Kin 132 IM Flashcards
What is the lymphatic system? What are its main functions?
network of organs and tissues that lymph flows through
Functions:
1. Drains excess interstitial fluid into the blood stream
2. Returns plasma proteins that escaped back to the blood stream
3. transports lipids
4. Imune roll
Explain lymph flow
- due to imbalance between filtration and absorption, ~3L per day of blood enters the lymphatic capillaries to become lymph
- Lyph enters lymphatic capillaries and flow one way through them through lymphatic organs and tissues until it leads to ducts that lead into the subclavian vein where it rejoins blood circulation
Do lymphatic capillaries have a afferent and efferent vessel?
No only an efferent. Enter into lymphatic capillaries is based off of a pressure gradient
Where does lymph drain into?
- Top right half of the body drain into the Right lymphatic duct which re joins the blood stream at the right subclavian vein
- The rest of the body drains into the thoracic duct re joining the blood stream at the left subclavian vein
Explain what drives lymph through the lymphatic vessels?
- Primarily:
- Distention causes contractions which drives lymph forward - Assisting:
- Skeletal and respiratory muscle pump. When they contract it squeezes lymphatic vessel and used lymph forward
What happens if theirs a blockage in the lymph flow?
- Interstitial fluid has nowhere to drain into causing swelling
Explain the lymphatic organs and tissues (residential population)
- Primary lyphoid organs:
- Sites of immune cell development and maturation
- Bone marrow (development and maturation)
- Thymus (Develop in bone marrow and mature in thymus) - Secondary typhoid organs:
- Sites of immune cell residence where they contact pathogens:
- Spleen: Blood filters through
- lymph nodes: Lymph filters through
- Lyphoid nodules:
Includes tonsils which around pharynx for injected or inhaled pathogens and linings which line systems such as urinary and reproductive tracts for pathogens that enter via external entry points
Explain the lymphatic system in circulation (circulating population)
- Immune cell population is circling in lymph and blood
- Immune cells circulating come into contact with pathogens in blood and lymph systems
- Some secondary lymph organs especial lymph nodes and spleen can release stores immune cells into circulation when signalled
What are some fundamental immune responses?
- Defending against pathogens
- Removing worn out cells
- Facilitating wound healing
- identifying and destroying abnormal cells that originated from within the body
Explain the human body’s external defences (barriers)
- Considered barriers not immune responses
- 1st line of defence
Falls into two catagories:L
- provides a physical barrier
- Skin: when not damages, forms barrier to outside
- Hairs: filter for nose
- Mucous: in upper respritory and sticks and binds to pathogens trying to enter
- Reflexes: coughing and sneezing, expels potential pathogens - Chemical
- Sebum: Oil on skin, hard for pathogen growth
- Lysozomes: in tears and saliva, kills some pathogens
- Stomach acid: highly acidic, kills some pathogens
Explain the body’s internal defences (white blood cells)
- White blood cells
- Formed in red bone marrow
types:
- neutrophils
- Eosinophils
- basophils
- Monocytes - form macrophages
- Dendritic cells
- Mast cells
- Lyphocytes - form B cells, T cells, NK cells
Explain innate vs adaptive immune responses
both begin by…
- Encounter stage:
- Pathogen and immune cell meet
- Locations for encounter could be residential population of circulating population meets a pathogen
Explain the internal defence ( Innate immune response)
- 2nd line of defence
- rapid but limited response
- Begins with the encounter stage
- Recognition stage:
- Pathogen and immune cell bind
- General recognition ( eg. detects shape not size or colour)
- Toll receptors on immune cell membrane can recognize patterns
- Toll receptors can recognize many patterns on the pathogen
- Binding of the two triggers innate immune response
- Often innate immune response is more to limit the spread of the pathogen whereas adaptive immune response deals with the pathogen - Cells infected with virus produce interferons which hinders virus replication
Explain the type 1 interferon
- released during innate immune response
- Produced by infected cells and releases them into interstitial fluid
- Most cells have a receptor for type 1 interferon so if a heathy cell comes into contact with it, it binds and heathy cell starts to produce antiviral proteins
- If at some point that health cell becomes infected, the antiviral proteins with prevent viral replication, limiting spread of virus
Explain what a phagocyte is
- Any cell that can perform phagocytosis
Phagocytosis stages:
- Recognition: Cell binds to pathogen
- Ingestion: Phagocytosis (endocytosis) brings pathogen into the cell forming a phagosome (pathogen held in a vesicle)
- Digestion: Lysome binds to the phagosome forming a phagolysosomne dumping its digestive content into it
- Kill: Digestive content kills the pathogen and end material is either dumped out of cell or released internally
What cells are the quickest to respond and which have the largest capacity for phagocytosis?
fastest to respond: Neutrophils
Largest capacity: Macrophages
Explain the different vessels in phagocytosis
- Pathogen enters cell into a vesicle forming a phagosome
- Phagosome binds with a lysosome to from a phagolysosome
Explain the innate alternative complement pathway
- Complement proteins are plasma proteins circulating in bloodstream
- C3 is a inactive complement protein that will bind to pathogens to become active and will enhance immune functions by…
- Opsonization
- C3 binds with pathogen then detaches, but leaves a small piece called C3b which acts makes the pathogen easier to spot and enhances phagocytosis - Membrane attack complex
- When C3 gets activated it starts a chain reaction activating C4 etc. Activated C5 to C9 form a pore in the pathogens cell membrane allowing fluid into the pathogen triggering apoptosis (programmed cell death)
Explain the innate response: Inflammation
- Local response to tissue damage
Stage 1:
- Release of inflammatory mediators: cytokines, prostaglandins and histamine which…
Local effects:
- Vasodilation to increase delivery of plasma proteins, immune cells etc
- Creates gaps between cells in the blood vessel wall
Non loca;l effects:
- Stores immune cells released into circulation from spleen and lymph nodes
- red bone marrow increases production of new immune cells
Stage 2:
- Phagocytes move to damage location with neutrophils coming early and monocytes mature into wandering macrophages arrive later
steps:
1. Margination:
- phagocytes and damages tissue form adhesion molecules so the phagocytes can stick to local area
- Diapedesis
- Phagocytes migrate through blood vessel walls into interstitial fluid - Chemotaxis
- Phagocytes move to damaged area following cytokines using chemoattraction. timing of release of cytokines is important for the timing of attraction of molecules
Stage 3:
- Worn out damages or dead cells are replaced
- may include new small blood vessels (angiogenesis)
- tissue repair may leave a scar
- remodeliong occurs wayyy after initial repair
What is a monocyte?
- can differentiate into macrophages
Where do cytokines that cause chemoattraction come from?
They get released from damages tissue and from cells that have travelled to the damaged tissue
Explain the adaptive immune response differences between the innate response
- Highly specific (lock and key)
- 3rd line off defence
- Specific recognition of the pathogen that its attacking
- creates memories from encounters with pathogens for future encounters
What is a antigen
Either a pathogen itself or a receptor on the pathogens cell membrane
Explain lymphocyte development
B cells:
- originate and mature in red bone marrow
T cells:
- Start in red bone marrow and migrate to thymus to mature
B and T cells:
- Once mature all cells move to secondary lymph structures and begin cloning themselves (clonal populations)
- At this point the lymphocytes are naive lymphocytes as they have not been exposed to a antigen
Explain the lymphocyte receptor: immunoglobulins
2 types:
- B cell receptors:
- Structure is on the surface of the B cell - Antibody
- Structure is free floating and not attached to a cell
Structure:
- Made of 4 chains, 2 heavy and 2 light
- has 2 ends:
1. constant end: has stem binding site to attach to B cell
2. Variable end: has 2 antigen binding sites
What are the 5 types of immunioglobins? (GAMED)
- lgG
- largest class - lgM
- 1st to arrive but short lived - lgE
- Late phase allergy involvement - lgA
- In breast milk - lgD
- Involved in B cell activation
Explain the lymphocyte receptors - T cells receptor
- T cell can’t bind to antigen directly so antigen must combine with a MHC protein and present antigen to T cell receptor
- Helper T cell requires antigen to be presented with a MHC class 2
What stage is the presentation of the antigen part of?
Part of the activation stage
Is it possible to have the same MHC proteins as someone else?
Only in identical twins
What MHC classes are needed by different molecules?
MHC class 2
- Needed by helper T cells
- most regulatory T cells
MHC type 1
- needed by Cytotoxic T cells
- Small amount of regulatory T cells
What MHC cell does NK cells need?
They don’t need one
Explain the presentation of a exogenous antigen
- Exogenous: antigen is outside cell
- Phagocyte ingests the antigen which gets broken down via vesicle of digestive fluid, and a piece of the antigen bind to a MHC class 2 inside the vesicle
- Vessicle moves to surface of the cell and presents it
- Helper T cell with the proper receptors on the variable end will bind to the antigen fragment activating the helper T cell (clonal selection)
- Cells that can do exogenous presentation are:
- Macrophages
- B cells
- Dendritic ends
Explain the presentation of a endogenous antigen
- Endogenous: Antigen is already inside cell
- A infected cell has antigens independently of if which get broken down and combined with MHC class 1 inside a vesicle
- Vessicle moves to surface where it is presented
- Cytotoxic T cell with correct receptor binds to antigen causing cytotoxic T cell to activate (clonal selection)
What cells can do what kind of presentation?
Exogenous:
- B cells
- dendritic ends
- Macrophages
Endogenouse
- Most body cells except red blood cells
Explain the adaptive immune response
- Activation stage
- After recognition gives clonal selection it causes proliferation which creates more copies and differentiation which creates variation
- All the clones formed from proliferation of differentiation are able to recognize specific antigen from clonal selection
- These clone cells can differentiate into…
1. Effector cells: carry out immune attack
2. Memory cells: Stored for future encounters with the same antigen
- Attack stage
- Cell mediated: cells attacking cells with no antibodies
- Antibody mediated: Antibodies formed from clone cells fight pathogens
Explain helper T cell activation
- Helper T cell binds to antigen which slightly activates it and beigins clonal expansion but this isn’t enough for full activation
To be fully activates it must…
- Antigen binding from presentation
- Costimulous: binding of a non antigen to helper T cell
- Secretion of cytokines (Interleukin 1)
- With full activation of helper T cell, it secretes Interleukin 2 which stimulates max clonal expansion creating clone cells which will release even more interleukin 2 creating a positive feedback loop
- It also releases type 2 interferon (or interferon gamma) to activate NK cells and macrophages
Explain the activation of NK cells and macrophages
- The type 2 interferon released by activated helper T cells activates macrophages and NK cells
- The activation of these cells can release cytotoxic chemicals which can kill pathogens
-
Explain the activation of cytotoxic T cells
- Activation begins with the binding of a antigen to the cytotoxic C cell causing clonal selection and beginning clonal expansion
- Maximal activation required IL-2 and other cytokines to stimulate the cytotoxic T cell for full clonal expansion
- Some clones become effector cells and some become memory cells
Explain the attack of cytotoxic T cells
- Activated Cytotoxic T cells will circulate and will bind to antigens on infected cells (specifically the antigen that the clones came from)
- When the cytotoxic T cells bind it…
- Releases perforin: creates channel in infected cell
- Releases granzymes: Digestive enzymes that enter infected cell via channel made by perforin - When the digestive enzymes enter infected cell it causes apoptosis killing cell but not the pathogen
- The virus is then released into the interstitial fluid where it is easily dealt with
Explain the roll of the regulatory T cell
- Deals with the problem of: If too many cytotoxic T cells are produced, they begin to attack health cells
- They suppress immune response so that it doesn’t overdo its job
- Exact method is unknown, possible that it inhibits proliferation of cytotoxic T cells or blocks the activation of cytotoxic T cells
Explain B cell activation
- Variable end of the B cell binds to a antigen for clonal selection and begins slow clonal expansion
- Maximal activation requires helper T cells to release IL-2 and other cytokines to reach maximal clonal expansion producing effector cells and memory cells. (proliferation and differentiation)
- Some effector B cells differentiate into plasma cells that form antibodies for specific antigen that bonded to B cell initially. This is differentiation
- The antibodies are released and go attack the specific antigen type that it was designed for
Explain antibody attacks - Direct attacks
- Direct attacks is when an antibody directly binds to the antigen. Can be 3 types:
- Neutralization:
- Antibody binding to antigen prevents it from binding to health cells or prevents it from doing some if its chemical reactions - Agglutination:
- When antibody binds to antigen they form a clump so that its more visible to phagocytosis - Precipitation
- Antigen and antibody are both soluble, so when they bind together they become insoluble, therefore easier to spot helping phagocytosis to occur
Explain antibody attacks - Indirect attacks
- Antigen and antibody bind together, but it triggers a additional response
- Enhanced phagocytosis
- Antibody binds to antigen and acts as a opsin (marker)
- Phagocyte with correct receptor binds to stem end of the antibody forming a bridge between phagocyte and antigen
- This makes phagocytosis easier - ADCC
- Antibody binds to antigen and acts as a opsin (marker)
- NK cell with correct receptor binds to the stem of the antibody forming bridge between them
- In réponse to NK cells binding to antibody, the NK cell releases cytotoxic chemicals to destroy the antigen
Explain the classic complement pathway
- Antibody binds to a antigen and acts as a opsin
- C1 compliment protein circulating inactive binds to the stem of a antibody which activates it
- Activation of C1 causes cascade that triggers C2…etc
- Same process as the alternative pathway (formation of MAC and insertion of C3b)
What’s the difference between the classic compliment pathway and the alternative compliment pathway?
The starting sequence.
Classic starts from C1
Alternative starts from C3
Explain immunity to antigens
- When encountering a antigen that you’ve seen before, the body has a quicker response, larger amounts of the specific antibody too fight it, and last for a longer time in blood
- This is due to stored memory cells allowing the body to know exactly what specific “key” (antibodies) works against the pathogen
Passive and active immunity
Active:
1. Active natural
- Exposure to antigen by chance
- Active artificial
- Deliberate exposure to antigen (vaccine)
Passive:
1.Passive natural:
- Antibody transfers from mother to infant
- Passive artificial:
- Antibodies transferred from person to person via injection
What is the downside to pre formed antibodies being injected into a individual?
They antibodies don’t last for long and don’t create memory cells
Explain resistance to infection
Reduces resistance:
- malnutrition (greatest contributor)
- pre existing disease
- Lack of sleep
- Immune system, isn’t functioning properly
- High stress and negative mind set can decrease resistance while little stress and positive mindset can increase resistance
- High exercise with little recovery can decrease resistance while medium resistance with good recovery can increase resistance
- poor physical condition can decrease while good physical condition can increase
Explain how stress and exercise can effect immunity
Stress:
- Stress reduces: good diet, sleep, positive outlook..etc which in turn reduces immunity
Exercise:
- Follows inverted J graph
- Moderate exerisize leads to the highest immunity
- With proper recovery intense exercise can have no detrimental effects to immunity
Explain the different types of tissue grafts
- Autografts
- Grafts from one part of the body to another within the same person - Isografts
- Grafts given to a identical twin - Allografts
- Grafts given to another person that’s not a identical twin, but within same species - Xenografts
- Graftys taken from another species
Explain tissue grafts
- The more similar the tissue the less likely it will be rejected. Histocompatibility is the matching of MHC proteins
- Different MHC proteins are recognizes as foreign tissue by your body and are destroyed by cytotoxic T cells with aid of Helper T cells
- Immunosupresent is given to suppress the immune system the tissue graft won’t be rejected
- Best type of graft is Autografts and isograft as they have the same MHC proteins and won’t need immunosupresent
Explain allergic responses (only looking at a specific types: immediate hypersensitivity)
- Over reaction by the immune system to substances that are usually tolerated my most people
- Substance that person is allergic to is seen as a antigen which is called a allergen
immediate Hypersensitivity:
- Sensitization
- first exposure to allergen produces IgE which binds to either mast cells or basophils “arming them” for future encounter - Within a few minutes after sensitization, the individual is re exposed to allergen
- Allergen attaches to IgE antibodies that are also attached to basal cells or mast cells. Attachment of allergen causes cells to release histamine and other cytokines
- The release of this causes:
- Vasodilation
- Increased blood vessel permeability
- Itchy and pain sesation
- smooth muscle contraction - Late phase can occur of immediate phase
- More inflammatory mediators are released hours or days after initial reaction that prolong reaction and cause more sensitization (binding of allergen to mast and basal cells) so a future exposure to allergen will cause a larger reaction
Explain what happens if its a very large immediate hypersensitivity reaction
- alergic reactions are usually localized
- If enough of a allergen or enough inflammatory mediators are released by basal and mast cells then they can enter blood stream causing anaphylaxis
Explain what self recognition and self tolerance are
self recognition:
- The ability to recognize your own MHC proteins
Self tolerance
- Body recognizes own tissue and won’t do anything
What does the loss of self tolerance lead to?
Autoimmune disease
Explain how the body trains immature T cells for the right function
Self recognition:
- If immature T cells don’t recognize the MHC cells they undergo apoptosis
Self tolerance:
- If immature T cells interact with self antigens they undergo apoptosis
This is to prevent autoimmune diseases
Explain what positive and negative selection are
positive selection:
- When immature T cells recognize own MHC proteins they survive
Negative selection
- When immature T cells bind to self antigens they are killed
