Microbes-L15- Adaptive Immunity 3:antiviral immunity (especially flu)

how do vaccines work?

• vaccines introduce an antigen- non infectious

• PC- antigen presenting cells like dendritic cells and macrophages in the innate immune system aka cup the antigen

• to make CD4 helper cells by presenting via MHC II cells to activate B cells and CD8 cells cytotoxic cells

• gives long term immunity

difference between being infected and vaccination?

with a vaccination you don’t need to get ill to be immunised

influenza virus structure

• has neuraminidase- which is a target for anti viral drugs like Tamiflu

• haemagglutin which triggers and immune response either by infection of vaccines

• nucleoprotein

• matrix protein

how does immunity to influenza virus work?

1. control of the infection: mediated by NK cells and cytotoxic T lymphocytes

2. cytotoxic T lymphocytes target the nucleoprotein on the virus- as it doesn’t change across subtypes

-CTL can recognise nucleoproteins across subtypes giving cross reactive immunity

3. prevention of re-infection by antibodies- HA is the target point of neutralisation - also targeted by CD4

   • HA is highly variable

difference between nucleoprotein and hemagglutin on influenza?

nucleoprotein is quite conserved across subtypes and so doesn’t vary much and recognised by the immune system

HA/hemagglutin- varies a lot through subtypes

innate and adaptive production in influenza

innate: production of interferon alpha, beta and TNF alpha and IL-12, NK cells killing of infected cells

adaptive: T cell mediated killing of infected cells

steps of immunity to the influenza virus:

1. virus enters the body and produces viral proteins- warning signals

2. macrophages- detect and phagocytose

3. NK cells kill infected cell

4. Th1 releases-interferon gamma

adaptive:

5. Th1/2 release IL-4 and IFN gamma which release B cells IgA/IgG antibodies

6. NK cells kill infected cells

7. along with macrophages

how do neutralising antibodies work in immunity?

1. virus binds to the receptors on cell surface

2. receptor mediated endocytosis

3. acidification of endosome- triggers fusion of virus with cell - entry of viral DNA

4. antibody blocks binding to the virus receptor and block fusion event

how does influenza virus evade immune response?

by antigenic variation- RNA segments are exchanged between viral strains in a secondary host

• as influenza have segmented genomes

• second host- is infected with 2 strains- RNA from both viruses mix- host no longer recognises HA

or- mutations in the epitopes- no longer recognised HA

adaptive immunity to bacteria: humoral and cell mediated- explain cells involved and what they do

humoral immunity:

• B cells and antibodies- presentation of infection and reinfection

• usually EXTRACELLULAR bacteria

cell mediated immunity

• T cells- help in making antibody production

• control of infection

• INTRACELLULAR bacteria

how does bacteria trigger inflammation?

• bacteria triggers macrophages to release chemokines and cytokines

• vasodilation and increased vascular permeability- heat, redness, swelling

• inflammatory cells migrate to tissues- and cause pain

cell mediated immunity to bacteria- examples of those that are resistant

• many intracellular bacteria- resistance to antibodies and compliment-TB and mycobacterium leprae

• CD4 Th1- produce IFN gamma and activates macrophages, MHC expression, killing mechanisms

• CD8+ T play a role in salmonella

• NK cells- early IFN-gamme production

discuss mycobacterium tuberculosis

• 2b people have latent- 10% will develop active

• Latent- immune responses control the infection

• active infection- weakened immune response- HIV,, older people

• antibiotics used to treat- but drug resistant have emerged

vaccines against Mycobacterium tuberculosis- and what are new vaccines based on?

BCG- bacille calmette guerin

• prevents TB meningitis

• poor efficacy against pulmonary TB

new generation vaccines based on purified antigens- in development

• AIM: to induce cell mediated immunity

what does an infected viral macrophage trigger?

Th1- to produce IFN gamma

what does a granuloma consist of?

• outside: Th1 cells releasing IFN - keeps the virus inside

• inside- epitheloid macrophages cells, multi nucleated giant cell

what can TB also result in? and what is the response?

mycobacterium leprae

• tuberculoid- trigger Th1 cell mediated immunity- IFN - gamma, IL-2, TNF-beta

• lepromatous- trigger Th2 cytokines- IL4, IL-5, IL-10