immunological overview infection: maleria Flashcards
What does a plasmodium need to cause infection
Two hosts: human and anopheles mosquito
What is the plasmodium life cycle in a human
11-14 days
Skin: sporozoites enter and travel to liver
Liver: invasion and replication
Blood: erythrocytic cycle = fever
What is the plasmodium life cycle in a mosquito
(7-14 days)
Gametocytes ingested and mature (sexual stage)
Fertilisation -> Ookinete -> oocyst gut wall
Release of sporozoites -> salivary gland
What response do sporozoites elicit
Elicit priming of cytotoxic T lymphocytes (CTL) in lymph nodes
What are the three steps sporozoites take to leave the skin
Migration
Destruction
Lymph node entry
What is the migration process of sporozoites
Sporozoite is motile and migrates through the dermis seeking a blood vessel
What is the destruction process of sporozoites
Immune system reacts to destroy invading sporozoites (macrophages)
What is the process of lymph node entry
Travel to draining lymph node where they are taken up by antigen presenting cells
How is the exogenous antigen, which is outside the cell, processed
Processed and loaded onto MHC class II, and presented to a T helper cell (Th, CD4+)
What is an exogenous antigen
An exogenous antigen refers to any antigen that originated outside the body
What is an endogenous antigen
An antigen that orgiginates from a cell
How is an endogenous antigen (inside the cells) processed
Processed and loaded onto MHC class I and presented to cytotoxic T lymphocytes (CTLs, CD8+)
What is cross-presentation
Process by APCs which is mediated by perforin 2 and can export antigen from an endosome into the cytoplasm
Why do sporozoites target the liver once entered the blood stream
Liver is Primary target organ for sporozoites to cross the liver sinusoidal barrier and enter hepatocytes
What are hepatocytes and their importance
Specialised epithelial cells important for protein synthesis and storage, production of bile and synthesis of blood clotting factors
What cells can take up sporozoites
Kuppfer cells (macrophage subset in the liver)
What do sporozoites trigger
Trigger a local innate response in liver
What happens to the infected hepatocyte
Infected hepatocytes recognise sporozoites
Release type I interferon
Signals to neighbouring hepatocytes
Reduces chances of infection
Increases antigen presentation
What is the FAS/FASL mechanism of killing infected hepatocytes
FAS/FASL => death receptor => activates caspases
What is the perforin and granzyme B mechanism of killing infected hepatocytes
Perforin + granzyme B => pore forming protein followed by family of serine proteases => induces apoptosis
What is hepatomegaly
Enlargement of the liver which is caused by malaria
What is splenomegaly
Enlargement of the spleen caused by malaria
Why is the spleen important
Filtration of parasitised red blood cells
Activates T and B cells
What is clinical malaria driven by
Driven by blood stage infection
What are the mechanisms leading to less RBC’s (red blood cells)
Lysis of parasitised (p) RBCs
Removal of pRBCs in the spleen
Decreased and/or suppression of erythropoiesis
Removal of uninfected RBCs
What is erythropoiesis
The process in which RBCs (red blood cells) are made in the body
Why can the removal of pRBCs cause the decrease of uninfected RBCs
For ever 1 pRBC, 12 uninfected RBCs are lost
What is haemozoin (Hz)
A product of haemoglobin metabolism by plasmodia
What is dyserthropoiesis
Suppression of erythropoiesis
What are 5 features of naturally acquired immunity
Effective in adults after uninterrupted lifelong heavy exposure
Lost upon cessation of exposure
Species specific
Somewhat stage specific
Acquired at a rate which was dependent on exposure
Why would immunity be hard to achieve with malaria
Antigenic variation
Regulation of the immune reponse e.g IL-10 preventing activation within cells
What does the T regulatory 1 cells produce
IL-10
What does IL-10 do
Inhibits immune cell function therefor efficient function and development of quality memory responses
