Second half diseases Flashcards
Graft Versus Host Disease
T-cells from the donor bone marrow migrate to secondary lymphoid tissues, bind host dendritic cells, proliferate and then re-enter inflamed tissue
Four grades
Skin - redenning, exfoliation
Intestines - diarrhea
Liver - increased levels of bilirubin
Treatment cyclosporin A/methotrexate to inhibit T cells
Ankylosing Spondylitis
HLA-B27 polymorphism
Relative risk 87.4, more prevalent in men
Chronic inflammatory arthiritis of axial skeleton
Fusion of spinal vertebrae
Type I Diabetes
Autoimmune destruction of beta cells in islets of langerhans Increased risk HLA-DQ8 (14) Further increased by HLA-DQ6 (20) DQ2 is protective (0.2) Asp57 is protective Val/Ser/Ala57 is associated with disease
Bronchial Asthma
Type I hypersensitivity
Allergens: dust mites, dander, German cockroach, fungus Alternania
Production/binding of IgE to allergen causes immune response due to mediator release – histamine, leukotrienes and prostaglandins
Bronchoconstriction, cell infiltration, increased mucus
Corticosteroids and immunotherapy
Haemolytic disease of the newborn
Type II hypersensitivity
ABO incompatibility
RhD (Rhesus) incompatibility
Red cells from the RhD+ fetus leak into maternal circulation, sensitizing T-cells to produce anti-RhD B-cells resulting in class-switching to IgG
In subsequent pregnancies the IgG cross the placenta causing erythrocyte destruction
Mild anaemia with transient jaundice (ABO)
Can be severe – neonatal jaundice, enlargement of the liver and spleen (RhD)
Hydrops fetalis and still birth
Treatment: Rhesus prophylaxis (anti-Rhd antibodies)
Autoimmune haemolytic anaemia
Warm-reactive antibodies: bind RBC at 37oC or above, mainly RhD specific
Cold-reactive antibodies: bind RBC in peripheral circulation at lower temperatures (winter), mainly IgM or Ii blood group specific
Reaction to drugs: either the drug binds the blood cells and generates antibodies, or the drug binds the antibodies and this complex binds blood cells
Phagocytosis and lysis of cells causes inflammation
Systemic lupus erythematosus
Type III hypersensitivity
Deposition of antigen-antibody complexes
Increased levels of immune complexes in blood leads to deposition in tissues
Increased vascular permeability due to production of vasoactive amines by platelets and basophils
Neutrophils are frustrated and cause tissue damage
Characterised by anti-dsDNA, histones, RBC, platelets, leukocytes and clotting factor antibodies (systemic autoimmune disease)
Associated with C1q, C4 and C2 complement deficiencies
Inflammation, necrotizing vasculitis or nephritis
Immune complexes form ‘lumpy’ deposits in blood
Fever, weakness, arthiritis, skin rashes, pleurisy and kidney dysfunction
10:1 in female:male
More common in African Americans and Hispanics
Leprosy
Type IV hypersensitivity
Infection of M.Leprae
Leprosy stimulates Th1 continuously causing them to secrete IL-10
Inactivates Th1 decreasing cell-mediated immunity
Stimulates IgG4 increasing antibody response
Chronic granulomatous disease of the skin and nerves
Tuberculoid – hypopigmented patches, intense lymphocytic and epitheloid cell infiltrate
Boderline – features of both
Lepromatous – confluent skin lesions, numerous bacilli, ‘foamy’ macrophages and lack of lymphocytes
Skin thickens, hair loss, nose collapses, blindness, ulcers, sterility, enlarged liver and lymph nodes, sensory loss, deformed fingers and toes
Agammaglobulinemia
Immunodeficiency
Defects in pre-B cell receptor signalling
Congenital: mutations in adaptor protein BLNK
X-linked: mutation in Burton’s tyrosine kinase blocking pre-B cell to immature B cell development
Lack of IgA, M, D and E, low IgG, no circulating B cells
No tonsils and tiny lymph nodes
Enteroviral infection causes encephalitis
Polio vaccine causes paralytic poliomyelitis
Treatment: regular IgG injections
Common Variable Immune Deficiency
Affected genes encoding ICOS, CD19 and CD20 components of the B-cell receptor
Permit infections of the respiratory tract
Lack of IgA
Autoimmune complications, granulomatous lesions, lymphoid hyperplasia and lymphomas risk
Most common immune deficiency
1 in 10,000
Hyper IgM Syndrome
Immunodeficiency
CD40L deficiencies cause lack of B-cell activation and so lack of germinal centre formation (where B-cell proliferation occurs)
Severe combined immunodeficiency
Affect numerous immune pathways Thymocyte survival – adenosine deaminase, purine nucleoside, phosphorylase Lymphoid progenitors – JAK-3, IL-7R Pre-T cell receptor – RAG1/RAG2 Pre-TCR signalling – CD3, CD45 Positive selection – HLA class II, ZAP-70 Calcium signalling – Stim1, Orai1 1 in 50,000 births
DiGeorge anomaly
Immunodeficiency
Congenital defect of organs derived from the 3rd and 4th pharyngeal pouches
Thymic problems – variable
Treatment: thymic transplant into muscle
Chronic Granulomatous Disease
Immunodeficiency Defective NADPH oxidase so cannot make superoxide anions and H2O2 following ingestion for antibacterial function of phagocytes Granuloma formation Pneumonia Infections in lymph nodes Abscesses in skin, liver etc
Leukocyte adhesion deficiency
Immunodeficiency
Type I – defective CR3 on phagocytes, which binds CR3bi on antibody bound bacteria (opsonized)
Type II – Sialyl Lewisx dysfunctional due to defect in fucose transporter – required for phagocyte adhesion
