IMM3042 - Exam

What are STH?

soil transmitted helminths

Where are STH usually an issue?

the developing world

At what life stage do STH enter humans?

larval

How due STH enter the body?

through skin & other tissues

Where do adult worm live in the human body?

GIT

What is the morbidity associated with in STH infections? (3)

malnutrition, cognitive impairment, bowel obstruction

Where is schistosomiasis found?

developing world

What is the intermediate host of schistoma?

snail

What are the symptoms of schistomiasis caused by?

immunopathological reactions to egg antigens

What do schistosoma mansoni & japonicum cause?

hepatosplenic & gastrointestinal disease

What does schistosoma haematobium cause?

urinary tract disease

What are 7 important cells in STH infections?

mast cell, eosinophil, M2 macrophage, Th2, B cell, smooth muscle cell, goblet cell

What is the role of the mast cell in STH infections?

Fc receptors crosslink w/ allergen, degranulates cell

What do mast cells release upon degranulation?

histamines, lipid mediators, cytokines

What is the role of the eosinophil in STH infections?

at the blood stage, kill larvae by ADCC & degranulation

What regulates eosinophils?

Il-5

What are the 4 roles of M2 macrophages in STH infections?

tissue repair, fibrosis, immunoregulation & anti-helminth immunity

What promotes the differentiation of M2 macrophages?

Il-4,13

What drives Th2 cell differentiation?

Il-4

What does Th2 secrete?

IL-4,5,9,13

What drives B cell to switch isotype in STH infections? And to switch to which isotype?

Il-4, IgE

What is the role of smooth muscle cells in STH infections?

contract

What makes smooth muscle cells perform their function?

Il-4,13 and mast cell mediators

What is the role of goblet cells in STH infections?

proliferation & mucous secretion

What promotes goblet cells to perform their action?

Il-4,13

What is the overall impact of all the cells in response to STH infections, mediated by Th2 cells?

weep & sweep response

What is acute schistosomiasis?

a Th1 disease, pro-inflammatory responses activated

What is chronic schistosomiasis?

a Th2 disease, granuloma formation occurs around trapped eggs

What is malaria cause by?

plasmodium falciparum

How do the symptoms of malaria range?

from asymptomatic to severe

Where is malaria an issue?

Africa

Who are the most vulnerable to malaria?

young children

What are the 4 challenges to eliminated malaria?

- insecticide & drug resistance

- poor coverage of current interventions

- COVID-19 interruptions

- vax is partially efficacious

What is the name of the parasite in the liver stage?

sporozoite

How many sporozoites are inoculated in the skin?

What is important to remember about sporozoites?

they are very motile

What do infected hepatocyte produce?

20,000 merozoites

What is the immune's defence against sporozoites?

Ab, complement & phagocytosis

What is the immune's defence against infected hepatocytes?

cytotoxic CD8+ T cells

What is the name of the parasite in the blood stage?

merozoite

How many merozoites does one produce?

20

What is bad about infected RBC?

they are adhesive & cause disease

What is the immune's defence against merozoites?

Ab, complement & phagocytosis

What is the immune's defence against RBC?

Ab & phagocytes

What is the name of the parasite at the sexual stage?

gametocyte

What happens to gametocytes?

transmitted to mosquitos, undergo sexual development into sporozoites

What is the immune's defence against gametocytes?

Ab, complement

What is the particularity of the immune's defence against gametocytes?

can only perform actions in mosquito (when the capsule thing is removed)

What are the 3 ways malaria avoids the immune system?

sporozoite motility - active migration to prevent uptake from phagocytes

PfEMP1 - highly polymorphic, involved in adhesion & sequestration

complement reg - m & g bind factor H to prevent complement activation

What is SMA?

severe malaria anaemia

What is the main cause of SMA?

the loss of uninfected RBC

What is altered in SMA?

complement regulation

How is complement regulation changed in SMA?

- express CR1 on uninfected RBC

- binds C3b to hold on to IC

- IC + C3b phagocytosed

- acquired loss of CR1

How is natural immunity acquire?

slowly

What is the natural immunity to malaria?

not sterile, mediated by Ab to blood stage

Who does the natural immunity benefit?

individual as they are asymptomatic but still carry malaria

What are the 3 approaches to malaria vaccines?

sporozoites - prevent infection

merozoites - prevent disease

gametocytes - prevent transmission

What are the 3 leading vaccines?

sporozoite focused

whole live attenuated

RTTS

R21

What is the whole live attenuated vax?

sterile immunity, more effective in niave populations

What is the RTSS vax?

only recommended vax, virus like, based on CSP antigen, moderate efficacy

What is the R21 vax?

promising new candidate, diff expression system & adjuvant, efficacy with phase 2 trial

What are the 2 challenges to malaria vaccines?

- poor efficacy & longevity in malaria exposed populations

- don't know what immune response should be activated

What is interesting about Mtb?

a lot of people are infected with it, but never present with symptoms

What are the 3 immune evasion mechanisms of Mtb (prior to entering macrophage)?

- privileged niche

- PDIM (hide PAMPS)

- PGL (induces secretion of CCL2)

What are the 2 virulence factors of Mtb (after entering the macrophage)?

- PknG (prevent fusion of phagosome + lysosome)

- ESX-1 / ESTAT6 (allows Mtb to escape from phagosome, induces secretion of MMP for more macrophages)

What cytokine is required for an effective immune response against Mtb?

IFNy

What has helped us understand the important cells & cytokines against Mtb?

biologics & animal studies

suppress immune system (in a particular way, eg cell or signal transduction pathway) latent infection become activated, deduce what was important

What are the 2 important cells and 2 important cytokines against Mtb?

CD4+ & macrophages

TNF-a & IFN-y

What 3 host cell pathways impact the controlling of Mtb?

intrinsic/extrinsic apoptosis

necrosis

Who promotes apoptosis vs necrosis?

apoptosis - host, want to kill Mtb properly & initiate CD4+ T cell response

necrosis - Mtb, don't want to kill itself, want an inflammatory response to increase transmission to other macrophages

What are the important parts of the extrinsic apoptotic pathway?

TNF activate, caspase 8 involved, kills macrophages

What are the important parts of the intrinsic pathway?

Bax/Bak involved, kills neutrophils

What are the 3 signals for T cell activation?

1. TCR + peptide/MHCI

2. co-stim

3. cytokines

What are the 3 types of CD8+ T cells?

- naive

- effector / CTL

- memory

What is the innate immune response to a virus-infected cell? (3)

- PAMP detection via PRR

- production of type 1 IFN

- IFNa/b inhibits viral replication, upregulates MHC class I & activates NK cells & DCs

What do activated DCs do? (3)

- produce IL-12

- induce Th1 response

- help activate CD8+ T cells

What 2 things do activated CTLs produce?

- perforin (punch holes)

- granzyme (activate intracell enzymes to induce apoptosis)

What 3 cytokines do CTLs produce?

- TNFa (pro-inflamm, activates endothelium)

- IFN-y (inhibits viral replication, activates macrophages)

- IL-2 (autocrine, increase CTL prolif & survival)

What are the 3 physical & chemical immune components of a viral infection?

epithelium, mucous, mucosal anti-viral peptides

What are 5 innate immune response components of a viral infection?

NKT cells, NK cells, TLRs, NLRs, type 1 IFNs

What are 4 adaptive immune response components of a viral infection?

plasma cells, CTLs, Abs, type 2 IFNs

What are the 2 determinants of an effective anti-viral CD8+ T cell response?

magnitude and function

What is immunodominance?

one epitope on an antigen produces a larger response than other epitopes

What are the 2 things that influence how functional a CD8+ T cell is?

cytotoxicity (cytotoxic granules & Fas-FasL engagement)

production of cytokines

What does IFNy do (in context of viral infections)? (3)

inhibit viral replication

induce MHCI upregulation

What does TNFa do (in the context of viral infections)? (3)

macrophage activation

lysis of infected cells

pro-inflamm

What are the two surface proteins of influenza?

hemagglutinin and neuraminidase

What is hemagglutinin? (2)

allows binding & entry to host cell

neutralising Ab stops entering to prevent infection

What is neuraminidase?

allows viral release from cells

What are seasonal flu epidemics a result of?

small mutations in HA/NA

How is a good vax made for the flu? (2)

requires correct predictions & the strains not to mutate

What is the first step in immunopathology of the flu?

viral peptide/MHCI complexes on epithelial cells are recognised by CTL

What occurs after the first step in the immunopathology of the flu?

1. infected cells produce chemokines - induces cellular infiltration & bystander epithelial cell death

2. CTL produces cytotoxic molecules

3. CTL produce cytokines to activate epithelial cells to produce chemokines

What do IL-8 & CXCL1 (produced from epithelial cells) do?

recruit neutrophils

What do CCL5 (produced from epithelial cells) do?

recruit CTL

What do CCL2/MCP-1 (produced from epithelial cells) do?

recruit macrophages

What are the 2 ways DC uptake viral antigens after epithelial cell dies from viral infection?

direct - endocytosis

indirect - they get infected

What occurs after DCs uptake viral antigens?

- migrate to DLN & present Ag

- prime T cells

- CTL to migrate to site of infection

- CTL produce antiviral cytokines & directly kill infected cells

What part of the immune system is inflammation important in?

innate

What is acute inflammation?

short lived, warranted to clear an irritant, triggered by innate