Disorders Associated with the Immune System

Transcription

1 PowerPoint Lecture Presentations prepared by Bradley W. Christian, McLennan Community College C H A P T E R 19 Disorders Associated with the Immune System

2

3 Disorders of the Immune System

4 Disorders of the Immune System Not necessarily infectious diseases Compromises response to infectious disease

5 Disorders of the Immune System 3 major groups of disorders 1 Hypersensitivity antigenic responses ie. Anaphylatic rxns., cytotoxic rxns. etc 2 Autoimmunity loss of self-tolerance. Ex. Lupus, rheumatoid arthritis, transplant rejection. 3 Immune deficiency congenital or acquired. Ex. HIV, DiGeorge syndrome

6 Hypersenitivity An inappropriate or out of control immune response Over reaction of the immune system causes tissue damage 4 types of hypersensitivity reactions Type I Anaphylatic, Type II cytotoxic, Type III immune complex, Type IV delayed cell mediated.

7 Type I Anaphylatic Anaphylaxis (against protection) Mechanistically, it is an immune response IgE mediated response to allergens

8 Type I Anaphylatic IgE binds to basophils and mast cells Ag binding stimulates degranulation Released vasoactive amines cause anaphylaxis Histamines, leukotrines (cause contractions of smooth muscle), and prostaglandins (increase mucus secretions)

9

10

11 Localized Anaphylaxis Cutaneous mast cells release histamine to local tissues Allergic rhinitis (hayfever) or asthma-like complex Food allergies

12 Systemic Anaphylaxis Usually injected antigen/allergen Subcutaneous mast cells release histamine directly to circulation Anaphylactic shock

13 Type II Cytotoxic Cytotoxic reactions Abs bind to cells and activate Complement or cytotoxic cells

14 Type II Cytotoxic Transfusion reactions Hemolytic disease of the newborn

15 Type II (Cytotoxic) Reactions Activation of complement by the combination of IgG or IgM antibodies with an antigenic cell Causes cell lysis or damage by macrophages ABO blood group system Antibodies form against certain carbohydrate antigens on RBCs A antigens, B antigens, or both Type O RBCs have no antigens

16 Table 19.2 The ABO Blood Group System

17 Type II (Cytotoxic) Reactions Rh blood group system Rh factor antigen (Rh + ) found on RBCs of 85% of the population Rh + blood given to an Rh recipient will stimulate anti- Rh antibodies in the recipient Hemolytic disease of the newborn (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

18

19 Type II Cytotoxic Drug induced cytotoxic reactions Thrombocytopenia purpura platelets coated with quinine. Agranulocytosis WBCs destroyed Hemolytic anemia penicillin induced, binds to RBC. Antibodies begin complement.

20

21 Type III Immune Complex Mediated by immune complexes Soluble Ag-Ab complexes Relative concentrations of Ag and Ab determine fate of complex Ag and Abs in equal amounts with slight excess of Ag leads to complex becoming trapped in the basement layer beneath endothelial cells.

22

23 Type III Hypersensitivity Ag excess Smaller complexes stay soluble longer Filtered at kidney Complex activates C at site Glomerulonephritis inflammatory damage to kidney glomeruli.

24 Type IV Delayed type hypersensitivity (DTH) Delayed type hypersensitivity (DTH) Mediated by activated TH1 cells Released lymphokines attract and activate macrophages which cause tissue damage Delayed because mediated by T-helper cells which then become T-memory cells. Ex. TB test. T-memory cells will proliferate.

25 Allergic contact dermatitis

26 Autoimmune Diseases Self-reactivity due to a loss of immunological tolerance Mechanisms somewhat parallel to hypersensitivity

27 Cytotoxic Autoimmune Reactions Ab binds cells, but may not result in lysis Graves disease Ab mimics TSH. Thyroid produces excess hormones. Myasthenia gravis Abs coat acetylcholine receptors (where nerve impulses reach muscles).

28 Immune Complex Mediated Autoimmune Reactions Soluble immune complexes mediate tissue damage Systemic lupus erythematosus (SLE)- many unusual Abs Rheumatoid arthritis- IgM, IgG, and complement accumulates in joints

29 Cell Mediated Autoimmune Reactions Cytotoxic T cells (T c ) attack self cells Multiple sclerosis attack myelin sheath by T c and macrophages. Insulin-dependent diabetes mellitus insulin secreting cells in the pancreas are destroyed by T c cells

30 Transplantation Reactions Major histocompatibility complex also called human leukocyte antigen (HLA) A gene complex that codes for tissue specific antigens. There are four types. MHC Ag s are recognized by T cells in transplantation reactions Probably resemble altered self immune systems thinks foreign tissue is actually damanged tissue.

31 HLA Testing

32 Immune Deficiency Impaired ability or inability to make immune responses Congenital (primary)- genetic based Acquired (secondary)- many specific and non-specific causes

33 Congenital Immune Deficiency Deficiencies affecting T cells result in a marked increase in viral and parasitic infections, and cancer

34 T Cell Deficiencies DiGeorge Syndrome no thymus gland therefore no cell-mediated immunity.

35 Acquired Immune Deficiency May be non-specific- Radiation or chemotherapy, nutritional, etc. May be infectious- Epstein-Barr Virus, cytomegalovirus (CMV), HIV, and others

36 Acquired Immunodeficiency Syndrome (AIDS) 1981: in the United States, a cluster of cases of Pneumocystis pneumonia, Kaposi's sarcoma, and loss of immune function are discovered in young homosexual men 1983: the discovery of a virus causing the loss of immune function (HIV) Selectively infects T helper cells (CD4+)

37 The Origin of AIDS SIV crossed over into the human population in west and central Africa from chimpanzees (around 1908, from bushmeat) Spread throughout Africa as a result of urbanization and increased sexual promiscuity Patient who died in 1959 in the Congo is the oldest known case Norwegian sailor who died in 1976 is the first known case in Western world

38 The Structure of HIV Genus Lentivirus Retrovirus Two identical strands of RNA, reverse transcriptase enzyme, phospholipid envelope gp120 glycoprotein spikes Death of CD4 cells results in loss of regulation of the immune system

39 Figure HIV structure and attachment to receptors on target T cell (2 of 3). Glycoprotein spike: gp120 gp41 transmembrane glycoprotein Envelope RNA Capsid Reverse transcriptase enzyme Envelope Core with protein coat 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.

40 The Infectiveness and Pathogenicity of HIV Spread by dendritic cells and carried to the lymphoid organs; contacts activated T cells gp120 combines with CD4 + receptor and CCR5 or CXCR4 coreceptors CD4 molecules are carried on T helper cells, macrophages, and dendritic cells Virus fuses and enters into the cell

41

42

43

44 AIDS Terminal stage of HIV infection Incubation time ~10 years

45 Diagnostic Methods Seroconversion is the period of time between infection and the appearance of antibodies Takes up to 3 months HIV antibodies detected by ELISA Viruses detected by Western blotting or APTIMA (RNA testing) Plasma viral load (PVL) is determined by PCR or nucleic acid hybridization

46 HIV Transmission HIV survives 6 hours outside a cell HIV can survive more than 1.5 days inside a cell Routes of transmission: intimate sexual contact, breast milk, transplacental infection, contaminated needles, organ transplants, and blood transfusion Anal-receptive intercourse is the most dangerous form of sexual contact

47