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Diseases Associated with hypersensitivity
- Transfusion Reactions
- Atopic Allergies
- Allergic Asthma
- Rh disease
- Serum Sicknes
- Food Allergies
- Contact dermatitis
- Anaphylaxis
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Diseases associated with Autoimmune Problems
- (Coombs +) Hemolytic Anemia
- Type I diabetes
- Multiple Sclerosis
- Rheumatoid arthritis
- SLE
- Pemicious Anemia
- Myasthenia Gravis
- Graves Disease
- Goodpasture's Syndrome
- Celiac Disease
- Sjoren syndrome
- SSS
- Polymyositis/Dermatomyositis
- Hashimoto thydroitis
- Pemphigus vulgaris
- MCTD
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Infection Related Diseases
- Septic Shock
- Toxic Shock
- Crohn's Disease
- Rheumatic Fever
- SIRS (not really, but sort of)
- Candidas
- Cytalomegalovirus pneumonia
- Histoplasmosis
- Kaposi Sarcoma
- MAI
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Transplantation Related Diseases
- Hyperacute Allograft Rejection
- Acute rejection
- Chronic Rejection
- GVHD
- Xenograft Rejection
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Monoclonal Diseases
- Multiple Myeloma
- MGUS
- Waldenstrom's Macroglobulinemia
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Diseases associated with immune deficiencies
- BLS (Type I and II)
- LAD
- XLA
- CVID
- AIDS
- Hyper IgM syndrome
- Chediak-Higashi Syndrome
- Selective IgA deficiency
- IgH chain Locus deletion
- Transient Hypogammoglobulinemia
- SCID (ADA, Gamma-C, RAG 1/2, JAK3 deficiencies)
- TCR-Initiated signaling defects
- Hereditary hemochromatosis
- Wiscott-Alrdich Syndrome
- Neonatal Neutropenia
- Chronic Granulomatus
- MPO deficiency
- IFNgamma deficiency
- Hereditary angioedema
- PNH
- C2 deficiency
- Factor B deficiency
- MBP deficiency
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Define Hypersensitivity
an undesirable reaction produced by a normal immune system
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Selective IgA deficiency, transient hypogammaglobulinemia, XLA, and IgH chain locus deletion are best classified as what type of deficiency?
Antibody
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DiGeorge syndrome, CD3 deficiency, ZAP-70 deficiency, BLS 1/2, IL-12 (R), IFNgamma receptor deficiencies, hyper IgM syndrome types 1/2 are best classified as what type of deficiency?
T cell
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Gamma chain deficiency, adenosine deaminase deficiency, RAG 1/2, and Wiscott-Aldrich syndrome are best classified as what type of deficiencies?
Combined immune deficiencies
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Cyclic neutropenia, LAD (1,2,3 and 4), Chediak-Higashi syndrome, chronic granulomatus disease, and neutrophil granule deficiency are best classified as what type of deficiencies?
Phagocytic cell deficiencies
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MBL and C2 deficiencies, Factor I and H deficiencies, HAE, C4b-BP deficiency, and PNH are best classified as what type of deficiencies?
Complement
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IRAK-4 mutations, MBL deficiencies, Defensin deficiencies, and Nod2 deficiency are best classified as what types of deficiencies?
Inherited defects in innate immunity; result in infectious diseases
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Transfusion reaction
- Hypersensitivity
- Abs against ABO carbohydrate antigens
- Type II
- Igm/IgG mediated
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Atopic Allergies
- Hypersensitivity; Type I
- IgE mediated
- APC presents an Ag to The2 cells; produces IL-4 and IL-13 (promotes class switchign to IgE)
- Overreaction of immune system to non-pathogenic substance
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Allergic asthma
- Hypersensitivity; type I
- IgE mediated
- Lumgs and airways primarily; mucous plugging and expiratory wheezing; hyperinflated lungs when having an attack
- Common in developed world
- Controlled with steroids and bronchodilators
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Rh disease
- Hypersensitivity
- Rh- mom; if not given Rhogan during first pregnancu (assuming Rh+ child), will become sensitized to Rh Ag and produce anti-Rh Abs
- Normal first pregnancy; subsequent Rh+ babies are attacked by mom's anti-Rh IgG Abs that cross placenta
- Give Rhogan during pregnancy (regardless of phenotype of fetus) and after delivery (if baby is RH+)
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Serum sickness
- Hypersensitivity; Type III
- Ag-Ab immunes complex reaction acts as anaphylatoxins; cause mast cell degranulation and anaphylactoid shock
- Induced by anti-thymocyte globulin (post-transplant), ant-toxin therapy (for hepatitis), and certain drugs (penicillin)
- Symptoms=fever, urticaria (hives), hypotension, vasculitis, hemorrhage, lymphdenopathy, arthralagia, and glomerulonephritis
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Food allergies
- Hypersensitivity; type I
- Similar to atopic allergies
- Loss of tolerance
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Contact dermatitis
- Hypersensitivity; type IV
- CAn be induced by poison ivy, metal, etc
- Localized reaction
- CTLs, macrophages, and NK cells cause production of TNFalpha, prostaglandinds (contraction and relaxation of smooth muscle), and leukotrienes
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Anaphylaxis
- Serious type I hypersensitivity; occurs upon 2nd exposure to Ag
- Systemic shock form of allergy that can occur in response to insect venoms, certain foods, radiocontrast media, latex (cross-reactivity with banana, avocado, and chestnut), and drugs (penicllin cross reaction with cephalosporin)
- IgE mediated; mast cell mediators include histamine, proteases (tryptase, chymase), PGs, Leukotrienes, Cytokines, and platelet activating factor
- cardiovascular, pulmonary, GI, and cutaneous systems involved; can have difficulty breathing due to allergic reaction inducing angioedema blocking of lungs; generalizd prurutis, apprehension, hypotension, abdominal crampling, tachycardia, tachypnea, and hives
- Treat (remember your ABCs): maintain airway, reverse bronchoconstriction, and ensure adequate circulation; timely injection of epinephrine is life saving
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(Coombs +) Hemolytic Anemia
- Autoimmune disease
- Auto-Abs to RBCs
- Decreased hemoglobin, hematocrit, and increased bilirubin
- Symptoms of anemia; fatigue, shortness of breath, pale skin due to poor O2 circulation; also hepatosplenomegaly, jaundice, etc.
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Type I diabetes
- Autoimmune disease
- Auto-Abs to beta cells in the pancreas that produce insulin
- Inability to produce insulin in order to lwoer blood sugar leads to hyperglycemia and subsequent diabetes
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Multiple Sclerosis
- Autoimmune disease
- Auto-Ab to myelinated cells in the CNS (Schwann cells); decreased production of myelin
- Scars in white matter of the brain and spinal cord which are normally filled with myelin
- Neurological symptoms; physical and cognitive disability
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Rheumatoid arthritis
- Autoimmune disease
- Ag-Ab complexes deposit in the sinovial joints (bilaterally); deformations of hands and joints; destruction of articular cartilage and ankylosis of joint
- Onset between 40 and 50; better with exercise, worse with rest
- Treat with anti-TNFalpha drugs; decrease impact of body's inflammatory response
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SLE
- Autoimmune disease; type III hypersensitivity
- Systemic lupus erythematosus; more common in females and African Americans
- Soluble immune complexes deposit in kidney, joints, capillaries, etc.; causes systemic issues
- Ab against DS-DNA
- Symptoms=butterfly rash on face (20%), fatigue, arthritis (90%), weight loss/gain, nephritis, and vasculitis (20%; bad prognosis)
- Tests for ANA and anti-DSDNA Ab are diagnostic
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Pernicious Anemia
- Autoimmune disease
- Auto-Ab against parietal gastric cells; causes lack of intrinsic factor and inability to absorb B12; leads to megaloblastic anemia (continued cell growth without division)
- Treated with B12 injections; NOT orally because no ability to absorb through GI tract
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Myasthenia Gravis
- Autoimmune disease
- Auto-Ab to ACh (acetylcholine) receptors; blocks transmission of NTs
- Muscle weakness, difficulty swallowing, etc.
- Treat with cholinesterase inhibitors, immunosuppressors, and sometimes thymectomy
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Graves disease
- Autoimmune disease
- Auto-Ab to TSH; hyperthyroidism; elevated T4; decreased TSH (thyroid stimulating hormone)
- more common in females
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Goodpasture's syndrome
- Autoimmune disease; type II hypersensitivity
- Only one that's more common in M than F
- Auto-Ab against basement membrane collagen
- Glomerulonephritis and pneumotitis; can see the aut-Ab using fluorescence; linear design as opposed to lumpy design
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Celiac disease
- Autoimmune disease; probably Ab-mediated hypersensitivity though some research says cell-mediated (role of MHC)
- Abormal reaction to gluten; damage to GI tract and destruction of villae; decrease in body's ability to absorb nutrients
- Presents with variety of symptoms
- Treat with gluten free diet; villi reform after time
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Sjoren Syndrome
- Autoimmune disease
- 90% women; most >40
- Dry eyes; dry mouth; neutrophil infiltration in salivary glands and conjunctiva results in decreased secretions
- 40 fold increased risk of lymphoma
- Infection by virus or bacteria may trigger (hypersensitivity)
- Testing; ANA for rheumatoid factor is usually (+)
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SSS
- Autoimmune disease
- Systemic Sclerosis Syndrome
- Female 3:1; >50
- Sclerosis of skin; Raynaud's phenomenon caused by vasoconstriction in fingers (70%); sclerodactaly; fragile skin; GI fibrosis; difficulty swallowing; renal failure caused by glomeruli closing (70%)
- Positive ANA in low titer; hypergammaglobulinemia; glomeruli closing visible on histo
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Polyositis/Dermatomyositis
- Autoimmune disease
- Females 2:1
- Joint pain without inflammation (Arthralgias); malar skin rash (facial); systemic vasculitis
- Associated with internal malignancies
- HLA linked; serum Abs against myosin, myoglobin, and ANA
- Abnormal EMG (proximal muscle groups and extremities); abnormal skin biopsy with elevated creatinine phosphokinase (MM fraction)
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Hashimoto thyroiditis
- Autoimmune disease
- Females 10:1
- Initial presentation of hyperthyroidism with end stage hypothyroidism (similar to Graves disease)
- Most common cause of goiters
- Anti-thyroglobulin staining; also, thyroid is large and disfigured
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Pemphigus Vulgaris
- Autoimmune disease
- Large, easily ruptured bullae; most common on scalp and mucous membranes
- Progress; fatal if untreated as a result of infection of exposed skin
- Abs to epidermal surface Ag (desmoglein)
- skin biopsy with immunofluorscence is diagnostic
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MCTD
- Autoimmune disease
- Mixed connective tissue disease
- 80% females
- Overlapping clinical and lab features of different autoimmune disease
- High titers to RNP (ribonuleic acid protein)
- Treat with corticosteroids
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Septic shock
- Infection-related
- Systemic reaction to LPS on surface of gram (-) bacteria; recognized by TLRs and NLRs; inflammatory cytokines (TNFalpha and AA metabolies PG and leukotrienes) are increased
- Symptoms=fever, severe hypertension, coagulopathies (DIC), impaired organ perfusion, hypoxia; death if left untreated
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Toxic shock syndrome
- Infection-related
- SuperAg binds TCR and MHC outside of peptide-Ag binding site; polyclonal activation of T cells and cytokine storm
- Symptoms=fever, diarrhea, coagulopathies (DIC), hypotension, rash, exfoliation of skin; death if left untreated
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Crohn's Disease
- Infection-related
- (aka Inflammtory bowel disease; IBS)
- Abs against normal flora in GI tract; loss of epithelial function; Macrophages and Th1 cells produce excess IL-12, IFNgamma, TNFalpha
- Chronic inflammation due to sustained macrophage and neutrophil activation
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Rheumatic Fever
- Infection-related
- Abs against strep (M protein) cross-react with Ags on cardiac valves (myosin, keratin, and laminin)
- 2-4 weeks post-strep pharyngitis infection
- Patient must take full dose of Abs when diagnosed with S. pharyngitis (common) to prevent activation of B cells; don't want too many Abs because may begin cross-reacting
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Candidas
- Infection-related
- Opportunistic infections
- Thrush in infants
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Ctyomegalovirus pneumonia
- Infection related
- Member of the herpes family-latent but always present in T cells
- Virus infects cells and makes it bigger
- Life-threatening in immunocompromised
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Histoplasmosis
- Infection related
- Intracellular yeast; it's a mold in the environment, but a yeast in your body
- Common in Missouri river
- Histo, looks like gunk in cell
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PCP
- Infection related
- Pneumocystis jiroveci pneumonia
- Inside a cyst-can see with silver stainm
- Can be protozoa or fungi
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Toxoplasmosis
- Infection related
- Protozoan parasite; in cat feces
- When you do a CT of the brain, you can see ring enhancing lesions with edema surrounding
- Present with headaches and neurological problems
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Kaposi Sarcoma
- Infection related
- Tumor caused by virus (Herpes 8); tumor of the blood vessels
- Looked at mouth and arm tumors in class
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MAI
- Infection related
- Mycobacterium avium intracellulare
- Histologically, looks like cytoplasm contains webs
- Can infect normal people; required bird contact
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Hyperacute allograft rejection
- Transplantation related
- Occurs within minutes; Type II hypersensitivity; mediated by IgG, complement, neutrophils, and platelets
- Preformed ABO Abs react with MHC of nonself tissue
- Prevented by not allowing exposure to blood when transplanting organs (common in liver but not other organs now; NOT seen in kidney because donor's blood cells are washed out prior to transferring)
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Acute Rejection
- Transplantation-related
- Weeks to months; Type II (?); mediated by Th1, CTLs, NK cells, and macrophages that infiltrate the graft in response to all-MHC I and II, but enhanced by IgG Ab (ADCC)
- Watch for fever, mononuclear cell infiltrate, organ tenderness, and loss of organ function
- Treat with immunosuppressants
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Chronic rejection
- Transplantation-related
- Months to years
- Tendency to form fibrosis, infarction, and ischemic injury
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GVHD
- Transplantation-related
- Graft vs. Host Disease: up to 80% of allogeneic HSCT
- Donor T cells attack host MHC I and II; problem in hematopoietic stem cell transfers where recipient expresses MHC not seen in donor
- Symptoms=rash, blistering, loss of epithelium, mucosal problems, pain, diarrhea, vomiting, anorexia, hepatomegaly, elevated bilirubin, and jaundice
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Xenograft rejection
- Transplantation-related
- Hyperacute rejection; transplant of organ from another species; increased risk of zoonotic infection
- membrane complement regulatory proteins (DAF) of animal do not inhibit the human C3 convertase; uncontrolled complement-mediated damage (Type II hypersensitivity)
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Multiple Myelomaq
- Monoclonal disease
- Cancer of the plasma cells; causes bone lesions; suppressed hematopoiesis
- Pancytopenia and Bence-Jones proteins (L chain) in the urine; spike in the gamma region of SPE
- Treat with IVIG
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MGUS
- Monoclonal disease
- Monoclonal gammopathy of undetermined significance
- Benign monoclonal gammopathy; age-related; no bone lesions; no Bence-Jones proteins or other symptoms
- Lower plasma cell and IgG levels than multiple myeloma; spike in gamma region is less distinct
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Waldenstrom's Macroglobulinemia
- Monoclonal disease
- Malignant IgM monoclonal gammopathy
- Similar to Hodgkin's lymphoma
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XLA
- Immune deficiency
- X-linked Agammaglobulinemia
- Mutation in Btk results in no B cell development and no Ab production
- Onset at 6 months-1 year; cogenital; males only
- Recurrent extracellular, encapsulated bacterial infections
- Symptoms=otitis media, diarrhea, pneumonia, sinusitis
- Treat with Abs and IVIG
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Hyper IgM Syndrome
- Immune deficiency
- CD154 absent on T cells; poor signaling for class switching; elevated IgM levels with little to no IgA/G
- Recurrent bacterial infections (because normal levels of T cells, poor B cell activation)
- Treat with Abs, IVIG, and gene therapy
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Selective IgA deficiency
- Immune deficiency (most common 1/330)
- Either block in plasma cell differentiation to make IgA or a defect in IgA secretion
- 50% patients show no symptoms because IgM compensates
- Present with sinopulmonary infections and diarrhea; increased incidence of atopic allergies
- Treat with Abs; NOT IVIG (leads to serum sickness)
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IgH chain locus deletion
- Immune deficiency
- Normal number of B cells with no detectable IgG1, IgG2, IgG4, or IgA
- No increased risk of bacterial infections because one Ig class can compensate for absence of another
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Transient hypogammaglobulinemia
- NOT an immune disease
- Normal in 6-9 months olds; delayed IgM and IgG production and no more maternal IgG
- Increased sinopulmonary infections; not necessary to give IVIG; should have normal levels of Ig by 1 year old
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CVID
- Immune deficiency
- Common variable immune deficiency
- Defect in humoral and cell-mediated immunity; normal B and T cell levels; poor Ab production; decreased cellular immunity
- Increased risk of general bacterial infections
- Similar to XLA (but autosomal)
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Chediak-Higashi Syndrome
(drunken cell syndrome)
- Immune deficiency
- Mutation in lysosomal trafficking regulation; cells show poor chemotaxis and impaired NK cells function
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AIDS
- Immune deficiency (msot prevalent one in US)
- Acquired immunodeficiency syndrome
- Depleted CD4 (Th) cells
- Opportunistic infections; commonly seen with the following diseases; Kaposi sarcoma, cytomegalovirus, PCP, etc.; also, common cause of thrush in infants
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DiGeorge Syndrome
- Immune deficiency
- Mutation in third and fourth pharyngeal pouches results in loss of thymus; parathyroid deficiency and heart defects
- Lack of T cells causes early onset of fungal and viral infections; lymphopenia; mderate hypogammaglobulinemia; calcium imbalance; cardiac disease
- Treat with thymic transplant and anti-microbial agents
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SCID
- Immune deficiency
- Severe Combined Immunodeficiency
- Combination of B, T, NK cell deficiencies; includes gamma chain, ADA, RAG 1/2, and JAK3 deficiency
- Avoid live viral vaccines
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Gamma C deficiency
- Immune deficiency: subset of SCID
- X-linked recessive; most common cause of SCID
- Absence of gamma chain of receptors for IL-2, 4, 7, 9, and 15
- Phenotype: T-/B+/NK-
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ADA deficiency
- Immune deficiency: subset of SCID
- (Adenosine Deaminase deficiency)
- Excess adenosine due to inability to break it down causes absent T, B, and NK cells
- Phenotype: T-/B-/NK-
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RAG 1/2 Deficiency
- Immune deficiency: Subset of SCID
- Blocks B and T cell development by preventing rearragement of heavy and light chains
- Phenotype: T-/B-/NK+
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JAK3 deficiency
- Immune deficiency: Subset of SCID
- Lack of receptor signaling; T and NK cells are present but fail to respond to cytokines; same phenotype as gamma chain deficiency, but it's different
- Phenotype: T-/B+/NK-
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LAD
- Immune deficiency
- Leukocyte adhesion defect
- Poor leukocyte adhesion to endothelial lining of blood vessels; defective complement-mediated opsonophagocytosis
- Delayed wound healing and poor pus formation because neutrophils are unable to exit vessels
- Recurrent pyogenic bacterial infections with no pus formation
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BLS: Type I
- Immune deficiency
- Bare lymphocyte syndrome
- No MHC class I due to defect in TAP (transport associated with Ag processing)
- No production of CTLs; lymphopenia
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BLS: Type II
- Immune deficiency
- Bare lymphocyte syndrome
- No MHC class II due to defect in CIITA (required for class II expression)
- No production of Th cells; lymphopenia
- First rule out HIV as it is the most common reason for decreased Th cells
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CD3 deficiency
- Immune deficiency
- No T cells; normal B and NK cells
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ZAP-70 deficiency
- Immune deficiency
- (responsible for T cell signaling)
- No T cells; normal B and NK cells
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Lck Deficiency
- Immune deficiency
- No T cells; normal B and NK cells
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HAE
- Immune deficiency
- Herediatary Angioedema
- Autosomal dominant
- Defect in C1 inhibitor; constitutive activation of the classical complement pathway
- Symtpoms=Acute, non-painful, non-pruitic, non-erythematous swelling of skin and mucous
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Hereditary Hemochromatosis
- Immune deficiency
- Excessive iron accumulation; body absorbs and stores too much iron; toxic levels damage and destroy organs
- HLA-H regulates function of transferring (involved in iron absorbency)
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Wiscott-Aldrich syndrome
- Immune deficiency
- Thrombocytopenia; causes bloody diarrhea and bruising; small non-functional platelets
- Defect in CD43 and decreased overall Ab production; decreased IgM; increased IgA and IgE\
- Recurrent extracellular bacterial infections
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Neonatal neutropenia
- Immune deficiency
- Defect in receptor for G-CSF; not responsibve to G-CSF therapy because of this
- Abormal number of neutrophils in peripheral circulation when no infection; bands on CBC; WBC will typically be normal
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Chronic granulomatus disease
- Immune deficiency
- Defective respiratory burst oxidase (NADPH); Granulomas form in liver, spleen, and lung
- Recurrent bacterial and fungal infections
- Diagnose with negative result on nitroblue tetrazoliumyde reduction test; presence of Langhan's giant cells
- Treat with prophylactic Abs, recombinant IFNgamma, and granulocyte transfusions
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MPO deficiency
- Immune deficiency (myeloperoxidase)
- Block in production of hypothalous acid; impaired intracellular killing
- Similar presentation to CGD, but positive NBT dye test because cells have NADPH oxidase activity, just incapable of forming bleach
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IFNgamma deficiency
- Immune deficiency
- Recurrent viral and intracellular pathogens
- Same phenotype as IL-12, IL-12R deficiencies because these are important inducers of IFNgamma
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PNH
- Immune deficiency
- Paroxysmal Nocturnal Hemoglobinuria
- Failure to express CD59 and CD55 for DAF causes RBCs to lyse (MAC from complement)
- Bloody urine in the morning
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C2 deficiency
- Immune deficiency
- Autosomal recessive
- Increased risk of bacterial infections due to defective complement cascade
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Factor B deficiency
- Immune deficiency
- Increased risk of bacterial infections due to defect in complement cascade
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MBP (MBL) deficiency
- Immune deficiency
- Increased risk of bacterial infections due to defect in complement cascade
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Cyclic Neutropenia
- Immune deficiency
- Neutrophil elastase deficiency; occurs periodically
- Gingivitis, periodontal disease, cuaneous infections, abscesses, pneumonias, and granulomas
- Treat with recombinant G-CSF therapy
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