03/06d Host-Pathogen Interactions & Vaccines Flashcards
(43 cards)
What are the five general features of immune responses to microbes, and microbe responses to the immune system?
1) Always involve innate and adaptive immunity
2) Distinct and specialized responses to different types of microbes for maximum effectiveness
3) Microbes evade or resist effector mechanisms
4) Many microbes can establish latent infections, that the immune system can control but does not eliminate
5) Tissue injury and disease can be caused by the host response rather than the microbe itself
For what types of things are immune responses specialized to fight? Name five
Extracellular bacteria Intracellular bacteria Viruses Fungi Parasites
What are the innate and adaptive responses to extracellular bacteria?
Innate - activation of complement, phagocytes, and inflammation
Adaptive - humoral (antibodies block infection, opsonize microbes, and neutralize toxins) and CD4 helper T cells (enhance phagocytic and microbicidal activities of macrophages and neutrophils, and stimulate antibody production)
What types of effector T cells are stimulated by extracellular bacteria? What are their responses?
Th1 and Th17 cells
Th17 responses - IL-17 induces production of cytokines, which recruit neutrophils and monocytes
Th1 responses - IFN activates macrophages to destroy phagocytosed microbes and induces opsonization and complement-binding
What are four immune pathologies associated with extracellular bacterial infection?
Excessive inflammation
Abscess formation
Septic shock
Toxic shock
How does your immune system cause excessive inflammation?
Result of reactions of neutrophils and macrophages
Local production of ROS and lysosomal enzymes can kill bacteria AND damage tissue
What is an abscess? How is it formed?
An abscess is the creation of a new anatomical space for the purpose of containing a bacterial infection
Neutrophils accumulate (pus), but are not sufficient to eliminate the infection
NOT penetrated by antibiotics - require surgical drainage
How is an empyema different from an abscess?
An empyema is the accumulation of pus in a preexisting anatomical space, rather than the formation of a new anatomical space
What is septic shock? What causes it?
Consequence of disseminated infection by certain bacteria (many have LPS)
Caused by widespread release of cytokines (TNF, IL-6, IL-1) by activated macrophages
Results in circulatory collapse and intravascular coagulation
Treatment - ICU, antibiotics
What is toxic shock? What causes it?
Caused by Staph and Strep infections which produce toxins that are superantigens - activate many T cells and cause cytokine storm
Disseminated infection is not required
Associated with anything that predisposes to Staph and Strep infections (surgery, childbirth, skin wounds)
How do extracellular bacteria evade the immune system? List six ways
1) Resist phagocytosis (polysaccharide-rich capsule) and complement (sialic acid residues)
2) Catalase - scavenges ROS
3) Antigenic variation - extensive mutation of dominant epitopes to evade detection
4) Molecular mimicry - if bacterial antigens resemble self proteins, the immune response may be weak, or may be directed at self
5) Coagulase and clumping factor cause fibrin to clot and deposit on cell surfaces
6) Proteins produced by Staph and Strep bind up Ig
What are the innate responses to intracellular bacteria?
Expression of NK cell-activating ligands on infected cells
Activated NK cells kill infected cells
Stimulation of dendritic cells and macrophages to produce IL-12 and IL-15
Innate response often fails to eradicate the microbe
What are the adaptive responses to intracellular bacteria?
Th1 cells produce IFN
IFN activates macrophages to destroy phagocytosed microbes and induces opsonization and complement binding
Th1 cells also activate macrophages through CD40L
Macrophages produce IL-12, which stimulates NK cells
If the macrophages fail to eliminate the infection, CD8 cytotoxic T cells kill the infected cells
How do intracellular bacteria evade the immune system?
Able to survive inside cells - hide from antibodies and complement
Stimulate inappropriate T cell polarization - Th2 cells inhibit Th1 cells, thus preventing the destruction of intracellular bacteria
What is the major immune pathology associated with intracellular bacteria?
Granulomas
What are the innate responses to virus infection?
PRRs recognize viral PAMPs
Immediate response - production of Type I Interferon, which induces an antiviral state in adjacent uninfected cells
PAMPs also induce NK cell activating receptors - NK cells kill virus-infected cells
What are the humoral adaptive responses to virus infection?
Antibody production - neutralizing antibodies block virus binding and entry, which can prevent both initial infection and spread
Effective against viruses only during their extracellular stage
Major determinant of immunity to most viruses
IgA - important for neutralizing viruses at mucous membranes (respiratory and GI tracts)
What are the cell-mediated adaptive responses to virus infection?
Activation of CD8 cytotoxic T cells, which recognize viral peptides presented on MHC I
If dendritic cells are not infected, they phagocytose infected cells and transfer viral peptides from the phagosome to MHC I (cross-presentation)
CD8 cells undergo massive proliferation
CTLs require cytokines produced by CD4 helper cells
How do viruses evade the immune system? List five ways
1) Can alter their antigen through mutation until they no longer evoke immune responses
2) Some inhibit MHC I-associated presentation of viral peptides
3) Produce MANY molecules that inhibit immune responses (cytokine and interferon production in particular)
4) Infect and kill/inactivate immunocompetent cells
5) Establish latency
What is antigenic drift?
Constant mutation of viruses, combined with strong selection pressure of the immune system, that leads to neo-epitopes that are not recognized by the immune antibodies
What is antigenic shift?
Different variants of a virus that both infect a single host, and are thereby able to exchange genetic material, possibly resulting in a “super virus” (one with multiple devastating characteristics)
What is viral latency?
Persistence of viral DNA in a host cell, without viral replication of destruction of the host cell (state of balance)
Virus reactivates when host immunity diminishes
Common with EBV and certain DNA viruses in the herpesvirus family
What are the immune pathologies associated with virus infection?
Anti-viral responses are extremely strong! can destroy local (uninfected) cells and induce systemic effects
CTLs may kill virus-infected cells even when the virus is not cytopathic (HBV)
What are the innate and adaptive response to fungi?
Innate - activation of phagocytes
Adaptive - activation of CD4 helper T cells (Th1 or Th17 responses)
Often have a combination of responses
