Immune System

INFECTION, IMMUNITY, MOLECULAR IMMUNOLOGY

DR. STEFAN FISCHER 65

Immune System
* Structure / Parts of the immune system
* Bacterial and viral infections
* innate immunity
* adaptive / acquired immunity
* molecular Immunology

DR. STEFAN FISCHER 66

 Trypanosoma brucei
Poliovirus

Vibrio cholera Ascaris nematodes

Type of pathogens

DR. STEFAN FISCHER 68

Pathogen localisation

DR. STEFAN FISCHER 69

Pathogens mediated damage

DR. STEFAN FISCHER 70

Bacteria

• Procaryotic microorganism
• Single dsDNA genome, circular chromosome
• Additonal DNA plasmids possible, can be used for genetic exchange
• Mobile by falgellum
• Modern classification system uses the genome

Y tambe, https://creativecommons.org/licenses/by-sa/3.0/deed.en
Classification of Bacteria

• By cell shape

• By cell wall:
classical system: gram-staining
- crystal violet dye
- gram-positive have a thick cell wall (many peptidoglycans)
- gram-negative show only a thin cell wall
Classification of Bacteria
Virulence and Bacteria
Virulence and Bacteria
Bacteria

• Bacterial growth via binary fission

• 4 phases of bacterial growth (generation time E.coli = 20 min)

c
Cell count
b
d a – lag phase: adjustment to new environment
b – log phase: maximum growth
c – stationary: nutrients getting rare
a d – death: bacteria dying
time
Virus I

• Infectious agent (in general can infect plants, animals, bacteria, …)

• Replicates only inside of cells, no own metabolism
• Outside of cells: virion
• Different kind of morphology
• Consists of:
- Genome (RNA or DNA)
- Capsid/Nucleocapsid (protein structure)
- Frequently a lipid envelope
• Millions of viruses, 75,000 genomes sequenced, 5,000 described in detail
• Baltimore classification:
Virus I
Virus I
Virus I
Virus I
* Baltimore classification

Class Genome Example

I dsDNA Herpesvirus
II ssDNA (+) Parvovirus
III dsRNA
Direct protein
IV (+)ssRNA Coronavirus
synthesis possible
V (-)ssRNA
VI ssRNA-RT Retrovirus
VII dsDNA-RT

+ means: can be translated as RNA => + DNA has same sequence as translatable RNA
+ = sense
Virus I

- Classification also via:

- Lipid envelope ?
- Kind of replikation
- Degree of sequence homology

https://talk.ictvonline.org/
 Virus II

• encodes for:
- Proteins for replication
- Proteins for packaging
- Proteins for influencing host cells => enhanced replication

Complex example: HIV

Virus II Transcription

ssDNA

+ RNA - DNA dsDNA

+ RNA

Medizinische Mikrobiologie und Infektiologie, Springer Verlag, 2016

Virus II Replication

Medizinische Mikrobiologie und Infektiologie, Springer Verlag, 2016

Replication

Medizinische Mikrobiologie und Infektiologie, Springer Verlag, 2016

Replication cycle of virus

• Adsorption
• Entering the cell (Endocytosis or Fusion of the lipid envelope with plasma membrane
• Uncoating
• Synthesis of non-structural viral proteins
• Replication of viral genome
• Synthesis of structural viral proteins
• Formation and Exit of the cell

50 – 1000 viral particles per cell

 Example I: Influenza virus

• Influnza virus A –D (A, B & can cause real flu)

• (-)ssRNA
• Lipid envelope with viral proteins
• Ribonucleoprotein complex
• Genome in segments: up to 8 RNA Molecules, only 1 Genome/ virus
• High genetic variability:
- Mixing of RNA molecules (antigenic shift)
- Frequent point mutation (ssRNA, viral polymerases without repair
CDC
mechanism)
 Example II: Retrovirus (e.g. HIV-1&2, HTLV)

• (+)ssRNA
• Inserts viral genome in host cell genome
• RNA-dependant DNA-polymerase – Reverse Transcriptase
• Integrase adds viral DNA to host genome
• Some show lytic life cycle, some are “silent hunters” showing
persistant or latent infectious cycle (e.g HBV, HCV, Herpes virus,
HPV)

By Raul654 https://creativecommons.org/licenses/by-sa/3.0/deed.en

gag – group specific antigen, pol – enzymes, env – envelope,

LTR – long term repeats, Ψ - Packaging
Virus III
Life cycle

YK Times
https://creativecommons.org/licenses/by-sa/3.0/deed.en
 Please describe shortly how a + ssRNA virus replicates in host cells. Start to describe this
by docking to the host cells until the release of new virus particle. (7 points)

• Adsorption (binding to cell receptor)

• Release of genome into cytosol
• Synthesis of virus protein by host ribosomes
• Replication of +RNA into –RNA
• Replication of -RNA into +RNA
• Packaging
• Release
 Strategies for intracellular invasion: Virus

John Snow is widely regarded as the father of modern

epidemiology. Most famously, he investigated an outbreak
of cholera in London in 1854 that killed more than
600 victims before it was finished.
Snow recorded where the victims (red dot) lived, and plotted
the data on a map, along with the locations of the water
pumps (blue dot) that served as the source of water for the
public. He concluded that the disease was most likely spread
in the water, although he could find nothing suspicious-looking
in it.
His conclusion ran counter to the then-current belief that
cholera was from “miasmas” in bad air. Very few believed his
theory during the next 50 years, with the “bad air” theory
persisting until at least 1901. What do you suppose Snow saw
in the data that led him to his conclusion? Why do you think
most scientists remained skeptical for so long?
Opportunistic vs primary pathogens

• Opportunistic pathogens: living as commensual microorganisms in our microbiom

=> By Chance (wound etc) they start colonising niches in our body

• Primary pathogens are specialised to infect: actively searching the corresponding niches in our body

=> frequently use of vector system, e.g. flies

Malaria – Plasmodium (falciparum)
Malaria – Plasmodium (falciparum)