immune invasion

Question 1

what barriers does the respiratory system have to infection?

Answer 1

respiratory epithelium has evolved to prevent microbes entering the submucosal spaces:
-is covered by a layer of mucous (secreted by goblet cells and distributed by cilia)

Question 2

describe the route of infection for respiratory pathogens (with reference to specific pathogens)

Answer 2

mode = inhalation, ingestion of infected material (e.g. saliva droplets)

e. g.
- influenza (orthomyxovirus) -> influenza
- EBV (herpesvirus) ->mononucleosis
- measles virus (paramyxovirus) -> measles
- varicella-zoster (herpesvirus) -> chickenpox
- streptococcus pyogens (gran-positive bacterium) -> tonsillitis
- haemophilis influeza (gram negative bacterium) -> pneumonia, meningitis
- Neisseria meningitis (gram negative bacterium) ->menincoccal meningitis

mode = spores
bacillus antharax (gram positive bacterium) -> inhalation antharax

Question 3

what is the normal course of infection

Answer 3

cross anatomical barrier - through specialised receptors or breach

trigger innate response

innate IS triggers adaptive

most often infection is controlled

Question 4

defining features of a true pathogen

Answer 4

avoid innate/adaptive defence long enough to replicate and spread to new host

Question 5

discuss viral mechanisms to immune evasion

Answer 5

antigenic variation - alters surface antigen to avoid host adaptive immune response

antigenic drift = accumulation of mutations within the genes that code for antibody-binding sites. Results in a new strain of virus particles which cannot be inhibited as effectively by the antibodies that were originally targeted against previous strains, making it easier for the virus to spread throughout a partially immune population

antigen shift = two or more different strains of a virus, or strains of two or more different viruses, combine to form a new subtype having a mixture of the surface antigens of the two or more original strains

Question 6

give an example how DNA viruses have evolved diverse mechanisms to evade or subvert the host immune system

Answer 6

inhibition of humoral response:

• inhibit the normal binding of antibodies by changing Fc receptor conformation
• eg. herpes simplex, cytomegalovirus

inhibition of inflammatory response
- e.g. SBV, Vaccinia, cytomegalvirus

immunosuppression of host
-e.g EBV

Question 7

what is viral immunoevasins?

Answer 7

viral encoded proteins that prevent infected host cells from presenting viral peptides in MHC class I molecules to CD8+ T cells

e.g. the herpes simplex virus 1 protein ICP47 blocks peptide entry into ER. it does this by blocking peptide binding to TAP (transporter on ER that normal facilitated peptide entry to ER during antigen processing and presentation in MHC molecules)

Question 8

what are CD8+ T cells?

Answer 8

cytotoxic T cells that primarily recognize and kill viral infected cells by recognising virus particle presented in MHC class 1 molecules

Question 9

what is a latent virus?

Answer 9

persist in the host by not replication

herpes simplex - recurrent cold sores

herpes zoster - chicken pox/shingles

human papilloma virus (HPV) - cervical cancer

HIV - AIDs

Question 10

use herpes simplex virus as an example of latent infection

Answer 10

• initial infection is cleared by host IS
• residual infection persists in the nuclei sensory neurons serving the inf. tissues
• virus transcribes a small part of the genome that codes for LAT that supresses the lytic cycle and interferes with the host cell apoptosis prolonging viral life
• when virus is re-activated by environmental factors, viral particles travel back along the neurons to the tissue and cause repeat infections

Question 11

extracellular bacteria typically elicit a type 3 immune response. what cells are involved type 3 immune response?

Answer 11

Th17 and neutrophil driven. e.g. pussy spot

• neutrophilic response
• drives opsonization and complement fixing antobodies
• microbial surface associates active innate immune system (shield these -invasion strategy)

Question 12

what do the microbial associated molecular patterns (MAMPs) present on gram negative LPS activate?

Answer 12

TLR4

Question 13

what do the microbial associated molecular patterns (MAMPs) present on gram positive peptidoglycans activate?

Answer 13

TLR 2, NOD1 and NOD2

Question 14

what evasion mechanisms are adopted by extracellular bacteria to stop/prevent adaptive and innate immunity?

Answer 14

shielding MAMPs (S.pnumoniae)

antigenic variation (N.gonorrhoeae)

inhibition of opsonization (S.pneumoniae, N.meningitidus)

inhibition/scaverging of reactive oxygen species (S.aureus)

resistance to antimicrobial peptides (Ecoli, S.aurus)

Question 15

what is the normal clearance of intracellular bacteria?

Answer 15

Th1 cells induce and activate macrophages. Bacterial infected macrophage presents ag to TH1 cells they enhance macrophage activity TH1 also attract and activate more T cells incl. CD8+ Cytotoxic T cells and attract monocytes to site of infection. Macrophages and T cells accumulate at the site of infection and clear the pathogen

Question 16

intracellular bacteria have developed mechanism to survive inside phagocytic cells - mainly macrophages. describe one strategy as an example

Answer 16

survival within phagolysosome. achieved by waxy, hydrophobic cell wall containing mycolic acids and other lipids. results in resistance against lysosomal enzymes. e.g M.tuberculosis and M.leprae

Question 17

Mycobacterium tuberculosis is one of the microbes that is phagocytosed by macrophages but prevents fusion of phagosome and lysosome and is therefore protected. what structure typically forms after?

Answer 17

Granuloma - mass of granular tissue, typically produced in response to infection, inflammation or to presence of foreign substance

Question 18

What occurs for granuloma formation after infection by TB?

Answer 18

TB infected macrophage. some are free in cytoplasm, some in phagosome, in some cases the phagosome does work, but there is a dampened down response. macrophage still presents to Th1 cell, but response is dampened. to keep infection from spreading, a localized inflammatory response develops and a granuloma forms

Question 19

What does a granuloma consist of?

Answer 19

a central core of infected macrophages - with fused multinucleated giant cells and surrounded by large macrophages call epitheloid cells - the core can become necrotic. the core is surrounded by T cells, mostly CD4+ Th cells.

Question 20

how can immune evasion be achieved by protozoa? e.g. plasmodium and trypanosoma

Answer 20

regularly change surface proteins - antigenic variation

Question 21

describe antigenic variation in trypanosome

Answer 21

is covered with variant surface antigens. approx. 1000 VSA genes but only one gene n a specific expression site, telomeric active site, is actively transcribed. if the host has made specific antibodies to the active VSA then another gene will be translocated to a telomeric active site. a new VSA is expressed and the host immunity needs to start all over again.