7. The main features of antibody deficiency Defective antibody production becomes critical 4-6 months after a full-term delivery when the maternally-derived IgG waned. The main manifestations are recurrent respiratory tract infections Defective CD40 ligand expression by T cells: no class-switching from IgM and no germinal centers. BtK deficiency: X-linked agammaglobulinaemia due to failure of B cell lymphopoiesis. Clinically antibody deficiency is secondary to lymphoid malignancies: myeloma and chronic lymphocytic leukaemia. The main features of T cell deficiency Defective T cell deficiency Increase in opportunistic infections: Pneumocystis carinii and Cryptosporidium . Mucosal yeast infection Defects in T-dependent antibody responses Di George syndrome HIV infection Defects in RAG genes, IL-2 receptors, and expression of MHC antigens. The main features of defects in neutrophils Severe invasive bacterial (mostly gram negative) infections that respond poorly to antibiotics and are often lethal and invasive fungal infection. Impairment of haemopoiesis Acute myeloblastic leukaemia: there is no stroma for neutrophil generation Cytotoxic drugs in cancer therapy -2 integrin deficiency: inability of neutrophils to migrate. The main features of defects in complement Deficiency of C3: recurrent bacterial infections and infants are usually lethal. Deficiency of C5-9: normal health. Only increased risk of infection by particular bacteria
23. Redness ( ruber ): Dilation of capillaries Swelling ( tumor ): fluid containing plasma proteins and blood cells Heat ( calor ): increase in blood flow Pain ( dolor ): pressure on nerve; chemical mediators (e.g., bradykinin) Loss of function ( functio laesa ): the fifth cardinal sign was, supposedly, added by German pathologist Rudolf Virchow (1821-1902). Cardinal Signs of Inflammation First described by Celsus (not Celsius ) (10 BC-?)
24. Heat Redness Swelling Pain Loss of Function Nature Reviews/Immunology
25.
26.
27.
28.
29.
30.
31.
32. Toll-like Receptors and Ligands Imidazoquinoline TLR7 dsRNA TLR3 Heterodimerizes with TLR2 TLR1 Bacterial DNA (CpG) TLR9 Agonist(s) (Pathogen-Associated Molecular Patterns) Receptor (Pattern Recognition Receptors) Unknown TLR 8,10 Heterodimerizes with TLR2 TLR6 Flagellin TLR5 Gram(-) LPS, Taxol, some LTA, HSP60 TLR4 PGN, some LPS, some LTA, lipoproteins, AraLAM TLR2
36. Hypersensitivities Immune responses which are damaging rather than helpful to the host (In most cases). Trends Immunol. 2003 Jul;24(7):376-9. Gell and Coombs proposed a classification scheme which defined 4 types of hypersensitivity reactions : (P.G.H. Gell and R.R.A. Coombs, The classification of allergic reactions underlying disease. In: R.R.A. Coombs and P.G.H. Gell, Editors, Clinical Aspects of Immunology , Blackwell Science (1963)) The first 3 are mediated by antibody (Th2), the fourth by T cells (Th1). I IgE-mediated hypersensitivity (Anaphylactic) II Antibody-mediated cytotoxic hypersensitivity (Cytotoxic) III Immune-complex mediated hypersensitivity (Immune Complex) IV Delayed-type hypersensitivity ( DTH ) V(?) Granuloma (?)
37. Type I Hypersensitivity -Rapid ('Immediate or anaphylactic') allergic reaction. -Prior exposure to an antigen sensitizes a person to produce IgE. Re-exposure causes rapid degranulation of mast cells. The granule mediators causes acute inflammation: increase granulocytes, chemotaxis, and extravasation -Primary mediators (stored): Histamine and serotonin: vascular permeability, smooth muscle contraction ECF-A-Eosinophil Chemotactic Factor of Anaphylaxis NCF-A-neutrophil Chemotactic Factor of Anaphylaxis Protease: Mucus secretion, connective tissue degradation -Secondary Mediator (to be synthesized): Leukotrienes: vascular permeability, sm contraction Prostaglandins: vasodilation, sm contraction, platelet activation Bradykinin: vascular permeability, sm contraction, Pain Cytokines: numerous effects e.g.: Hayfever, asthma and allergic reaction to penicillin ( phenoxymethylpenicillin and benzylpenicillin). Expulsion of worms and insect infections. Tests: wheal-and-flare reaction (skin prick test for IgE) and RAST (radioallergosorbent test, blood allergen)
38. Type II Hypersensitivity -By specific antibody (IgM or IgG) binding to cells or tissue antigens. FcR causes ADCC Ab-dependent cellular immunity to bacteria and parasites Autoimmunity -By activating the classical complement pathway. Blood transfusion (ABO incompatibility reaction) IgM Rhesus disease (haemolytic disease of the newborn) IgG
39. Type III Hypersensitivity Immune complexes: IgG with soluble antigens. Similar to type I except that IgG is involved. Preformed immune complexes bind to the low affinity Fc RIII. Pulmonary reactions to inhaled antigens: Occupational related diseases: Farmer’s lung. The Arthus reaction A local type III hypersensitivity reaction in experimental models. Because the threshold for activation via Fc RIII is higher than for Fc RI, the reaction is slow (maximal at 4-8hrs) and more diffuse. Generalized or systemic reactions Large amount of soluble Ag-Ab complexes in circulation and deposition in various organs such as skin joints, kidneys and blood vessels. The deposition causes inflammation, lesions and infection. Rheumatoid Arthritis, Systemic lupus erythematosis, and serum sickness.
40. Type IV Hypersensitivity -Delayed type hypersensitivity (DTH) -Mediated by antigen-specific type I helper T cells, not Ab. APC (dendritic cells, or DC) present Ag in class II MHC groove, recognized by an antigen-specific T H 1 cell. Cytokines (IFN, TNF) and chemokines are produced. Macrophages, other T cells and, neutrophils accumulate to form granuloma. It is usually maximal at 48-72 hours. The classical example is in tuberculosis: tuberculin test ( Discovered by Robert Kock, 1905 Nobel Prize). Allergy to metal salts and small reactive chemicals coupled to hapten. Rejection of transplanted organs Skin contact reaction to poison ivy. http://www.info.gov.hk/dh/diseases/CD/photoweb
41.
42. Summary of Hypersensitivity Reaction TYPE NAME INITIATION MECHANISM EXAMPLES I IgE-mediated hypersensitivity (Anaphylactic) 2-30 mins Ag cross-linking of IgE bound to mast cells; release of vasoactive mediators Systemic anaphylaxis, Local anaphylaxis, Hay fever, Asthma, Eczema II Antibody-mediated cytotoxic hypersensitivity (Cytotoxic) 5-8hrs IgG to cell-surface antigens; cell destruction via ADCC or complement ABO reactions; Rh in newborn; Autoimmune Haemolytic anemia III Immune-complex mediated hypersensitivity (Immune Complex) 2-8hrs Ag-Ab complex formed in serum and deposited in tissues; mast cell degranulation via Fc RIII; chronic inflam. Arthus reaction (Localized); autoimmune diseases IV Delayed-type hypersensitivity ( DTH ) 24-72hrs T H 1 cells release cytokines that recruit and activate macrophages Contact dermatitis, Tubercular lesions V Granuloma (?) Months to Years Formation of granuloma to encapsulate or isolate pathogens. Mediated by innate immunity or type 1 or type II cytokines TB, Schistosomiasis
![[object Object],[object Object]](data:image/gif;base64,R0lGODlhAQABAIAAAAAAAP///yH5BAEAAAAALAAAAAABAAEAAAIBRAA7)