Killing Extracellular Pathogens Flashcards
“Complement” is a series of soluble proteins in the serum, which have roles in activating the immune response to extracellular pathogens, encouraging their phagocytosis, and killing pathogens directly. Which complement components are responsible for the following effects?
- Lysis of bacterial cells via the membrane attack complex
- Activation of complement through antibody complexes via the classical pathway
- Activation of complement through the alternative pathway
- Release of anaphylatoxins
- Activation of the complement pathway through binding to pathogen carbohydrates
A. MBL
B. C1
C. C3
D. C3, C4 & C5
E. C6-C9
E. C6-C9
B. C1
C. C3
D. C3, C4, C5
A. MBL
Complement can be activated via the classical pathway, by C1 binding antibody-antigen complexes; via the MBLpathway, by MBL binding mannose on bacterial surfaces; and by the alternative pathway, through C3 binding to pathogen surfaces. Each of these pathways then leads to release of anaphylatoxins consisting of C3a, C4a and C5a, and finally formation of the membrane attack complex, which can lyse bacterial cells and is a complex of complement components C6-C9.
Phagocytes “eat” pathogens and then kill them through a number of mechanisms. Select the correct mechanisms used by phagocytes to kill pathogens.
- Hypochlorite
- Oxygen radicals
- Pore-forming proteins
- UV light
- Alkali
- Acid
- Witholding nutrients
- Ethanol
- Nitric Oxide
- Arsenic
-Hypochlorite
-Oxygen radicals
-Acid
-Witholding nutrients
-Nitric Oxide
Once a phagocyte such as a macrophage or a neutrophil phagocytoses a pathogen such as a bacteria, it can then kill the pathogen via acidification of the phagolysosome (through vacuolar ATPases pumping H+ ions into the vescicle); release of oxygen radicals (such as superoxide, hydrogen peroxide and hypochlorite, all of which are dependent on the action of the NADPH oxidase complex); nitric oxide (made by inducible nitric oxide synthase, iNOS); and through binding and withholding of nutrients such as metal ions from the bacteria.
Different phagocytes have different abilities. Match the ability to the cell:
- Can make hypochlorite/bleach
- Can secrete DNA to trap pathogens
- Worst at killing
- First to be recruited to pathogen site
- Reside in tissues and can kill invading pathogens
- Best at killing pathogens
- Are best at stimulating T cells
A. Dendritic Cell
B. Macrophage
C. Neutrophil
C. Neutrophil
C. Neutrophil
A. DC
C. Neutrophil
B. Macrophage
C. Neutrophil
Neutrophils, macrophages and dendritic cells are all phagocytes, but there are some important differences in how these cells treat phagocytosed pathogens. Neutrophils are the “shock troops” of the immune system, recruited rapidly and in large numbers from the circulation to the site of infection. They are the best of the phagocytes at killing pathogens, and the only phagocyte that can produce highly toxic hypochlorite through the action of myeloperoxidase. They can also extrude their genomic DNA to form NETs (Neutrophil Extracellular Traps) to trap pathogens so that they cannot disseminate further into the host. Macrophages are multifunctional phagocytes, with the ability to both present antigen to T cells (like dendritic cells) and kill pathogens (like neutrophils), depending on the situation. They reside in the tissues throughout the body scanning for invading pathogens.
Antibodies can have multiple functions: neutralisation, opsonisation, complement activation and Antibody Dependent Cell-mediated Cytotoxicity (ADCC). Match the description with the activity.
- Binding to a bacteria and encouraging phagocytosis
- Binding to a parasite and resulting in eosinophil degranulation
- Binding to a toxin to prevent it killing cells
- Binding to a bacteria and activating C1
- Binding to a virus to prevent it entering a cell
A. Opsonisation
B. Neutralisation
C. Complement activation
D. ADCC
A Opsonisation
D. ADCC
B. Neutralisation
C. Complement activation
B. Neutralisation
Antibodies of various subtypes have multiple functions. Antibodies such as IgA are good at neutralising toxins, to prevent them from binding to their receptor and causing damage, and preventing pathogens such as viruses from entering cells. Antibodies such as IgG3 are best at opsonising pathogens (encouraging phagocytes to eat and kill them), and activating the C1 complement component through the classical complement activation pathway. IgE, bound to the surface of helminth parasites, can be recognised by eosinophils, resulting in their degranulation and damage to the parasite, through the process of ADCC.
Why do we need different types of immune response to deal with different microbes?
Because the innate response clears small challenges and buys time for the adaptive response to develope against big problems
What is the intial inflammatory response to extracellular pathogens?
- Microbe enters skin
- Microbes/ injury activate sentinel cells
- Sentinels secrete inflammatory mediators
- Inc vascular permeability and fluid/proteins enter tissue
- Complement, antibodies, and anti microbial proteins kill microbe
- Adhesion molecules & chemo lines cause leukocyte migration into tissue
Phagocytosis and killing of microbes
Describe the activation of T-cells in response to extracellular pathogens?
APCs recognize antigens on pathogen, presents it to naive T cells, which then secrete cytokines to activate other cells, proliferate and differentiate into Effector T cell or Memory T cell
CD4: activates other macrophages, B cells, other cells
CD8: kills infected cells, macrophage activation
What are the different Th cell subsets and their general functions?
Th1: IFN-y; targets macrophages
Th2: IL-4/5/13; targets eosinophils
Th17: IL-17/23; targets neutrophils
Tfh: IL-21/IFN-y/IL-4; targets B cells
What is the role of signal 3 in driving Th cell subset differentiation?
What is a plasma cell?
What are the different effector functions of antibodies? How they work in cooperation with innate cells?
How do antibodies make complement fixation (activation) more effective?
What are the effector roles of complement?
What are the different types of phagocytes and their differences?
Explain the steps of phagocytosis
