infections: evading immune systems july 29, 2014 tanaya bhowmick md assistant professor dept. of...

Infections:Evading Immune Systems

July 29, 2014Tanaya Bhowmick MD

Assistant ProfessorDept. of Medicine

[email protected]

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


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


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


Categories of Infectious Agents

• Bacteriophages, Plasmids, Transposons• Bacteria

– Extracellular– Intracellular

• Chlamydiae, Rickettsiae, Mycoplasmas• Fungi• Parasites

– Helminths– Ectoparasites

• Prions• Protozoa• Viruses


Immunity


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


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


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



Immune Evasion by Microbes

Infections


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


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


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

Gingivostomatitis (Herpes)

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

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


infections: evading immune systems july 29, 2014 tanaya bhowmick md assistant professor dept. of...

Documents

host barriers

host relationshipsmutualistic

unnatural host

pathogenic species

larger species

species of organism

examplethe rabies virus

immune systemsjuly