L9 Immunity against infection (viruses and parasites)

what MHC molecule would be present in a processed peptide from extracellular microorganisms

MHC II APCs

define a virus

obligate intracellular parasite, but may also be extracellular at some stage in infection

what are innate defences of viruses

• interferons

• natural killer cells

what is induced in virus infected cells as an early response to infection

synthesis of IFNalpha and IFNgamma (type I)

describe type II interferons in viruses

IFNgamma secreted by activated T cells and by NK cells

• inhibits TH2 response (antibodies) and promotes TH1 (cell killing)

• recruits macrophages

what can rIFNalpha be used to treat

hepatitus B and C

describe therapeutic use of interferons

• some cancers

• side effects can be severe

what are type of lymphoid cell are natural killer cells

innate

what type of lymphocyte are natural killer cells

large granular

what do natural killer cells recognise

structures on viral infected cells

• can recognise stress cells in absence of Igs and MHC

how do natural killer cells kill

by extracellular mechanism-perforin and granzyme

what do NK cell receptors need to distinguish between

infected and uninfected host cells which otherwise would be a disaster

what do activating NK receptors recognise

carbohydrate ligands, triggers killing

what do inhibitory NK receptors recognise

MHC class I molecules

• (no binding, only TCRs can do this)

viruses that reduce MHC expression make cells…

more susceptible to NK killing

describe NK killing occuring

• missing or absent MHC class I cannot stimulate a negative signal

• the NK cell is triggered by signals from activating receptors

• activated NK cell releases granule contents, inducing apoptosis in the target cell

what are cytotoxic T cells (CTL)(CD8+)

recognise viral peptide and MHC class I

give an example of cytokines with anti-viral activity

IFNgamma

• class II helps activate macrophages

what are the 2 mechanisms of killing by cytotoxic T cells

• secretion of cytotoxic granules

• fas ligand on T cell interacts with Fas on target

describe the secretion of toxic granules

• perforin, polymerises in membrane

• granzymes (proteases) enter cell

describe how CTLs (cytotoxic T cells) work

• CTL recognises and binds virus-infected cell

• CTL programs target for death, inducing DNA fragmentation

• CTL migrates to new target

• Target cell dies by apoptosis

no release of virus, no inflammation

what happens when CTLs secrete IFNgamma

• inhibits viral replication

• upregulates MHC class I and II expression and antigen presentation

• increases macrophage phagocytosis of death cells

• promotes NK cell killing activity

what do antibodies do in specific immunity

neutralise free virus

how do antibodies neutralise the free virus?

prevent entry into and spread between cells

what does neutralising the free virus do

• prevents spread within the body

• protect mucosal surfaces against reinfection

give an example of neutralising the free virus preventing spread within the body

poliovirus

give an example of neutralising the free virus protecting mucosal surfaces against reinfection

flu

what do antibodies opsonise to increase

phagocytosis

what do antibodies activate complement leading to

lysis (enveloped viruses)

give a fact file of seasonal influenza

• there are a billion cases of seasonal influenza annually, 3-5 million of severe illness

• causes 290000 to 650000 respiratory deaths annually

• 99% of deaths in children under 5 years of age in developing countries

• symptoms begin 1-4 days after infection and usually last around a week

what response does acquired immunity in antibody and cell mediated immunity in inflenza infection induce

antibody and cytotoxic T cell (CTL) response

what do antibodies in acquired immunity influenza recognise

viral haemagglutinin and neuraminidase

what does high levels of CTL activity correlate with

reduced viral shedding

how do epidemics arise

new strains not being recognised by antibody (vaccine strains)

what does HIV attack

the specific immune system

what does HIV target

CD4 T cell, macrophages and dendritic cells

what does the progressive development of AIDS lead to

opportunistic infections

give examples of symptoms of specific immunity HIV

• oral candidiasis

• kaposi’s sarcoma

• pneumocystis pneumonia

antibodies to HIV do not seem to…

protect

what may HIV infection be controlled by

cytotoxic T cell responses

what do patients with higher levels of CTL activity show

slower disease progression

what do virus mutations that escape CTL recognition lead to

progression of AIDS

what does SARS-CoV-2 do

immune dysregulation

when was SARS-CoV-2 first reported

2019

what had very similar disease outbreaks in the past 20 years

SARS and MERS

describe the symptoms of SARS-CoV-2

2-14 days post exposure

• cough, fever, change in taste, pneumonia

• can be variable across ages and altered following vaccination

describe the RNA of SARS-CoV-2

22-32 kilobase ss +ve

what does spike glycoprotein (S) bind to on host cells to gain entry

ACE 2 receptors

what animals did SARS-CoV-2 come from

• bats

• pangolin

what is the mutation rate of SARS-CoV-2

high

what does the dampening of anti-viral type I interferon aid in SARS-CoV-2

viral replication

what can viral proteins of SARS-CoV-2 inhibit

RIG1 (a PRR)

what can viral proteins of SARS-CoV-2 stimulate

NFkB activation

• proinflammatory

what are the severe cases of SARS-CoV-2 immune responses

• lymphopenia (decreased white blood cells)

• eosinopenia

• extensive pneumonia

• lung damage

• cytokine storm (high levels of cytokines) → acute respiratory distress syndrome

• multiple organ failure

describe parasites

• unicellular or multicellular

• often in multiple complex stages of life cycle

• different defence mechanisms are important

how may the antibody of parasites protect

• opsonisation

• complement lysis

• ADCC (antibody-dependent cell-mediated cytotoxicity)

what do some helminths induce (parasites)

a strong IgE response

what are the roles of IgE helminths induce (for parasites)

• mast cell mediated inflammation

• eosinophil ADCC (antibody-dependent cell-mediated cytotoxicity)

what is cell mediated immunity important for in parasites

protozoa that can survive in macrophages, hidden from Igs

give an example of protozoa that can survive in macrophages

leishmania

what are cytokines important in (parasites)

inducing macrophage activation

give an example of cytokines inducing macrophage activation in parasite cell-mediated immunity

IL1

what does C57BL/6 do in mice in T cell immunity to leishmania

resolve infection

what does BALB/c do in mice (T cell immunity to leishmania)

fatal progressive disease

where is the RNA that responds to mouse strains to leishmania

cytokine RNA in the lymph node

what cytokine is present in C57BL/6

• IFN-gamma (+++)

• IL-4 (-)

what T helper cells are present in C57BL/6

TH1

what T helper cells are found in BALB/c

TH2

what cytokines are found in BALB/c

• IFN-gamma (±)

• IL-4 (++)

give key facts of malaria

• globally in 2023 there were an estimated 263 million cases and 597000 malaria deaths in 83 countries

• the WHO African Region carries a disproportionately high share of the global malaria burden

• in 2023, the WHO African Region was home to 94% of malaria cases (246 million) and 95% (569000) of malaria deaths

• children under 5 accounted for about 76% of all malaria deaths in the Region

what may be susceptible to the antibody in malaria

Sporozoite and merozoite

what may the antibodies in malaria also kill

infected red blood bells

what are cytotoxic T cells active against in malaria

infected liver cells

what the vaccine for malaria

• RTS, S vaccine since 2019

• R21/Matrix M vaccine more recently (children)