1 Quick overview of immune system 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.

2 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.

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

4 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.

5 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

6 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

7 Attack and defense 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

8 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

9 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)

10 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.

11 Herpes Simplex viruses 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.

12 Herpes family: Varicella Zoster 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

13 Herpes family: Cytomegalovirus 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.

14 Hepatitis 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.

15 Hepatitis B 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

16 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.

17 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

18 Hepatitis C 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

19 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

20 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

21 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.

22 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 killed 20 million –Asia watched very carefully –Flu vaccines made from deactivated viruses Slow process, so every year correct strains are “guessed”.

23 HIV/AIDS 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

24 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