Transcript Infections: Evading Immune Systems

Infections:
Evading Immune Systems
July 29, 2014
Tanaya Bhowmick MD
Assistant Professor
Dept. 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
Developed as part of the RCSB Collaborative Curriculum Development Program 2014
Emerging Infectious Diseases
Infectious agents identified within the last twenty years
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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
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
Immune
Evasion by
Microbes
Developed as part of the RCSB Collaborative Curriculum Development Program 2014
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 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
Mycobacterium
Phagocytosis/i tuberculosis
ntracellular
killing resistant
-Adapted to
survive within
host cells
Developed as part of the RCSB Collaborative Curriculum Development Program 2014
Viral Infections
Pathogen
Innate
immunity
Adaptive
immunity
Evasion of
immunity
Virus
- Type 1 IFNs - Antibodies block - Latent
- NK cells
viral binding to and infections
entry into cells,
Promote viral
elimination,
activate the
complement
system and block
the spread of
viruses from
infected cells
- Cytotoxic T cells
Example
--HIV
-Rubeola
-Herpes
Simplex Virus 1
and 2
Gingivostomatitis (Herpes)
Developed as part of the RCSB Collaborative Curriculum Development Program 2014
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
Developed as part of the RCSB Collaborative Curriculum Development Program 2014
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