Immunology Flashcards
When would immunosuppression be utilitised?
Patients may be artificially immunosuppressed in the event of an autoimmune disease
Describe the properties of the skin as a physical barrier to infection
It is constantly renewed
It has a low pH
It has low oxygen tension
Sebaceous glands secrete hydrophobic oild whick make it hard for pathogens to bind
Mucous line all _____ ________ that come into contact with the ___________
Body cavities
Environment
Mucous contains many constitutes which can fight potential pathogens, what are these?
- Secretory IgA
- Lysozymes
- Defensins
- Antimicrobial peptides
- Lactoferrin - starve invading bacteria of iron
What are commensal bacteria?
Bacteria that reside in the body and on epithelial surfaces naturally.
They have a symbiotic relationship with the body and can eradicate most normally infections
They ensure there is no undefended ecological niche
The components of the immune system can be split into which two categories?
- Cells
- Humoral immunity (soluble factors)
Which 3 main groups of cells are involved in the immune system?
- Phagocytes
- Lymphocytes
- Granular
When a cell is infected with a virus what will it secrete?
Interferons (alpha and beta)
The antiviral state inititiated by interferons achieves what?
It down regulates protein synthesis which slows virus production
What is an antigen?
An substance able to stimulate an adaptive immune response - it can be protein, carbohydrate, nucleic acid, lipid, metal etc
Where are T and B cells formed?
Bone marrow
Where do B cells mature?
Bone marrow
Where do T cells mature?
Thymus gland
In response to an infection B cells will produce what?
Antibodies and memory cells
What are the two types of T cell?
Helper T cell (CD4+)
Cytotoxic T cell (CD8+)
How does a virus evade the immune system?
It will usually hide within body cells
How can cytotoxic T cells discover viruses hiding in body cells?
The host cell constantly samples its cytoplasm and displays proteins on its surface - this is mediated by MHC class 1 proteins
These displayed proteins can “show” cytotoxic T cells which cells are infected
How do viruses evade the process of cytoplasm sampling mediated by MHC class I proteins?
They downregulate the production of MHC class I proteins
This reduced cytoplasm sampling
How do natural killer (NK) cells retaliate to viruses that downregulate MHC class I production?
NK cells can detect a lack of MHC class I proteins on a cell surface
They can then attack and destroy such cells
How are parastitic works (helminths) attacked by the immune system?
Antibodies and mast cells
What is the complement system and where is it produced?
Family of around 30 different proteins produced in the liver
How does the complement system function?
When activated, the proteins activate eachother in a cascade fashion
This involves great amplification and playes a role in inflammation
When do monocytes differentitate into macrophages?
When they exit the blood and migrate to peripheral tissues
What are Kupffer cells?
Macrophages of the liver
What are mesangial cells?
Macrophages of the kidney
What are macrophages of the nervous sytem called?
Microglia
How can neutrophils be differentiated from macrophages?
Their multi-lobed nucleus
What is the role of dendritic cells?
They engulf pathogens, phagoytose and then present antigens on their surface to T cells
What are the main functions of neutrophils?
Killing and degredation
What are the main functions of macrophages?
Killing, degregation, wound healing, anti-inflammatory and antigen presentation
What is the main fucntion of dendritic cells?
Antigen presentation
What is lymphodema and why may it result in infection?
It a condition characterised by a lack of draining of tissue fluid by the lymphatic system
The fluid builds up and is not cleaned as effectively leading, potentially, to infection
The immune system itself is composed of two halves - what are these halves and how are they connected?
- Innate immune system
- Adaptive immune system
Joined through the action of dendritic cells
What is meant by “direct contact” between immune cells and pathogens?
A receptor/ligand interaction
What is meant by “indirect contact” in the immune system?
Communication between cells and pathogens through the use of cytokines
What are autocrine signals?
Signals produced by a cell that lead to self-activation
Interferons have the role of activating an _______ ______
Antiviral state
Which cells may secrete interferons?
Infected cells
Release of interferons has two main outcomes, what are they?
- Protein synthesis is downregulated
- Employment of particlular mlcules into the cell membrane is upregulated such as MHC class I - allows for detection
Interferons can also instruct cells to undergo apoptosis
What are the signs of acute infammation?
- Redness - vasodilation
- Swelling - vascualr permeability
- Heat - high metabolic function
- Pain
- Loss of function
What are the three phases of the innate response?
- Recognition
- Activation
- Effector
Describe recognition as a phase in the innate response
Innate immune cells recognise pathogens due to the expression of PAMPs which bind to PRRs on innate immune cells
What are PAMPs?
Pathogen associated molecular patterns
These are ligands expressed on the surface of pathogens which allow them to be detected by immune cells
What are PRRs?
Pattern recognition receptors
Found on innate imune cells that are receptors for PAMPs found on pathogens
How do macrophages differentiate between apoptotic cells and normal cells?
Normally phospholids called phosphatidlyserine are held facing inward to the cytoplasm by the enzyme flippase
In the event of apoptosis, phosphatidlyserine is fliiped to face outwards by the acion of the enzyme scramblase
These outward facing phosphatidlyserine lipids act as signals for macrophageal engulfment
PAMPs have the ability to activate which three immune cells
- Macrophages
- Mast cells
- NK cells
Injured cells release which type of signals?
Danger signals
(e.g. IL 33)
What happens when macrophages cannot kill a pathogen?
Infected macrophages are walled off forming granulomas
The purpose of this is to prevent the spread of infection
What will be present on the surface of macrophages after engulfment of a pathogen?
Fragments of pathogen protein
This allows for recognition by antigen presentation
Interferon gamma can cause what change in a macrophage?
It will cause superactivation
This allows for expression of inducible nitric oxide synthase - an enzyme allowing for production of toxic oxygen and nitrogen species
The antigen presentation capacity of macrophages will also increase
Where are mast cells found most prominently?
Mucosal surfaces
Which two processes occur when a PRR on a mast cell is bound by a PAMP?
- Degranulation - release of pre-formed pro-inflammatory mediators are released allowing for acute inflammation
- Gene expression - production of new pro-inflammatory mediators commences within mast cells
Why do NK cells not kill normal helathy cells?
Normal cells have MHC class I protein on their surface which is bound to self proteins (antigens)
NK cells have a receptor on their surface that binds to the MHC class I protein and the antigen
When the antigen/MHC class I combination is of self-origin, inhibitory signals are sent to the NK cells
How do viruses evade cytotoxic T cell killing?
They cannot be detected by the antigen/MHC class I receptor system because they downregulate MHC class I production meaning it is more difficult for foreign antigens to be “seen”
How do NK cells kill cells in which viruses have downregulated MHC class I production?
If no ligand (MHC class I + antigen) is present, NK cells cannot be inhibited so the cell is killed regardless
NK cells take no chances
Upon activation NK cells secrete pro inflammatory mediators such as _________ gamma
Interferon
In what two ways are NK cells activated?
- Detection of no/foreign MHC class I
- Interferon alpha and beta released from infected cells
Which pro-inflammatory mediator acts upon macrophages to superactivate them?
Interferon gamma
(produced from NK cells)
Which cytokines act on the hypothalamus to increase prostaglandin production?
TNFalpha, IL-1 and IL-6
What is the function of prostaglandin production by the hypothalamus during an infection?
Induces fever
What effect do cytokines TNFalpha, IL-1 and IL-6 have on bone marrow?
Act on haematopoetic stem cells to drive production and differentiation of more neutrophils
What is increased production of neutrophils called?
Neutrophilia
Where is C reactive protein produced and what increases its production?
Liver
Pro-inflammatory mediators TNFalpha, IL-1 and IL-6
Clinically, why are CRP levels usefult to monitor?
They are very indicative of the level and severity of inflammation
CRP has which two functions in the immune system?
- Promotes phagocytosis
- Activates complement
What are the symptos of the local effects of inflammation?
- Rubor - redness
- Calor - heat
- Tumour - swelling
- Dolor - pain
- Loss of function
Pro-inflammatory mediators can cause systematic effects as well as local ones, what are these?
- Neutrophilia
- Fever
- Activation of complement
- Promotion of phagocytosis