Immune response to virus
- 2. VIRUS • Viruses are small segments of nucleic acid with a protein or lipoprotein coat • require host resources for their replication • Entry - cell-surface receptor and • Biosynthetic machinery to replicate all components of itself, including its genome. • error prone - generating numerous mutations
- 4. Virus survival strategies • When outside of cells, viruses are surrounded by a protein coat – the capsid. • Enveloped viruses - capsid is enclosed by a lipid bilayer that, derived from host cell membrane, also incorporates viral proteins required for cell attachment. 1. Do not kill the host ! 2. Long latency period 3. Facile transmission - such as with influenza and the smallpox virus 4. Advantage of non-human host- additional reservoir
- 6. VIRUS ENTRY INTO A HOST • Passage across the mucosa of the respiratory, genitourinary, or GI tracts accounts for - viral transmission • Also occur through broken skin, usually as a result of an insect bite or puncture wound. • Effectiveness - determined by host immune response I. The innate immune response to viral infection primarily begins - recognition of pathogen associated molecular patterns (PAMPs) and leads to the generation of antiviral effectors.
- 7. RESPONSE BY OUR IMMUNE 1. Innate immune response begins – recognition of PAMPs • For example, (dsRNA) & other virus-specific structures – bind PAMP receptors - induce the expression of type I interferons (IFN- and IFN- ), the assembly of intracellular inflammasome complexes, and the activation of NK cells. • Type I interferons - antiviral response - by binding to the IFN- /- receptor - activating the JAK-STAT pathway leads to viral RNA degradation • IFN- /- binding also induces ds RNA-dependent proteinkinase (PKR), which leads to inactivation of protein synthesis, thus blocking viral replication in infected cells.
- 8. • The binding of type I interferon to NK cells induces lytic activity, making them very effective in killing virally infected cells. • killer activatory receptors bind to carbohydrate and other structures expressed collectively by all cells, and • killer inhibitory receptors recognize MHC class I molecules
- 10. II : Many Viruses Are Neutralized by Antibodies • Antibodies specific for viral surface antigens - crucial in containing the spread of a virus during infection and in protecting against reinfection. • Antibodies – effective at localized site • For example, • influenza virus binds to sialic acid residues in cell membrane glycoproteins and glycolipids, • rhinovirus binds to inter cellular adhesion molecules (ICAMs), and • Epstein Barr virus (EBV) binds to type 2 complement receptors on B cells
- 13. III. Cell-Mediated Immunity Is Important for Viral Control and Clearance • Antibodies – not the heroes we need when virus has incorporated into our genome • cell-mediated immune mechanisms - most important in host defense • Both CD8 + TC cells and CD4 + TH 1 cells - cell-mediated antiviral defense • Activated TH 1 cells produce cytokines - IL-2, IFN-Ɣ , and (TNF-α) • IFN-Ɣ - direct action - inducing an antiviral state in nearby cells. • IL-2 acts indirectly by assisting the development of cytotoxic T cells (CTL) precursors into an effector population • Both IL-2 and IFN-Ɣ activate NK cells - important role in host defense and lysis of infected cells during the first days • “Strain specific response”
- 15. Viruses constitute a formidable enemy • HIV and influenza virus, among others, can quickly change their antigens by genetic mutation. •SARS-CoV- 2002 A BRIEF EPIDEMIC – And in 2019 ----------------------NOT AGAIN !!!
- 16. Viruses Employ Several Different Strategies to Evade Host Defense Mechanisms 1. The outer physical and chemical barriers of the body 2. Intrinsic antiviral factors 3. Innate immunity, and 4. Adaptive immunity • Antiviral factors /restriction factors are collectively able to block each stage of the viral life cycle; entry, uncoating, replication, translation, assembly and release - TRIM5α & APOBEC3 cytidine deaminases
- 17. Immunity can be evaded by antigenic changes • The influenza virus infects the upper respiratory tract and major central airways in humans, horses, birds, pigs, and even seals. • Between 1918 and 1919, the largest influenza pandemic (worldwide epidemic) occurred, killing between 20 million and 50 million people. Influenza Has Been Responsible for Some of the Worst Pandemics in History !!
- 19. Properties of the Influenza Virus • Influenza virions - surrounded by an outer envelope, a lipid bilayer derived plus various virus-specific proteins. • Two key viral glycoproteins, hemagglutinin (HA) and neuraminidase (NA) • HA trimers are responsible for the attachment of the virus to host cells, binding to the sialic acid groups on host-cell glycoproteins and glycolipids. • NA - enzyme that cleaves N -acetylneuraminic (sialic) acid from nascent viral glycoproteins and host-cell membrane glycoproteins, facilitating viral budding from the infected host cell. • Essential for viral attachment and for exit of new virus from infected cells— new strains of influenza based on their antigenic subtypes of HA and NA (e.g., H1N1 versus H5N1 virus)
- 24. Influenza viruses change antigens by drift and shift • In the course of their constant duel with the immune system – Continuous change in antigenic structure • Influenza A – adopted 2 mechanisms • “Antigenic shift” and “Antigenic drift” • Antigenic drift involves a series of spontaneous point mutations that occur gradually, resulting in minor changes in HA and NA over time. • Antigenic shift results in the sudden emergence of a new subtype of influenza, where the structures of HA and/or NA are considerably different from that of the virus present in a preceding year.
- 26. ANTIGENIC DRIFT
- 27. ANTIGENIC SHIFT
- 29. Rhinovirus – the common cold virus
- 32. Mutation can produce non-functional T‐cell epitopes • A number of viruses, including hepatitis B and C viruses and HIV, are capable of making mutations that prevent stimulation of cytotoxic T‐cells. • Such mutations modify residues that could contribute to peptides able to bind to MHC or be subsequently recognized by the TCR
- 34. Viruses can interfere with immune effector mechanisms - Playing games with the host’s humoral responses • Herpes simplex virus (HSV) types 1 and 2, pseudorabies virus, varicella zoster virus, and murine cytomegalovirus all bear proteins that, by binding antibody “the wrong way round,” may inhibit Fc‐mediated effector functions. • The vaccinia virus complement control protein (VCP) binds C3b and C4b, making both the classical and lectin C42b a as well as the alternative C3bBbC3 convertases susceptible to factor I‐mediated destruction. • Epstein–Barr virus (EBV) infects B‐cells by the high‐ affinity binding of its gp350/220 envelope glycoprotein to the CR2 complement receptor.
- 35. • Members of the regulators of complement activation (RCA) family are also used as cellular receptors for various viruses, such as CD46 (membrane cofactor protein) by measles virus and human herpesvirus 6 (HHV6), and CD55 (decay accelerating factor) by echoviruses and coxsackieviruses. • Antibodies that mediate this effect are, for obvious reasons, referred to as “enhancing antibodies.”
- 36. CARE TO IDENTIFY ?
- 38. CORONAVIRUS 19 (SARS-CoV 19) • Coronavirus disease (COVID-19) is an infectious disease caused by a newly discovered coronavirus. • Most people infected with the COVID-19 virus will experience mild to moderate respiratory illness and recover without requiring special treatment. • Older people, and those with underlying medical problems like cardiovascular disease, diabetes, chronic respiratory disease, and cancer are more likely to develop serious illness • The COVID-19 virus spreads primarily through droplets of saliva or discharge from the nose when an infected person coughs or sneezes • Coronavirus is a family of the virus and can cause illness such as the common cold, severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome (MERS)
- 41. THANK YOU