Failures of the Body's Defenses Flashcards
Genetic variations within pathogens
Some species of pathogens evade protection from antibodies that detect surface macromolecules by existing in different strains, which differ in antigenic macromolecules on their outer surface
Example of pathogen with genetic variation
Streptococcus pneumoniae
- has 90 known stereotypes that can result in 90 primary immune responses
____ allows influenza virus to escape from immunity
Mutation
- binding of neutralizing antibodies to hemagglutinin of virus V prevents binding to cells in person P –> in person Q, mutation occurs in virus V to produce V* with an altered hemagglutinin –> neutralizing antibodies against virus V in person P do not block binding of virus V* to cells
Type of mutation that most commonly occurs
Point mutation
- point mutations in hemagglutinin and neuroaminidase viral genes = antigenic drift
Recombination
Secondary host is infected 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 expressing a novel hemagglutinin
Antigenic shift
Appearance of new antigens as a result of genetic recombination between two or more viral strains
Gene rearrangement by Trypanosomes
- antigenic variation allows trypanosomes to escape from adaptive immunity
- antibody mediated clearance of pathogen expressing dominant form of VSG (variable surface glycoproteins)
- one minority form will dominate in pathogen population
- # of parasite expressing dominant form of VSG will stimulate production of antibodies, etc = cycling of parasites within the infected person
Persistance by hiding from the immune response
- Herpes virus persist in latent state in the trigeminal ganglion
- Ncp BVDV
Mycobacterium tuberculosis
Phagocytosis prevents fusion of the phagosome with the lysosome = protection from lysosomal enzymes, surviving within the cells vesicular system
Salmonella typhimurium
Changes selective phagocytosis into non-selective macropinocytosis = avoid fast and effective antigen recognition
Listeria monocytogenes
Escapes from phagosome into the cytosol = replication, but will eventually be caught in cytosol by cytotoxic T cells
Toxoplasma gondii
Creates own vesicle environment = prevention of binding to MHC and their presentation to T cells
Treponema pallidum
Coat with human proteins = evasion of specific antibodies
Survival strategies of intracellular proteins
- interfere with antigen uptake, avoiding antigen recognition
- create own vesicle environment, preventing MHC binding
- prevent fusion of phagosome with lysosome, protecting themselves from enzymes
- escape from phagosome into cytosol to grow and replicate
Toxoplasma gondii host interaction
Obligate intracellular parasite
- invade/replicate in all nucleated cells of warm-blooded animals
- regulates immune activation and host cell effector mechanisms by specific parasite effector proteins
- T. gondii effectors are master regulators of proinflammatory response
Leishmania host interaction
Traid of vector borne disease
- infectious agent, vector, and host immune system
- effect on host immunity is to promote Th2 regulated humoral responses above the host protective Th1-regulated cellular immune response
What is the target cell for Leishmania?
Host macrophages
Plasticity of CD4+ T cell subsets
- sterilizing immunity is prevented by action of T cells with regulatory function
- Tregs prevent complete elimination of the infection, but are crucial in inhibiting the development of secondary immunopathology
Leishmania-specific Th1 cells may be reprogrammed to ____
IL-10 producing Tregs
Sterilizing immunity
Get rid of every single pathogen
- no Tregs to stop macrophage activation
- Th1 secretes IFN-gamma to activate macrophages
Chronic infection
Tregs become regulatory too early to cause rogue immunopathology
Superantigens
Stimulates T lymphocytes in an uncontrolled manner = fever, shock, death
- bind as intact molecules to MHC 2 expressed on APCs outside the peptide-binding groove –> binds to TCR via variable region of TCR beta chain
If a large number of T cells are activated by SAgs, then the result is
Massive systemic release of pro-inflammatory cytokines (tumor necrosis factor-alpha, IL-1beta) and T cell mediators (IL-2) = fever and shock
Superantigen mode of stimulation
- does not prime an adaptive response for the specific antigen
- stimulates large numbers of T cells
- causes massive production of cytokines by CD4+
- contributes to microbial pathogenicity
______ can contribute to disease
Immune responses
- for some infectious diseases, all pathology is due to immune response
- ex: RSV, wheezy bronchiolitis (Th2), Schistosoma mansoni (Th2)
How helminths go viral
Cellular signals during helminth infections can skew the immune response to favor viral spreading
Altered immunity
Helminth infection activates Th2 to release IL-4 and IL-13 –> ligate IL-4R on macrophages harboring latent herpesvirus –> IL-4R activates host STAT6 to act on key viral gene that initiates viral replication
OR, M2 macrophage activated by IL-4 or IL-23 directly inhibits production of virus specific T cells = subsequent infection by virus is not controlled
Ideal immune response
Terminates infection before the pathogen damages tissues or saps the body’s resources
Ideal situation for a pathogen
Immune system does not interfere with growth and replication
- other parts of the body provide food/water
Evolved ways of pathogen reducing effectiveness of immune responses
Passive:
- antigenic variation preventing maturation of adaptive immunity and immune memory
- latency (avoiding immune response)
Active:
- interference with key elements of immune response by inhibiting normal immune function or recruiting response to the pathogen’s advantage
