X-Linked version is caused by defect in BTK (a signal transduction kinase required for B cell maturation). This causes arrest of B cells at the pre-B cell stage Reduced B cells in lymphoid tissues and peripheral blood; no germinal centers (no tonsils!); low/absent immunoglobulin.
Defect in B cell isotype switching, caused by defects in a. CD40L, b. CD40 or c. enzymes required for Ig class switching and somatic hypermutation. Increased susceptibility to opportunistic organisms such as CMV, Cryptococcus, PCP (Pneumocystis carinii [jiroveci] pneumonia), mycobacteria.
Relatively mild genetic immunodeficiency. People with this deficiency lack IgA, a type of antibody that protects against infections of the mucous membranes lining the mouth, airway Most common of the primary antibody deficiencies. (1:500 healthy blood donors)
A primary immunodeficiency disorder characterized by impaired B cell differentiation with defective immunoglobulin production. Cause is “elusive” acc to syllabus. Patients have Hx of recurrent infections. Reduced serum IgG, IgA and/or IgM Impaired specific Ab responses to previous infection or vaccination.
The pathogenesis of this deficiency is not fully understood. Symptoms are: a. deficient-specific antibody response to polysaccharide antigens in an individual with normal responses to protein antigens/vaccines (e.g. diphtheria and tetanus), b. normal serum levels of immunoglobulins, and normal IgG subclass concentrations. c. Normal B and T cell numbers. Very common immunodeficiency. Kids or adults have recurrent sinopulmonary infections.
Cause unknown. Recurrent sinopulmonary infections. Low IgG with normal Ab to dip/tet/pneumo; normal lymphocytes. Onset 6 months age, when mother’s IgG (red, below) disappears. Can resolve by 4 years.
Various types: loss of early components results in increased autoimmune disease. Loss of C3 leads to impaired MAC and phagocytosis. Loss of late components causes Neisserial infect
Reduced levels/function of C1 esterase inhibitor (regulates complement) Recurrent episodes of swelling without urticaria or pruritus
Accum. 2,deoxyadenosine results in accum. of deoxyATP -> toxic for B, T, and NK cells Profound lymphopenia
X-linked immunodeficiency. Likely due to loss of function of IL-7R. IL-7 essential for thymocyte development. Lack of NK cells likely due to loss of IL-15R. Most common form of this syndrome-- B cells ok.
Recombination of variable region genes responsible for generation of antibody and TCRs fails to occur. Arrests B and T cell development. NK cells not affected.
Immunodeficiency characterized by loss of essential component of the TCR. Loss of T cell function.
Low to normal T cell numbers with oligoclonal T cells and more than 80% of their CD4+ cells are CD45RO+, ie, memory T cells. These cells lack the normal diverse T cell repertoire, being oligoclonal in nature and therefore are not functional. These babies present with a diffuse, erythematous rash before 3 months of age, lymphadenopathy, hepatosplenomegaly, diarrhea, and failure to thrive. Peripheral eosinophilia and elevated IgE level.
An x-linked combined immunodeficiency. Mutation in WASP gene. TCR activation stimulates WASP, which causes changes in actin polymerization. a) Eczema, b) Thrombocytopenia c) Immunedeficiency, ranging from poor polysaccharide responses to more global antibody deficiency and T lymphocyte dysfunction.
Dysmorphogenesis of 3rd and 4th pharyngeal pouches. Remember CATCH-22: C. Cardiac abnorm’s. A. Abnormal Facies T. Thymic aplasia C. Cleft palate H. Hypocalc/hypoparaT. 22. Del 22 Partial: Normal thymic function, T/B cells ok. Complete: no thymic function, low CD4, susc. to inf., GVHD
Most due to mutations in STAT3 signaling, with impaired function of TH17 pathways (affects neutrophilic inflammation) a.Recurrent staphylococcal abscesses, sinopulmonary infections, Candida and bone fractures b. Severe eczema c. Retained primary teeth d. Recurrent Candida e. Recurrent bone fractures f. Very elevated IgE level.
Defect in phagocytic cells. These cells can ingest but do not kill bacteria due to a failure to form bactericidal oxygen radicals by the cell. Caused by absent, reduced, or altered membrane proteins (x-linked forms, the gp91 phox protein) or cytosolic proteins (autosomal recessive forms) of the cytochrome b558 complex in the neutrophils. Recurrent bacterial infection with catalase positive organisms (staph, Serratia; also Aspergillus). The pathognomonic organism: Chromobacterium violaceum. Granulomas
SCID that presents the same as an absence of the common γ chain.
Lack of neutrophil surface glycoproteins important in cell migration: Neutrophils cannot migrate toward inflammatory stimuli or adhere to vascular endothelium. Most commonly due to absent beta subunit (CD18) of 3 cell surface glycoproteins. Diagnosis suggested by recurrent soft tissue infections, delayed umbilical cord separation, severe periodontal disease, and no pus formation despite high white blood cell counts
Caused by various deficiencies: MyD88, IRAK4, UNC93b. Lead to: recurrent pyogenic/pneumococcal infections, pneumococcal disease at young age, and susceptibility to HSV encephalitis, respectively.
Results from a failure to maintain central T lymphocyte tolerance. Autosomal recessive disease. Gene responsible is the autoimmune regulator (AIRE). AIRE regulates transcription of many tissue-specific antigens (TSAs) expressed on medullary thymic epithelial cells. Hypoparathyroidism, adrenal insufficiency, and chronic mucocutaneous candidal infections. Also exhibit other aspects of organ-specific autoimmunity.
The gene responsible, FOXP3, encodes a transcription factor that functions as a transcriptional suppressor: It inhibits endogenous cytokine expression promoted by NFAT and NFκB response elements. FOXP3 deficiency leads to a failure of CD4+CD25+ regulatory T cell development, resulting in unregulated T-cell activation. • neonatal autoimmune type I diabetes • autoimmune enteropathy • eczema • food allergy • autoimmune hemolytic anemia • severe infections.
Uncontrolled expansion of potentially self-reactive lymphocytes. Most have autosomal dominant mutations producing truncated or dysfunctional Fas, Fas-L, or Caspase 8/10. Patients present with chronic non-malignant lymphadenopathy +/- splenomegaly. Increased susceptibility to hematological malignancy, particularly lymphoma in approximately 10% of patients, and the development of autoimmune disease
Type I hypersensitivity reaction caused by reexposure to allergen and activation of mast cell. Affects nerve endings (Itch), blood vessels (vasodilatation → hives in skin; hypotension) and smooth muscle contraction (bronchospasm; cramping/diarrhea/vomiting) b. Prostaglandin release (more vasodilatation) c. Leukotrienes stimulate smooth muscle contraction. d. Cytokine release (TNF-alpha, IL-4) → late phase reaction.
IgE-mediated inflammatory reaction, massive release of histamine Sputum, spasm and swelling. Rescue treatment with short acting beta-agonist (albuterol) and control of inflammation
Chronic, pruritic, inﬂammatory skin disease that occurs most frequently in children, but also affects many adults Skin dryness, erythema, oozing and crusting, and lichenification. Pruritus is a hallmark of the condition.
Risk factors: family history of atopy, male sex, birth during the pollen season, firstborn status, early use of antibiotics, maternal smoking in first year of life, exposure to ind Characterized by paroxysms of sneezing, rhinorrhea, and nasal obstruction, often accompanied by itching of the eyes, nose, and palate. Postnasal drip, cough, irritability, and fatigue are other common symptoms
Severe allergic reaction – It’s not just hives. Food is responsible for up to 50% of reported cases presenting to emergency departments in developed countries Often caused by food. Typically appears within a few seconds to two hours after the exposure and arise from massive mediator release from mast cells and basophils. Massive histamine release everywhere. – Hives and flushing – Airway constriction (Upper and Lower Airways) – Vomiting/Diarrhea – Lightheadedness/mental status change due to drop in blood pressure (get a BP when this is suspected) – Palpitations
Anti-basement membrane protein. Leads to complement and FcR-mediated inflammation. Nephritis, lung hemorrhages
Condition in which the red cells of the fetus or newborn are destroyed by maternally-derived alloantibodies. Direct result of a blood group incompatibility between the mother and f With the advent of antenatal and postpartum Rh immune globulin administration Rh(D) sensitization is infrequently seen nowadays
Anti-TSH receptor antibodies. Stimulates TSH Receptor, causing hyperthyroidism. Symptoms characteristically include anxiety, emotional lability, weakness, tremor, palpitations, heat intolerance, increased perspiration, and weight loss
Anti-Ach receptor antibodies, affect the NMJ. Causes weakness and paralysis.
Anti-cadherin in epidermal junctions A group of autoimmune mucocutaneous blistering disorders characterized by acantholysis in epithelium of mucous membranes or skin
Post-strep infection, anti-strep antibodies also react with myocardial antigen Myocarditis, arthritis
Antibodies generated against intrinsic factor of gastric parietal cells, neutralization of intrinsic factor, no absorption of Vit B12 Abnormal erythropoiesis, anemia
Anti-strep antibodies react against glomeruli of kidney. Causes Nephritis.
Immune complexes (Ab-Ag) occur at small blood vessels. Can be drug-induced. Present as palpable purpuric papules and plaques and blisters, esp. on lower extremities.
caused by reaction against Medications (especially high dose IV antibiotics e.g. some CF patients) Systemic vasculitis, nephritis, arthritis, Rash, fever, polyarthralgia. Symptoms begin 1-2 weeks after first exposure (IgM to IgG transition), resolve within weeks of discontinuation, with readmin drug rxn occurs within 24-36h
Post strep, ANCA, Lupus nephritis Lumpy-bumpy histological pattern in glomerulus.
Possible causes: Poison ivy, nickel, PPD test for TB, topical meds (e.g. neomycin), cosmetics, nail polish and resins. Due to either CD8 T cells or CD4 T cells causing self tissue damage. Site of tissue injury becomes indurated (raised and hard – it’s cells, not fluid (edema)) and red and warm – potentially followed by a necrotic, open, oozing lesion