Introduction to Immunology (Lecture 9-14) Flashcards
What are the 3 major classes of phagocyte?
- Neutrophil
- Eosinophil
- Macrophage
Describe characteristics of a neutrophil
- Short-lived cells
- Abundant in blood
- Not present in normal healthy tissues
Describe a neutrophil’s defense mechanism
Phagocytose and destroy microrganisms esp bacteria
How are neutrophils recruited to sites of infections?
- Release of cytokines by activated macrophages
- Presence of peptide fragments of cleaved complement proteins
- Recognition of PAMPs by PRRs
Describe characteristics of macrophages
- Larger than neutrophils
- Longer-lived than neutrophils
Describe a macrophage’s defense mechanism
- Recognize and remove senescent, dead and damaged cells in tissues
- Able to ingest large microorganisms (e.g. protozoa)
Describe a macrophage’s defense mechanism
- Recognize and remove senescent, dead and damaged cells in tissues
- Able to ingest large microorganisms (e.g. protozoa)
What do eosinophils help to do?
- Destroy parasites
- Modulate allergic inflammatory responses
What are granules?
Dense membrane-bound lysosomal derivatives
Describe a granule’s defense mechanism
They fuse w the phagosome membrane and release their contents (lysozyme acid hydrolase) to digest the pathogen’s cell walls
Also contain defensins → destabilize the pathogen’s membranes
Describe shock
Widespread inflammation
Swelling and blood clotting
What does shock lead to?
Significant decrease in blood pressure → blood supply to vital organs (e.g. brain, heart and kidney) is reduced
What does the innate immune system rely on?
- Recognition of CpG motifs in viral DNA by TLR9
- Recognition of viral dsRNA that is an intermediate in the life-cycle of many viruses
Describe TLRs
- Usually found on the plasma membrane
- Active on internal membranes, where they aid in detecting internal pathogens
Describe how IFN limits viral replication
- Limit viral spread by promoting apoptosis (programmed cell death) of the infected cell
- Make the virally infected cell and its neighboring into much less efficient factories for making new viruses
- Warn neighbouring cells of infection and indue expression of other cytokines → communication b/w cells is increased
- Activate a ssRNA nuclease → degrades host ssRNA non-specifically, reducing host protein synthesis
- Activate other mechanisms that shut down host cell synthesis in neighbouring cells by inhibiting the process of translation
Describe other processes done by IFNs apart from limiting viral replication
- Upregulate display of viral peptides on the outer membrane of the infected cell → provides signals for recognition by activated T cells
- Stimulate expression of the immunoproteasome to process and destroy viral proteins
- Provide a call for help, attracting natural killer cells and also activate macrophages
- Fight cancers
- Inflame the tongue and cause dysfunction in taste bud cells
Describe how natural killer cells operate
- Recognize their targets by monitoring the level of expression of these molecules at the cell surface
- Attracted to virally-infected cells by IFNs
- Persuade such cells to commit suicide → the target cells die apoptosis
How do NK cells persuade their clients to apoptose?
Kill by triggering apoptosis of the infected/ transformed cells
Apoptotic bodies left behind are typically engulfed and destroyed by phagocytes
Method of persuasion is the same as that of cytotoxic T cells
Describe characteristics of the adaptive immune system
- Destroy/eliminate invading organisms or toxins
- Raise immune system responses against pathogens that hv never been encountered before by host organisms
- Highly specific to a particular pathogen
- Long-lasting protection (memory)
- Recruited and trained by the innate immune system
What is an antigen?
Substance capable of generating an adaptive immune response
Describe immunization experiments
- Antigen is injected into the animal in the form of a suspension containing adjuvant
- Adjuvant activates innate immunity responses
- It comprises immunological stimulants such as inactivated mycobacterial proteins and irritants (e.g. aluminum hydroxide)
- Activated innate response also responds to the antigen in the vaccine
- Innate immune response trains adaptive immune response
Where do lymphocytes develop?
- Central / primary lymphoid organs
- Bone marrow
- Thymus
- They then migrate to the peripheral or secondary lymphoid organs
- Adenois
- tonsils
- Lymph nodes
- Spleen
- Peyer’s patches
- Appendix
- Skin
- Respiratory tract
Describe how experiments established that lymphocytes were responsible for adaptive immune responses
- Rats were injected w antigen in the presence of the adjuvant
- Antigen is part of the disease pathogen that we want the immune response to
- Adjuvant is used to activate innate immune response
- Normally, there is a stimulation of the adaptive immune response
- Other group was heavily irradiated to cause tissue damage
- Resulted in mice being unable to develop adaptive immune response
- Could still react via some innate immune response
- Result suggest that radiation must hv killed some of the adaptive immune response’s cells that were required to initiate and maintain it
What do activated DC do?
- Phagocytose and degrade invading microorganisms
- Peptides from the degraded organism are displayed on the cell surface of these dendritic cells
- DC then migrates to the nearest lymphoid organs and activate adaptive immune response
- Train them to recognize the peptides on its surface
Describe what happens when a bacteria breaches the cell tissue
- Bacteria cells breach the tissue, causing an infection
- DC hv PAMP then bind n engulf the bacteria
- DC mature to APC
- Present the antigen on cell surface
- As they’re maturing, they roll to lymphoid organs where T cells are present
- T cells hv T cell receptors
- Activated when they find a matching antigen
Describe how T cells develop
- In adults, they arise from bone marrow
- In fetus, they arise from liver
- Within the bone marrow, there are haemopoietic stem cells which develop into common lymphoid progenitor
- These cells migrate to the thymus by the blood and the lymph
- They then develop further into a thymocyte
- T[hymocyte]-cell
- Initial training in the thymus result in being able to recognize foreign material
- Inappropriate responses (e.g. attacking own tissues) will result in killing by apoptosis
- Important in the prevention of autoimmune disease
- Once they pass the “training”, they will migrate to the peripheral lymphoid organs where they mature to become T cells
- T cells do not respond to self antigen but can respond to foreign antigens
- Inappropriate responses (e.g. attacking own tissues) will result in killing by apoptosis
How does DC activate T cells?
- DC present peptides to TC in the lymphoid organs
- T cell TCR recognizes non-self antigen: activation, mitosis and clonal expansion of specific TC
Why do APC only present to TC?
- Highly specific interaction b/w the groove w the peptide on its surface and the TCR
- To stop similar proteins from activating T cells, there is a second interaction (co-stimulatory molecules)
- Present in the antigen presenting cell and on T cell
- 2 step process: both hv to interact
- If it can bind n the protein in the groove can interact w the TCR, this leads to T cells being activated n clonal expansion occurring
- No recognition leads to no action, cells undock
Why does the innate immune system need to kick in first?
Activation and clonal expansion takes time
What do Helper T cells do?
Activate macrophages, DC, B cells and maintain cytotoxic TC activity by secreting a variety of cytokines
What do regulatory T cells do?
Inhibit the function of Th, Tc and DC
What do cytotoxic T cells do?
Kill infected host cells by persuading them to commit suicide apoptotically
How do cytotoxic T cells kill?
- Cytotoxic TC that has been trained by the innate immune system to recognize n target cells which could be virally infected
- Recognizes the peptides that hv been shown in the lymphoid organ (“trained”)
- Upon recognition of the foreign antigen, CT binds specifically to the target cell
- This forms an immunological synapse
Describe the 2 methods cytotoxic T cells use
- B/w the 2 cells are an immunological synapse
First method
- T cell wants to cause apoptosis to remove target cell n program cell death
- Apoptosis will cause target cell to break into membrane bound blebs so pathogens are removed as well
- Perforins form channels thru the target cell plasma membrane (punches holes essentially)
- Opens up spaces for granzymes
- Granzyme is a portease (good at chewing up proteins)
- Has a specific target protein called caspase
- Granzyme will cleave caspase to activate it
- Caspase will bind n cleave the substrate
- Often part of the cytoskeleton
- Caspase will chew up cytoskeleton molecules, which triggers apoptosis
Second method
- T cell binds receptors on the target cell that send a signal that activates caspases (the effector proteins of apoptosis)
Where are T and B cells derived from?
Common lymphoid progenitor cells
These cells are derived from hemopoietic stem cells, which originate from the liver or bone marrow
Describe what happens once a B cell is activated
- Once B cells are activated, they differentiate into a plasma cell
- Hv the ability to secrete antibodies into the surrounding environment
- Recognize specific antigen using membrane bound antibodies
- Massive expansion in ER
- Important for entry point of secretion
- Helps cell to become a secretory machine
- Don’t last v long bc of high lvl of activity
Describe an antibody’s basic structure
- Tetrameric structure
- 4 polypeptide chains
- 2 identical heavy chains (H)
- 2 identical light chains (L)
- Chains are held together by covalent disulfide bonds at the hinge
- Antigen binding site is made up of a combination of N terminal domain of both the heavy n light chain
How does the basic structure of an antibody allow for multiple antibody interactions?
- Antibodies hv identical antigen binding sites so they can cross link antigens
- Antigens w 2 identical antigenic determinants can form large 3D lattices that readily precipitate out of solution
- Most antibodies hv many different antigenic determinants and different antibodies that recognize different determinants can cooperate in cross linking the antigen into large 3D lattices
What characteristics of an antibody allow for different spatial geometries of antigen binding?
- Ability to cross-link antigens
- Flexible hinge region
What is the benefit of these large networks?
Make it easier for phagocytes to engulf pathogens or soluble antigens, which can then be degraded and re-presented into T cells thus amplifying the immune response
Describe the structure of IgM
- Pentamer of basic tetrameric unit
- Held together by a J chain, which is thought to aid polymerization of the complex
What is the valency of IgM
- Valency (how many antigens it can bind to): 10
- 2 antigen binding sites
- 5 antibodies in IgM
What is the valency of IgM
- Valency (how many antigens it can bind to): 10
- 2 antigen binding sites
- 5 antibodies in IgM
What is the difference between IgM and IgD?
IgM can be secreted while IgD cannot
What pathway does IgM trigger?
Classical pathway via their tail regions
Starts w the activation of C1 that goes onto cleave and activate C2, which does the same for C4
Explain the maturation and activation of naive B cells
- Immature naïve B cell in bone marrow expresses surface IgM
- It migrates to the lymphoid tissue and expresses IgD
- IgD can be developmental marker to show
more mature B cell
- IgD can be developmental marker to show
- Once the B cell has both IgM and IgD, it can now respond to soluble antigens
- Process helped by T helper cells, which aid
clonal expansion and differentiation of B cells
and conversion to plasma cells
- Process helped by T helper cells, which aid
- Plasma cells hv an increase in ER
- Able to secrete antibodies
- Hv an IgM receptor so antibodies they are
secreting will also be IgM - IgM binding site will be specific to the
antigen that activated the B cell
Define an opsonin
Molecule that targets antigens for phagocytosis
Complement is also an opsonin
Define opsonization
Coating of a target w IgM (or other antibodies) or complement
Describe the structure of IgG
Standard tetrameric structure
2 heavy chains n 2 light chains
Functions of IgG
- Toxin neutralization
- Binding to microorganisms n opsonization thus leading to phagocytosis
- Provision of passive immunity to fetuses n newborns
What region of IgG is able to interact w FC receptors?
Tail region
Describe the process in which IgG crosses the placenta (passive immunity)
- Placental cells take up maternal IgG by pinocytosis
- Placental endosomes hv receptors (FcRn receptors) that recognize n bind the tail region (Fc) of IgG antibodies
- IgG molecules are transported across the placental cells in vesicle carriers (transcytosis)
- IgG is released into the fetal circulation
Describe how IgG is secreted into maternal milk
- FcRn receptors on neonatal gut cells (enterocytes) recognize n bind the tail region (Fc) of IgG antibodies
- IgG molecules are transported across the enterocytes in vesicle carriers (transcytosis)
- IgG is released into the neonatal circulation
Describe the process of opsonization by IgG
- Bacterium is coated in IgG
- Macrophages n neutrophils express the FC receptor hence can interact w IgG
- Macrophage binds to the bacterium due to the IgG
- This activates the macrophage to start phagocytosis
- Movement of cytoskeleton out to engulf the pathogen
Describe IgA’s structure
- Dimer of 2 tetrameric structures
- Held together by a J chain n S (secretory component) chain
- S chain allows secretion into saliva, tears, milk n mucus
Function of IgA
Protects our mucosal surfaces n provides some passive immunity to newborns via milk
Function of IgA
Protects our mucosal surfaces n provides some passive immunity to newborns via milk
Describe how IgE triggers mast cell/basophil degranulation
- Mast cell is full of secretory vesicles, which contain histamine
- Mast cells hv FC receptors which are IgE specific
- Can capture IgE antibodies, which effectively act as a receptor on the surface
- Mast cell has a receptor, which binds to IgE
- IgE that it binds is specific to a certain antigen
- Once the antibodies hv managed to come across the antigen which it’s originally activated by, cross-linking by the 2 IgE antibodies
- Mast cell becomes activated, which leads to degranulation (massive release of histamine)
Describe how IgE acts as a receptor of eosinophils
The IgE-specific Fc receptors on mast cells, basophils and eosinophils allow these cells to be targeted to different antigens/pathogens
Antibody arm of the adaptive immune system can direct parts of the innate immune system
Describe how IgE acts as a receptor of eosinophils
The IgE-specific Fc receptors on mast cells, basophils and eosinophils allow these cells to be targeted to different antigens/pathogens
Antibody arm of the adaptive immune system can direct parts of the innate immune system
