Immune response to infection Flashcards
How does the immune response start?
Detection of tissue damage - damage associated molecular patterns DAMP
Detection of pathogenic structures - pathogen associated molecular pattern PAMP (molecular detection of microbes)
Inter-cellular signalling using interleukins
Activation of the innate immune system, non-specific immune response
Communicate with adaptive immune cells
Non-immune cells can produce antimicrobial peptides
How does a response to infection stop?
After pathogen is cleared, immune cells undergo apoptosis
Suppressed production of inflammatory cytokines mediated by the same mechanism as immune tolerance
After the cell population contracts and some memory cells form tissue repair and remodelling occurs
What are the four different pathogen niches during infection? Give examples of each
Extracellular don’t invade host pathogens - staphylococcus, candida, microbiota, worms
Surface adherent - enteropathogenic and enterohaemorrhagic E.coli sticks to the surface of intestinal wall cells
Intracellular vacuolar - stay within a compartement - salmonella, chlamydia, plasmodium, legionella
Intracellular cytosolic - viruses, Liberia, mycobacterium, burkholderia, TB -break open the compartment they infect and reside in the cytosol
Define innate immunity.
Fast acting, first line of defence germ-line encoded receptors so all cells of one lineage have the same receptors
Pre-determined and present at birth
non-specific
What are the physical, humeral and cellular components of the innate response?
Physical - skin, mucous, epithelial cells, commensal bacteria
Humoral - complement, lectins (neutralise and opsonise pathogens), pentraxins and antimicrobial peptides
Cellular - Neutrophils, macrophages, dendritic cells, natural killer cells
What are the four roles of the innate immune system?
Anaphylatoxins - proteins which can lead to vascular permeability
Chemokines - attract immune cells
Opsonisation - coating of a cell membrane setting it up to be phagocytosed
Membrane attack complex
What organ is the innate humeral response mediated by? What does it produce?
Liver
Lectins
Iron chelation proteins - siderocalins
Complement system
What are the three pathways for the complement cascade?
Classical pathway – activated by C1 binding to antibodies that have bound to antigens
Lectin pathway – activated by C1 binding to lectin that has bound to microbial carbohydrate structures
Alternative pathway – factor C3 gets directly activated onto the surface of the pathogen
How does a membrane attack complex cause cell destruction?
Creates a whole in the cell which can lead to an imbalance of sodium and potassium, disrupting the cell surface tension and causes it to swell and explode due to higher osmolarity
Which cells are involved in the innate immune response?
Granulocytes
Natural killer cells
Dendritic cells
Why do innate immune cells have less than 100 possible receptors? What are the four types?
Innate immune cells recognise structural patterns thus cells of the same lineage have the same receptor
- Toll like receptors
- fc receptors
- Complement receptors
- scavenger receptors
What are the first few responders in an infection?
Neutrophils first - short lived 6hrs
Followed by macrophages
What happens when naive cells are activated by pathogens?
Start secreting cytokines and chemokine
Why is uncontrolled phagocytic activity not good?
Leads to:
Granulomas
Excessive inflammation and adaptive immunity
Tissue damage
Where do macrophages come from?
From monocytes which circulate for 2-3 days then migrate to tissues and develop into macrophages
What type of response to phagocytes show?
Pathogen-type specific
What are macrophages activated by and what is enhanced when they are?
Activated by T helper cells
- phagocytosis and migration
- cytokine/chemokine production
- Expression of cell surface molecules
- antimicrobial activities
- antigen presentation and T-cel activation
What are interferons and how do they work?
Cytokines produced by immune cells and infected cells in response to viruses and gram-negative bacteria
Signals surrounding cells and circulating immune cells
Produce antiviral proteins in response
What are the three types of interferons and their roles?
Type I and III promote antiviral responses
Type II promote antibacterial immunity
What do antiviral genes include?
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 are MHCI and where are they found?
Receptor found on all nucleated cells
Give an idea of what peptides are inside the cell
What do MHCI molecules interact with and what does this achieve?
Interact with cytotoxic T cells and NK cells and detect changes in the cells MHCI
Where are MHCII cells found and what is their function?
Found on dendritic (APCs) only
Detect peptides outside their cell, once they phagocytose the pathogen they present small sections of its proteins on its surface to be detected by other cells
Why do NK cells kill cells without MHCI?
All nucleated cells should present MHCI however virus cells and some cancer cells try to evade detection by lack of MHCI molecules so NK cells target these cells
What are the humoral and cellular components of the adaptive immune system?
Humoral- Antibodies (immunoglobulins) and complement
Cellular- Cytotoxic T cells, T helper cells, T-regulatory cells, B-lymphocytes and plasma cells
What are the four cellular effector mechanisms in innate immunity?
- Phagocytosis of microbe into phagosome
- Phagocyte oxidase which is a reactive oxygen species ROS
- iNOS -nitric oxidase
- Cytokines released
What are the four soluble mechanisms in humoral immunity?
Complement mediated bacterial destruction Lectin-binding to neutralise cell attachment or entry Iron chelation (siderocalins) to prevent replication Antibiotic like peptides
What does IL-12 do? When is it released?
Promotes T-cell replication
Produced by APCs when pathogen is detected
What is the role of IFN gamma and IL-17 with T cells?
Interferon gamma allows a T cell to differentiate into a TH1 cell
It also up regulates MHCII expression
IL-17 converts T cell into Th 17 cell
What are the two types of receptors in the adaptive immune response?
TCR
BCR - cell surface bound IgM
Where can memory cells be found?
Lymphoid tissues - lymph nodes, spleen GI mucosa (peters patches), mucosal epithelia, bone marrow
Circulation
T cells - migrate to and from lymphoid tissues constantly
B cells - can differentiate into plasma cells
What three things are antibodies good at enhancing?
Phagocytosis (opsonisation)
Complement activation
Neutralising pathogen
What are the four main functions of T cells?
Activate phagocytes
Activate B cells
Directly kill infected cells
Regulate the immune response
What are the two functions of B cells?
Present soluble antigen to T cells - can present it Produce antibodies (main)
Name the three different effector T cells and their defining cytokines
Th1: IFN-γ
Th2: IL-4, IL-5, IL-13
Th17: IL-17, IL-22
What is the principle target cell of Th1 cells and their immune reaction?
What host defence and role in disease do they have?
Macrophages - macrophage activation
Intracellular pathogens - autoimmunity, chronic inflammation
What is the principle target cell of Th2 cells and their immune reaction?
What host defence and role in disease do they have?
Eosinophils - eosinophil and mast cell activation
Helminths (parasitic) - allergy
What is the principle target cell of Th17 cells and their immune reaction?
What host defence and role in disease do they have?
Neutrophils - neutrophil recruitment and activation
extracellular bacteria and fungi - autoimmunity and inflammation
What is thymic involution ?
Thymus stops producing new naive T cells and it shrivels away
Over time the T-cells become activated and change from naive T cells to memory cells
Explain the sequence of the immune response
- Innate immune cells recognise pathogen and become activated
- They start secreting cytokines and phagocytose pathogens
- Antigen presenting cells move to lymph nodes to find specific lymphocytes
- Lymphocytes proliferate and differentiate into specific types
- Cellular and humoral specific immune response to pathogen
Differences between a primary and secondary antibody response?
Primary - peak 2 weeks after infection, smaller peak
Secondary - Higher peak and peaks sooner (1 week)
Why are two doses of vaccines given?
After re-exposure to an antigen, more plasma cells keep producing protective serum antibodies
