Learning Objectives Flashcards
What are Antigen Presenting Cells?
Antigen-presenting cells (APC) are cells that can process a protein antigen, break it into peptides, and present it in conjunction with class II MHC molecules on the cell surface where it may interact with appropriate T cell receptors.
Professional APCs include dendritic cells, macrophages, and B cells.
Dendritic cells, macrophages, and B cells are the principal antigen-presenting cells for T cells, whereas follicular dendritic cells are the main antigen-presenting cells for B cells.
Give a very top-line overview of innate and adaptive immunity as they respond to a single pathogen
Draw the family tree of blood cells
Notes:
- Look at top left for how Dendritic cells fit in
- Natural Killer cells can be formed by either lineage
What are phagocytes?
Phagocytes are a type of white blood cell that use phagocytosis to engulf bacteria, foreign particles, and dying cells to protect the body. They bind to pathogens and internalise them in a phagosome, which acidifies and fuses with lysosomes in order to destroy the contents.
They are a key component of the innate immune system. There are three main groups of phagocytes:
- Monocytes/Macrophages
- Granulocytes
- Dendritic cells
What are the three different types of granulocyte?
There are three types of granulocytes in the blood: neutrophils, eosinophils, and basophils.
Neutrophils
The most phagocytic of these cells:
The most abundant white blood cell, and can be identified by their granular cytoplasm and lobulated nuclei (usually 2-5 lobules)
During the acute phase of infection they are among the first inflammatory cells to reach the site of infection.
They are particularly specialised at killing intracellular pathogens due to cytoplasmic granules with toxic substances such as antimicrobial peptides, enzymes, and reactive oxygen species.
Neutrophils are short-lived cells and normally die following phagocytosis and use of their granules – dying or dead neutrophils are a major part of the pus seen with infection.
Neutrophils are also important for inducing inflammation and recruiting inflammatory cells through release of cytokines and other inflammatory factors.
Eosinophils
Eosinophils are used in many, if not all, immune system responses. Notably, they are involved in allergic reactions, but they can also combat multicellular parasites such as worms.
Basophils
Also take part in allergic reactions. These cells release histamine, which causes inflammation, and heparin, a blood thinner which prevents clotting.
What are monocytes?
Monocytes are a type of phagocyte found in the bloodstream. They circulate around the body, and when a tissue is infected or inflamed they may leave the bloodstream and enter the tissue.
In the tissue they differentiate into macrophages, which form the major resident population of phagocytes in normal tissues.
(Monocytes are phagocytic but since most infections occur in tissues, it is the ability of monocytes to differentiate that is particularly key)
Monocytes can also differentiate into dendritic cells in the tissues, if a particular set of signals are present,
Monocytes are the largest type of phagocyte, with a kidney bean shaped nucleus when seen under a microscope.
What are Macrophages?
Macrophages are derived from monocytes and are found in the tissues.
As well as phagocytosis, they also help initiate the adaptive immune response by presenting antigens to T cells and secreting factors to induce inflammation and recruit other cells.
Macrophages may be termed differently depending on their location: microglia are present in the CNS and Kupffer cells are in the liver.
What are Dendritic cells?
The major function of dendritic cells is as a link between the innate and the adaptive immune systems. As immature dendritic cells they travel in the bloodstream and migrate through tissues and continually sample the pathogens they find via macropinocytosis.
Following phagocytosis, the cell becomes mature and migrates to a peripheral lymphoid organ such as a lymph node, the spleen, or gut-associated lymphoid tissue to present the antigen to a T cell. This then activates the T cell to initiate an adaptive immune response.
Appearance
Dendritic cells can be recognised by the presence of multiple cytoplasmic projections from their surface, giving them a large surface area to volume ratio that aids close contact with multiple cells. These processes look similar to the dendrites of neurons, which gave dendritic cells their name.
What is the difference between phagocytosis and pinocytosis
While phagocytosis involves the ingestion of solid material, pinocytosis is the ingestion of surrounding fluid(s).
This type of endocytosis allows a cell to engulf dissolved substances that bind to the cell membrane prior to internalization.
Unlike phagocytosis, pinocytosis is a “drinking” mechanism wherein a cell actively engulfs external fluids over time.
Even though pinocytosis differs from other forms of receptor-mediated endocytosis, these terms overlap with one another due to their similarities.
What are Mast Cells?
A mast cell (also known as a mastocyte or a labrocyte[1]) is a resident cell of connective tissue that contains many granules rich in histamine and heparin.
Specifically, it is a type of granulocyte derived from the myeloid stem cell.
The mast cell is very similar in both appearance and function to the basophil, another type of white blood cell. Although mast cells were once thought to be tissue-resident basophils, it has been shown that the two cells develop from different hematopoietic lineages and thus cannot be the same cells.[5]
Draw a diagram of the links from Pathogen-Phagocyte-Antigen-T Cell Differentiation, and the two different types of T cell
What happens when a naive B-cell is activated?
Note: Once activated, the B cells can then either become plasma cells and secrete antibodies, or become memory cells with MHC II cell surface proteins that can become activated by future antigens of the same kind
What are the two different types of T cell?
Draw a table of the major differences between your innate and adaptive immune system
What are the life-threatening features of a Fever in an infant?
Sepsis signs,
Meningitis (bacterial) and meningococcal septicaemia
Kawasaki disease
How can you diagnose a fever in an infant?
0-3 months >38
3-6 months >39
Under 4 weeks: electronic thermometer in axilla
4W-5yr: electronic thermometer in axilla, chemical dot on axilla, infra-red tympanic thermometer.
Parental perception of fever considered valid and should be taken seriously
What anti-pyretic interventions can we take with a child?
Ibuprofen 8hrs
Fluids and antibiotics
Not both simultaneously.
Continue as long as child in distress
Medications will not prevent febrile convolution
Do not undress or over-wrap child
What is the traffic light system of assessing the risk of serious disease is febrile children?
What are the five most serious conditions associated with a fever in a child, and what are their specific symptoms?
Which part of the body/receptors are responsible for regulating body temperature?
Regulated by HYPOTHAMALUS
Core temp maintained by anterior hypothalamus.
Internal
- Increased temp – sensed by anterior hypothalamus
- Decreased temp – sensed by posterior
External
Temp detected by skin thermoreceptors:
COLD (TRPM8)
HOT (TRPV3 and TRPV4)
What is the overall pathophysiology of a fever? And which pharmaceutacal agents can we use to interfere?
> Infectious agents
> macrophages release endogenous pyrogens
> pyrogens increase IL-1
> anterior hypothalamus release prostaglandins
> reset hypothalamus temperature to higher value.
What are the main signs of infection in children?
What investigations should be ordered for signs of fever/infection in children?
Link to traffic light system
Helpful mindmap for different types of rash
Macule
Circumscribed area of change in normal skin color, with no skin elevation or depression; may be any size
Papule
Solid, raised lesion up to 0.5 cm in greatest diameter
Nodule
Similar to papule but located deeper in the dermis or subcutaneous tissue; differentiated from papule by palpability and depth, rather than size
Plaque
Elevation of skin occupying a relatively large area in relation to height; often formed by confluence of papules
Pustule
Circumscribed elevation of skin containing purulent fluid of variable character (i.e., fluid may be white, yellow, greenish or hemorrhagic)
Vesicle
Circumscribed, elevated, fluid-containing lesion less than 0.5 cm in greatest diameter; may be intraepidermal or subepidermal in origin
Bulla
Same as vesicle, except lesion is more than 0.5 cm in greatest diameter
Helpful table for different types of rashes
Macule
Circumscribed area of change in normal skin color, with no skin elevation or depression; may be any size
Papule
Solid, raised lesion up to 0.5 cm in greatest diameter
Nodule
Similar to papule but located deeper in the dermis or subcutaneous tissue; differentiated from papule by palpability and depth, rather than size
Plaque
Elevation of skin occupying a relatively large area in relation to height; often formed by confluence of papules
Pustule
Circumscribed elevation of skin containing purulent fluid of variable character (i.e., fluid may be white, yellow, greenish or hemorrhagic)
Vesicle
Circumscribed, elevated, fluid-containing lesion less than 0.5 cm in greatest diameter; may be intraepidermal or subepidermal in origin
Bulla
Same as vesicle, except lesion is more than 0.5 cm in greatest diameter
What is the mechanism of Inflammation? Include the 5 R’s
Give an overview of the vascular events of inflammation
Give an overview of the cellular events that take place during inflammation
Which 3 kinds of adhesion molecules are vital in the attraction of leukocytes in endothelium in inflammatory response
Give an overview of the leukocyte ‘rolling’ phase
Selectins are expressed as a result of histamine and TNF-a
Give an overview of the ‘tight binding’ phase of leukocytes in inflammation
What are leukocyte integrins?
Beta2-integrins are complex leukocyte-specific adhesion molecules that are essential for leukocyte (e.g., neutrophil, lymphocyte) trafficking, as well as for other immunological processes such as neutrophil phagocytosis and ROS production, and T cell activation.
Give an overview of the ‘diapedesis’ phase of leukocytes in inflammation
Give an overall overview of leukocyte migration in inflammation
What are the 4/5 cardinal signs of inflammation
What are the differences between the three most common outcomes of inflammation - Full recovery, repair, and chronic outcomes.
Draw that table of meningitis physiology and it’s resultant clinical signs
Draw a table of which organisms commonly causes meningitis at different ages
Draw a table of the normal values expected in CSF and in bacterial/viral disturbances
What does germline mean
The DNA in germ cells (egg and sperm cells that join to form an embryo).
Germline DNA is the source of DNA for all other cells in the body.
What is sepsis? What is septicemia?
Sepsis is a life-threatening condition that arises when the body’s response to infection causes injury to its own tissues and organs.[4] This initial stage is followed by suppression of the immune system.[8] Common signs and symptoms include fever, increased heart rate, increased breathing rate, and confusion
Septicaemia is when bacteria enter the bloodstream, and cause blood poisoning which triggers sepsis.
How does meningitis cause a bulging fontanelle?
- Pathogens reach the subarachnoid space (SAS) through the bloodstream or from contiguous sites (spread of infections) and penetrate the blood-brain barrier (BBB) through complex molecular and cellular mechanisms.
- Meningitis causes an imbalance between the water content of the brain parenchyma, CSF volume, and cerebral blood flow (CBF), resulting in an increase of ICP.
- Cerebral edema caused by inflammation as well as arterial dilation due to loss of autoregulation and CSF outflow impairment in the SAS are all integral factors in meningitis associated with intracranial hypertension
- Additionally, thrombosis of the cerebral sinuses has been implicated in elevated ICP in both bacterial and viral infections.
Why is CSF from a lumbar puncture cloudy in meningitis?
Because of elevated proteins and white blood cells
Give an overview of the anatomy of the Meninges
How is CSF produced?
How does the CSF flow from the lateral ventricles to the rest of the cranium and spinal cord?
Why is an LP done between L3 and L4? (L4-L5 on a child)
Since the spinal cord ends as a solid structure around the level of the second lumbar vertebra (L2) the insertion of a needle must be below this point, usually between L3 and L4 (Fig 2).
The spinal cord continues below L2 down into the sacrum as many separate strands of nerve pathways, the cordae equina, bathed in CSF. Putting a needle into the spaces between the strands to collect fluid is much safer than taking the risk of hitting the solid cord higher up the spine.
The spinal vertebrae are held together by ligaments. Those penetrated in a lumbar puncture are the interspinous ligaments (which bind adjacent spinous processes together) and the ligamentum flavum (which binds adjacent vertebral laminae together and, in so doing, lines the posterior wall of the spinal canal).
What are the normal vital sign registers for paediatric patients?
What are the normal temperature ranges for paediatric patients?
Outline the actions to be taken on day 1, 2 and so on in bacterial determination of pathogen
What CSF parameters would we expect in bacterial, viral, and normal Adult/Child samples?
Which bacteria turn which colour under gram staining, and why?
Gram positive bacteria stain violet due to the presence of a thick layer of peptidoglycan in their cell walls, which retains the crystal violet these cells are stained with.
What are the two main morphologies of bacteria?
How does a latex agglutination test work?
Why is the streak plate technique important in bacterial cultures?
Streak plate technique is used for the isolation into a pure culture of the organisms (mostly bacteria), from a mixed population. The inoculum is streaked over the agar surface in such a way that it “thins out” the bacteria. Some individual bacterial cells are separated and well-spaced from each other.
Hemolysis is the breakdown of red blood cells. The ability of bacterial colonies to induce hemolysis when grown on blood agar is used to classify certain microorganisms. This is particularly useful in classifying streptococcal species.
Alpha-hemolysis
When alpha-hemolysis (α-hemolysis) is present, the agar under the colony is dark and greenish.
Streptococcus pneumoniae and a group of oral streptococci (Streptococcus viridans or viridans streptococci) display alpha hemolysis.
Alpha hemolysis is caused by hydrogen peroxide produced by the bacterium, oxidizing hemoglobin producing the green oxidized derivative methemoglobin.
Beta-hemolysis
Beta-hemolysis (β-hemolysis), sometimes called complete hemolysis, is a complete lysis of red cells in the media around and under the colonies: the area appears lightened (yellow) and transparent.[1]
Streptolysin, an exotoxin, is the enzyme produced by the bacteria which causes the complete lysis of red blood cells. Streptolysin O is an oxygen-sensitive cytotoxin, secreted by most Group A streptococcus (GAS) and Streptococcus dysgalactiae
Streptolysin S is an oxygen-stable cytotoxin also produced by most GAS strains which results in clearing on the surface of blood agar. Streptococcus pyogenes, or Group A beta-hemolytic Strep (GAS), displays beta hemolysis.
Some weakly beta-hemolytic species cause intense beta hemolysis when grown together with a strain of Staphylococcus. This is called the CAMP test.[2] Streptococcus agalactiae displays this property. Clostridium perfringens can be identified presumptively with this test. Listeria monocytogenes is also positive on sheep’s blood agar.
Gamma-hemolysis[edit]
If an organism does not induce hemolysis, the agar under and around the colony is unchanged, and the organism is called non-hemolytic or said to display gamma-hemolysis (γ-hemolysis).
Enterococcus faecalis (formerly called “Group D Strep”), Staphylococcus saprophyticus, and Staphylococcus epidermidis display gamma hemolysis.
What is the common presentation of meningitis in children and infants?
What are the standard treatments you can give for suspected septicemia or meningitis if you are in doubt?
What treatment can you give for Kawsaki’s disease?
What should recurrent infections and failure to thrive make you consider in a pediatric patient? And how does one screen for it?
Immunodeficiency
What is the difference between bactericidal and bacteriostatic antimicrobials?
The result is either killing of the bacterium (bactericidal) or inhibition of growth of the bacterium (bacteriostatic)
What is an antigen?
What are the primary and secondary organs of the immune system
Draw a table of the chemical, mechanical and microbial defenses present in Skin, Gut, the Lungs and the Nose/Eyes
Note: Defensins and cathelicidins are the two major families of mammalian anti-microbial proteins.
How are microbes recognised by pathogens?
What are PAMPs?
Pathogen-associated molecular patterns (PAMPs) are small molecular motifs conserved within a class of microbes. They are recognized by toll-like receptors (TLRs) and other pattern recognition receptors (PRRs) in both plants and animals
PAMPs activate innate immune responses, protecting the host from infection, by identifying some conserved nonself molecules.
- Self/non-self discrimination: very good; never fails
What are some different types of PRR?
Give 4 examples of oxygen-generated chemicals that detroy pathogens
Give 4 examples of oxygen-independent chemicals that destroy pathogens
What are the three main roles of the complement system?
What roles do the following cytokines have?
IL 1
IL 6
TNF-a
CXCL8
IL12
How do Dendritic Cells link the innate and adaptive responses?
What are the main 4 subsets of B-cells?
What are the three ways a DC can activate a T-cell?
What are the main systemic effects of inflammation
What are the four main types of exudate?
Give an overall overview of how inflammation starts and ends
What are the four main processes in neutrophil destruction of pathogens?
What does NETosis encompass?
What timescale do neutrophils and macrophages work on in terms of inflammation?
When do different bacteria affect different ages?
When do different bacteria affect different ages?
Different types of bacteria
