Principles Immunology Flashcards
Revise Principles Immunology
Give two basic ways in which the immune system identifies and eliminates harmful organisms
- Distinquishes self from non self proteins
- Identifies danger signals such as inflammation
(or combination of the two!)
What balance much the immune system strike?
Balance between clearing the pathogen and causing accidental damage to the host.
What is “severe combined immune deficiency”?
A rare disorder in which there is a failure of development of lymphocytes
Give four things that can happen when the immune system goes wrong.
Recurrent infections Allergy Autoimmune Disease Transplant Rejection Cancer
How does immunisation with cowpox prevent against small pox?
Cross reactive antibodies that neutralise the small pox virus.
Give 6 reasons for the prevalence of new infectious diseases
- Global Village
- Population growth
- Changes in human behaviours (sex)
- Changes in dynamics of other infections (HIV led to TB outbreaks)
- Loss of natural habitat
- Interactions of pathogens with humans (development of resistance)
Briefly describe the evolutionary arms race
The pathogen selects host based on defensive flaws.
Host then evolves to correct these
Pathogen replicates and evolves to evade those and exploit other barriers.
Name two ways in which pathogens can enter the airway?
- Inhaled droplet
2. Spores
What is the most important barrier to infection?
Skin
Name 5 anatomical structures that prevent infection
- Skin
- Speen
- Lymph nodes
- Bone Marrow
- Lymphatics
Name 5 cells types that protect the body against infection
Neutrophils Monocytes & Macrophages Eosinophils Mast cells Lymphocytes
Name 5 proteins that protect the body against infection
Immunoglobins Complement proteins Cytokines Mucous Stomach acid
How does the skin act as a barrier to infection? Give 6 ways
- Physical barrier (tightly packed, highly keratinised, multilayered cells) Also constantly renews making colonisation difficult.
- Low pH at 5.5. which most pathogens are sensitive to.
- Sebaceous glands secrete hydrophobic oil and repel microorganisms
- Lysozyme destroy bacterial cell walls
- Secretes ammonia
- Antimicrobial peptides such as defensins
How does secreted mucous act as a barrier to infection?
Give 4 ways
- Physically traps invading pathogens
- Secretes IgA which prevents penetration to epithelia
- Contains enzymes (lysozyme, defensins and anti microbials) Also contins lactoferrin
- Cilia trap pathogens and remove them in mucous
What doe lactoferrin do?
Starves invading bacteria of iron
Give 5 functions of commensal bacteria
- Synthesis Vitamins K & B12
- Produces anti microbial short chain fatty acids
- Competes with pathogens for essential nutrients, limiting pathogenic growth
- Reduces pH in large bowel
- Produce bactericides which influence other bacteria
Give three features of the innate immune system
- Rapid, general response
- Targets groups of pathogens (can only respond to a small number of structures)
- No immunological memory
Give three features of the adaptive immune system
- Gradual response
- Targets specific pathogens as it can respond to a huge array of structures
- Possesses immunological memory
Name the components of the innate immune system.
- Antibodies
- Complement proteins
- Acute phase proteins
- Cytokines
- Phagocytes (neutrophils, monocytes, macrophages, dendritic cells)
- Natural killer cells
- Eosoniphils
- Basophils and mast cells
Name the components of the adaptive immune system
- Antibodies
- Cytokines
- Dendritic cells
- Lymphocytes (T cells and B cells)
Which components of the immune system occur in both active and innate systems?
- Antibodies
- Cytokines
- Dendritic cells
Which components of the immune system are exclusive to the innate system?
- Complement proteins
- Acute phase proteins
- Phagocytes (neutrophils, monocytes and macrophages)
- Natural killer cells
- Eosinphils
- Basophils and mast cells
Which components of the immune system are exclusive to the adaptive system?
- Lymphocytes (T cells and B cells)
What are soluble factors? Name four.
Proteins.
Antibodies, complement proteins, acute phase proteins and cytokines
What are leukocytes? Name five
White blood cells.
Phagocytes, Lymphocytes, Eosonophils, Basophils, Mast cells
Name three types of phagocyte.
Neutrophils, monocytes and macrophages, dendritic cells
Name three types of lymphocytes.
T cells, B cells, Natural killer cells.
What are antibodies also known as?
Immunoglobulins
What is an antibody? What do they do?
A protein that is produced in response to a particular antigen molecule and can bind specifically to that antigen. They provide defence against extracellular microbes.
What is an antigen?
Any substance which can stimulate the adaptive immune system.
What produces antibodies?
B lymphocytes
What are cytokines? What do they do?
A diverse collections of small proteins and peptides which are produced in response to antigen inflammation and tissue damage.
The modulate the behaviour of cells. They act locally and systemically, have multiple functions and a short half life.
Name three cytokines and their functions.
- Interferons: Anti viral
- Tumour necrosis factor: Inflammation
- Chemokines: Direct cell migration
How many proteins are in the complement system?
30
Where are complement proteins produced?
Liver
What does the complement system do?
- Circulate in blood
- Enter infected tissue in response to inflammation
- They are then activated via interaction with microorganisms
- Once they are activated they can then activate other complement proteins to amplify the response.
They have a critical role in inflammation and defence against bacteria.
Where are acute phase proteins produced?
Liver, in response to inflammation
Give four inflammatory signals that would cause the production of acute phase proteins
- Infection
- Autoimmune disease
- Tissue damage
- Malignancy
What is the function of acute phase proteins?
Modulate the immune response to microorganisms and dead/dying cells
Tissue repair and healing
What is C reactive protein?
Prototype acute phase proteins
Levels rise dramatically in response to infection/inflammation
Short half life
Useful clinically
What are the primary lymphoid tissues?
Bone marrow and thymus
What do mast cells do?
Reside in tissues such as mucousal tissues
What do basophils do?
Circulate in blood (make up less that 1% of circulating leukocytes) and are recruited to sites of inflammation
Describe basophils and their functions
Highly granular
Secrete histamine, toxic substance, cytokines when activated.
Important in defence against parasites
Key role in driving allergic response
What is the function of eosinophils?
Circulate in blood (less than 1% blood leukocytes usually)
Recruited into inflamed tissue
Defend against large pathogens,, such as parasitic worms, that cannot be dealt with by phagocytes.
Key role in allergic diseases such as allergic asthma
What are phagocytes? What do they do?
Eating cells!
- Ingest microorganisms by phagocytosis
- Clear cellular debris
- Involved in tissue repair processes
- Source of inflammatory cytokines
- Antigen presentation
What phagocytes are present in the blood?
Neutrophils and monocytes
What phagocytes are present in the tissues?
Macrophages and dendritic cells.
What % of circulating leukocytes are neutrophils?
50 - 70%
What are the first immune cells recruited to a site of inflammation?
Neutrophils
What do neutrophils do?
Phagocytosis and killing of pathogens
What are monocytes?
Monocytes are the circulating precursors of the tissue resident macrophages. They are involved and destruction of pathogens and dead cells.
Also involved in antigen presentation and cytokine production.
What are dendritic cells responsible for?
The initiation of adaptive immune responses. They are specilised cells that capture and process antigens and then present them to T cells which then induce an adaptive immune response.
Where would you find dendritic cells?
- As immature cells in peripheral tissues; especially those exposed to the external environment (skin, lungs and intestine)
- Present in secondary lymphoid tissues for antigen presentation.
What lymphocytes are present in the innate immune system?
Natural killer cells
What lymphocytes are present in the adaptive immune system?
T cells and B cells.
What is the major function of natural killer cells?
Detect and kill abnormal cells such as viruses or cancer cells.
Where do T cells and B cells originate?
Bone marrow
Where do T cells mature?
Thymus
How do T and B cells work?
The circulate all around in body, being found in lymph and lymphoid tissue. The are activated by antigens and will eliminate any cells that express these antigens. Some act as me more cells.
Part of the adaptive immune response.
What are B cells responsible for?
Production of antigen specific antibodies directed against pathogens.
Their key role is in defence against extracellular organisms (mucosal tissues, bloodstream)
What are the two major types of T cells? What do they each do?
T cells defend us against viruses, fungi and bacteria. Two types:
CD4 + T cells (helper T cells): These are responsible for cytokine production which is a key central regulator of the entire immune response.
CD8 + T cells (cytotoxic T cells): These are very important for defence against intracellular pathogens. These kill virally infected body cells and cancer cells
What do primary lymphoid tissues do?
Sites of leukocyte development
Name all the primary lymphoid tissues.
Bone Marrow
Thymus
What do secondary lymphoid tissues do?
Sites for generating adaptive immune responses.
Contain lymphocytes and dendritic cells.
name all the secondary lymphoid tissues.
Adenoid, tonsil, lymph nodes, spleen, peyers patch in small intestine, large intestine.
What is the function of lymph nodes?
House lymphocytes and are sites for lymph drainage.
Monitor the lymph for signs of infection.
What are the four signs of acute inflammation?
- Pain
- Redness
- Heat
- Swelling
(Also may lose function)
Give two positive aspects of inflammation
- Disposes of cell debris and pathogens
2. Promotes tissue healing and repair
Name two antimicrobial proteins and give their function.
Lysozymes (present in tears and saliva) It digests bacterial cell walls.
Defensins (secreted by epithelial cells at mucosal surfaces) Disrupt the cell membranes of bacteria, fungi and some viruses.
What are the three pathways of the complement system?
- Classical
- Lectin
- Alternative
What is the main, central reaction in the complement pathway?
C3 ——–> C3b +C3a
How is the classical pathway activated? What does it do next?
Binding of complement C1 complex to antibody - antigen complexes.
It then activates C4 and C2, to form C3 convertase, C4b2a
How is the lectin pathway work?
Host lectins (such as MBL) bind carbohydrates in cell walls of microorganisms. This activates MBL serene proteases, MASP 1 and 2. This then activates C4 and C2 to form C3 convertase, C4b2a
How is the alternate pathway activated? What does it do next?
By spontaneous hydrolysis of C3, and binding of C3b to bacterial cells wall components.
C3b then interacts with other complement proteins to form an alternate C3 convertase, C3bBb.
It is vital is the protection against menigococcus and other encapsulates bacteria.
It allows an amplification loop.
Whars are the effector function of the complement system?
- Membrane attack complex
- Opsonisation
- Chemotaxis
- Clearance of immune complexes
- Inflammation
What is opsonisation?
Coating of microorganisms by immune proteins (opsonins)
Give three opsonins:
C3b, antibodies, CRP
How does opsonisation work?
Phagocytes express receptors for opsonins of their cell surface. Opsonisation makes them more likely to eat pathogens, and so there is a faster response time! You get an complement + bacteria + antibody!
What does C3b binding do?
It dissolves the immune complexes that trigger the classical complement activation pathway
Describe complement mediates lysis. When is it particularly important?
C5b binds to the surface of pathogens.
C6, C7, C8 and C9 assemble with C5b forming the membrane attack complex
This inserts into target cells walls and causes osmotic lysins of a pathogen.
Important is defence against encapsulated bacteria.
Describe complement mediated inflammation:
- C3a and C5a are known as anaphylatoxin and these bind to receptors on mast cells/basophils(both granulocytes)
- This then causes granule release of of vasoactive substances such as histamine
- This increases vascular permeability and causes inflammation.
- This then causes recruitment of phagocytes to site of infection
Describe complement mediated chemotaxis:
- C3a and C5a are known as anaphylatoxin and these bind to receptors on mast cells/basophils(both granulocytes)
- This then causes the release of chemotactic factors
- This results in the recruitment of phagocytes to the site of infection
Give three ways in which the complement system is regulated:
- Only cleaved components are active, these have a very short half life
- Complement inhibitors. C1 inhibitor, Factor 1, factor H, C4 binding protein.
- Free antibodies can’t activate the classical complement pathway in the absence of an antigen.
What is a deficiency of the complement pathway often associated with?
Menigococcal infection.
Give three actions of natural killer cells:
- Kill infected cells
- Complement mediated lysis of micro-organisms
- amplification of innate inflammatory response
What does dectin 1 do?
Component in anti fungal defence. Binds with a component of fungi cell wall.
What do toll like receptors do? Give an example
Bind specifically to different pathogen components like dsRNA, DNA, extracellular proteins (e.g. flagellin) or sugars (e.g. LPS)
Example: Bacterial lipopolysaccharide (LPS)
Major constituent of outer cell membrane of some bacteria
Binds to Toll-like Receptor 4
What do inflammatory mediators promote?
- Changes in local vasculature
- Recruitment chemotaxis of neutrophils into sites of inflammation.
- Stimulation of bone marrow to produce more neutrophils.
What happens to endothelial cells at the sites of inflammation?
The become activated and express adhesion molecules (selections and ICAMs) and chemokines)
What do selections do in inflammation?
Allow circulating leukocytes to bind weakly to endothelial cells and roll along the endothelial cell surface.
What do chemokines do in inflammation?
They activate the leukocytes (now bound weakly) and allow them to find firmly to the endothelial cells via integrins(leukocytes) binding to ICAMs (endothelial cells). The leukocytes then arrest on endothelial cell layer.
What happens after firm attachment in the sequence of an inflammatory response?
The leukocytes flatten out to resist the shear flow and crawl along the endothelium looking for a suitable place to extravasate from the vessel. The final stage is the leukocytes squeeze through the endothelial layer (transmigration)
What happens once the leukocyte is inside the tissue?
It follows a chemokine gradient to the site of inflammation.
Give the three different types of phagocytes?
- Neutrophils
- Macrophages
- Dendritic cells
What is the function of neutrophils?
Pathogen lysis
What are the 4 functions of macrophages?
- Pathogen lysis
- Inflammation
- Tissue repair and healing
- Antigen presentation
What are the two functions of dendritic cells?
Antigen presentation
Inflammation
What is oxidative killing and what cells carry it out?
Neutrophils and macrophages can phagocytose and them destroy pathogens by generating lethal toxic oxygen and nitrogen free radicals. (especially important in neutrophils)
What is the crucial enzyme in oxidative killing? What does it do?
NADPH oxidase complex
Converts oxygen into toxic reactive oxygen and nitrogen intermediates.
What is pus made up of? Why is it formed?
Dead and dying neutrophils + tissue cells + microbial debris.
Formed as phagocytosis depletes the energy stores of neutrophils.
Residual enzymes/toxins are released resulting in tissue damage
Macrophages and dendritic cells secrete pro inflammatory cytokines and chemokines. What does this do?
Initiates and amplifies acute inflammation
What do macrophages and dendritic cells do during the resolution phase of inflammation?
- Debris scavenging
- Angiogenesis
- Wound healing
- Anti inflammatory cytokines
What is a granuloma?
A collection of immune cells that walls of the the pathogens, such as mycobacterium but does not eradicate them.
What are the clinical implication of phagocyte deficiencies?
- Recurrent bacterial infections (Staph Aureus and enteric bacteria) which are poorly responsive to antibiotics
- TB and other atypical mycobacterial infections
- Recurrent fungal infection such as aspergillus and candida albicans
What is meant by non oxidative killing?
Neutrophils and macrophages which secrete a plethora of toxic antimicrobial agents both into the phagolysosome and out into the surrounding tissues.
