Microbial Invasion of Immune Responses

How Get Infectious Diseases?

Organism factors overcome host factors

Host Factors
-immune system
—innate and adaptive immunity

Organism Factors
-dose (# of organisms)
-virulence (ability to cause disease)

→leads to host colonization and invasion
-evading host defenses
-damage to host

Sequences of Events in Microbial Invasion

1. Portal of entry

2. Colonization and Adhesion

3. Invasion and Multiplication

4. Evasion of Host Defense Mechanisms

5. Damage to host

6. Disease

7. Portal of Exit

Microbial Invasion

process which pathogens avoid or inactive host immune system to ensure survival in a host

Strategies Used to Evade Immune System

Inhibition of phagocytes

Release of proteins to interfere with immune factors (IgA proteases)

Antigenic Variations

Complement Inhibition

Intracellular Survival

Diseases Caused by S.aureus

Staph aureus-stains purple on slide

can cause different forms of disease/infections

versatile

Strategies to Inhibit Phagocytosis

Toxin Release
-destruction of phagocytes by cytolytic toxins

Opsonization Prevention
-inhibition of opsonization
-Staphylococcus aureus forms Protein A that binds to Fc part of Ig and prevents opsonization between Ab and phagocyte

Contact with Phagocyte Prevented
-organism can have capsule to prevent contact
-ex is streptococcus pneumoniae

Release of Proteins to Interfere with Immune Factors

IgA Protease
-destroy mucosal IgA
-effects local immunity from IgA (nullified)
-some can inhibit complements
-neisseria gonorrheae (GU tract)
-haemophilus influenzae (resp tract)
-streptococcus pneumoniae (resp tract)

Antigenic Variations

Borrelia recurrentis changes antigens frequently during course of infection

Trypanosoma cruzi undergoes antigenic variations of Variant Specific Glycoproteins (VSG)

Change their antigen during infections so the produced Ab to original variant doesn’t work and body has to keep producing new ones

Complement Inhibition

Outer capsule prevents complement activation (staphylococcus aureus)

Config of outer surface so complement receptors can’t access C3b
-some recruit Factor H to surface to escape

Membrane bound enzymes can degrade complement/cause to be shed
-Pseudomonas aeruginosa forms proteases that degrade complements
-Streptococcus pneumoniae produces C5-ase

Intracellular Survival

Phagolysosomes-kill microbes with ROS after engulfing

How evade
-block phagosome-lysosome fusion (mycobacterium tuberculosis)
-escape phagosome and enter cytoplasm (listeria monocytogenes, salmonella serotype typhi)
-resist lysosome products (mycobacteria, certain salmonella spp)
-block activation by gamma-IFN (mycobacteria)

Sit inside cell cytoplasm and hide

Summary of Microbes and Viruses

Mycobacteria
-survive within phagosome

Herpes (HSV), CMV, EBV viruses
-inhibition of antigen presentation

EBV
-inhibition of macrophage activation

Pox Virus
-block cytokine activation of effector cells

Viral Pathogens Interfere with Signaling to IFN Genes/Receptors

Ex-members of Flavivirus family (Hep C virus, west nile virus)

interfere with RNA sensors ability to work and interferons to work
-interferes with signaling molecules by binding to IFN receptors

Viral Pathogens can Interfere with NK Cell Function

Interference w/ NK activation

Decoying NK receptors via viral HLA class 1 homologous
-fake HLA class 1 molecule, trick NC cells

Done by cytomegalovirus and rubella virus (German measles)

Viral Interference with MHC Class 1 Antigen Presentation

Interference with MHC class 1
-prevents producing peptides and transport
-can’t get on HLA class 1 molecule, keeps MHC 1 in cell
-speeds up degradation and prevents signaling to T cell

Interferes with adaptive response of T cells

Viral Evasion of T and B Cell Immunity: Mutation

Viral RNAse lacks the repair component of eukaryotic cells
-as a result can accumulate a lot of mutations
-mutations are enough to prevent binding peptide to epitope

ex: escape from HLA-A24 mediated cellular immunity
COVID variants escape neutralization by vaccine humoral immunity

Why we need flue virus vaccine each year

Two Types of Mutations Allow Influ A Virus to Repeat Infect Hosts

Antigenic drift
-due to point mutations
-why yearly flu vaccine needed
-selective process
-neutralizing Ab no longer binds

Antigenic shift
-due to nucleic acid exchange
-results in pandemics every 20-30 years
-viral RNA segments swap with each other
-makes a brand NEW virus, not just mutation

Antigenic Drift

-due to point mutations
-why yearly flu vaccine needed
-selective process
-neutralizing Ab no longer binds

Antigenic Shift

-due to nucleic acid exchange
-results in pandemics every 20-30 years
-viral RNA segments swap with each other
-makes a brand NEW virus, not just mutation

Immunity Against Rhinoviruses

Strain specific

About ~ 160 strains of rhinoviruses cause common cold

Subsequent infection w/ diff strain of rhinovirus is unaffected by immune response to first strain

Why hard to make a vaccine to the common cold

Viral Latency

Viruses of herpes family hide from immune system in neurons

Herpes simplex 1 virus (cold sores)-trigeminal root ganglion

Varicella zoster virus (chickenpox)-dorsal root ganglion→cause shingles

When hide in neurons they are invisible
-when stress affects immune system, virus is activated and can infect epithelial cells

HIV Virus Causes AIDS

-by killing CD4+ T helper cells (most important cells of adaptive immune system)

leads to opportunistic infections by other pathogens