L10 Evasion of host defenses and immunopathology in infection

what are 4 examples of evasion mechanisms

• concealment of antigens

• antigenic variation

• immunosuppression

• interference with effector mechanisms

give examples of virus’s inhibiting antigen presentation by MHC class I

• herpes simplex virus

• adenovirus

give examples of privileged sites (concealment of antigens)

• latency of HSV or herpes zoster virus in CNS

• hydatid cysts in Echinococcus granulosus infection (dog tapeworm)

give an example of uptaking of host molecules (cloak effect) (concealment of antigens)

Schistosomes (bilharzia)

describe antigenic variation

• large number of antigenic types

• mutation (antigenic drift)

• recombination (antigenic shift)

• gene switching

give an example of a large number of antigenic types (antigenic variation)

Streptococcus pneumoniae

give examples of mutations- antigenic drift (antigenic variation)

• flu

• polio

• HIV

(RNA viruses)

give an example of recombination -antigenic shift (antigenic variation)

flu

give an example of gene switching (antigenic variation)

trypanosomes

what is streptococcus pneumoniae a leading cause of

serious bacterial infections

what does streptococcus pneumoniae cause

• otitis media

• sinusitis

• brinchitis

• pneumonia

• bacteremia and meningitis

describe the structure of streptococcus pneumoniae

gram positive

• surrounded by a thick polysaccharide capsule which protects it from phagocytosis

what do antibodies to the capsule of streptococcus pneumoniae do?

opsonise the bacteria and protect

how many different capsular types are there of streptococcus pneumoniae

91

how many subunits of capsular polysaccharide does the vaccine for streptococcus pneumoniae have

23 major disease causing polysaccharide capsules

describe the antibody response of streptococcus pneumoniae

• individual infected with a type of streptococcus pneumoniae

• antibody response clears infection

• subsequent infection with a different type of streptococcus pneumoniae is unaffected by response to first type

• now activity response clears second infection

what do the many types of streptococcus pneumoniae differ in

their capsular polysaccharides

what are 2 vaccines for streptococcus pneumoniae

• pneumovax

• prevnar 13

what type of vaccine is pneumovax for streptococcus pneumoniae

polysaccharide vaccine (contains antigens to all 23 capsules)

what is pneumovax not effective in as a vaccine for streptococcus pneumoniae

children under two or those with poor immune function (e.g. HIV)

• low level response

• just B cell IgM response

what type of vaccine is Prevnar 13 for streptococcus pneumoniae

conjugate vaccine

describe the structure of Prevnar 13 as a vaccine for streptococcus pneumoniae

13 capsule antigens

• bound to the diptheria toxoid (protein) which is highly immunogenic but non-toxic

• T cell and B cell (all Ig) response

what antibody response does pneumovax have on streptococcus pneumoniae

B cell IgM

what antibody response does Prevnar 13 have on streptococcus pneumoniae

T cell and B cell (all Ig) response

what us TI-2 polysaccharide antigen converted into

TD form

what is the structure of influenza virus

RNA virus

• negative sense segmented genome

what can influenze infect

• humans

• birds

  • other animals

what can influenza cause

epidemics and pandemics

what are the major surface antigens of influenza

• haemagglutinin

• neuraminidase

how does influenza get updated

annually

• Global influenza surveillance and response system

what can influenza undergo

• antigenic drift (mild epidemics)

• antigenic shift (major pandemic)

what is antigenic drift

mild epidemic

what is antigenic shift

major pandemic

describe mild antigenic drift

• neutralizing antibodies against haemogglutinin block binding to cells

• mutations after epitopes in haemagglutinin so that neutralising antibody no longer binds

what is trypanosoma brucei

a protozoal parasite that causes african sleeping sickness

what is trypanosoma brucei spread by

the Tsetse fly

what do trypanosoma brucei patients undergo

bouts of parasitaemia

what does trypanosoma brucei parasitaemia correlate with

changes in the major surface antigen of the trypanosome, brought about by genetic rearrangement

what type of glycoprotein is trypanosoma brucei

variant specific glycoprotein (VSG)

describe variant specific glycoprotein in trypanosoma brucei (VSG)

• many inactive trypanosoma brucei VSG genes but only one site of expression

• inactive genes are copied into the expression site by gene conversion

• many rounds of gene conversion can occur, allowing the trypanosome to vary the VSG gene expressed

• clinical course of trypanosome infection

describe immunosuppression in the evasion of immune defences

• infection of immune cells

• induction of regulatory T cells

give an example of infection of immune cells in immunosuppression

HIV -T cells (CD4+/macrophage/dendritic cells

give an example of infection of regulatory T cells in immunosuppression

chronic infection with Helicobacter pylori

what are regulatory T cells

a type of CD4+ cell

what do regulatory T cells do

regulate the immune system

• suppress differentiation and proliferation of TH1 and TH2 cells

give an example of regulatory T cells as immunosuppressive

IL10

what do regulatory T cells maintain

tolerance to self antigens

what do Treg cells help prevent

autoimmune disease

what do Treg cells express

CD4 and CD25 on the surface and FoxP3 (transcriptional factor) expressed

what does Helicobacter pylori cause as an example of infection of regulatory T cells in immunosuppression

gastric and duodenal ulcers

• gastric adenocarcinomas

what bacteria is Helicobacter pylori as an example of infection of regulatory T cells in immunosuppression

gram negative

what is Helicobacter pylori found in as an example of infection of regulatory T cells in immunosuppression

one in 3 people

• causes disease in only 10% of people infected

what cells are found in Helicobacter pylori as an example of infection of regulatory T cells in immunosuppression

regulatory T cells establishing a persistent infection

what is the parasite for Leishmania

genus of trypanosomes

what is leishmania

induction of regulatory T cells

what is the vector for leishmania

sand fly

what can leishmania hide and survive in

macrophages

what can leishmania increase expression of

T_REG cells

what does leishmania decrease

the immune response

what type of virus is Measles virus

RNA virus

what is measles virus associated with

a rash accompanied by profound malaise and respiratory symptoms

what do complications of Measles include

secondary bacterial respiratory infections

what does measles virus cause

immunosuppression which can lead to secondary infections

what cells does measles infect

dendritic

what do infected dendritic cells show with measles

• increased apoptosis

• decreased stimulation of T cells

• decreased IL-12 production (NK cells and TH1 affected)

what is the Dendritic cell

antigen presenting cell (MHC I and MHC II)

what do dendritic cells act as

messengers between the innate and adaptive immune systems

describe interference with effector mechanisms as an evasion of immune defenses

• molecules interfering with antibody function

• molecules interfering with complement

• molecules binding cytokines

• subvert responses by producing molecules with cytokine activity

• inhibition of phagocytic killing

give examples of molecules interfering with antibody function (effector mechanisms)

• IgA proteases

• Fc binding molecules

give examples of IgA proteases

• streptococcus pneumoniae

• neisseria spp

give examples of Fc binding molecules

• staphylococcal protein A

• herpes simplex virus

give examples of molecules interfering with complement (effector mechanisms)

• enzymes that break down C3a/C5a

• molecules that inhibit complement activation

give an example of enzymes that break down C3a/C5a

pseudomonas

give an example of molecules that inhibit complement activation

• vaccinia

• smallpox virus

give an example of molecules binding cytokines (effector mechanisms)

Vaccinia

give an example of vaccinia

small pox, IFN gamma

give an example for subverting responses by producing molecules with cytokine activity (effector mechanisms)

Epstein Barr Virus produces vIL-10

• downregulates T_H1 response

give an example of inhibition of phagocytic killing (effector mechanisms)

tuberculosis

describe mycobacterium tuberculosis persisting in macrophages

on reaching host’s lungs, cells of myc.tuberculosis bind to the TLR-2 receptor on the surface of a macrophage

what may an infectious disease pathology result from

• direct effects of pathogen

• host responses

give an example of direct effects of the pathogen

toxins

give an example of host responses

innate or specific

what does LPS induce in innate immune responses

macrophage cytokine secretion

• IL1, TNF alpha via TLR4

what are systemic effects of the innate immune response

• fever

• endotoxic shock

• cytokine storms

describe activity of TNF alpha in the innate immune response

• activates vascular endothelium and increases vascular permeability which leads to increased entry of IgG, complement and cells to tissues and increased fluid drainage to lymph nodes

• fever, mobilisation of metabolites, shock

what are specific responses as a pathological consequence of the immune response

antibodies or T cell reactions may contribute to pathology

give an example of specific immune response - pathological consequences

• skin rashes in measles due to T cell response

• granuloma formation in TB due to chronic macrophage activation

give an example of microbes playing an important role in initiating autoimmune responses

Abs to streptococcal M protein may cross-react with the heart muscle (eg rheumatic fever)

what is ebola as a filovirus

enveloped, non-segmented negative stranded RNA with filamentous particles

what does ebola cause

haemorrhagic fever

describe the fatality rate of ebola

70% reported

• outbreak in West Africa is largest in history- Sierra leone, liberia, guinea

what cells does ebola infect

immune cells including dendritic cells and macrophages

what does ebola inhibit

maturation of infected dendritic cells so they do not present antigens effectively

what does ebola cause in cells

apoptosis leading to reduced numbers of circulating T lymphocytes and NK cells and weakened immune responses

what does ebola interfere with

• production of type I interferon

• cellular response to interferon

describe the induction of the cytokine storm by macrophages playing a central role in pathogenesis

shed glycoprotein from virus binds macrophages and dendritic cells leading to cytokine release and increased vascular permeability

infected macrophages express abundant tissue factor which initiates the coagulation cascade…

disseminated intravascular coagulation → death

describe the 2014-2015 ebola outbreak in western africa

• 28,616 cases

• 11,310 deaths

• june 2016- end of epidemic in liberia and guinea

• vaccination success

• but still ongoing