PH1124 - Immune sytem Flashcards
What is the innate immune system ?
The innate immune system is NON SPECIFIC It will defend against anything foreign Its fast (minutes or hours)
What is the adaptive immune system ?
The adaptive immune system is HIGHLY SPECIFIC It identifies pathogens and differences in molecular structures Its Slow (days)
Name the different parts of the innate immune system
Physical barriers - skin, hair, cilia etc
Defense mechanisms- Mucus, saliva
General immune responses, complement system
What is the role of neutrophils and macrophages (phagocytes) ?
Ø Macrophages and neutrophils are primarily phagocytic cells that engulf pathogens and destroy them in intracellular vesicles, a function they perform in both innate and adaptive immune responses. They release lysozyme and other substances into the formed vesicle in order to break it down. they then present the protein of the pathogen on their surface.
Many phagocytes are antigen presenting cells.
◦ Enter an infected site from circulation
◦ Bind, engulf and kill a wide variety of microbial agents
◦ Produce immunomodulatory substances, e.g. cytokines, chemokines, which regulate the immune response
◦ Act as first line of defense against infection
What is the function of eosinophils
Eosinophils are thought to be involved in attacking large antibody-coated parasites such as worms, whereas the function of basophils is less clear.
What is the function of mast cells ?
Ø Mast cells are tissue cells that trigger a local inflammatory response to antigen by releasing substances that act on local blood vessels.
They release histamines which cause
What are some functions of the spleen ?
it fights invading pathogens in the blood (the spleen contains infection-fighting white blood cells, for instance B cells and T cells)
it controls the level of blood cells (white blood cells, red blood cells and platelets)
it filters the blood and removes any old or damaged red blood cells
Describe the two different types of T cells
T-cells
2 types of T- cells:
T- cells with CD4 proteins on them and some with CD8 receptors.
Most CD4+ T cells are helper t cells and are attracted to MHC2 complexes.
CD8 proteins are attracted to MHC1 complexes. Most of the time CD8+ t cells are cytotoxic T cells.
CD8 t cells kill infected/abnormal cells.
CD8 differenciates into memory cytotoxic t cells and effector cytotoxic t cells once activated.
CD4 cells once activated differentiate into effector helper t cells which can activate b cells. It also releases cytokines.CD4 cells also produce memory cells.
A mental hook to try and help you remember the CD proteins: CD4 - “It’s here 4 you” - Helper T Cell CD8 - “CD HATE”, It HATES the infected cells and tries to kill them - Cytotoxic T Cell
CD8+ (cytotoxic t cells) Kill by:
Protein called Perforin which punches holes in the target-cell membrane
What are the first, second and third lines of defence ?
The first line of defence are the physical and chemical barriers, which are considered functions of innate immunity.
The second line of defence is nonspecific resistance, which also is considered a function of innate immunity.
The third line of defence is specific resistance, which is considered a function of acquired immunity.
What are the TWO categories of cells in the adaptive immune system ?
B cells developed in bone marrow
T cells which mature in the Thymus
Explain the role of B cells
B lymphocytes are part of the humoral response.
B cells have membrane bound antibodies
Activated helper T cells can activate B -cells.
Once the B cell is activated it can differentiate into memory cells and effector B cells.
Effector B cells (plasma cells) produce antibodies.
The antibodies are uniquely able to bind to the new pathogen.Antibodies then tag the pathogens and make them easier for pick up.
Describe the function of major histocompatibility complexes
The function of MHC molecules is to bind peptide fragments derived from pathogens and display them on the cell surface for recognition by the appropriate T cells. The consequences are almost always deleterious to the pathogen—virus-infected cells are killed, macrophages are activated to kill bacteria living in their intracellular vesicles, and B cells are activated to produce antibodies that eliminate or neutralize extracellular pathogens. Thus, there is strong selective pressure in favor of any pathogen that has mutated in such a way that it escapes presentation by an MHC molecule.
Every nucleated cell in the body has MHC1 complexes. MHC 1 binds to ‘shady’ things inside the cell and then present them on the outside
MHC2 bind to ‘shady things on the outside of the cell and then present them.
MHC 2 are presented on the surface of phagocytes after phagocytosis
What is the difference between the cellular and humoral adaptive response ?
Cellular adaptive response – effected by cytotoxic T cells (CD8+)
◦ Targets infected body cells (e.g. viruses)
◦ Targets malignant cells (e.g. cancer)
Humoral adaptive response – effected by B cells (antibodies)
◦ Targets pathogens or antigens that are free in the blood stream or on mucosal surfaces
◦ T helper cells (CD4+) are important ‘gatekeepers’
◦ Once activated helper T cells can shape the subsequent immune response by secreting effector molecules (e.g. cytokines)
◦ Controlling the activation of other cell types
describe the process of T cell differentiation
T cell precursor cells from the bone marrow travel to the thymus where they differentiate into CD8+ and CD4+ cells.
These cells then travel to the lymph node where they further differentiate:
CD8+ cells: differentiate into cytotoxic T cells
CD4+ cells: differentiate into helper T (Th) cells
what are the functions of an antibody?
Antibody function:
Opsonisation – the antibody promotes phagocytosis (via Fc receptors on phagocytes recognizing antibody-antigen complexes and binding antibody via its Fc fragment).
Neutralisation – the antibody inhibits the antigen (e.g. bacterial adherence by binding and blocking a surface protein on bacteria required for adhering to cell surfaces).
Complement activation – antibody-antigen complexes bind C1q within the C1 complex and trigger the classical pathway of complement.
Classical pathway activation creates opsonins C4b and also C3b and amplification via the alternative pathway.
describe the function of cytokines
Cytokines are a large group of proteins, peptides or glycoproteins that are secreted by specific cells of immune system. Cytokines are a category of signaling molecules that mediate and regulate immunity, inflammation and hematopoiesis.
what is immunity?
- ability of the body to fight infection or foreign invader by producing antibodies or killing infected cells
what is the role of the immune system? (2)
- maintaining homeostasis by recognizing and differentiating between harmful and non-harmful organisms
- produces an appropriate response
what are the functions of immunity? (3)
- immune defense
- immune homeostasis
- immune surveillance
what are the layer of immune defence? (4)
- barrier (skin or mucous)
- soluble components (hurmoral)
- specialist immune cells (cellular)
- new defences that our bodies learn (adaptive)
what are humoral factors of innate immunity? (4)
- complement
- lysosomes
- interferons (IFN)
- C-reactive proteins
what is the complement humoral factor?
- blood proteins / proteolytic cascade leading to opsonisation (phagocytosis) or formation of lytic pore on cell
what are interferons?
- signalling proteins made and released by host cells in response to the presence of several pathogens
what are C-reactive proteins?
- binds to lyphosphatidylchloine expressed on the surface of dead or dying cells (or some types of bacteria) and activates the complement system
what are examples of humoral innate immunity? - complement
what are examples of cellular innate immunity? (5)
- neutrophils
- monocytes
- macrophages
- natural killer cells
- mast cells
what are examples of humoral adaptive immunity?
- antibodies
where do all immune cells, red blood cells and platelets originate?
- bone marrow
where do all white blood cells originate from?
- hematopoietic stem cells
what are myeloid progenitor cells?
- they are the precursor cells of granulocytes (neutrophils, macrophages and mast cells)
what are lymphoid progenitor cells?
- they are the precursor cells of lymphocytes (B cells and T cells)
what are naïve lymphocytes and where do they circulate? (2)
- have antigen receptors but have not yet encountered the antigen
- they circulate continuously from blood into the peripheral tissues
- returned to blood via lymphatic vessels
how are lymphocytes activated? (2)
- in the event of infection antigens are taken up by phagocytic cells which travel to the lymph nodes to display antigens to circulating lymphocytes
- lymphocytes activate and undergo proliferation and differentiation
where do neutrophils and monocytes differentiate? - in the blood
what are antigens?
- toxins that are produced by pathogens that cause harm to an organism
what are the functions of macrophages? (5)
- remove debris
- secrete enzymes, defense proteins and lymphokines
- ingest bacteria
- inflammatory reactions
- antigen processing
what molecules do macrophages secrete? (3)
- enzymes
- cytokines
- bioactive lipids
what are cytokines?
- chemical messengers produced in response to a stimulus
what are the stages of phagocytosis? (5) - chemotaxis
- adherence of microorganism to surface of polymorph or macrophage
- membrane activation of actin-myosin contractile network to extend around microorganism
- complete enclosure of organisms within vacuole (endosome formation)
- rapid fusion of endosome with lysosome to form primary/secondary lysosome
- large group of messenger molecules
- interferon, interleukin, and growth factors that are secreted by certain cells of the immune system and have an effect on other cells
what is type 1 hypersensitivity? (2)
- IgE mediated which involves mast cells and basophils
- causes anaphylaxis, hayfever, asthma etc.
what are natural killer cells? (2)
- large granular lymphocytes
- kills cells infected with certain viruses and tumor cells
how do natural killer cells work? (2)
- interact with glycoproteins expressed on the surface of tumour or virally infected cell
- activation of natural killer cells results in extracellular release
what are dendritic cells?
- present in tissues that are in contact with external environment eg skin
what are the function of dendritic cells?
- function is phagocytosis and can act as APCs
what is immune defense?
- identify, kill and clear pathogens
what is immune surveillance
- identify and clear infected/dysfunctional cells
what is the complement system?
- a group of serum proteins that act in a cascade to destroy invading microbes; these function to keep blood pathogen-free
what are the main proteins involved in the complement system? (3)
- B
- C1 to C9
- D
- they are enzyme precursors and catalyze a series of enzymatic reactions
what are zymogens?
- inactive enzyme precursors in the complement system
how many plasma proteins are part of the complementary system and where are they produced? (2)
- (more than) 20
- produced in the liver then distributed (also produced by immune cells)
what are the activation pathways of the complement system? (3)
- classical pathway
- alternative pathway
- MBL pathway
what are the main biological functions of the complement system? (3)
- opsonization of microorganisms
- activation of the leucocytes
- lysis of target cells (pathogens)
what proteins are involved in the classical pathway? (3)
- C1
- C2
- C4
what proteins are involved in the alternative pathway? (3)
- C3
- factor B
- factor D
what proteins are involved in the MBL pathway? (4)
- MBL
- MASP
- C4
- C2
what does the suffix a and b denote on complement proteins? (2)
- b denoting the larger fragments that stay with the membrane
- a denoting the smaller fragments that diffuse away
what is the C3 tickover?
- C3 hydrolysis into C3H2O (C3b-like)
what is MAC?
- membrane attack complex (C5b6789)
how is C3bBb formed? (3)
- C3 hydrolysis to C3H2O/C3b
- C3b converted to C3bB by factor B
- C3bB converted to C3bBb by factor D
what is the purpose of the C3 tickover?
- to provide low levels of starting material eg C3b for the activation of the alternative pathway
what is the alternative pathway amplification loop?
- once C3b has bound to the membrane it causes factor B to cleave more C3bB to amplify the pathway this also amplifies the classical pathway
what does C5a do?
- neutrophil chemotaxis and inflammation
what are the membrane-anchored regulators? (2) - DAF
- MCP
what is DAF and what does it do? (2)
- decay accelerating factor
- decays/dissociates the C3 cleaving enzyme (C3bBb) into its subunits C3b and C3B
what is MCP and what does it do? (2)
- membrane co-factor protein
- membrane bound complement control protein that makes C3bBb fall apart and makes C3b susceptible to cleavage by factor I (like factor H does)
how does MAC lead to cell death? (2)
- lytic pore in the cell membrane
- osmotic imbalance which leads to cell death
what is the terminal pathway?
- how the membrane attack complex is formed (MAC)
what is the terminal pathway regulator? - CD59
what is chemotaxis?
- movement of a motile cells in a direction corresponding to a gradient of increasing or decreasing concentration of a particular substance
what is a chemoattractant?
substance that attracts motile cells of a particular type
what type of immune response is inflammation?
- innate
what does PAMP stand for and what does it do?
- pathogen associated molecular patterns
- detects distinct evolutionary conserved structures on pathogens PAMPs
where are PAMPs usually found?
- often on glycoproteins projecting from the bacterial surface
what is the inflammatory response? (4)
- injury to cells cause release of chemical messengers (eg prostaglandins)
- phagocytosis of pathogens by macrophages
- signalling to other cells
- changes in local blood vessels
how do cytokines affect blood vessels? (2)
- induce changes in endothelial lining of local capillaries to allow the expression of adhesion molecules
- allows neutrophils in the blood to attach to the cell and follow trail of chemokines to site of infection
what do injured cells release?
- prostaglandins
how are prostaglandins produced? (2)
- phospholipids are released when the membrane is broken this activates phospholipase
- causes PGH2 to be released and broken down into subunits one of those being prostaglandins
what are the prostaglandins involved in inflammation (and tumor growth) and how? (2)
- PGE2
- they induce immune cell activation and chemotaxis resulting in inflammation
why is pain associated with inflammation?
- prostaglandins can bind to pain receptors on nerves which causes pain
why can It be problematic if you inhibit all prostaglandins?
- they are important in the protection of gastric mucosa so if inhibited can lead to gastric ulcers
what is the difference between interleukins and chemokines? (2)
- interleukins are cytokines derived from leukocytes to act upon leukocytes
- chemokines are cytokines that have chemotactic properties eg attract cells to sites of inflammation
what is a cytokine storm? (2)
- these produce even more pro-inflammatory cytokines this is a positive feedback loop and leads to a cytokine storm
- when your immune cells release cytokines that tell the body to produce more cytokines
It leads to:
- damage organs especially lungs and kidneys and even lead to death (eg sepsis)
what are the ways cytokine inhibitor drugs work? (3)
- reduces the amount of cytokine producing cells
- inhibiting cytokine synthesis without affecting the cytokine producing cells (eg glucocorticoids)
- monoclonal antibody against cytokines
how does the innate response help the adaptive response? (3)
- dendrtic cells ingest invading microbes/ their products at site of infection
- the dendritic cells then mature and migrate in the lymphatic vessels to serve as APCs
- APCs present as antigens for T cells which activate them so they can migrate to sign of infection
how do lymphocytes become specific to one receptor?
- during maturation most of the genes are eliminated only 5 to 6 selected genes are spiced together which encodes for one receptor
how does the adaptive immune system produces a much faster and powerful response to a challenge the second time? - immunological memory is learnt from previous encounter with an antigen by the memory T and B cells
In the innate immune response what cytokines are produced and by which cell?
Produced mainly by monocytes/macrophages produced IL-1. IL-8 and IFNa
in the adaptive immune response what cytokines are produced and by what cell?
IL-2 and IFNy produced by T-lymphocytes.
What is the difference between interleukins and chemokines?
Interleukins are cytokines derived from leukocytes to act upon leukocytes, chemokines are cytokines that have chemotactic properties e.g attract cells to sites of inflammation.
What is inflammation important for?
Innate immune cell such as neutrophils and macrophages are recruited to phagocytose pathogens and produce additional cytokines that activate lymphocytes and adaptive immune responses.
Why can inflammation have a negative impact when it is chronic?
Neutrophils and macrophages produce reactive oxygen species and growth factors, if these are constantly being produced it can lead to tissue destruction, fibroblast proliferation (thickening and scarring of connective tissue) and collagen accumulation.
What is sterile inflammation?
Inflammation as a result of a trauma in the absence of microorganisms.
How does the complement system activate leukocytes?
Proteolytic cascade that generates activation fragments for example C3a and C5a that stimulate neutrophils and macrophages to stimulate respiratory burst.
How does the complement system opsonize microorganisms?
Binds complement proteins to the surface of microbes so they are labelled e.g the C3b opsonin for phagocytic uptake.
How does the complement system cause lysis of target cells?
The MAC membrane attack complex inserts into the microbial membrane.
What protein by opsonisation attracts phagocytes to the pathogens?
C3b
What protein causes inflammation and immune cell recruitment?
C5a
How is C3bBb formed?
C3 is cleaved into C3b by the tickover mechanism and plasma proteins. Factor by then coverts C3b into C3bB. Factor D then converts C3bB into C3bBb.
What is the most abundant complement protein in our plasma?
C3
What is the purpose of C3 tickover?
To provide low levels of starting material e.g C3b for the activation of the alternative pathway.
Describe the process of tickover?
C3h20 is formed and is as activator of the laternative pathway but can not attach to cell surfaces,
C3b can attach to cells, this is formed from C3h2o being coverted to C3h20b by factor be and then C3h20Bb and this is then formed back to C3b.
How is the complement system activated (alternative)
Once C3BB is bound to the cell membrane it forms into C3Bb by fD. C3Bb then binds with C3b to form C3bBbC3b during this C3a is released. This new complex can then bind to C5b forming the start of the MAC.
What is the classical pathway activated by?
Antibodies or antibody-antigen complexes.
