Session 9 - Immunity system 2 Flashcards
What are antigens
Antibody generators.
o Substances that are recognized as foreign and provoke immune responses are called antigens (Ags)
• Can be entire microbes, parts of microbes, bacterial toxins, pollen, transplanted organs, incompatible blood cells
(whole cells, parts of cells or chemicals)
Characteristics of antigens
- Immunogenicity = ability to provoke immune response
- Reactivity = ability to react to cells or antibodies it provoked
Describe the entrance of antigens and where they end up - why?
when they get past the bodies nonspecific defenses (physical and chemical barriers) antigens are directed to lymphatic tissues.
- enter the bloodstream to be deposited in spleen
- penetrate the skin and end up in lymph nodes
- penetrate mucous membranes and lodge in mucosa associated lymphoid tissue
** remember B cells and T cells are sitting there trying to detect antigens
Structure of Antigens/ Epitopes
o Structure: Large, complex molecules, usually proteins
o Epitope: small part of antigen that triggers/ creates the immune response
– antigenic determinant
Antigen Receptors
Where are they found and What casues diversity?
o Antigen Receptors: Present on plasma membranes of lymphocytes that can recognize and respond to a billion different epitopes - even artificially made molecules
o Diversity: Genetic recombination of few hundred small gene segments produce a huge variety of antigen receptors
o Specificity: Each B or T cell has its own unique set of gene segments that codes its unique antigen receptor in the cell membrane
Major Histocompatibility Complex Antigens - what are they and what are the two types ?
Self antigens, surface markers (flags that say ‘this is me !’)
o They define our cells as ‘self’
o They also serve as a signal to lymphocytes that antigens/ pathogens are present
- Glycoproteins located in the plasma membrane of all body cells
- Also called Human Leukocyte Antigens (HLA)
**o Two types:** • MHC class I antigens • MHC class II antigens
Major Histocompatibility Complex Antigens :
MHC-I antigens - where are they located and their function
built into the cell membrane of all cells except red blood cells
o Function: If a cell is infected with a virus, the MHC-I contains bits of virus marking the cell so T cells recognize that there is a problem in that cell
Major Histocompatibility Complex Antigens:
MHC-II antigens: where are they found and their function
Appear only on membrane of Antigen Presenting Cells (Dendritic cells, macrophages, B cells)
o Function: If antigen presenting cells ( Dendritic cells, macrophages, B cells) ingest foreign proteins, they will display some as part of their MHC-II
* this will tell innitate immune response!
Antigen recognition
B and T cells must recognize a foreign antigen before beginning their immune response
- B cells can bind to antigens in lymph, interstitial fluid, or blood plasma.
- T cellscan only recognize fragments of antigens that have been processed and presented to them as part of a MHC molecule
–Helper T cells “see” antigens if part of MHC-IImolecules on surface of antigen presenting cell
–Cytotoxic T cells “see” antigens if part of MHC-I molecules on surface of body cells
Processing of Exogenous Antigens
o Exogenous Antigens: Foreign antigens that are present in fluids outside body cells
•These include bacteria and bacterial toxins, parasitic worms, inhaled pollen and dust, and viruses that have not yet infected a body cell.
oProcessed by: Antigen-presenting cells (APCs) and presented together with MHC class II molecules to T cells to alert that “intruders are present”.
Refer to diagram ** when the MHC11 has something attached to it, this is an indication for B and T cells to start working
Processing of Endogenous Antigens
oEndogenous antigens: Foreign antigens that are present within the body cells
•include viral proteins or proteins produced by cancer cells
oProcessed by: Most of the body’s cells can process endogenous antigens
- Fragments of endogenous antigen are associated with MHC class I molecules inside the cell.
- The antigen-MHC-I complex moves to the cell’s surface where it alerts T cells
Interleukin 2 - Cytokine
Describe and what is their function
Small protein hormones secreted by lymphocytes and antigen presenting cells, fibroblasts, endothelial cells, monocytes, hepatocytes, and kidney cells
oFunctions:
ostimulate or inhibit many normal cell functions, such as cell growth and differentiation.
oAre essential in the immune responses of T and B cells through the process of ‘co-stimulation
A T Cell is activated when it recieves two signals - Explain
There are two types of T Cells.
•Helper T cells & Cytotoxic T cells
oFirst signal: Antigen recognition by a T-cell receptor (TCR)
•T-cell receptors (TCRs): recognize and bind to specific foreign antigen fragments that are presented in antigen–MHC complexes
oSecond signal: Costimulation by costimulators or plasma membrane molecules
•Costimulators: cytokines such as interleukin-2 (IL-2)
Activation of Helper T Cells
The helper T cell becomes activated through
- Antigen recognition: TCRs on Helper T cells bind to foreign antigen fragment associated with MHC-II at the surface of an APC with the help of CD4 proteins
- Costimulation: by interleukin-2
Clonal Selection of Helper T Cells
Clonal Selection: activated helper T cell undergoes clonal selection to form a clone of helper T cells:
- Active helper T cells: secrete cytokines including interleukin-2 (IL-2), ( Once they are activated the helper T cells actively divide so now we have clones of that exact same helper T cell which recognises that specific antigen that it was just bound to)
- Memory helper T cells: Available for swift response if a second exposure should occur ( Sit in your lymph nodes and recognise antigens that have infected before)
oInterleukin-2 (IL-2): act as a costimulator for resting helper T cells or cytotoxic T cells, and it enhances activation and proliferation of T cells, B cells, and natural killer cells.
Activation of Cytotoxic T Cells
The Cytotoxic T cell becomes activated through
- Antigen recognition: TCRs on a Cytotoxic T Cell binds to the foreign antigen fragment part of MHC-I on the surface of body cells infected by microbes, some tumor cells, and cells of a tissue transplant
- Costimulation:By IL-2 and other cytokines from helper T cell
Clonal Selection Cytotoxic T Cells (cells that kill cells)
oClonal Selection:activated cytotoxic T cell undergoes clonal selection to form a clone of cytoxic T cells:
•Active Cytotoxic T cells: attack other body cells that have been infected with the antigen
•Memory Cytotoxic T cells: Available for swift response if a second exposure should occur
Elimination of invaders - Cytotoxic T cells
Cytotoxic T cells: Act as soldiers in cell mediated response
oMigration: Cytotoxic T cells leave secondary lymphatic organs and tissues, migrate to site of infection, tumour formation, or transplanted tissues
oCytotoxic T cells recognize and attach to target cells.
How do Cytotoxic T cells kill infected cells
1.Releasing Granzymes: Protein-digesting enzymes that trigger apoptosis ( death of cells )
2.Releasing proteins from their granules
- Perforin: creates channels in the plasma membrane of a target cell causes cell lysis. (the dissolution or distruction of cells)
- Granulysin: Enters through the channels and destroys the microbes by creating holes in their plasma membranes
3.Secreting Lymphotoxin that activates enzymes in the target cell causing its DNA to fragment ( therefore it can no longer replicate)
4.Secrete gamma-interferon to activate phagocytic cells
Immunological surveillance (T cell mediated immunity)
What is a tumor antigen?
oTumor antigen: Surface molecules displayed by Cancerous cells
oImmunological surveillance: Immune system finds, recognizes and destroys cells with tumour antigens
- Carried out by cytotoxic T cells, macrophages and Natural Killer cells
- most effective in finding tumours caused by viruses
oTransplant patients taking immunosuppressive drugs suffer most from viral-induced cancers as their immune system is supressed ( T cells are supressed )
What is the immune systems response to graft rejection
oThe immune system can recognize proteins in transplanted organs as foreign and mount a graft rejection.
oAfter an organ transplant, the immune system has both cell-mediated and antibody-mediated immune responses = graft rejection
immunosuppressive drugs (cyclosporine) are used suppressing the immune system
–inhibits secretion of interleukin-2 by helper T cells
–little effect on B cells so maintains some resistance
What are antibodies
A protein circulating in our blood that can combine specifically with the antigenic determinant on the antigen that triggered its production.
What cells are responsible for making antibodies?
–B cells transform into plasma cells,
–Plasma cells synthesize and secrete specific proteins called antibodies
what is antibody-mediated (humoral) Immunity (AMI)
Destruction of antigens by antibodies.
- works mainly against antigens dissolved in body fluids (humours) and extracellular pathogens, primarily bacteria, that multiply in body fluids but rarely enter body cells. - because the blood is where our antibodies are circulating!
- Specificity: Millions of different B cells, each capable of responding to a specific antigen
What are the major steps in antibody-mediated immune response?
oActivation of B cells
oClonal selection and Antibody secretion
oAntigen antibody complex formation
When are B cells activated? and how are B cells presented with an antigen?
Stimulation: B cells sit still in lymph nodes, spleen or mucosa-associated lymphatic tissue.
• Activated when an antigen is presented to them.
How are they presented? When a macrophage has digested bacteria it is circulating in the lymphatic tissue and comes via a lymph node and that’s where our B cells are located and they are essentially screening the fluids of our body and if an antigen presenting cell (macrophage) comes through with a mhc11 that has an antigen fragment attached to it and it finds a B cell that has a b cell receptor for that fragment then we have antigen binding
Explain activation of B cells:
Antigen binding
Antigen processing
Co-stimulation
Colonal selection
Antigen Antibody
- Antigen Binding: During activation of a B cell, an antigen binds to B cell antigen receptors on the cell surface
- Antigen processing: Antigen is taken into the B cell, broken down into peptide fragments and combined with the MHC-II self-antigen, and moved to the B cell surface.
- Co-stimulation: Helper T cells recognize the antigen-MHC-II combination and produce interleukin-2 and other cytokines that function as costimulators to activate B cells.
- Clonal selection: Once activated, clones of B cells are produced.
oRapid cell division and differentiation occurs to form
•Long-lived memory B cells: quickly proliferate and differentiate into more plasma cells and memory B cells against the same antigen if re-attacks.
•Plasma cells: produce and secrete antibody at 2000 molecules/sec for 4-5 days
- Antigen antibody complex formation: Antibody leaves the lymph nodes and enters blood circulation to attack the antigen.
What are the 5 actions of antibodies ?
oNeutralize antigens: by blocking the effects of toxins or preventing its attachment to body cells
oImmobilize bacteria: by attacking cilia/flagella
oAgglutinate and precipitate antigens: by cross-linking them causing clumping and precipitation
oComplement activation: Antigen–antibody complexes initiate the complement system which is a sign for phagocytosis to occur
oEnhancing phagocytosis: through precipitation, complement activation or opsonization (coating with a special substance)
How is immunological memory achieved? and what does it provide?
oImmunological Memory achieved due to:
- the presence of long-lasting antibodies and
- very long-lived lymphocytes that arise during clonal selection of antigen-stimulated B cells and T cells(decades)
- sitting in our lymph nodes surveying the lymph fluid going through our spleen, kindneys etc waiting to see
oProvides the basis for acquired immunity including immunization by vaccination against certain diseases
Explain Immunologic memory primary response
• a slow rise in the antibody titre (how much antibody is in your blood) after an initial contact with an antigen, followed by a gradual decline with the recovery from an infection.
- we may feel sick during this period, get a fever, inflammation
• Memory cells are formed during this phase that may remain for decades
Immunological secondary response
- rapid proliferation of memory cells when the same antigen re-attack results in a far greater antibody titre ( in the blood) (mainly of IgG) than during a primary response.
- provides protection should the same microbe enter the body again.
- Quicker recognition and intense and removal occurs- may not even feel sick. a little but of pain, inflammation that gives us a sign that our immune system is in action
Ways to acquire adaptive immunity
Explain Self recognition and self tolerance of Mature T and B cells
oMature T and B Cells must recognise but not react to self. This is defined by their responses to MHC proteins.
Self recognition: Abilty to recognise the normal MHC1 or MHC11 as being self and launches an immune response when something different is associated with the MHC proteins
o Process happens in bone Marrow (B Cells) and Thymus (T Cells)
They go through a postive and negative process to decide which ones can recognise self and which can’t. Those that can’t recognize self, or react to it are destroyed or neglected
What are the 4 basic types of hypersensitivity reaction
- Type I (anaphylaxis) reactions
- Type II (cytotoxic) reactions
- Type III (immune complex) reactions
- Type IV (cell-mediated) reactions or delayed hypersensitivity reactions
** listen to lecture part 4 around 24mins for a brief explanation of them
what is an Autoimmune disease and name some
o In an autoimmune disease the immune system fails to display self-tolerance and attacks the person’s own tissue.
- Due to T or B Cells being produced that are not self tolerant.
- Due to CytoxicT or Helper T cells reactivity to self.
- Due to B Cells → Plasma Cells production of Auto-antibodies
- Systemic lupus erythematosus is a chronic autoimmune, inflammatory disease that affects multiple body systems.
- Type I Diabetes: Autoimmune destruction of pancreatic cells that produce insulin
- Rheumatoid arthritis: Autoimmune destruction joints (mostly a IgM autoantibody)
- Multiple Sclerosis: T Cells bind to parts of the myelin sheath of nerve axons.
How does stress affect immunity
Stress affects habit, lifestyle and health:
oUnder stress, people are less likely to eat well or exercise regularly, two habits that enhance immunity.
o Cortisol, a hormone secreted by the adrenal cortex in association with the stress response, inhibits immune system activity.
oFeelings, moods, and beliefs also influence the level of health and the course of a disease
What are the effects of aging on immune function
oWith aging, the immune system functions less effectively
•T cells less responsive to antigens
- age-related atrophy of thymus
- decreased production of thymic hormones
•B cells less responsive
- production of antibodies is slowed
- Produce more auto-antibodies (causing auto-immune diseases)
o Individuals become more susceptible to infections and malignancies (decreased T and B cell responses)
oResponse to vaccines is decreased
