EXAM #1: IMMUNOLOGY OF INFECTIOUS DISEASE Flashcards
How do extracellular bacteria evade the immune system?
1) Induction of vigorous inflammation
2) Production of toxins that kill host cells
*So we try to kill the bacteria and neutralize the toxins
What is the major innate immune response against extracellular bacteria?
Phagocytosis via neutrophils (blood) and macrophages (tissue)
What is the first cell to arrive in acute inflammation?
Neutrophils
What do phagocytes recognize on extracellular bacteria?
Bacterial structure including:
1) Polysaccharides
2) Peptides (RGD sequence)
What is the main immunologic responder to blood-born pathogens?
Spleen
What is the main immunologic responder to tissue-born pathogens?
Lymph nodes
What is the role of unmethylated CpG dinucleotide motifs in the immune system?
Activation of macrophages
What metal is required for many bacteria to survive?
Iron
What is MOA of lactoferrin? What cell releases lactoferrin?
- Neutrophils
- Lactoferrin lowers iron concentrations (starves bacteria of iron)
What does a deficiency in C5-C9 lead to?
Susceptibility to N. meningitidis infection
What is the principal immune defense against extracellular bacteria?
Humoral immunity i.e. antibodies
How does humoral immunity combat extracellular bacterial infection?
1) IgG opsonization
2) Toxin-specific antibody neutralization
3) IgM and IgG activate classical complement pathway
What infections are neonates susceptible to as maternal antibodies disappear?
- S. pneumoniae
- N. meningitidis
- H. influenzae
What antibody can opsonize bacteria at mucosal sites?
IgA
What is the most common immunodeficiency?
Selective IgA
*Note that IgM can compensate
What complement pathway is specifically inhibited by a polysaccharide capsule?
Alternative pathway
*Note that IgG and C3b can bind and opsonize these bacteria for elimination
What organism drastically alters its surface adhesion proteins?
Neisseria
What organisms can produce IgA1 protease?
1) S. pneumoniae
2) Neisseria
3) Hemophilus
How does S. pyogenes evade immunity?
Interferes with complement activation via M proteins
How does S. pneumoniae evade immunity?
C3 protease
How does S. typhi evade the immune system?
Type III secretion system
*Prevents NFkB mediated signaling and secretion of TNF-a
What organisms are most associated with septic shock?
Gram negative
What cytokines mediate septic shock?
TNF-a
IL-1
What are superantigens?
- Toxin that binds Class II MHC on APCs and T-cells
- Causes the production of TNF-a
What causes Rheumatic Fever?
Cross-reactive antibodies induced by strep M-protein
What causes poststreptococcal glomerulonephritis?
Antibodies form immune complexes that deposit in the kidney
*Type III hypersensitivity
What are the three major spirochetes?
1) Treponema pallidum (Syphillis)
2) Borrelia burgdorferi (Lyme)
3) Leptospira
How do spirochetes enter the body?
Broken skin or vector
*Cannot penetrate intact skin
What is the major mechanism of immunity against spirochetes?
Adaptive immunity
*Note a very good response from innate immunity
What is the role of cell-mediated immunity (Th1) in spirochete infection?
Clearing infection
What is the role of humoral (Th2) immunity in spirochete infection?
Protection against reinfection
How does T. pallidum evade the immune system?
Lacks virulence factors ; is simply very resistant to normal host mechanisms
How does B. burgdorferi evade the immune sytem?
Coats self with amorphous host material
What are the manifestations of an overzealous immune response against spirochetes?
1) Rash of secondary syphilis is Type III hypersensitivity reaction
2) Lyme arthritis is caused by T-cells
What is the major innate immune response to fungal infections?
Neutrophils
*Note that neutropenic patients highly susceptible to C. albicans
What is the major adaptive immune response to fungal infections?
Cell mediated immunity (Th1)
*Can lead to granuloma formation
What is the major immune response to helminth/worm infections?
IgE production (Th2)
What are the major adaptive immune responses to protozoa (Leshmania and Trypanosoma)?
These organisms infect macrophages and produce a Th1 response
What happens after macrophages are exposed to IFN-gamma?
1) NO production
2) Depletion of intracellular tryptophan that is essential for some parasites
What is the major immune mechanism against Plasmodium?
Th1, CTLs against intrahepatic stage
What is the major deletarious effect of the immune response to Plasmodium?
High levels of TNFa production
What strategies do parasites use to evade the immune system?
1) Conceal in intestinal lumen
2) Coat with host proteins
3) Inhibition of complement activation
4) Production of enzymes that cleave membrane bound antibodies
What is a high level of TNF-a production in childhood malaria infections prognostic for?
Death
What do you need to remember about vaccines and parasite infected areas?
- Vaccines= Th1 immune response
- Chronic parasite infestation can induce strong Th2 response
*Thus, b/c of the reciprocal relationship between these two immune reactions, vaccines may not be as efficacious
