1. Infections: Evading Immune Systems
Pathology - Infectious Disease Lecture
Infections: Evading Immune Systems
July 29, Tanaya Bhowmick MD
Assistant Professor
Dept. of Medicine
Developed as part of the RCSB Collaborative Curriculum Development Program 2014

2. Historic Perspective 19th century – 20th century – Present day –
Pathology - Infectious Disease Lecture
Historic Perspective
19th century –
proof that diseases are caused by infectious agents
founded the discipline of microbiology
20th century –
development of antimicrobial agents
vaccines to effectively treat diseases raised hopes for the eventual elimination of many of the diseases
Present day –
infectious diseases cause more than 20% of all deaths
Infections occur in both the resource-rich and the resource-poor world
Understand what is infectious disease – they are caused by pathogens, such as bacteria, virus, fungi, parasites etc. Agents that can remove or destroy the pathogens can treat the disease.
Developed as part of the RCSB Collaborative Curriculum Development Program 2014

3. Emerging Infectious Diseases
Infectious agents identified within the last twenty years
Hanta virus
Human herpes virus 8
Hepatitis E-G
Variant Creutzfeldt-Jakob disease (vCJD)
Hendra virus
Nipah virus
Vibrio cholerae 0139
Cryptosporidium
Cyclospora
Severe acute respiratory syndrome (SARS) associated coronavirus
Epizootic avian influenza H5N1
Human T-cell lymphotropic virus 3 (HTLV-3)
HTLV-4
Xenotropic MuLV-related virus
While we have developed treatments for various infectious diseases, new infections have also been identified in the past 20 years
Developed as part of the RCSB Collaborative Curriculum Development Program 2014

4. Microorganism : Host Relationships
Pathology - Infectious Disease Lecture
Mutualistic - provide reciprocal benefits for the two organisms involved. Example
Bacteria and protozoa living in the stomachs of domestic ruminants play an essential role in the digestion and utilization of cellulose, while receiving both an environment and the nutrition essential for their survival
Commensal - occur when one species of organism lives harmlessly in or on the body of a larger species. Example
Humans support an extensive commensal microbial flora on the skin, in the mouth and in the alimentary tract
Commensal microbes can benefit the host preventing colonization by more pathogenic species (e.g. the intestinal flora)
Parasitic - where the relationship benefits only the parasite
all pathogens are parasites
many 'parasites' establish benign associations with their natural hosts but become pathogenic if there are changes in the host's health or if they infect an unnatural host. Example
the rabies virus, coexists harmlessly with many wild mammals but can cause fatal disease in humans
Different types of relationships of microbes and human (or other organisms) as their hosts. The parasitic relationships are most harmful and should activate an immune response - the subject of this discussion.
Developed as part of the RCSB Collaborative Curriculum Development Program 2014

5. Categories of Infectious Agents
Pathology - Infectious Disease Lecture
Categories of Infectious Agents
Bacteriophages, Plasmids, Transposons
Bacteria
Extracellular
Intracellular
Chlamydiae, Rickettsiae, Mycoplasmas
Fungi
Parasites
Helminths
Ectoparasites
Prions
Protozoa
Viruses
The pathogens colored in blue are discussed further in the following slides
Developed as part of the RCSB Collaborative Curriculum Development Program 2014

6. Immunity
Developed as part of the RCSB Collaborative Curriculum Development Program 2014

7. Host Barriers to Infection
Innate Immune response
Exists before infection occurs
Physical barriers to infection,
Cells - phagocytic cells, NK cells,
plasma proteins (complement proteins, cytokines, acute phase reactants)
Adaptive Immune response
Stimulated by exposure to microbes and increase in magnitude, speed & effectiveness with successive exposures to microbes
Mediated by T and B lymphocytes
Innate and adaptive immune responses
Developed as part of the RCSB Collaborative Curriculum Development Program 2014

8. Evasion of Host Barriers
Pathology - Infectious Disease Lecture
Evasion of Host Barriers
Skin
penetrate through breaks in the skin e.g. cuts, burns, foot sores, animal/human bites
penetrate unbroken skin (some specific parasites)
Gastro-intestinal tract
Cut/break in mucosa
Respiratory tract
Non-functional mucosa and ciliary function e.g. in smokers, individuals with Cystic Fibrosis
Toxins that paralyze mucosal cilia (e.g. causing the flu, pertussis)
Urogenital tract
Entry through urethra leading to kidney infections
How do pathogens evade the immune system at various sites – skin, GI tract, Respiratory tract, UG tract.
Developed as part of the RCSB Collaborative Curriculum Development Program 2014

9. Immune Evasion By Microbes
Pathology - Infectious Disease Lecture
Immune Evasion By Microbes
Hiding from immune cells
Change/shed antigens
remain inaccessible to the host immune system
Resist innate immune defenses
Carbohydrate capsule prevents phagocytosis
Replication within phagocytes
Resistance to antimicrobial peptides
Activate/interfere with signaling pathways
Inhibit antigen presentation
How do pathogens hide from immune cells and immune system molecules
Developed as part of the RCSB Collaborative Curriculum Development Program 2014

10. Immune Evasion by Microbes
Pathology - Infectious Disease Lecture
Immune Evasion by Microbes
How do pathogens hide from immune processes
Developed as part of the RCSB Collaborative Curriculum Development Program 2014

11. Infections
Developed as part of the RCSB Collaborative Curriculum Development Program 2014

12. How Do Microorganisms Cause Disease?
Pathology - Infectious Disease Lecture
Contact or enter host cells and directly cause cell death.
Release toxins that kill cells at a distance
Release enzymes that degrade tissue components
Damage blood vessels and cause cell injury or death due to lack of blood supply.
Induce host cellular responses that, although directed against the invader, cause additional tissue damage, usually by immune-mediated mechanisms
Pathogens cause pathogenesis or disease in the above ways
Developed as part of the RCSB Collaborative Curriculum Development Program 2014 12

13. Bacterial Infections Pathogen Innate immunity Adaptive immunity
Pathology - Infectious Disease Lecture
Bacterial Infections
Pathogen
Innate immunity
Adaptive immunity
Evasion of immunity
Example
Extracellular bacteria
-Phagocytosis
-Activation of complement pathway.
-Cytokines (TNF, IL-1 and IL-6)
-Antibodies block infection, neutralize toxins, promote microbial elimination
- Bacterial proteins activate T helper cells
-Resistance to complement activation
-Antigenic variation
Staphylococcus aureus
Intracellular bacteria
- Injury to host due to immune responses
- Secondary infections
- Cell mediated immunity by Cytotoxic T cells
- Persistent bacteria leads to granuloma
-Phagocytosis/intracellular killing resistant
-Adapted to survive within host cells
Mycobacterium tuberculosis
Bacterial infections – to treat infections antibiotics may have to be used
Developed as part of the RCSB Collaborative Curriculum Development Program 2014

14. Viral Infections Pathogen Innate immunity Adaptive immunity
Pathology - Infectious Disease Lecture
Viral Infections
Pathogen
Innate immunity
Adaptive immunity
Evasion of immunity
Example
Virus
- Type 1 IFNs
- NK cells
- Antibodies block viral binding to and entry into cells, Promote viral elimination, activate the complement system and block the spread of viruses from infected cells
- Cytotoxic T cells
- Latent infections
--HIV
-Rubeola
-Herpes Simplex Virus 1 and 2
Viral infections – when immune system fails to check the infection drugs that destroy the virus lifecycle have to be used. Antibiotics are not effective.
Gingivostomatitis (Herpes)
Developed as part of the RCSB Collaborative Curriculum Development Program 2014

15. Parasitic Infections Pathogen Innate immunity Adaptive immunity
Pathology - Infectious Disease Lecture
Parasitic Infections
Pathogen
Innate immunity
Adaptive immunity
Evasion of immunity
Example
Parasite
Animal (vertebrate) stages of most parasites are resistant to innate immunity.
Distinct cell mediated immune responses for different parasites
- Hiding away from immune system in special compartments
- Masking Ag
-Change coat/shed Ag
-Suppress immune response
- Plasmodium falciparum
-Schistosoma haematobium
Schistosomiasis
Parasitic infections – when immune system fails, specific medications to disrupt the parasite’s life cycle may be used to treat the infection
Developed as part of the RCSB Collaborative Curriculum Development Program 2014

16. Summary Infectious diseases understood as recently as 19th century
Many new pathogens recently identified
In Infectious diseases - pathogens have parasitic relationship with human hosts
Pathogens have figured out a number of different ways to bypass the immune processes – leading to disease
Bacterial, viral and parasitic infections are handled by different components of the immune system
Developed as part of the RCSB Collaborative Curriculum Development Program 2014