CMB2004/L10 Immunity Against Infection III Flashcards
Give 3 evasion mechanisms of pathogens.
Concealment of antigens
Antigenic variation
Immunosuppression
Interference with effector mechanisms
Describe concealment of antigens using an example.
Viruses inhibit antigen presentation by MHC class I
HSV
Uptake of host molecules (cloak effect)
Define a ‘privileged site’.
An area of the body where the immune response is limited or altered to protect tissues from potentially damaging inflammation
Give an example of a pathogen using a privileged site to its advantage.
Latency of Herpes zoster virus in CNS (chicken pox -> shingles)
Hydatid cysts in Echinococcus infection (dog tapeworm)
Give 2 kinds of antigenic variation.
Mutation - antigenic drift
Recombination - antigenic shift
Gene switching
Give 2 pathologies caused by Streptococcus pneumoniae.
Otitis media
Sinusitis
Bronchitis
Pneumonia
Bacteremia
Meningitis
Describe the structure of Streptococcus pneumoniae. (3)
Gram +ve
Surrounded by thick polysaccharide capsule protecting from phagocytosis
Ab to capsule opsonise bacteria and protect
91 capsular types
Give 2 vaccines for Streptococcus pneumoniae.
Pneumovax
Prevnar 13
Describe the Pneumovax vaccine for S. pneumoniae.
Polysaccharide vaccine (ag to all 23 capsules)
Not effective in children u2 or poor immune function
Low level B cell IgM response
Describe the Prevnar 13 vaccine for S. pneumoniae.
Conjugate (weak + strong Ag)
13 capsule Ag bound to diphtheria toxoid - highly immunogenic & non-toxic
B and T cell response
Explain how antibodies are produced in response to tetanus toxoid protein. (4)
B cell binds bacterial polysaccharide epitope linked to tetanus toxoid protein
Ag internalised and processed
Peptides presented to T cell
Activated B cell produces Ab against polysaccharide antigen on surface of bacterium
Describe influenza virus.
-ve sense segmented genome
Can infect humans, birds, other animals
Causes epidemics and pandemics
Major surface Ag. haemagglutanin and neuraminidase
Can undergo antigenic drift and shift
Describe antigenic drift in influenza. (2)
Neutralising Ab against haemagglutanin block binding to cells
Mutations after epitopes in haemagglutanin so that neutralising Ab no longer binds
Describe antigenic shift in influenza. (2)
RNA segments exchanged between viral strains in secondary host
No cross-protective immunity to virus expressing novel haemagglutanin
Describe Trypanosoma brucei.
Protozoal parasite causing African sleeping sickness
Spread by Tsetse fly
Patients undergo bouts of parasitaemia
Genetic rearrangement
Variant-specific glycoprotein (VSG)
Describe the clinical course of trypanosome infection. (3)
Many inactive trypanosome VSG genes but only one site for expression
Inactive genes copied into expression site by gene conversion
Many rounds of gene conversion allowing trypanosome to vary VSG gene expressed
Describe immunosuppression by pathogens. (2)
Infection of immune cells
Induction of regulatory cells
Describe regulatory T cells (Treg).
CD4+ cell
Regulate and suppress differentiation and proliferation of TH1 and TH2 cells
Maintain tolerance to self-antigens
Help prevent autoimmune disease
Express biomarkers CD4 and CD25 on surface and FoxP3 (transcriptional factor)
Describe how Helicobacter pylori interferes with immune response.
Boosts level of Treg suppressing immune response
What does the Gram -ve bacterium Helicobacter pylori cause in humans?
Gastric and duodenal ulcers
Gastric adenocarcinomas
Describe Leimania.
Parasite transferred by sand flies
Increase expression of Treg cells
Decrease immune response
Describe measles virus.
RNA virus
Complications - secondary bacterial respiratory infections
Causes immunosuppression
Infects dendritic cells
Give 3 signs of infected dendritic cells.
Increased apoptosis
Decreased stimulation of T cells
Decreased IL-12 production (NK cells and TH1 affected)
Define a dendritic cell.
APC (MHC I and MHC II)
Act as messengers between innate and adaptive immune systems
Give 3 methods of interference with effector mechanisms.
Molecules interfering with Ab function
Molecules interfering with complement
Molecules binding cytokines
Subvert responses by producing molecules with cytokine activity
Inhibition of phagocytic killing
Give an example of interference with antibody function.
IgA proteases by S pneumoniae, Neisseria
Fc-binding molecules by Staphylococcal protein A, HSV
Give an example of molecules interfering with complement.
Enzymes that break down C3a/C5a - pseudomonas
Molecules that inhibit complement activation - vaccinia/smallpox virus
Give an example of molecules binding cytokines.
Vaccinia (smallpox) binds IFNy
Give an example of subverting responses by producing molecules with cytokine activity.
Epstein Barr Virus produces vIL-10 (downregulates TH1 response)
Give an example of an organism that inhibits phagocytic killing.
M. tuberculosis
Describe how M. tuberculosis persists in macrophages.
When reaching host’s lungs, cells bind to TLR-2 receptor on macrophage surface
Prevent fusion of phagosomes with lysosomes so allow bacteria survival
Give 2 innate pathological consequences of immune responses.
LPS induces macrophage cytokine secretion
Fever
Endotoxic shock
Cytokine storm
What is the role of TNF-a?
Activates vascular endothelium
Increases vascular permeability
Leads to increased entry of IgG, complement and cells to tissues and increased fluid drainage to lymph nodes
Fever
Mobilisation of metabolites
Shock
Describe local infection with Gram -ve bacteria. (6)
Macrophages activated to secrete TNF-a in tissues
Increased release of plasma proteins into tissue
Increased phagocyte and lymphocyte migration to tissue
Increased platelet adhesion to blood vessel wall
Phagocytosis of bacteria, local vessel occlusion
Plasma and cells drain to lymph node
Describe systemic infection with Gram -ve bacteria. (4)
Macrophages activated in liver and spleen secrete TNF-a into bloodstream
Systemic edema causing decreased blood volume, hypoproteinemia and neutropenia, followed by neutrophils
Decreased blood volume causes collapse of vessels
Disseminated intravascular coagulation leading to wasting and multiple organ failure
Describe Ebola. (2)
Filovirus - non-segmented -ve RNA with filamentous particles
Causes haemorrhagic fever
Outbreak in West Africa largest in history
70% fatality rate
Describe how Ebola evades the immune responses. (3)
Infects immune cells including dendritic cells and macrophages
Inhibits maturation of dendritic cells so no APC
Causes apoptosis (low T lymphocytes and NK cells)
Interferes with T1 interferons production & cellular response to interferon
Describe the immunopathogenesis of Ebola.
Induction of cytokine secretion (‘storm’) by macrophages plays central role
Shed glycoprotein from virus binds macrophages and dendritic cells - cytokine release and increased vascular permeability
Infected macrophages express more tissue factor = coagulation cascade & disseminated intravascular coagulation & death
