Immunology Flashcards
What are the physical/ chemical barriers that pathogens must cross to invade the body?
Skin
Mucosa–> Respt tract, GI tract, Genitcal tract/ urinary system
Chemical barriers–> Stomach acid, Lysozyme (sweart and tears)
What is the initial response to a pathogen invading tissue?
Complement system activation
What is the complement system?
Part of the immune system that enhances the ability of antibodies and phagocytic cells to clear microbes and damaged cells, promote inflammation and attack pathogen’s cell membrane.
What is the next step after the complement system has been activated?
Macrophages recognise pathogens and activate hte innate immune system
What happens after the innate immune system has been activated?
Dendritic cells pick up antigens and activate the specific immune system
What does ‘Baso’ mean?
Foundation
What does ‘Blast’ mean?
Immature cells
What does ‘cyte’ mean?
cell
What does ‘Eosin’ mean?
Red coloured
What does ‘Haemo’ mean?
Blood
What does ‘Karyo’ mean?
Nucleus
What does ‘Kine’ mean?
Motion
What does ‘Myelo’ mean?
Bone marrow
What does ‘Neutro’ mean?
Neutral
What does ‘phage’ mean?
eat
What does ‘Phil’ mean?
Attraction
What does ‘Poietic’ mean?
Creative
What does ‘Potent’ mean?
Potential
What does ‘Pro’ mean?
Moving forward
What does ‘Reticulo’ mean?
Net like
What is the first phase of a blood cell?
Pluripotent Haematopoietic stem cell
What are the 3 types of undifferentiated heamatopoeitic stem cells?
Myeloid Stem Cells
Lymphoid Stem Cells
Dendritic Cells
What do Myeloid Stem Cells become?
Megakaryocytes–> Platelets
Reticulocytes–> RBC’s
Promyelocytes
What do Megakaryocytes produce?
Platelets
What do Reticulocytes become?
Red Blood Cells
What do Promyelocytes become?
Monocytes--> Macrophages Neutrophils Eosinophils Mast Cells Basophils
Where do lymphoid stem cells travel to?
Thymus gland
What do Lymphoid Stem cells differentiate into?
B lymphocytes (B cells)
T lymphocytes
Natural killer cells
Where do B cells mature and what do they differentiate into?
Mature in the bone marrow Differentiate into :
- Plasma cells
- Memory B Cells
Where do T cells mature and what do the differentiate into?
Mature in the Thymus
- CD4 Cells (T helper cells)
- CD8 Cells (Cytotoxic T cells)
What are Megakaryoctyes?
Large cells
Big lobulated nucleus
Produce platelets
What are Reticulocytes/ what do they contain/ where are they released from?
Immature RBC’s
Contain remnant RNA material (reticulum) in cytoplasm
Released from bone marrow
What percentage of RBC’s are reticulocytes and what does a higher percentage indicate?
1%
Higher indicated rapid turnover of blood (e.g. acute blood loss, haemolysis)
What happens when reticulocytes loose their reticulum?
They become red blood cells
How long do red blood cells survive?
120 days
What is the difference between monocytes and macrophages?
Monocytes circulate the blood stream
Once they enter the tissues, they differentiate into macrophages
What do monocytes/ macrophages do?
Use their Toll-like receptors to recognise molecular patterns on pathogens.
They then kill pathogens by phagocytosis and release cytokines that initiate the inflammatory response
What are TLR’s?
Toll like receptors–> Pattern recognition receptors that play a key role in the innate immune response
What are PAMPs?
Pathogen-associated molecular patterns
What is the action of neutrophils?
Circulate through the blood and lymphatic system
Migrate to areas of inflammation.
Kill pathogens and abnormal cells by phagocytosis
What do eosinophils contain
Contain granules with:
-Proinflammatory cytokines -Chemicals toxic to pathogens
What are the functions of eosinophils?
Exocytosis of their granules
Phagocytosis
* Important in response to parasites
Where are eosinophils usually found?
Sat waiting in tissues
Where are mast cells vs Basophils found?
Mast cells are fixed in place in tissues.
Basophils circulate through the blood.
What is the main action of mast cells/ basophils?
Contain cytoplasmic granules that release pro-inflammatory cytokines
Where to B cells mature?
Bone marrow
What do B lymphocytes have on their cell surface?
A specific antibody for a specific antigen
What can B cells become once activated?
Plasma cell
Memory cell
What is a plasma cell?
A cell that secretes antibodies
Where do T cells mature and from what?
Pro-thymocytes leave the bone marrow and travel to the thymus gland where they mature
What are the cell surface of T cells lined with?
T-cell receptors –> specific type for a specific antigen
What receptors do CD4 cells have and what do they recognise?
CD4 TcRs that recognise MHC class 2 receptors
What receptors do CD8 cells have and what do they recognise?
CD8 TcRs that recognise MHC class 1 receptors
What do CD4 cells become when activated?
T-helper cells
What is the action of T-helper cells?
Help other cells (such as CD8 cells) become activated
What do CD8 cells become when activated?
Cytotoxic T cells
What is the action of cytotoxic T cells?
Destroy infected cells via granule exocytosis and activating the Fas pathway, causing cell apoptosis
What activated natural killer cells?
Cytokines from macrophages and interferons
What is the action of natural killer cells?
Recognise infected/ abnormal cells and destroy then by cytokines.
Also release IFN-γ that activates macrophages
What is the action of dendritic cells?
Antigen presenting cells: Take up antigens, process then and display them on their cell surface.
Also act as messengers, taking antigens from infectes tissues to lymph nodes to activate T cells.
What is the name of the specialised dendritic cells found in the skin?
Langerhans cells
What is the origin of all immune cells?
Bone marrow
Where is the bone marrow found?
Inside (inner medullary cavity of) long bones
Where is the thymus and how many lobes does it have?
Located in the mediastinum behind the sternum
2 lobes
What is the outer/ inner areas of the thymus called and what occurs in each?
Outer= Cortex–> Where T cells proliferate and start to develop into specialised cells
Inner=Medulla–> Where mature T cells are found before they enter the blood
What is the lymphatic system?
Network of lymphatic vessels similar to blood vessels
How does the lymphatic system circulate?
Relies on the muscles surrounding the vessels to pump
How does the lymphatic system direct the flow of lymph?
Contain valves
Where does the lymphatic circulation drain into the main circulation?
Via the thoracic duct (between left subclavian and internal jugular veins)
Right lymphatic duct (entering at right subclavian or internal jugular veins)
What is lymph and what does it contain?
Interstitial fluid that has drained from the interstitial space.
Contains a high concentration of lymphocytes and dendritic cells.
What is the role of lymph nodes?
Filters:
Hold cells of the immune system (particularly lymphocytes) and act as filters for pathogens and abnormal cells which become trapped there and are destroyed by the immune cells
Where are lymph nodes typically found?
Concentrated near junctions of the major lymphatic vessels, most prominently in the neck, groin, and armpits.
What is the shape of lymph nodes and what are they surrounded by?
Shapes like a kidney and surrounded by a capsule
What are the different areas of lymph nodes and what does each part contain?
Cortex–> Contains B cells and follicles
Paracortex (inner)–> Contains T cells and dendritic cells
Medulla–> Contains plasma cells, T, B cells and macrophages
Hilum–> Where the efferent and blood vessels enter
What are the follicles of the lymph nodes?
Areas where groups of B cells clump together and wait to be activated
What do primary follicles contain?
Contain unstimulated B cells
Do not have germinal centres
What do secondary follicles contain?
Germinal centres
Activated B cells that are generating plasma cells and memory B cells
What are germinal centres?
Sites within secondary lymphoid organs (lymph nodes and the spleen) where mature B cells proliferate, differentiate, and mutate their antibody genes
What are the two routes by which cells enter the lymph nodes?
Lymph (and its cells) enters through the afferent lymphatic vessels.
Lymphocytes usually enter through specialised blood vessels ( HEV’s)
What is the spleen made up of?
Red pulp and white pulp
Where is the spleen located?
Upper left quadrant of the abdomen
What is red pulp?
80% of spleen parenchyma
Made up of cords and venous sinus.
What is the function of the red pulp?
Where old red blood cells are removed by being filtered through a web of reticular fibres
What is white pulp?
Lymphatic tissue
Comprises lymph-related nodules called malpighian corpuscles.
How is white pulp formed?
Immune cells wrap themselves around the arterioles in the spleen forming the white pulp.
What are the 3 zones of the white pulp?
Periarteriolar lymphoid sheats
Marginal zone
Lymphoid follic;es
What is the name of the cells immediately around the splenic arteriole and what does it contain?
Peri-arteriolar lymphoid sheath (PALS)
Contains T cells and dendritic cells
What surrounds the PALS and what does it contain?
Marginal zone, containing B cells and macrophages
What happens if antigen presenting cells enter the white pulp?
T-lymphocytes stored there are activated, which in turn activates B lymphocytes in the follicles, converting them to plasma cells which produce IgM antibodies and then IgG antibodies.
What happens if pathogens enter the white pulp follicles directly?
B- cells detect them and present the antigen to T-lymphocytes in a process called co-stimulation. The B cell is then able to become a plasma cell and produce antibodies against the pathogen.
What is mucosa-associated lymphoid tissue and what does it contain?
Random lymphoid tissue associated with the mucosa of the GI, respiratory and urinary tracts. Contains primary follicles and germinal centres.
What are some examples of structures MALT (mucosa-associated lymphoid tissue)?
Tonsils, Adenoids, Appendix, Peyer’s patches (in ileum of small intestine)
What is the role of the innate immune system?
Provides a local and generalised response to infection with a pathogen.
What are cytokines?
Proteins that act like local hormones- send signals and stimulate a response
What are opsonins?
Any molecule that binds to a pathogen and signals to phagocytes to destroy it by phagocytosis (e.g. antibodies, complement proteins)
What are the main phagocytes?
Monocytes, macrophages, neutrophils, tissue dendritic cells, and mast cells
What are the main cells of the innate immune system?
Macrophages
Neutrophils
Interferons
Natural killer cells
How do macrophages recognise pathogens and how do they act once recognised?
Their TLR’s recognise PAMPs
They then:
-Phagocytose
-Release cytokines that cause inflammation
-Release interferons that prevent viral entry/ replication in cells.
What are the first line of defence in the innate immune response and why?
Macrophages as they are always present in tissues
What is the second line of defence once a pathogen invades tissues and the inflammatory response has started?
Neutrophils circulating in the blood are recruited into the tissues to help with phagocytosis
What are the 4 stages of phagocytosis?
- Attachment
- Ingestion
- Killing
- Degredation
What cytokines do macrophages release and what do these cause?
- Interleukins
- Colony-stimulating factor
- Tumour necrosis factor
- Growth factor
- Chemokine
Lead to inflammation
How does inflammation help the innate immune system?
- Activate more macrophages
- Recruit monocytes that can differentiate into macrophages in the tissue
- Recruit/ activate neutrophils and natural killer cells
- Bring opsonins that aid macrophages and neutrophils in phagocytosis
What are interferons and what is their action?
Cytokines that act by blocking viral entry into cells, block viral replication in cells and activate macrophages/ natural killer cells
What cells produce interferons?
Macrophages, lymphocytes (natural killer cells), endothelial and epithelial cells.
What differentiates natural killer cells (type of lymphocyte) from B and T lymphocytes?
Not specific to one antigen
Part of innate immune system.
What is the special function of natural killer cells?
Can recognise an infected or abnormal cell without requiring MHC or specific antigen receptors
What stimulates natural killer cells?
Cytokines from macrophages:
Interleukin-2 and -12
What are the 2 main functions of natural killer cells?
- Spray target with cytokines that either stimulates apoptosis in the cells (killing virus inside) or creates a hole in the cell membrane causing cell lysis.
- Secrete interferon-gamma (IFN-γ), a cytokine that further activates macrophages.
In what ways can inflammation be triggered?
- Macrophages recognising a pathogen and releasing cytokines
- Complement system triggering degranulation of mast cells, basophils and eosinophils, releasing cytokines.
- Mast cells, basophils and eosinophils responding directly to allergens or tissue damage by degranulation, releasing cytokines.
What are the 4 main actions of inflammation?
- Localised effect on tissues
- Activation of pro-inflammatory systems
- Recruitment and activation of cells of the immune system
- Acute Phase response
What localised effects on local tissues does inflammation cause?
- Activation of endothelial cells to display adhesion molecules
- Vasodilation
- Increased vascular permeability
What pro-inflammatory systems does inflammation activate?
Clotting system
Kinin system
Complement system
What cells of the immune system does inflammation recruit/activate?
- Further macrophages
- Monocytes (to become macrophages)
- Mast cells/ basophils to release more cytokines
- Eosinophils
- Neutrophils–> recuited to site of inflammation for phagocytosis
What is the acute phase response activated by inflammation?
When neutrophils and macrophages respond to inflammation by releasing even more cytokines:
IL-1–> Acts on CNS to cause fever, lethargy and anorexia
IL-6–> Stimulates liver to produce acute phase proteins (opsonins)
IL-8–> Recruits and activates neutrophils
IL-2/-12–> Activate natural killer cells
How does inflammation recruit more cells to the site of infection?
Localised vasodilation and increased vascular permeability allowing cells to easily leak to site of infection.
Activation of localised adhesion molecules on endothelial cells, catching immune cells.
What do mast cells and basophils release on degranulation triggered by inflammation?
Prostaglandins Leukotrienes Heparin Histamine Enzymes
What is the action of prostaglandins?
Cause vasodilation and inhibit platelet aggregation (clot formation)
What is the action of leukotrienes?
Cause contraction of airway smooth muscle, attraction of neutrophils to the area of inflammation and increased vascular permeability
What are acute phase proteins and what triggers their release?
Opsonins released by the liver on stimulation by Interleukin-6.
(CRP can be measured as a marker for inflammation)
What is the kinin system?
Bradykinin causes contraction of airway smooth muscle, vasodilation, increased vascular permeability and pain.
What is the complement system and what does it involve?
A series of reactions that happen along the membrane of a pathogenic cell, resulting in the destruction of that cell.
Involves complement proteins C1-C9.
What are the triggers of the complement system?
Classical pathway
Lectin pathway
Alaternative pathway
What is the classical pathway that activates the complement system?
Complement fixation: Activation by antibody-antigen complexes binding to C1.
What is the Lectin pathway that activates the complement system?
Activation that occurs when mannose binding protein binds to mannose on pathogens, which then binds to MBL-associatied serum protease (MASP), activating the pathway.
What is the alternative pathway that activates the complement system?
C3 is spontaneously activated along cell membranes.
In normal cells, the membrane contains proteins that deactivate the pathway. However, in pathogens the pathway remains activated.
What are the main actions of the different proteins in the complement system?
C3b–> Acts as opsonin for phagocytosis of attached cell
C5a–> Attracts cells to the site of inflammation
C3a, C4a, C5a–> Activate mast cell degranulation
C3a, C5a–> Activate eosinophil degranulation
Membrane Attack Complex–> large molecule that enters cell membrane, creating a hole that leads to cell lysis.
Where are complement proteins made and stored?
Made in the liver and circulate in their inactive form until needed
What is the overall aim of the complement system?
Complement other parts of the immune response by opsonising pathogens and triggering inflammation.
What do all three complement system activation pathways involve?
Activation of enzymes (e.g. C3 convertase) that cleave their substrates to form a cascade.
What is the action of C3?
Activates C5, which then activates C6,7,8 and 9 in a cascade
What are the main effects of the complement system?
Opsonisation
Lysis of pathogens
Chemotaxis
Inflammation
Why is the specific immune system needed as well as the innate one?
Many pathogens have developed ways of avoiding detection by the innate immune system
What does the specific immune system produce to help fight pathogens?
Pathogen specific antibodies and cytotoxic T cells.
How often do lymphocytes circulate the body and why? Where do they spend the majority of their time?
Several time a day, spending the majority of their time in the lymph nodes and spleen. This is to maximise their chances of coming across an antigen that matches their T cell receptor or antibodies.
How long can it take for the specific immune response to kick in?
3-5 days
How do T cells recognise specific antigens?
Via T-cell receptors
What is the end of the TcR called and how is it developed?
Variable domain.
They are randomly generated for each T cells during their development, giving the potential for millions of different shapes and therefore potential to match millions of different antigens.
Can T cells recognise free floating antigens?
No- require antigen presentation by major histocompatibility complex molecules.
What is a major histocompatibility complex?
A molecule that sits on the surface of cells that can be used to present antigens to T cells.
What is HLA?
Human Leukocyte Antigen–> Name of major histocompatibility complexes in humans.
What is the main reason why people reject organ transplants from another person/ species?
Everyone has a specific unique shape of MHC coded for by over 100 genes.
What are the two types of MHC molecule?
Class 1 and Class 2:
Where are Class I MHC molecules found and what do they do? What cells are they recognised by?
- Found on almost all cells with a nucleus
- Present antigens that come from within the cells (e.g. virus)
- Recognised exclusively by CD8 cells.
Where are Class II MHC molecules found and what do they do? What cells are they recognised by?
- Found mostly on Dendritic cells, macrophages, monocytes and B cells.
- Present antigens that come from outside the cell. (pick it up, digest it then present it)
- Recognised by CD4 cells.
What is the first step in activating the specific immune system?
Activation of CD4 cells.
What do dendritic cells do when they recognise pathogenic material?
- Absorb and present it on their Class II MHC molecules.
- Leave the tissues, enter the blood and travel to the lymphatic tissue.
- Enter the paracortex in lymph nodes or the PALS in the spleen in search of the matching CD4 cell to their antigen.
- Also wait in these areas for free floating antigens they can pick up and display for CD4 cells.
What happens once CD4 cells are activated?
They proliferate greatly over a few days
What happens after CD4 cells have proliferated?
They differentiate into T helper (Th1 and Th2) cells
What do the T helper cells do?
Stimulate B cells (displaying the antigen on their MHC class II molecules) to proliferate and differentiate by releasing cytokines
What do T helper 1 cells stimulate B cells to produce?
IgG
What do T helper 2 cells stimulate B cells to produce?
All antibodies, but particularly IgE
What are the actions of T helper 1 cells?
- Stimulate B cells to produce IgG antibodies
- Secrete IL-2, stimulating the proliferation/ differentiation of other CD4/8 cells
- Help CD8 cells differentiate into cytotoxic T cells
- Travel to site of infection and release cytokines that recruit other immune cells.
What are CD4 cells otherwise know as? And CD8?
CD4= T helper cells CD8= T killer cells
What is the Type IV hypersensitivity reaction and what is responsible for it?
Delayed hypersensitivity reaction.
Caused by Th1 cells travelling to the site of infection and releasing cytokines that stimulate the recruitment and activation of monocytes/ macrophages.
What are the actions of Th2 cells?
- Stimulate B cells to produce antibodies.
- Travel to the site of infection and release cytokines that recruit/ activate mast cells and eosinophils
What reactions are Th2 cells most important in?
Parasitic infection, Type 1 hypersensitivity reactions (allergy) and asthma
What makes dendritic cells unique considering they have class 1 MHC molecules?
They are able to display antigens without getting infected.
What cells recognise/ respond to antigen presentation on dendritic cells?
CD8 cells that have TcRs specific to that receptor
What do dendritic cells do when they pick up antigenic material?
Display it on MHC molecules and travel to lymphatic tissue
What happens when the right CD8 cell recognises the antigen on the dendritic cell>
They undergo dramatic proliferation and differentiation into cytotoxic T cells specific to that antigen. (helped by T helper cells)
What are cytotoxic T cells?
Differentiated CD8 (T killer) cells that are essential for the destruction of cells that have been invaded by pathogens.
How do cytotoxic T cells know which cells to invade?
The infected cell will process the antigen from the invader and present it on Class I MHC molecules on its cell surface that the cytotoxic T cell can recognise and destroy.
How do cytotoxic T cells destroy infected cells?
- Granule exocytosis–> Spray infected cell with enzymes that destroy the membrane and cause cell lysis and death.
- Activate the Fas molecule–> A self-destruct switch that causes the cell to undergo apoptosis.
What is the structure of antibodies?
Two heavy and two light chains in a Y shape.
What is the ‘Fc’ portion of antibodies?
The bottom of the Y that remains the same amongst all antibodies. It is what binds to cells of the immune system via the Fc receptor.
What is the top of the Y?
The variable region. Part that matches a specific antigen.
What are the 5 different classes of antigen?
IgA IgD IgE IgG IgM
What is the main role of IgA antibodies? + what is its structure?
Heavily secreted in mucous to protect mucous membranes from infection.
In blood: Y structure
In secretions: Pairs of Y’s attached at Fc portion
What is the main role of IgD antibodies?
Found on B cell membranes and activates them- unstable and don’t last long when secreted into blood .
What is the function + structure of IgE antibodies?
Important in asthma and allergy.
Has simple Y structure in blood (found in low levels)
What is the function + structure of IgG antibodies?
Most common antibody.
Simple Y structure in blood.
What is measured to detect a patients immunity.
What is the function + structure of IgM antibodies?
First antibody produced in acute infection.
Snowflake appearance in blood–> 5 molecules combined at Fc portion
What are the most common antibodies on B cell surfaces?
IgM or IgD
Where do B cells sit and do they do when they recognise an antigen?
In lymph nodes, spleen or MALT and process antigens and present it on their MHC Class II molecules.
What happens when B cells are activated by antigens and T helper cells?
They differentiate into either plasma cells or memory B cells
Where does differentiation of B cells occur?
In the germinal centre of lymph nodes, the spleen and MALT
What happens during B cell differentiation into plasma cells?
Affinity maturation: the cell changes to be even more specific to the antigen it encountered. Antibody class switch: The cell chooses which antibody to produce and from then on can only secrete this class. The cell starts to produce vast amounts of antibodies
What are the 6 ways antibodies help fight off infectino?
- Activate the complement system
- Neutralise toxins
- Bind to pathogen receptors and prevent certain functions.
- Agglutination (clump together around pathogens to slow the spread)
- Act as opsonins
- Antibody- dependent cell-mediated cytotoxicity
What is antibody-dependent cell-mediated cytotoxicity?
Antibodies can attach themselves to pathogens and are recognised by immune cells that then kill the pathogen.
Why does the specific immune response take a few days?
When encountering an antigen for the first time the body only has a few B and T cells that match that antigen. Therefore it takes time to find the relevant cells, multiply them to the required number and activate the specific immune response.
How are B cells changed into memory B cells?
Undergo affinity maturation and antibody class switch when activated.
Which antibody is responsible for the memory B cell response?
IgG
What are memory T cells?
Specific CD4 and CD8 cells that stick around and wait for subsequent infections where they can proliferate and differentiate faster.
What are the different types of vaccines?
- Subunit –> only contain specific part of the organism (e.g. exact antigen)
- Inactivated vaccines–> Pathogens that have been killed but still contain the antigens
- Live attenuated vaccines- Contain a weakened version of the vires
What are examples of inactivated vaccines?
Polio
Flui
Hep. A
Rabies
What are examples of subunit/ conjugated vaccins?
Pneumococcus Meningococcus Hep. B Whooping cough HPV Shingles
What are examples of live attenuated vaccines?
MMR BCG Chickenpox Nasal influenza Rotavirus
What vaccines are given at 8 weeks?
6 in 1
Meningococcal type B
Rotavirus
What is in the 6 in 1 vaccine?
Diptheria Tetanus Pertussis Polio Haemophilus influenza type B (Hib) Hep. B
What vaccines are given at 12 weeks
6 in 1 (booster)
Pneumococcal
Rotavirus (booster)
What vaccines are given at 16 weeks?
6 in 1 (booster)
Meningococcal type B (Booster)
What vaccines are given at 1 year?
2 in 1 (heamophilus influenza type B and meningococcal type C)
Pneumococcal (booster)
MMR
Meningococcal type B (booster)
What vaccines are given at 3 years 4 months?
4 in 1 (diptheria, tetanus, pertussis and polio)
MMR
What vaccines are given at age 12-13?
HPV (2 doses given 6-24 months apart)
What vaccines are given at 14?
3 in 1 (tetanus, diptheria and polio)
Meningococcal A, C, W and Y
When does autoimmune disease occur?
When the mechanisms that allow the body to recognise its own antigens fail.
What is B cell self tolerance?
When B cells do not initiate an immune response to an antigen (self antigens.)
What happens if developing B cells develop antibodies that match antigens in the bone marrow (self-antigens)?
- Clonal deletion- Cells die
2. Clonal anergy- Cells are made inactive do that they can be released but can’t respond to antigens
What are the two ways a TcR cell can go wrong?
- Receptor recognises self-antigens, causing autoimmune disease
- Self-MHC molecules can’t be recognised, making the T cell useless.
What is T cell education?
The complex process thymocytes go through to become specialised CD4 and CD8 cells.
What is the first step of T cell education?
Thymocytes in the thymus arrange proteins to form random TcRs and become either a CD4 or CD8 cell.
What is the second step of T cell education?
Thymus epithelial cells present the Thymocytes with MHC proteins. If they recognise them, they move on to the next step. If not, they are destroyed.
What is the third step in T cell education?
To meet dendritic cells in the thymus that present them with self-antigens. If the thymocyte can recognise the self-antigen, they are destroyed. If not, they leave the thymus and become working T cells.
When does hypersensitivity occur?
When the immune system over-responds to harmless antigens that results in harm to the body.
How many types of hypersensitivity reaction are there?
4
What is Type I hypersensitivity?
Classical allergic reaction-
What antibody is involved in a type 1 hypersensitivity reaction?
IgE
What is a Type II allergic reaction?
Antibody-mediated immune reaction, where antibodies bind to antigens on cells or tissues leading to cell or tissue damage
What antibodies are involved in a type II hypersensitivity reaction?
IgG and IgM
What is a type III hypersensitivity reaction?
When antibody-antigen (immune) complexes are deposited in tissues, where they activate the complement system and cause inflammation
What is a Type IV hypersensitivity reaction?
Delayed hypersensitivity reaction caused by T helper cells travelling to the site of antigens, recruiting macrophages and causing inflammation.
What are allergens?
Antigens that produce allergic reactions (e.g. peanuts, penicillin, pollen, house dust mites)
What are the main atopic conditions IgE mediated allergy is responsible for?
- Food/ drug allergy
- Asthma
- Allergic rhinitis
- Hayfever
- Eczema
What is sensitisation?
The initial event that leads to the specific IgE being developed for an allergen.
What happens during sensitisation?
- CD4 cells recognise the allergen
- They proliferate and differentiate into Th2 cells
- Th2 cells release IL-4 that stimulates the production of IgE specific to that allergen
- The IgE then circulates the blood and binds to mast cells.
What happens during the first partallergic response?
On re-exposure, the allergen binds to IgE and causes mast cell degranulation, releasing cytokines (histamine and TNF-a)
What does histamine trigger?
Vasodilation
Increased vascular permeability
Broncho-constriction
Symptoms of allergy (Itch, flushing, rash, wheeze, angioedema)
What does TNF-a cause?
A localised inflammatory process at the site of exposure
How long does histamine action take to work compared to TNF-a?
Histamine happens within minutes of exposure
TNF-a takes a few hours: LATE PHASE REACTION.
What can be measures to confirm the diagnosis of anaphylaxis?
Mast cell tryptase
What are some examples of type II hypersensitivity?
Blood transfusion reactions
Heamolytic disease of the Newborn
Goodpastures syndrome
What happens during blood transfusion hypersensitivity reactions?
If the ABO group of the donor does not match the reciept, the antibodies attack the donors blood, causing haemolysis of the donor red blood cells, releasing the contents of the cells and causing a toxic reaction.
What is the difference between Type II and Type III hypersensitivity?
In Type II, it is the antibodies binding to the target that causes inflammation/ damge. In Type III, the antibodies bind to antigens and it is these complexes that travel to their target organ and cause inflammation/damage.
What are two examples of Type III hypersensitivity?
Rheumatoid arthritis
Farmers lung
How long does Type IV hypersensitivity take to happen?
24-72 hours
What happens during Type IV reactions?
- Antigens enter tissues and get picked up by dendritic cells.
- Dendritic cells deliver the antigens to the relevant CD4 cells which proliferate and differentiate into T helper cells.
- T helper cells travel to the tissues where the antigen was first presented and release cytokines.
- These cytokines recruit macrophages and release pro-inflammatory cytokines, causing inflammation.
What does Type IV hypersensitivity present as in skin?
Contact dermatitis
What are some examples of Type IV hypersensitivity?
Poisin ivy
Nickel and gold
Mantoux test
What is an epitope?
The part of the antigen that binds to the antibody/receptor binding site.
What is humoral immunity?
Antibody-mediated immunity
What is the Fab region of immunoglobulins?
The part that binds to specific antigens
Where are all antibodies produced?
Plasma cells (derived from B lymphocytes)
What are interleukins?
Cytokines that act between cells of the immune system
What are chemokines?
Cytokines that induce chemotaxis of leucocytes (move white blood cells to areas that they’re needed)
What are NLR’s?
Nod-like receptors–> detect intracellular microbial pathogens
What is atopy?
Inherited tendency for overproduction of IgE antibodies to common environmental antigens
How can allergy be treated?
- Desensitisation via immunotherapy
- Preventing mast cells activation with Beta 2 agonists or glucocorticoids
- Reducing mast cell products–> histamine receptor/ prostaglandin antagonists, Tryptase inhibitors
What happens in haemolytic disease of the newborn?
Mother has rhesus negative blood and baby has rhesus positive. When the mothers blood is exposed to the babies in pregnancy, the mothers blood begins making antibodies against the babies blood and becomes sensitised. If she has a second rhesus positive baby, then the antibodies begin destroying the babies red blood cells.
What is passive immunity?
When a person is given antibodies to a disease rather than producing them through their own immune system
What is natural passive immunity?
The transfer of maternal antibodies across the placenta to the developing foetus
When is artificial passive immunity used?
When there is no time for active immunisation to give protection
When an immunocompromised patient is exposed to a disease that could cause complications
To treat those with B cell defects.
What is active immunisation?
Immunity which results from the production of antibodies by the immune system in response to the presence of an antigen.
What is primary immune deficiency?
A group of >300 rare chronic disorders in which part of the immune system is missing or functions improperly
What is acute inflammation?
The initial (and often transient) series of tissue reactions to injury
How long does acute inflammation last?
A few hours to a few days
What are the benefits of inflammation?
- Exudation helps to deliver plasma proteins, dilutes toxins and increases lymphatic drainage
- Infiltration of neutrophils leads to removal of pathogens and cellular debris
- Vasodilation helps increase delivery of necessary cells/ proteins and increases temperature.
What are the limitations of inflammation?
May compress vital surrounding structures
Fibrosis may occur from chronic inflammation
What are the 5 main clinical features of acute inflammation?
- Rubor (redness)
- Tumor (Swelling)
- Calor (Heat)
- Dolor (Pain)
- Loss of function
Why do rubor and calor occur in inflammation?
During the first few seconds after injury, there is vasoconstricion of arterioles followed by vasodilation of arterioles and capillaries, increasing blood flow to the tissue.
Why does tumor occur in acute inflammation?
There is increased permeability of blood vessels, resulting in exudate (protein rich fluid) forming in the tissue.
The circulation is also slowed.
What mediates blood flow changes in acute inflammation?
Histamine from mast cells, basophils and platelets
What is exudation of fluid?
Fluid that filters from the circulatory system into lesions or areas of inflammation.
Why does exudation of fluid occur?
Occurs due to Starling’s Law: vasodilation of arterioles leads to an increase in hydrostatic pressure which leads to increased fluid movement out of vessels.
Also increased permeability of vessels results in protein moving to the interstitium, increasing colloid osmotic pressure, furthing increasing fluid movement out of vessels.
What are the main cells involved in acute inflammation?
Neutrophil (polymorphs)
What is margination?
When the stasis of circulation allows neutrophils to line up along the endothelium near the site of injury
What do neutrophils do after margination?
They roll along the endothelium, sticking intermittently. (adhesion)
What happens after adhesion of neutrophils to the endothelium?
They emigrate through the blood vessel walls
How are neutrophils able to leave the blood vessels?
Through relaxation of inter-endothelial cell junctions and digestion of the vascular basement membrane
By what mechanism do neutrophils move to areas of damage?
Chemotaxis
What is neutrophil action once it reaches the damaged tissue?
Phagocytosis of pathogens and cellular debris, facilitated by opsonins.
What are the main causes of acute inflammation?
Microbial infections Hypersensitivity reactions Physical agents (e.g. trauma, radiation, heat/cold) Chemicals (e.g. corrosives, acids) Bacterial toxins Tissue necrosis
What are the different outcomes of acute inflammation?
Resolution
Suppuration (pus formation)
Organisation/ Repair (healing by fibrosis)
Progression to chronic inflammation
How can chronic inflammation arise?
- May continue on from acute inflammation
- Arise de novo (e.g. autominnume conditions like rheuatoid arthritis which leads to excessive/inappropriate immune system activation)
- May develop alongside acute inflammation in severe and persistent irritation.
What are the main features of chronic inflammation?
- Infiltration with mononuclear cells (macrophages, lymphocytes, and monocytes have longer life-spans and replace neutrophils)
- Tissue destruction
- Damaged tissue attempting to heal through fibrosis and angiogenesis
What are giant cells and why do they form?
Multi-nucleated cells made by the fusion of multiple macrophages which form as a result of frustrated phagocytosis (when a phagocyte fails to engulf its target).
*Different types of giant cells can be found in different conditions.
What are granulomas?
A collection of macrophages (epithelioid histiocytes) that may from in chronic inflammation.
Why do granulomas form?
As a result of persistent, low-grade antigenic stimulation of hypersensitivity. The immune system is unable to eliminate it and so attempts to wall it off.
What are the effects of chronic inflammation?
Fibrosis
Impaired function
Atrophy
Stimulation of immune response
What is the diagnostic histological feature of acute inflammation?
The accumulation of neutrophil polymorphs in the extracellular space
What 4 enzymatic cascade systems does the plasma contain?
- Complement
- Kinins
- Coagulation factors
- Fibrinolytic system
What is the role of macrophages in acute inflammation?
- Secrete IL-1 and TNF-a which stimulate endothelial cells to attract neutrophil polymorphs.
- Don’t predominate over neutrophils until later stages of inflammation.
What are the potential systemic effects of inflammation?
- Pyrexia
- Malaise
- Anorexia/ Nausea/ Weight loss
- Reactive hyperplasia (of spleen or lymph nodes)
- Haematological changes ( incresed WBCs, anaemia)
- Amyloidosis
What are the main cells involved in chronic inflammation?
Lymphocytes
Plasma cells
Macrophages
Why does necrosis occur in chronic inflammation?
When macrophages die, they release lysosomal enzymes
What is organisation (in terms of inflammation)?
The repair of specialised tissues by the formation of a fibrous scar.
What cells in the body regenerate?
Hepatocytes Pneumocytes All blood cells Gut epithalium Skin epithelium Osteocytes
What cells of the body do not regenerate?
Myocardial cells
Neurones
What is the main goal of cancer immunotherapy?
To induce anti-tumour immune responses that would discriminate between tumour cells and normal cells in cancer patients.
What kind of cancer cells can the immune system recognise?
Newly transformed neoplastic cells
What are TSA’s and TAA’s?
Tumour specific antigens–> Peptides only found on the surface of tumours
Tumour Associated antigens–> Antigens found on normal and tumour cells but are overexpressed on tumour cells.
What are some ways tumours avoid immune recognition?
- Tumour treated as self-antigen
- Antigenic modulation
- Tumour induced immune suppression
- Low immunogenicity
