Download How to be a good pathogen

Bio260 – Microbiology, North Seattle College, Colleen Sheridan
Welcome class! As aspiring pathogens, you are likely here today to learn how to be a really great pathogen.
I’m assuming that you all have inherited some genetic variations that allow you to become virulent. Now,
before you go entering someone’s body and causing a ruckus, if you want your progeny to survive, you’ll need
to know this very simple plan.
How to be a good pathogen:
1. Avoid the immune response
2. Make more of yourself
3. Exit the host to get to another
In order to be a good pathogen, you’ll need to choose one of the following ways that you’d like to cause
disease.
Four (4) Mechanisms of Pathogenesis
1. Ingested toxins
2. Colonization of mucous membranes and toxin production
3. Invasion of host tissues
4. Invasion of host tissues and toxin production
OK, let’s begin.
1. Avoid the immune response
How to Avoid the Immune Response in 50 Easy Ways
1. Hide in a host cell
A. Directed uptake by Cells
B. Antigen-Sampling
2. Avoid Complement
A. What is complement? Where do you find it? How does it get activated? How is it regulated? What
happens once it gets activated?
B. How can you avoid complement?
1. Bind to host complement regulatory proteins and inactivate C3b
a. inhibits MAC formation
b. inhibits opsonization by C3b
c. bacterial structures that bind regulatory proteins
i. capsules (S. pnuemoniae)
ii. M protein (S. pyogenes)
2. Make C5a peptidase to chew up C5a and inhibit attraction of phagocytes and inflammation
3. Avoid Destruction by Phagocytosis
A. What is phagocytosis? How do phagocytes get called to the scene? What makes it easier for
phagocytes to grab onto bacteria? How does phagocytosis work?
B. How can you avoid being destroyed by phagocytosis?
1. Avoid encounters
a. C5a peptidase (keep phagocytes from coming to the scene)
b. Membrane-damaging toxins (kill phagocytes as well as neighboring cells)
2. Avoid recognition and attachment (inhibit opsonization)
a. bind to complement regulatory proteins to inactivate C3b (no C3b - no opsonization by
C3b!)
i. capsules and M protein
b. bind to antibodies the “wrong way” to hide
i. Fc receptors (protein A, protein G)
3. Survive in the phagocyte
a. escape from phagosome
b. inhibit phagosome-lysosome fusion
c. survive in the phagolysosome
4. Avoid Antibodies
A. What are antibodies (also called immunoglobulins or Igs)? What do they bind to? What kinds of
protection do they provide? Where can you find them? How are they made? How long does it
take to make a “substantial amount” of antibody in a primary response?
B. How do you avoid antibodies?
1. IgA protease (cut up IgA antibody)
2. Antigenic variation (change your surface structures to avoid recognition by antibodies)
3. Mimic the host (make and coat yourself in molecules similar to the host)
OK, while you are keeping the immune response at arms length, its time to multiply!!
2. Make more of yourself!
See Stage 02 for details.
Made more of yourself? Now time to exit host and get to another naïve host whose immune system has not
been alerted to your presence yet.
3. Exit the host to get to another.
Damage to the Host
1. Toxins
A. Exotoxins (what is the general mechanism of how each of these works?)
1. A-B toxins
2. Membrane-damaging toxins
3. Superantigens
B. Endotoxin – Lipid A of LPS (lipopolysaccharide) found on outer membrane of Gram (-) cells.
1. Localized – stimulate local inflammation
2. Systemic – septic shock
2. Inflammation
A. Can destroy tissue because of release of toxic products and tissue-degrading enzymes
How do viruses cause disease?
1. Binding and invasion
2. Avoid immune responses
A. shut down interferon response
B. inhibit apoptosis
C. inhibit recognition by cytotoxic T cells (CD8 T cells, Tc cells) by inhibiting MHC I
D. tricking NK cells by making “fake” MHC I
E. Avoid antibodies through antigenic variation