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Quick overview of immune system 1 • Immune system: acquired immunity – After exposure to a foreign substance, your body is able to rapidly react against it next time. • Immune system is a complex interplay between cell signals (cytokines such a interleukins) and different cell types. • Although macrophages are involved, the immune system features T cells and B cells, types of lymphocytes. Nature of antigens • The immune system recognizes, responds to, and remembers molecules that are antigens. • An antigen: – Is foreign – Is large – Is molecularly complex. • Proteins and polysaccharides on the surface of bacteria are antigens, as are viral proteins on the surface of your infected cells. – Also, molecules on pollen and animal skin flakes: allergies are an immune response as well. 2 3 Dual Nature of the immune system • Humoral and cell mediated – Humoral refers to body fluids, specifically that this branch of the immune system uses antibodies which are protein molecules dissolved in blood, body fluids, and secretions. • B lymphocytes are the source of antibodies – Cell mediated refers to the direct involvement of cells to attack an infection • T lymphocytes either kill cells directly or recruit macrophages to kill cells directly Basic Antibody structure •Classic lock & key like an enzyme; sites bind specifically to antigens. Antibodies attach to antigens, cover up binding sites, and preventing the action of the molecules, agglutinating, precipitating, and neutralizing. 4 Pathogenic Viruses • Name of virus; what family it belongs to; what disease it causes. – DNA or RNA? Ss or ds? – Characteristics of disease, symptoms. – Viral virulence factors • Epidemiology: reservoirs, vectors • Immunizations 5 Brief review • Non-cellular “life forms” – Consists of nucleic acid and capsid (protein) – Some types possess envelope, spikes, accessory proteins • Obligate intracellular parasites – Nucleic acid enters host cell, directs operations – Ultimately, new copies of viral N.A., proteins made • Virus depends mostly on host cell machinery – Following assembly, new virions escape to infect new hosts 6 Attack and defense 7 • Virus has ways of attacking – Specific binding to host cell receptor • Receptors involved in normal cell functions – Virus may regulate cell division for its own replication – Insertion of viral DNA into chromosome allows virus to hide from immune system Defense by host • Host has ways of defending – Cell mediated immunity (T cells): infected cells killed. – Antibodies intercept virions between cells, in fluids – Interferon produces anti-viral state, prevents replication 8 Our selections for Sp 2005 • Herpes Virus family – HSV 1 & 2; VZV; and CMV • Hepatitis viruses – Hep A, B, and C: all unrelated, and transmitted differently, but cause similar disease. • Mosquito-borne viruses of Arkansas • Influenza • HIV (info repeating or supplementing guest speaker Debbie Biazo) 9 Herpes virus family • Human herpes viruses now numbered – But common names easier to use. • As a family: – ability to become latent; – predilection for either nervous tissue or lymphocytes; – ability to cause cancer. • Herpes roster: – Herpes simplex, Varicella zoster, cytomegalovirus, Epstein Barr, roseola, Kaposi’s sarcoma virus. 10 Herpes Simplex viruses 11 • HHV1 (above the waist) – Typically oral, cold sores; flu-like symptoms, etc. • HHV2 (genital), STD and neonatal – Painful, contagious sores on genitals, overlap w/ HHV1. • Latency – Viruses enter nearby nerve cells, remain until activated by stress of some sort, cause disease, then return. • Spread and treatment: – Person to person by direct contact; spread within host by forming syncytia, escape immune system. – Acyclovir helps; no cure, lifetime infection. Herpes family: Varicella Zoster 12 • Varicella: chicken pox; Zoster: shingles – Chickenpox (not a pox virus), respiratory, disease becomes systemic with fever, malaise, skin lesions. – Very contagious; usually mild, esp. in children – Virus can become latent in nerves like Herpes simplex • Recurrence: shingles; rash, pain, on one side • Acyclovir can lessen symptoms – Beware of salicylates + viruses: Reyes syndrome – Vaccination: Varivax: attenuated vaccine Herpes family: Cytomegalovirus 13 • CMV (HHV5): Infection results in enlarged cells – Widespread asymptomatic infections, latency – Virus shed in body fluids: sex, birth, transplants – Problem for unborn, immunosuppressed, transplant patients; major cause of viral-induced birth defects. Hepatitis 14 • Hepatitis is inflammation of the liver – Liver especially important in metabolism • Breakdown of drugs, toxins, waste products – Damage results in accumulation of bilirubin • Bilirubin is stage in hemoglobin breakdown • Results in yellow color: jaundice – Hepatitis can be caused by several different viruses • Hepatitis A, B, and C viruses all cause liver damage, but are unrelated viruses. Hepatitis B 15 • A DNA virus: “Hepadnavirus” • Hepatitis B released from live cells, so accumulates in high numbers in body fluids. – Blood of infected person is rather infectious – Cuts, piercing, sex, childbirth, etc. – Large amounts of empty capsids ties up antibodies. • After exposure, long incubation, long disease – 10% have chronic infections – The younger the host, the likelier chronic infection Hep B continued • Chronic infection correlated with liver destruction – Liver tissue replaced by scar tissue; liver failure – Long term exposure to virus increases risk of liver cancer • Insertion of HBV DNA into chromosome may activate oncogenes • Vaccination now recommended – Because of bad result of early infection and great danger of liver damage, liver cancer. – Recombinant vaccine. 16 Hepatitis A virus • A small RNA virus, “Picornavirus” – Transmitted by fecal-oral route – Incubation for 1 month, followed by fever, nausea, anorexia, jaundice • T cells attack infected liver cells – No chronic infections, patients recover. • Note comparisons to Hepatitis B: – RNA vs DNA – Shorter disease, few long term problems – Mode of spread completely different 17 Hepatitis C 18 • Another RNA virus, different group: “Flavivirus” – Causes chronic infections • Can be mild, or destructive • Long term infections increase risk of cancer. – Transmission like Hep B: blood, sex, transplants Arkansas Arboviruses • Not an official taxonomic group, but short for “arthropod-borne” – Includes Flaviviruses, Togaviruses, and others. – Zoonotic, spread from animals to people by arthropod vectors, especially mosquitoes. • Reservoirs may be birds, various mammals – Result in two main types of illnesses • Encephalitis, inflammation of the brain • Hemorrhagic fever: high fever with bleeding 19 Arkansas Arboviruses • Encephalitis: spread by skeeters – In Arkansas: Eastern Equine; • Togavirus; • Also infects, kills horses. Most dangerous. – St. Louis encephalitis, • Flaviviral diseases; Human disease. • Usually not serious. – West Nile virus • Flavivirus; imported to US, spread from NYC • Disease mostly in young and elderly 20 Orthomyxovirus • Influenza: a serious respiratory disease – Virus has a segmented genome • 8 different RNA molecules – Spikes: Hemagglutinin (for infecting cells) and neuraminidase (for escaping them) – Antigenic drift and shift • Drift: small mutations, making host susceptible • Shift: major mixing of RNAs, whole new virus. – Attack on respiratory tract • Kills ciliated epithelial cells, allows bacterial infections. Release of interferon causes symptoms. 21 influenza • Changes in H and N (antigenic shift) – Mixing of viruses that infect birds, pigs, produce new strains able to jump to humans. – New antigenic type leaves population unprotected – Numerous epidemics throughout history • Flu of 1918-1919 killed 20 million – Asia watched very carefully – Flu vaccines made from deactivated viruses • Slow process, so every year correct strains are “guessed”. 22 HIV/AIDS 23 • Infection – 4 main types of cells infected, esp. T helper cells • Have CD4 glycoprotein on surface – After RNA is copied into cDNA, cDNA inserts • Infection is for life – Chronic infection • T cells continually made, continually destroyed • Eventually, host loses – AIDS diagnosis: • CD4 count below 200/µl; opportunistic infections Treatment and prevention • Prevention is easy – Practice monogamous sex, avoid shared needles – HIV cannot be spread by casual contact, skeeters – Fastest growing victim demographic is YOU. • Not just a “gay disease” • Treatment is expensive, but usually works – Nuceloside analogs, protease inhibitors • Processing viral proteins requires protease – About $1500 a month for drugs 24