Infection + Vaccines Flashcards
How to combat infectious diseases? (improvement vs challenges)
= ~25% of all mortality globally due to infectious disease
(+ more due to consequences of infection)
= many infections now treatable (used to be fatal)
Due to improvement in:
= sanitation (clean water, safe sewage disposal)
= vaccination (e.g. Measles a good example of effective vaccination)
= treatments (antibodies, anti-vials, anti-fungals, anti-protozoals)
Challenges remain:
= large variation in healthcare and sanitation globally
= emerging resistance to current treatments
= emerging diseases due to new strains of pathogens which are more virulent / transmissible or cross species barrier (zoonoses)
Why are not all microbes pathogens?
Pathogen
= microbe or parasite that can cause disease
= each pathogen has unique challenge for immune system
= + is vulnerable to different components of the immune response
Pathogenicity
= ability to cause disease in a host
= it is a qualitative trait
= organism is either pathogenic or not to a particular individual host, but not all hosts the same
Virulence
= quantify the effect of a pathogen on its host
= quantitative trait
= highly virulent organism will cause a lot of damage to its host
How does pathogen location dictate the response elicited?
= intracellular vs extracellular
= innate and adaptive immunity triggered is different
How does the immune system respond to viruses?
= viruses can have RNA genome (e.g. SARS-CoV-2, Influenza A)
= or can have a DNA genome (e.g. HSV, variola)
= both surrounding by a protein coat (+ sometimes a membrane envelope)
= viruses are intracellular = rely on host for replication
(they are obligate intracellular pathogens)
= DNA/RNA from genomes or replication intermediates are detected as PAMPs
= type I interferons (IFNα/β) are produced from infected cell / APC that has phagocytosed virus
= interferons signal in an autocrine + paracrine manner
(= establish an anti-viral state in infected cell + neighbours)
= NK cells and CTLs = can kill virus-infected cells
What is the immune response to bacteria?
= bacteria can be extracellular or live inside host cells
= intracellular bacteria eliminated through killing of infected cells (NK cells, CTLs)
= defense against extracellular bacteria = antibodies
= which neutralise bacterial toxins, activate complement and promote phagocytosis by macrophages and neutrophils
(NOTE antibiotic resistance becoming major issue, antibiotic resistance genes often located on plasmids - can be shared between bacteria)
e.g MRSA, multi-drug resistant TB
What are the antibody mediated mechanisms against extracellular bacteria?
- Antibodies can bind to and neutralise toxins
- Complement activation and lysis
- Antibodies and C3b opsonise bacteria for phagocytosis
- C3a and C5a anaphylotoxins
= stimulate mast cell degranulation
= released mediators cause vasodilation and attract neutrophils
= macrophages are attracted by C3a and C5a
What is the immune response to parasites?
= eukaryotic pathogens (exluding fungi) including:
Protozoa
= single cell eukaryotes
= e.g. Plasmodium - malaria, Trypansosoma brucei - sleeping sickness
= immunity to protozoa is species-specific, stage-specific and strain-specific (infection is common)
= antibodies against one stage or strain are not effective against others
(also a problem for vaccine design)
Helminths
= multicellular worms
= e.g. Schistosoma - swimmer’s itch, Ascaris - tapeworms
= immunity to helminths involves a Th2 response, with IgE antibodies and activation of granulocytes (mast cells and eosinophils)
= release of histamine and leukotrienes from granulocytes causes smooth muscle contraction and mucus production
(aims to expel the parasites - same response involved in allergy)
What is the immune response to fungal infections (mycoses)?
Innate mechanisms often sufficient to control fungal infections in immunocompetent individuals
= Marcrophages = detect fungal cell wall components (e.g. chitin and beta-glucans) using Toll-like receptors and Dectin-1 receptor
= Antibodies and complement enhance phagocytosis of fungak cells by neutrophils and macrophages
Fungi can cause issues for immunocompromised (e.g. HIV) or if normal microbiota disrupted (e.g. after antibiotics)
= fungal pathogens include Candida alibicans - oral/vaginal thrush
= Cryptococcus neoformans, Coccidioides immitis and Histoplasma capsulatum can affect immunocompromised infividuals, systemic infections are diagnostic of AIDS
What is a case study for immune evasion?
= all pathogens need to evade host’s immune defences to establish an infection
e.g. Influenza A Virus
= -ve ssRNA virus with segmented genome encoding 11 proteins
= surface proteins are highly variable
(H - haemagglutinin, N - Neuraminidase)
Non-structural protein NS1 is a multifunctional immune evasion protein
= it binds the viral RNA to prevent recognition by PRRs and inhibits the RNA receptor RIG-I
= inhibits gene expression by the cell (host cell shut-off)
= promotes transcription of viral genes
What is an example of evasion of adaptive immunity?
= antigenic drift and antigen shift
= common seasonal flu H3N2 changes slightly every year through antigenic drift
= antigenic shift = reassortment of genome fragments from swine, avian and human viruses led to swine flu H1N1 in 2009
Antigenic drift
= point mutations due to error-prone polymerase
= gradually yield a protein not recognised as efficiently by original antibodies
Antigenic shift
= co-infection with different strains in an animal host creates a new virus with different HA and N proteins
(only with segmented genome)
How did vaccination start?
Variolation
= ancient Chinese practice of intentional inoculation with small amounts of dried smallpox pustules
Edward Jenner
= innoculated children with pus containing cowpox to protect against smallpox
(type of live vaccine)
(smallpox was first and only disease to be eradictaed - 1979)
What are some key terms in Vaccination?
Immunisation
= process of generating long-lived immune protection against a pathogen
= either by recovering or by vaccination
Vaccination
= intentional exposure to components of pathogen that do not cause disease
= an effective vaccine causes development of memory B and T cells
(that recognise antigens on the target pathogen)
Vaccination does not only protect vaccinated individual but also whole society
Herd Immunity
= if many individuals in population are immune, there is less spread of infection to other vulnerable people that cannot be vaccinated
Eradication of disease
= pathogen dies out when there are no susceptible individuals left
= may not be possible if there are animal reservoirs
= e.g smallpox - 1979 - had no animal reservoir, virus did not change quickly, vaccines started along time ago
How do vaccines work?
First exposure (adaptive response)
= infection
= transport of antigen to lymphoid organs (innate response, antigen presentation)
= recognition by naive B and T cells (recognition of specific antigens)
= clonal expansion and differentiation to effector cells (memory cells)
= removal of infectious agent
Subsequent exposures
(protective immunity)
= re-infection
= recognition by preformed antibody and effector T cells
= removal of infectious agent
(immunological memory)
= re-infection
= recognition by memory B and T cells
= rapid expansion and differentiation to effector cells
= removal of infectious agent
(protective and memory responses are much faster, more effective than initial response to infection)
What are the components of vaccines?
To be able to stimulate an adaptive immune response including immunological memory vaccine needs:
Antigens
= (usually proteins) from pathogen that can be recognised by T cells, B cells and antibodies
Adjuvants
= molecules that help activate the innate immune system
(e.g. pathogen components, synthetic formulation like alum salts or isolated PAMPs - e.g. dsRNA)
= needed for the development of effective adaptive immunity
= vaccines containing live or inactivated pathogens already contain PAMPs
= BUT additional adjuvants needed for subunit vaccines
What is the History of Vaccination?
