consisting of IgG or IgM and the antigen
- SLE, Serum sickness, vasculitis
Type IV Hypersensitivity
- T cell mediated, delayed type hypersensitivity (Th1 cells)
- Tuberculosis, Leprosy, Leishmaniasis, IBD, poison ivy, nickel contact, RA, IDDM, MS, Wegener’s Granulomatosis, Toxic Shock syndrome
Transient Hypoglobulinemia of Infancy
- loss of materanl Igs and failure to produce adequate levels of IgG (typically occurs 3-6 months)
- treat infections as needed, but do not give IvIgs
- deficiency will resolve on its own as the immune system develops, but if not, consider alternative diseases such as Bruton’s Disease
Common Variable Immunodeficiency
- most prevalent immunodeficiency
- manifests at any time from infancy to 40 years old
- normal to low peripheral B cells, but NO plasma cells leading to variable low Igs
- recurrent infections and predisposition to autoimmune disease/malignancy
- treat with IvIg therapy or bone marrow transplant
- etiology unknown
Bruton’s Agammaglobulinemia
- X-linked agammaglobulinemia (XLA)
- x-linked
- defect in Bruton’s tyrosine Kinase gene
- B lymphocytes unable to differentiate and therefor no Igs produced; T cells are normal
- Recurrent pneumoni, sepsis, diarrhea
- bone marrow treatment is the best option
IgA Deficiency
- low serum IgA
- autosomal inheritance
- pulmonary and GI infections are common
- May react to IgA serum during transfusions so always check
- depending on severity of symptoms, patient may not know they have this
X-linked Lymphoproliferative Syndrome (Duncan’s Disease)
- x-linked
- defect in SH2D1A gene that encodes SAP proteins
- rare defect in the immune response to Epstein Barr Virus
- results in infectious mononucleosis, hypogammaglobulinemia, and B cell lymphomas
- fail to make anti-EBV antibody, defective cytokine production, and low CD4/CD8 ratio
DiGeorge Syndrome
-sporadic disturbed development of 3rd/4th pharyngeal pouches leading to deletion in chromosome 22
Cardiac defects
Abnormal facial features - micrognathia, hypertelorism
Thymic aplasia -no T cells produced; low Igs becuase no T/C cell interaction
Cleft palates
Hypothyroidism/hypoparathyroidism - hypocalcemia leading to tetany
22
Chronic Mucocutaneous Candidiasis
- T cell dysfunction against candidiasis (fungal infection)
- candidial infections in skin, nails, mucus membranes
- IL17 and IL-17R deficiencies
Hyper IgM type 1
- CD40L/CD40
- X-linked
- failure of immunoglobulin isotype switching due to B cells not receiving T cell interaction
- No germinal centers formed
- Normal T/B cells; hyper IgM, all other Igs low
Hyper Igm Type 2
- AID deficiency
- autosomal recessive
- Large germinal center
- Normal T/B cells; hyper IgM, all other Igs low
SCID-ADA deficiency
- adenosine deaminase deficiency
- autosomal recessive - accumulation of toxic metabolites to T/B cells
- Pseudochondrodysplasia - defect in cartilage
SCID-PNP deficiency
- purine nucleoside phosphorylase deficiency
- build up of toxic metabolites to T cells but not B cells
- reduced T cells; normal B cells, but Ig production is low do to lack of stimulation by T cells
SCID-Reticular Dysgenesis
- mitochondrial adenylate kinase 2 deficiency
- most severe form of SCID
- no T-cells, no B-cells, no granulocytes
- often born still born or die shortly after birth
X-linked SCID
- Bubble Boy syndrome
- x-linked
- lack of common gamma chain
- T cells reduced
- Normal B cells but low Igs
Bare Lymphocyte Syndrome
-deficient in either MHC I or MHC II molecules
Jak 3 SCID mutation
- few T cells
- normal B cells, but low Igs
Omenn Syndrome
–autosomal recessive SCID
-mutation in Rag1/Rag2/Artemis
-oligoclonal autoreactive T cells producing IL-4
-Hyper IgE
Symptoms: erythroderma and desquamation of skin, allopecia, lymph node enlargement,
-treatment with allogeneic bone marrow transplant
-If artemis mutation, radiosensitive and must not X-ray since they are predisposed to cancers
-occurs early in life unlike Job Syndrome
Job Syndrome
- autosomal dominant mutation of STAT3
- occurs later in life unlike Omenn Syndrome which occurs early in life
- hyper IgE
- recurrent infections
- Coarse facial features, skin abscesses, dental problems
Wiskott-Aldrich Syndrome
- X-linked recessive
- defect in Wiskott Aldrich Syndrome protein (WASp)
- triad: thrombocytopenia, immunodeficiency, eczema
- always a T cell deficit; poor response to polysaccharide antigens such as flu, streptococcus, staph
- Symptoms: bleeding diarrhea, petechia, ecchymosis, skin/oral mucosal infections
- rarely survive childhood
Ataxia-Telangiectasia (A-T)
- autosomal recessive
- defect in ataxia telangiectasia
- Ataxic movements, dysarthric speech, choreoathetosis, ocular teangiectasia (dilated blood vessels of eye, spider angiomas
- Radiosensitive like Artemis mutation in Omenn syndrome
- Effects both T and B cells
- decreased IgA
Insulin Dependent Diabetes Mellitus (IDDM)
- autoreactive T cells against pancreatic Beta cell antigens (insulin, glutamic acid, etc) leading to the destruction of Islet Beta cells
- Type IV hypersensitivity
Multiple Sclerosis
-Autoreactive T cells against myelin basic protein or proteolipid protein leading to brain invasion by CD4+ cells, destruction of myelin, and paralysis
Goodpasture’s Disease
- autoantibodies (IgG) against glomerular basement membrane (collagen Type IV)
- reacts with glomerular and alveolar basement membrane
- bloody urine, decreased urine output, hemoptysis, nonspecific chest pain
- linear smooth distribution of antibody immunofluoresence
- Type II hypersensitivity
Myasthenia Gravis
- autoantibodies (IgG) against the acetylcholine receptor
- Activation of complement plays a major role in mediating cell injury
- loss of membrane surface area, fibrotic repair of membrane tissue, internalization of cross linked AchR
- usually young women
- Muscle Weakness worsening with muscle use
- Ptosis
- diploplia
- misaligned gaze
- thymectomy scar
- Type II Hypersensitivity
Graves’ Disease
- antibodies against TSH receptor formed
- Type II Hypersensitivity
- Goiter
- Exopthalmos/proptosis
- Hyperthyroidism
- Low TSH and high Thyroid hormone
- Treat with anti-thyroid drugs
Hashimoto Thyroiditis
- combined Type II and Type IV hypersensitivity
- autoantibodies directed at thyroglobulin and thyroid peroxidase
- Intense mononuclear infiltrate destroying thyroid
- Hypothyroidism
- Goiter
- Treat with Thyroxine
Systemic Lupus Erythematosus (SLE)
- Type III hypersensitivity
- Anti-Nuclear Antibodies formed; Anti-dsDNA and Anti-Smith confirm lupus diagnosis
- Malar Rash - AA see bumps
- Photosensitivity
- Discoid Rash
- homogenous pattern of nuclear staining (sometimes speckled too)
- antibody staining ring formation
Scleroderma
- Type II and Type IV hypersensitivity
- Autoantibodies against: topoisomerase 1 (most severe), RNA transcription factors, centromere
- Nucleolar staining pattern with autoantibody
- Autoimmunity, Small vessle obliterative disease, Fibrosis
- radial furrows of mouth, scattered telangiectasia, tight skin
- Raynaud’s phenomenon
- Digital Ulcers
- systemic involvement
- CREST syndrome if anti-centromere antibody produced
Rheumatoid Arthritis
- mixed Type II, III, and IV hypersensitivity
- antibodies against own antibodies
- Rheumatoid Factor - Anti-IgG
- Anti-citrullinated protein antibody, diagnostic when RF is negative
- Autoreactive T cells react against unknown synovial joint antigens
- HLA-DR4 association
- Synovial Pannus
- Joint inflammation/breakdown
- Treat with NSAIDS, biologics (anti TNFs), methotrexate
