infections: evading immune systems july 29, 2014 tanaya bhowmick md assistant professor dept. of...
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Infections:Evading Immune Systems
July 29, 2014Tanaya Bhowmick MD
Assistant ProfessorDept. of Medicine
Developed as part of the RCSB Collaborative Curriculum Development Program 2014
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
Developed as part of the RCSB Collaborative Curriculum Development Program 2014
Emerging Infectious Diseases
• 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
Developed as part of the RCSB Collaborative Curriculum Development Program 2014
Infectious agents identified within the last twenty years
Microorganism : Host Relationships• 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
Developed as part of the RCSB Collaborative Curriculum Development Program 2014
Categories of Infectious Agents
• Bacteriophages, Plasmids, Transposons• Bacteria
– Extracellular– Intracellular
• Chlamydiae, Rickettsiae, Mycoplasmas• Fungi• Parasites
– Helminths– Ectoparasites
• Prions• Protozoa• Viruses
Developed as part of the RCSB Collaborative Curriculum Development Program 2014
Immunity
Developed as part of the RCSB Collaborative Curriculum Development Program 2014
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
Developed as part of the RCSB Collaborative Curriculum Development Program 2014
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
Developed as part of the RCSB Collaborative Curriculum Development Program 2014
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
Developed as part of the RCSB Collaborative Curriculum Development Program 2014
Developed as part of the RCSB Collaborative Curriculum Development Program 2014
Immune Evasion by Microbes
Infections
Developed as part of the RCSB Collaborative Curriculum Development Program 2014
How Do Microorganisms Cause Disease?
• 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
Developed as part of the RCSB Collaborative Curriculum Development Program 2014
Bacterial InfectionsPathogen Innate immunity Adaptive
immunityEvasion 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
Developed as part of the RCSB Collaborative Curriculum Development Program 2014
Viral Infections
Developed as part of the RCSB Collaborative Curriculum Development Program 2014
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
Gingivostomatitis (Herpes)
Parasitic Infections
Developed as part of the RCSB Collaborative Curriculum Development Program 2014
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
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