Diseases to Remember Flashcards
Leprosy
Clinical Features: Cutaneous lesions, neuropathic changes and deformities
M. Leprae colonizes macrophages and other host cells and multiplies within
Macrophages need to be activated in order to kill it
Grows best at 86 degrees, so likes to hang out at joints
IFN-y can help
Mycobacteria
Evades the immune system by preventing the fusion go phagosome to lysosome, prevents degradation
Herpes Simplex Virus (HSV)
Evades immune system by reducing the function of TAP
Cytomegalovirus (CMV)
Evades immune system by preventing proteasomal activity and preventing Class 1 MHC from pinching off ER
Epstein Barr Virus (EBV)
Evades immune system by prevent proteasomal activity and inhibiting macrophage activity by releasing IL-10
Pox virus
Evades immune system by releasing soluble CXCRs
Toxic Shock Syndrome
Associated with localized S. aureus (gram +) infection, food poisoning, local colonization
Tampons provide a good food source
Toxic Shock Protein = super antigen that binds to B chain of TCR and does not require antigen or co-stimulatory receptors to process response
What are the consequences of super antigen?
Fever, rash, edema, hypotension, shock
TNF-a and IL-1 contribute to increase in vascular permeability that lead to leakage of fluid
Hyper IgM Syndrome
5 types --> inability to class switch X-linked = defect in CD40L, autosomal = defect in CD40 X-linked --> probs with T-cell activation, suffers from opportunistic infections Syndrome with defect in AID --> probs with B-cells
C3 Deficiencies (Alternative pathway)
Life threatening, severe, recurrent infections
Deficiencies in Factor H and I mimic C3 deficiencies, because exhausts C3 from system
Pyogenic infections, SLE
Alternative pathway - Factor D, Properdin Def = Nisserial
MAC deficiencies
Generally healthy
Increase in infection by Nisseria gonorrhea and N. meningitis
Deficiencies in early complement activation (Classical)
C1, C2, C4 –> C2 most common
With C2 def. pts have high degrees of SLE
May arise from failure to clean immune complexes which deposit on blood vessel walls and tissues
Produces local inflammation –> may lead to breakdown of tolerance to self –> autoimmunity
C1inh Deficiency and Hereditary Angioneurotic Edema (HAE)
C1 not regulated properly –> C4/2 chronically low
Hereditary Angioneurotic Edema (HAE)
Pt have attacks with swelling involving extremities, GI tract, and Face
may affect upper respiratory tract leading to suffocation
Tx: Berinet, purifies human C1inh
Paroxysomal Nocturnal Hemoglobinuria (PHN)
Hemolytic disorder with spontaneous episodes of complement-mediated RBC lysis (also leks and platelets)
Tx: erythropoietin, corticosteroids, eculizumab
Defect in phosphatidylinositol glycan class A gene (PIG-A)
It is required for synthesis of glycosyl phosphatidylinositol (GPI) anchor
Lack of CD59 and CD55 complement reg proteins
Leads to complement mediated intravascular hemolysis
Class 1 HLA gene (HLA-B27) increases risk of…
Ankylosing Spondylitis (by 90)
Class 2 HLA genes (HLA-DR4) increase risk of…
Type 1 DM (25), Pemphigus vulgaris (14), RA (4)
Describe PTPN22 role in autoimmunity.
Abnormal TYROSINE PHOSPHATASE reg of T-cell selection and activation
Disease association: RA, T1D, autoimmune thyroid diseas
Describe CTLA4 role in autoimmunity.
Impaired inhibitory checkpoint and Treg function - loss of B-cell, T-cell function
Diseases: T1D, RA, many autoimmune diseases
Describe AIRE role in autoimmunity.
Reduced expression of peripheral tissue antigens in thymus, leading to defective elimination of self-reactive T - necessary for thymic expression of self-proteins
Diseases: Autoimmune Polyendocrine syndrome (APS-1), DM, adrenal, parathyroid
Describe FAS role in autoimmunity.
Defective apoptosis of self-reactive T and B cells in periphery - splenomegaly, lymphadenopathy
Disease: Autoimmune lymphoproliferative syndrome (ALPS), adrenals
Describe FOXP3 role in autoimmunity.
Deficiency of T-regs
Disease: Immune dysregulation X-linked polyendocrinopathy and enteropathy - IPEX - widespread autoimmunity
Infection - Disease association to remember
Streptococcus - Rheumatic Fever
Chlamydia - Reiter’s Syndrome (HLA-B27)
Shigella, Salmonella - Reactive Arthritis (HLA-B27)
Coxsackie, echovirus, rubella - IDDM (HLA-DQ..)
SLE
Polytrophic Immune Complex Disease
Defective apoptotic process leading to increased nucleic acid Ags available to stimulate immune response
Susceptible gene + UV radiation
RA
Inflammation in synovium
Th1/17 cytokine release sustains inflammation
Ab production against rheumatoid factor (Fc portion of Ig)
Defective clearance of immune complexes; failure of B cell tolerance
Immunodeficiencies associated with lymphocyte MATURATION of BOTH Ts and Bs
X-linked SCID
ADA and PNP Def
JAK3 Def
RAG1/2 Def
Immunodeficiencies associated with lymphocyte MATURATION of B-CELLS
X-linked Agammaglobulemia
Ig Heavy chain def
Immunodeficiencies associated with lymphocyte MATURATION of T-CELLS
Di-George Syndrome
Immunodeficiencies associated with lymphocyte ACTIVATION and FUNCTION of BOTH Ts and Bs
X-linked lymphoproliferative syndrome
Immunodeficiencies associated with lymphocyte ACTIVATION and FUNCTION of B-CELLS
X-linked Hyper IgM syndrome
Common Variable Immunodeficiency
IgA Def
Isolated IgG subclass def
Immunodeficiencies associated with lymphocyte ACTIVATION and FUNCTION of T-CELLS
Bare Lymphocyte Syndrome
MHC Class 1 Def
Wiskott-Aldrich syndrome
IPEX
Immunodeficiencies in Innate Immunity
Chediak-Higashi disease Leukocyte Adhesion disease Chronic Granulomatous disease G6PD Def Myeloperoxidase def Severe Chronic Neutropenia
Characteristics of Complement Deficiencies
Defects in Classical more common - Pt have high number of autoimmune disorder, including LUPUS-like syndrome
Defects in Alternative - present with Nisserial infections
Type 1 Hypersensitivity Diseases
Anaphylaxis - Tx with Epi
Bronchial Asthma - Tx with corticosteroids, leukotriene antagonists, phosphodiesterase inhibitors
Allergies - Tx with desensitization, Anti-IgE, Antihistamine
Type 2 Hypersensitivity Diseases
Autoimmune Hemolytic anemia Autoimmune thrombocytopenia purpura Good pasture syndrome - C'/Fc receptor-mediated inflam Graves disease Myasthenia graves Pemphigus Vulgaris Pernicious anemia Rheumatic Fever
Type 3 Hypersensitivity Diseases
SLE Polyartertitis nodosa Poststreptococcal glomerulonephritis Serum sickness Arthus reaction
Type 4 Hypersensitivity Diseases
RA Multiple Sclerosis Type 1 DM Crohn's Contact sensitivity Chronic infection Viral Hepatitis Superag mediated diseases
