Failures of the Body's Defenses

Question 1

Genetic variations within pathogens

Answer 1

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

Question 2

Example of pathogen with genetic variation

Answer 2

Streptococcus pneumoniae

- has 90 known stereotypes that can result in 90 primary immune responses

Question 3

____ allows influenza virus to escape from immunity

Answer 3

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

Question 4

Type of mutation that most commonly occurs

Answer 4

Point mutation

- point mutations in hemagglutinin and neuroaminidase viral genes = antigenic drift

Question 5

Recombination

Answer 5

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

Question 6

Antigenic shift

Answer 6

Appearance of new antigens as a result of genetic recombination between two or more viral strains

Question 7

Gene rearrangement by Trypanosomes

Answer 7

• 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

Question 8

Persistance by hiding from the immune response

Answer 8

• Herpes virus persist in latent state in the trigeminal ganglion
• Ncp BVDV

Question 9

Mycobacterium tuberculosis

Answer 9

Phagocytosis prevents fusion of the phagosome with the lysosome = protection from lysosomal enzymes, surviving within the cells vesicular system

Question 10

Salmonella typhimurium

Answer 10

Changes selective phagocytosis into non-selective macropinocytosis = avoid fast and effective antigen recognition

Question 11

Listeria monocytogenes

Answer 11

Escapes from phagosome into the cytosol = replication, but will eventually be caught in cytosol by cytotoxic T cells

Question 12

Toxoplasma gondii

Answer 12

Creates own vesicle environment = prevention of binding to MHC and their presentation to T cells

Question 13

Treponema pallidum

Answer 13

Coat with human proteins = evasion of specific antibodies

Question 14

Survival strategies of intracellular proteins

Answer 14

• 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

Question 15

Toxoplasma gondii host interaction

Answer 15

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

Question 16

Leishmania host interaction

Answer 16

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

Question 17

What is the target cell for Leishmania?

Answer 17

Host macrophages

Question 18

Plasticity of CD4+ T cell subsets

Answer 18

• 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

Question 19

Leishmania-specific Th1 cells may be reprogrammed to ____

Answer 19

IL-10 producing Tregs

Question 20

Sterilizing immunity

Answer 20

Get rid of every single pathogen

• no Tregs to stop macrophage activation
• Th1 secretes IFN-gamma to activate macrophages

Question 21

Chronic infection

Answer 21

Tregs become regulatory too early to cause rogue immunopathology

Question 22

Superantigens

Answer 22

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

Question 23

If a large number of T cells are activated by SAgs, then the result is

Answer 23

Massive systemic release of pro-inflammatory cytokines (tumor necrosis factor-alpha, IL-1beta) and T cell mediators (IL-2) = fever and shock

Question 24

Superantigen mode of stimulation

Answer 24

• 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

Question 25

______ can contribute to disease

Answer 25

Immune responses

• for some infectious diseases, all pathology is due to immune response
• ex: RSV, wheezy bronchiolitis (Th2), Schistosoma mansoni (Th2)

Question 26

How helminths go viral

Answer 26

Cellular signals during helminth infections can skew the immune response to favor viral spreading

Question 27

Altered immunity

Answer 27

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

Question 28

Ideal immune response

Answer 28

Terminates infection before the pathogen damages tissues or saps the body’s resources

Question 29

Ideal situation for a pathogen

Answer 29

Immune system does not interfere with growth and replication

- other parts of the body provide food/water

Question 30

Evolved ways of pathogen reducing effectiveness of immune responses

Answer 30

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