Lecture 22: Immune Response to Infection Flashcards
Outline the 4 steps of the immune response to infection.
- Microbial detection (bacteria, viruses, fungi etc.)
- Innate immune response (epithelia, phagocytes, NK cells etc.)
- Adaptive immune response (lymphoid tissues, T and B lymphocytes)
- Memory response (memory T and B cells)
What areas of difference are there between innate and adaptive immunity?
- timing of response
- cell types
- receptors and ligands
- cytokines and chemokines
- molecular effector machineries
What are some pathogen niches during infection?
- Extracellular (e.g. staphylococcus, streptococcus_
- Intracellular (e.g. Salmonella, Plasmodium)
- Surface adherent (e.g. enteropathogenic E. Coli)
- Intracellular but cytosolic (e.g. viruses, Listeria)
What immune cells are first to respond once a pathogen has been detected?
Neutrophils followed by macrophages
How long do neutrophils live for in the first response to infection?
Approx. 6 hrs
What happens to naïve cells when they interact with microbes?
They become ‘activated’
What do phagocytes do?
Control infection and limit/repair tissue damage
What can uncontrolled activities of phagocytes lead to?
- granulomas
- excessive inflammation and inappropriate adaptive immunity
- tissue damage
What is the general sequence of events of communication within the immune system?
Microbial ligands (detection) –> naïve host-cells (gene-expression changes) –> cytokines and chemokines (signal transduction) –> activated host- cells
What are macrophages?
large phagocytic cells that ate tissue resident or circulatory (from bone marrow)
What is macrophage activation?
Expression of many new genes induced by microbes and cytokines
Activated macrophages display enhanced…?
- phagocytosis and migration
- cytokine/chemokine production
- expression of cell surface molecules
- antimicrobial activity
- antigen presentation and T cell activation
What are ‘alternatively’ activated macrophages?
They are anti-inflammatory
What are interferons?
Special cytokines that have direct antiviral activities - they promote antiviral defence
What can be included in antiviral genes?
- nucleases
- inhibitors of virus entry and exit
- inhibitors of viral uncoating and replication
- inhibitors of protein translation
What immunomodulatory roles do interferons have?
- enhanced T cell responses
- anti-inflammatory actions
- tissue repair
What 2 types of cell are responsible for directly killing virus-infected cells?
Cytotoxic T lymphocytes (CTLs or CD8+) Natural Killer (NK) cells
What is the purpose of cell death when fighting a viral infection?
Removes viral replicative niches
Can host cells infected with intracellular bacterial pathogens also undergo forms of cell death?
Yes
What are the humoral/soluble effector mechanisms of immunity?
- complement mediated bacterial destruction
- lectin-binding to neutralise cell attachment or entry
- iron chelation (siderophores) to prevent replication
- antibiotic-like peptides
What are the cellular effector mechanisms of immunity?
- reactive oxygen and nitrogen radicals
- acidification and digestion within phagosomes
What do activated macrophages and dendritic cells do?
present antigens in combination with MHC-I or MHC-II to T cells
Give an example of how cytokines produced by APCs produce a suitable type of environment for T cell activation.
IL-12 (interleukin 12) promotes T cell replication
Given an example of how T cells provide cytokines that activate phagocytes.
IFNy (interferon gamma) upregulates MHC-II expression for antigen presentation
How do T and B cells interact?
T cells help B cells produce antibodies (become activated) against the antigen they recognised via MHCs
How do T and B cells enhance antimicrobial activity?
- phagocyte activation
- direct killing of infected cells
- B cell activation
- Innate lymphoid cells
The sequence of the immune response depends on what?
The sequential change from ‘resting/naïve’ to ‘activated’ state - differentiation of ‘precursor’ cells into specific lineages of cells
What happens within 0-12 hours after initial infection?
Innate immune response:
- microbe detected
- mast cells, phagocytes, dendritic cells
- complement
- NK cells and ILCs (innate lymphoid cells)
What happens within approx. 1-5 days after initial infection?
Adaptive immune response:
- B cells –> plasma cells –> antibodies
- T cells –> effector T cells
At what point approximately does the primary antibody response peak?
Approx. 2 weeks
What is the impact of age on the immune response?
- no. of naïve T cells decreases
- no. of memory T cells increases
- thymic output decreases
Innate and adaptive immune responses are specific to what?
The broad classes of pathogens and their virulence strategies
