Subversion of immunity/immunodeficiency Flashcards
Immunity to microbes and subversion of the immune response
how pathogens make their way in the face of the human defenses
Effective immunity to extracellular bacteria
Antibody
- neutralization
- opsonixation and Fc receptor-mediated phagocytosis
Complement activation
- Phagocytosis of C3b coated bacteroa (opsonization)
- Inflammation
- Lysis of microbe
^ work together with phagocytes to lead to the destruction of extracellular bactera.
Th17 type
T helper response is favorable for clearance of extracellular bacteria
It recruits neutrophils.
immunity to intracellular bacteria
Innate and adaptive immunity
Live inside host cells
Must be either killed by T cells or killed by the host cell which has to be activated.
intracellular bacteria molecules
IL12
IFNy
work in both innate and adaptive immunity
IL 12 secreted by macrophages
can activate NK cells, and T helper to make IFNy.
IFNy can perform macrophage activation
and cells (Th1)
intracellular bacteria response
- IL12 response from macrophage or APC
- IL12 acts on T cell which makes IFNy
- Leads to macrophage activation
- phagocytosis and bacterial killing
IFNy produced by
CD4 T helper cells, not only supports macorphage activation but also supports CD8 T cell actvivation and killing of infected cell.
virus immunity (live inside cells)
Innate response
- type I interferon (IFNalpha and Beta) - creates an anti viral state
- NK cells
Adaptive response
- Antibody - neutralization
- CD8 + CTL - killing and eradication of established infection
Extracellular bacteria key players
- Th17
- neutrophils
- antibodies
- complement
Intracellular bacteria key players
- Th1
- IFN-gamma
- macrophage activation
viruses - key playeres
- Type I IFN
- NK cells
- Neutralizing antibody
- CTL
Kinetics of immune response to virus
Virus titer - highest at day 5. cleared by day 12
Innate response
1. Type I interferon
2. NK cells
Adaptive response
1. Virus specific CTL
2. Antibody
What are strategies pathogens use to survive in human host?
- Change what they are “wearing” (changes in their antigens)
- hide out and rest
- disrupt antigen processing and presentation
- inhibit or suppress innate or adaptive immunity
- Live as a community in a biofilm
S. pneumoniae, comes in different
serotypes
- type of antibody response, based on capsule polysaccharides
- “changing what they are wearing”
serotype
- many bacteria evade host immunity by existing as different strains which differ in the antigenic molecules on their surface
- serological assays are used to determine the identity of bacterial strains based on the antibodies that bind them
- Following an infection with one bacterial serotype, a patient will have protective immunity to that strain, but not a different serotype
Vaccines against streptococcus pneumoniae
- Polysaccharide vaccine
- Conjugate vaccine
Polysaccharide vaccine
consists of purified polysaccharides from 23 different serotypes
- Pneumovax
- T-independent, IgM produced (type 2 response)
- Immunity is not as robust or long lasting, but serotype coverage is broad
Conjugate vaccine
capsular polysaccharide coupled to diptheria toxoid
- Prevnar 7 and Prevnar 13 are two brands
- T dependent immunity, other isotypes, B cell memory
- Immunity is more robust, but serotype coverage is more limited
antigenic drift
way for influenze to change its “antigenic clothes”
- small change in one person, let another person unable to have a secondary immune response
small changes to viral genome that result in changes in the anitgens and their desired binding to surfaces
antigenetic drift definition
viruses such as influenza are prone to mutations. Point mutations in certain antigens (H and N) are sufficient to alter antibody binding, creating a means of escape from the existing antibody response
antigenic shift
more dramatic changes in the virus in which new recombinant viral genomes are generated in cells infected with two distinct viruses (human and avian) leads to more spread, pandemic.
anitgenic shift - more dramatic
results in a different virus that no one has pre-existing immunity to
- a secondary host is infectied with a human and an avian strain of virus
- recombination of viral RNA in the secondary host produces virus with a different hemagglutinin
- No cross protective immunity in humans to virus expressig novel hemaggluthinin
human influenza virus
8 RNA segment genome
Neuraminidase
Hemaglutinin
avian influenze virus
- HA gene
- NA gene
Latency
a dormant, a state in which replication does not occur.
Ex: herpes simplex virus.
- little viral gene expression is observed
- virus can hide in this state for long periods
- Upon reactivation, the immune response can respond to viral infection
stress induce reactivation of the virus.
Virus that is immunosuppressive
Epstein Barr Virus
Produces cytokine homoloh of IL10
Inhibits Th1 lymphocytes
Reduces IFNy production
Viral mechanism to inhibit antigen processing and presentation
Removal of Class I from ER: CMV
Reduces expression of MHC class I expression on the cell surface
Biofilms
- surface attached community of bacteria encased in polymeric matrix
- protected from a number of stresses or immune defenses
- less sensitive ROI, phagocytosis, complement, neutrophil attack
Characteristics of many mucosal infections: Otitis, pneumonia
change what they are wearing
streptococcus pneumonia
influenza
- antigenic shift
- antigenic drift
hide out and rest
Herpes Simplex Virus (HSV)
Disrupt antigen processing and presentation
several viruses, CytoMegalo Virus (CMV) is best example
Inhibit or suppress innate or adaptive immunity
EBV-IL10-Homolog
live as a community in biofilm
Haemophilus influenzae
Extracellular bacteria
- complement
- neutrophils
- antibody
- Th17
intracellular bacteria-
- macrophages
- IL12, which leads to IFN gamma production from CD4+ Th1 cells
- macrophage activation
- CTL contributes too
