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Transcript
CH 19 - DISORDERS IN IMMUNITY 1 Stephanie Lanoue HYPERSENSITIVITY Learning Objectives 19-1 Define hypersensitivity. 19-2 Describe the mechanism of anaphylaxis. 19-3 Compare and contrast systemic and localized anaphylaxis. 19-6 19-7 19-8 Describe the mechanism of cytotoxic reactions and how drugs can induce them. Describe the basis of the ABO and Rh blood group systems. Explain the relationships among blood groups. 2 BIG PICTURE: HUMAN MICROBIOME AND INTESTINAL DISEASE 3 IMMUNITY RESPONSE Immunity process is a powerful system of _______ Seek out, recognize, and ______ foreign materials to prevent disease BUT, On the other side, overreactivity or underreactivity of immune system can be challenging 1. 2. 3. Overreactivity, hypersensitivity Immunodeficiency, hyposensitivity Autoimmune 4 HYPERSENSITIVITY Antigenic response beyond ________ Occurs when sensitized by _______ exposure to an antigen (allergen) Question – Are you hypersensitive to anything? 5 TABLE 19.1 TYPES OF HYPERSENSITIVITY 6 HYPERSENSITIVITY, TYPE I Occurs -____________ after a person sensitized to an antigen is reexposed to that antigen Histamine: increases the permeability of blood capillaries Resulting in 1. Edema, ____________ 2. Erythema, redness 3. Increased mucous secretion, running nose 4. Smooth muscle cells contraction, breathing difficulty 7 HYPERSENSITIVITY, TYPE I, CONT. Systemic anaphylaxis (anaphylactic shock) Results when an individual sensitized to an antigen is exposed to it _________ May result in circulatory collapse and _______ Treated with epinephrine Localized anaphylaxis Usually associated with ingested or inhaled antigens Symptoms depend on the route of entry Hives, hay fever, and asthma 8 HYPERSENSITIVITY, TYPE II Activation of complement by the combination of ____________ with an antigenic cell Causes cell lysis or _________ by macrophages Antigen located on cell or tissue Cellular damage ABO blood group system Antibodies form against certain carbohydrate antigens on RBCs A antigens, B antigens, or both Type O RBCs have no antigens 9 HYPERSENSITIVITY, TYPE II, CONT. Rh blood group system Rh factor antigen (Rh+) found on RBCs of ___% of the population Rh+ blood given to an Rh– recipient will __________ anti-Rh antibodies in the recipient Hemolytic disease of the ________ (HDNB) Rh– mother with an Rh+ fetus causes the mother to produce anti-Rh antibodies Second Rh+ fetus will receive anti-Rh antibodies, damaging fetal RBCs 10 Figure 19.4 Hemolytic disease of the newborn. Placenta Rh+ father. Rh– mother carrying her first Rh+ fetus. Rh antigens from the developing fetus can enter the mother's blood during delivery. In response to the fetal Rh antigens, the mother will produce anti-Rh antibodies. If the woman becomes pregnant with another Rh+ fetus, her anti-Rh antibodies will cross the placenta and damage fetal red blood cells. 11 HYPERSENSITIVITY, TYPE III Type III, Immune complex reaction Antibodies form against soluble antigens in the __________ Form immune complexes that lodge in the basement membranes beneath the cells Activate complement, causing inflammation 12 Figure 19.6 Immune complex-mediated hypersensitivity. Immune complexes Immune complexes are deposited in wall of blood vessel. Ag Presence of immune complexes activates complement and attracts inflammatory cells such as neutrophils. Endothelial cell Basement membrane of blood vessel Neutrophils Enzyme Enzymes released from neutrophils cause damage to endothelial cells of basement membrane. 13 HYPERSENSITIVITY, TYPE IV Type IV, __________ hypersensitivity Mediated by __ cells (not antibody, hormonal immune response) Appears after a ______ or more Time required for participating T cells and macrophage to immigrate and accumulate near the antigen Ex. Transparent rejection, allergic contact dermatitis 14 HYPERSENSITIVITY, TYPE IV Allergic contact dermatitis _________ combine with proteins in the skin, producing an immune response Allergic response to _______ _____, cosmetics, metals, and latex Google now! What is a Hapten? 15 AUTOIMMUNE DISEASES Immune system responds to _____ antigens, causing damage to the organs Autoimmunity is ______ of self-tolerance Ability to discriminate self from nonself Cytotoxic, immune complex, or cell-mediated 16 AUTOIMMUNE DISEASE Response to self antigens and cause damage to one’s own _________ __% of population __% in women ??? Antibody producing B cells are more abundant in female mice Activate via Toll like receptor , on X chromosome When there is a loss of self tolerance, can not distinguish themselves 1. T cells target host cells 2. Production of antibody 17 CYTOTOXIC AUTOIMMUNE REACTIONS Antibodies react with _____-surface antigens _________ disease Abnormal antibodies in the thyroid produce excessive amounts of hormones Myasthenia gravis Antibodies coat acetylcholine receptors; muscles fail to receive nerve signals 18 IMMUNE COMPLEX AUTOIMMUNE REACTIONS Immune complexes of antibodies and complement deposit in tissues Systemic _______ erythematosus Immune complexes form in the kidney glomeruli Rheumatoid __________ Immune complexes form in the joints 19 CELL-MEDIATED AUTOIMMUNE REACTIONS Mediated by __ cells that attack tissues Insulin-dependent _________ mellitus T cell destruction of insulin-secreting cells Psoriasis and psoriatic arthritis Autoimmune disorders of the skin 20 HYPOSENSITIVITY Immunodeficiencies __________ of a sufficient immune response Two categories: ___________ disease _________ at birth, genetic disorder B cell development and expression T cell development and expression Abnormal development of thymus Secondary disease After birth, cause by natural and artificial agents and develop during an individual's life Infections Radiation Chemotherapy Ex. AIDS 21 ACQUIRED IMMUNODEFICIENCY SYNDROME (AIDS) 19___: the discovery of a virus causing the loss of immune function (HIV) Selectively infects T helper cells 22 AIDS Arisen by the mutation of virus from some area of ________ HIV virus, Genus Lentivirus, Retrovirus two identical strands of RNA reverse transcription an envelope of phospholipid Glycoprotein spikes (gp120) 23 Figure 19.13 HIV structure and attachment to receptors on target T cell (2 of 3). Glycoprotein spike: gp120 gp41 transmembrane glycoprotein Envelope Reverse transcriptase enzyme Envelope RNA Core with protein coat Capsid Structure of HIV and infection of a CD4+ T cell. The gp120 glycoprotein spike on the membrane attaches to a receptor on the CD4+ cell. The gp41 transmembrane glycoprotein probably facilitates fusion by attaching to a fusion receptor on the CD4+ cell. 24 THE INFECTIVENESS AND PATHOGENICITY OF HIV Inside the cell, viral _____ is transcribed into DNA using reverse transcriptase DNA is ________ into the host's chromosomal DNA Active infection: new viruses bud from the host cell Latent infection: DNA is hidden in the chromosome as a provirus Some become memory T cells that serve as the reservoir for HIV Virus undergoes rapid antigenic changes and a high rate of mutation 25 Figure 19.14 Latent and active HIV infection in CD4+ T cells. Chromosomal DNA HIV CD4 receptor Provirus CCR5 or CXCR4 receptor Provirus Viral proteins gp120 CD4+ T cell gp41 Latent infection. Viral DNA is integrated into cellular DNA as a provirus that can later be activated to produce infective viruses. Virus beginning to bud from T cell mRNA Viral envelope proteins Viral RNA gp120 gp41 Active infection. The provirus is activated, allowing it to control the synthesis of new viruses. Final assembly takes place at the cell membrane, taking up the viral envelope proteins as the virus buds from the cell. Progeny HIV 26 Figure 19.15 Latent and active HIV infection in macrophages and dendritic cells. Chromosomal DNA Provirus HIV Vacuole HIV Provirus Macrophage Latently infected macrophage. HIV can persist either as a provirus or as a complete virion in vacuoles. mRNA Viral RNA Vacuole fuses with plasma membrane and releases virus. Activated macrophage. New viruses are produced from provirus. Completed virions are either released or persist in the macrophage within vacuoles. HIV being released 27 THE STAGES OF HIV INFECTION Phase 1: ____________ or lymphadenopathy Phase 2: T cells ________ steadily; only a few infected cells release the virus; few serious disease symptoms (persistent infections, fever, and oral leukoplakia) Phase 3: AIDS develops; the T cell count is below norm of 200 cells/μl 28 HIV TRANSMISSION Direct contact with infected body _______ HIV survives (____ days) in the cells within fluids or (__ hrs) outside of cells Blood 1000 to 100,000 viruses per mm Semen 10 to 50 viruses per mm Saliva 1 viruses per mm ? Kissing ? Routes of transmission: __________ transmitted infections (men to women ) Breast milk Organ transplants 29 DISTRIBUTION OF HIV 30 PREVENTING AND TREATING AIDS Use of condoms and discouraging ______ promiscuity Use of ________ needles Availability of medications 31 CHALLENGES OF DEVELOPING HIV VACCINES No model of natural immunity to _________ Lack of inexpensive research ________ Basic mechanisms of recognizing retrovirus by body is __________ Quickly integrate into the DNA of host cell and become _____________ to the immune system High mutation rates, required _________ vaccine _____________ strains An ideal vaccine would : Induce immunity before reservoirs of latent virus are established Antibodies T cells Be affordable 32