8. Responding to Antigens Flashcards
What is immunity?
Resistance to infectious disease
Where are cells of the immune system derived from?
All the cells of the immune are white blood cells derived from multipotent cells in the bone marrow.
What is a phagocyte?
Important defence cell that engulfs invading organisms and clears debris after infection is defected.
What is the lymphatic system?
It consists of a network of thin walled lymphatic vessels containing lymph tha teaches all tissues of the body and interconnects the lymphoid organs.
What is bone marrow?
forms the soft tissue in the hollow centre of long bones
• is the source of pluripotent stem cells, from which all the cells of the
immune system (and other blood cells, such as red blood cells and platelets)
originate
• is the site of development of B cells.
What is the thymus?
is located just behind the sternum (breastbone) of the rib cage
• shrinks with age, from about 70 grams in infants to about 3 grams in elderly
people
• is the site where T cells develop after being released from the bone marrow.
What is the spleen?
is a flattened organ lying in the upper-left sector of the abdomen
• filters the blood passing through it, clearing the blood of bacteria and viruses
as well as worn-out red blood cells
What is Lymph?
Fluid that floats through the lymphatic system. Same composition as blood except for red blood cells and platelets.
What are lymph vessels?
Allow B and T cells to enter and exist lymph nodes. Collect lymph that leaks into the tissue and returns it back to the circulatory system.
What is the function of lymph nodes?
- Small bean like structures located along the lymphatic vessels along various locations.
- are located along blood vessels and lymphatic vessels, which enable
B cells and T cells to enter and exit the lymph nodes. - are the sites where any ‘new’ foreign antigen meets and activates B cells and T cells and where immune responses occur
• swell when infections occur, because the numbers of B and T cells in the lymph nodes increase — this produces the so-called ‘swollen glands’ - trap cancer cells or bacteria travelling in lymph vessels
What is the structure of lymph nodes?
– The outer cortex contains follicles with large numbers of B cells that divide and diversify; antigen-presenting cells, such as dendritic cells, are also found here.
– The inner cortex mainly contains T cells and other immune cells such as dendritic cells.
– The medulla contains B cells, including special antibody-producing B cells called plasma cells.
What are the two subdivisions of the immune system?
- innate or non specific immunity (first and second line of defence)
- adaptive or specific immunity (third line of defence)
What organisms have which type of immunity?
Innate immunity is present in animals, plants, fungi and invertebrates.
Adaptive immunity is present only in jawed vertebrates.
What types of immunity are antigen specific?
Innate immunity has a response which is not antigen specific.
Adaptive immunity has an antigen specific response.
Are the responses specific in innate and adaptive immunity?
Innate immunity produces non specific responses against classes of pathogens, not specific pathogens.
Adaptive immunity produces specific responses with tailor made antibodies against each particular microbe.
Where do the immune responses occur in each type of immunity?
In innate immunity immune responses occur mainly at sites of infection.
In adaptive immunity immune responses occur mainly in the secondary lymphoid organs, such as lymph nodes.
Are the two types of immunity present from birth?
Innate immunity is present from birth
Adaptive immunity develops only after infection so that the maximum response is slower
Do both types of immunity have memory?
Innate immunity responses have no memory of prior infections to that an identical response occurs with every infection.
Adaptive immunity has memory of prior infections so that the response is faster, stronger when some microbes re-infect.
What are the major responses of the two types of immunity?
Innate immunity: 1. Cellular attack on bacteria and virus infected cells. 2. Attack by soluble proteins
Adaptive immunity responses: 1. Cellular response attacks infected cells (intracellular pathogen)
2. Antibody responses target extracellular pathogens and non self antigens
What are physical barriers in the first line of defence?
Intact skin, mucous membrane, Cilia, earwax, blood clots
What are chemical barriers?
Intact skin (sebum) Mucous membrane Acid in the stomach Saliva Natural microflora.
How does intact skin contribute to the first line of defence?
- The intact skin constitutes an important physical and chemical barrier to microbial infection
- the constant shedding of dead surface cells is an effective barrier against entry of pathogens
- sebaceous glands in the skin produce a secretion called sebum which provides a protective and antimicrobial film on the skin and sweat secrets dermcidin which acts as an antimicrobial against against a wide range of pathogens
How does the mucous membrane contribute to the first line of defence?
-The inner spaces of the airways, the gut and the urogenital tract are lined by mucous membranes consisting of epithelial cells that have tight junctions between them that prevent the entry of microbes
What are some examples of the mucous membrane?
- Special cells in the mucous membrane secrete a thick gelatinous fluid called mucus that can trap pathogens
- cilia are the hair like out foldings found in the air easy which trap pathogens and regular beating of the cilia moves mucus from deep in the airways to the back of the throat where the mucus is swallowed and the pathogens are destroyed by acid in the stomach or mucus is expelled through coughing or blowing of the nose
- some mucous membranes are washed constantly, such as the mouth and throat are washed by saliva and the surfaces of the bladder and the urethra are regularly washed by urine which prevents pathogens from becoming established
How does the presence of normal flora contribute to the first line of defence?
- the term natural flora refers to the non pathogenic bacteria that are normal residents in particular regions of the body including the gut the mouth and the throat and the genital tract
- the presence of these harmless bacteria inhibit the growth of pathogenic microbes which could outcompete pathogenic bacteria
What is the first line of defence for plants?
- thick intact cuticle or waxy leaf surface
- thick bark
- hairs on leaf surface
- thorns or spines on plant surface
- hairs around stomatal openings
- gall formation around infected area to prevent spread
What is the plants second line of defence (chemical strategies)?
- unlike animals plants do not possess a circulatory system that can efficiently transport their defence mechanism so the response tends to be more localised
- wounds caused by a pathogen can be quickly plugged by resin
- secretion of enzymes and antibiotic like substances destroy pathogens
- chemicals with unpleasant smells or tastes deter all by a few predators (tannins)
- molecules which mimic predators hormones and disrupt their normal life cycle
- specialised proteins (lectins) which bind to and inactivate many bacteria viruses and insects
- specialised hair like structures on leaves secrete a sticky substance which when touched by insects they are trapped can’t move and will starve to death
- produce gun to seal off infected area
What is the second line of defence?
The second line of defence depends on the recognition of self from non self.
Involves the action of immune cells and soluble proteins that produce inflammation
What are the components of the second line of defence?
Cells= phagocytes and natural killer cells
Soluble proteins= complement proteins and interferons
What is the role of phagocytes?
They engulf and destroy microogranisms and other foreign material that enters the body by phagocytosis
What are neutrophils?
Located in the blood
Identify and mount phagocytic attack on microbes
Kills engulfed microbes by toxic chemicals
First cells to arrive at infection site
What are macrophages?
Located in the tissue Identify and eliminate pathogen by phagocytosis Also remove dead cells and cell debris Secrete cytokines Also antigen presenting cells
What are dendritic cells?
Located in tissue
Mobile cells that identify pathogens and secrete antiviral cytokines
Present in skin and surface lining
Apc
What are eosinophils?
Located in the blood
Defence against larger parasites
Attsck using toxic chemicals released from granules
What are basophils?
Located in the blood
Release histomines are part of the inflammatory response and play a role in allergic responses
What are the steps in phagocytosis?
- The pathogen is identified by a pattern recognition receptor on the surface of the macrophage and is engulfed by outfoldings of the plasma membrane of the macrophage
- The pathogen is completely enclosed in a vesicle called a phagosome.
- Lysosomes fuse with the phagosome (forming a phagolysosome) and release toxic chemicals that attack the pathogen. Toxic chemicals include oxygen radicals and nitric oxides that damage macromolecules, lysozymes that attack the cell walls of Gram-positive bacteria, and proteases and other digestive enzymes.
- The pathogen undergoes digestion from this combined chemical attack.
- Indigestible material is discharged from the phagocytic cell by a process of exocytosis.
What is degranulation?
The release of antimicrobial and toxic molecules from membrane bound granules stored in the cytoplasm of some innate immunity cells.
What are the steps in degranulation?
The granules in NK cells contain active protease enzymes, known as granzymes, and a pore-forming protein called perforin. The combined action of these proteins destroys the target cell. Perforin molecules form a ring structure that punches a hole in the plasma membrane of the target cells, enabling entry of the proteases into the target cell. Once inside the cytoplasm of an infected target cell, the proteases induce apoptosis. Elimination of an infected cell or a cancer cell by degranulation of an NK cell is completed within hours.
How do natural killer cells identify abnormal body cells?
NK cells identify targets for elimination even though the targets are body cells. The decision: ‘kill or don’t kill’ by an NK cell is believed to be determined by receptors on the plasma membrane of the NK cell: one receptor is for ‘kill’ and another is an inhibitory receptor that blocks the kill signal.
All body cells carry ligands that can bind to ‘kill’ receptors on NK cells. This binding activates the ‘kill’ receptors that signal an NK cell to eliminate any cell bound to it. However, this kill signal is inhibited by normal HLA markers on healthy body cells. The activation of the inhibitory receptors sends a signal that blocks the kill signal. As a result, an NK cell does not identify healthy body cells as targets for elimination.
How can viral or cancer cells affect the expression of HLA markers?
Virus infections of body cells suppress the expression of class I HLA markers. Likewise, cancer cells produce abnormal HLA markers. These missing or abnormal HLA markers make these cells susceptible to being killed by NK cells because they cannot inhibit the ‘kill’ signal.
When contact is made with an infected cell that is missing or has abnormal HLA markers, the NK receptor for the inhibition of the ‘kill’ signal is not activated. As a result, the NK cell responds to the ‘active kill’ signal and degranulates, spilling the lethal contents of its granules onto the target cell.
What are complement proteins?
Dissolved in the plasma of your blood are proteins that form what is called complement.
What is the complement?
a system of more than 30 plasma proteins that form part of the innate immune system, and, when activated by contact with the surface of a pathogen, set in train actions to destroy it
Are complement proteins circulating in the blood active?
- the complement proteins circulating in the blood are inactive enzymes
- they are activated when they make contact with a pathogen
- the activation of one kind of complement protein results in a cascade effect where each activated complement protein then activates another, and so on down the chain
How do complement proteins assist phagocytes?
- Stick to invading pathogens (opsonisation) making them more susceptible to elimination by phagocytosis
- Stimulate phagocytes to become more active by chemotaxis
- Attract phagocytes involved in the inflammatory response to the site of infection
- Destroy the plasma membrane of invading micro organism by forming membrane attack complexes and defend against bacteria, some unicellular parasites and enveloped viruses
What is an interferon?
An antiviral agents secreted by body cells infected with a virus which acts on uninflected cells making them more resistant to the virus
How do interferons act on body cells to make them more resistant to viruses?
- Induce transcription of specific genes that encode the production of antiviral enzymes that block the synthesis of viral proteins and destroy viral RNA
- Make the plasma membrane less fluid making it difficult for the virus to infect these cells
- Cause virus infected cells to undergo apoptosis
- Activate immune cells such as natural killer cells that eliminate virus infected cells by apoptosis
What is inflammation?
A reaction that develops in local tissue when cells are damaged or killed by infection punctures or burns.
How does inflammation happen?
- The area becomes hot, red, swollen and tender which is a result of an increase in blood flow to the area.
- The increase in blood flow results in more phagocytes being brought to the injury. These phagocytes release chemicals such as histomines which promotes vasodilation and increase blood flow bringing more phagocytes to the area.
- Phagocytes engulf and destroy bacteria
What does the third line of defence involve?
Lymphocytes, b and T cells
Antibodies (immunoglobulins)
Lymph nodes where b and T cells are activated
What are the similarities between b and T cells?
- Both b and T cells are made in the bone marrow
- both b and T cells migrate to the lymph nodes when mature
- both have receptors that recognise only one kind of antigen
- both retain a memory of antigen met previously
What are the differences between b and T cells?
- B cells mature in the bone marrow while T cells mature in the thymus
- T cells are activated by exposure to antigens presented to them on the surface of cells while B cells are activated by direct exposure to raw antigens
- b cells are apc’s but T cells are not
- T cells differentiate into various types of T cells including helper T cells and cytotoxic T cells. B cells develop into plasma cells that produce specific antibodies against a specific antigen.
What are the two types of adaptive immunity?
Humoral immunity
Cell mediated immunity
What is humoral immunity?
Humoral immunity involves the action of antibodies that identify and bind to extracellular pathogens, to toxin and other extracellular foreign antigens. Antibodies are the products of special B cells termed plasma cells
What does cell mediated immunity involve?
Cell mediated immunity involved various actions of T cells. Cytotoxic T cells eliminate body cells that are infected by pathogens or have abnormal or missing self markers.
Cell mediated responses do not directly attack pathogens but remove infected cells, and hence eliminate intracellular pathogens
What is igG antibodies?
Able to cross the placenta
Found in breast milk
Not found in tears saliva and mucous membrane
Active against viruses and bacteria (some)
Not involved in allergic reactions
What antibody is involved in allergic reactions?
IgE
How do antibodies act on antigens?
- Do not directly destroy pathogens but defend against infectious pathogens and toxins
- Bind to surface antigens on pathogens and form a coating that neutralises pathogens
- Antibodies bind to bacterial toxins animal toxin and venoms which neutralises the harmful effects of the toxin or venom
- Tag pathogens for destruction and the elimination is carried out by either complement proteins or by phagocytic cells such as macrophages.
How is the diversity of B cells with their associated antibodies generated?
- B cells are produced from immature or naive B cells, genes rearranged during B cell development
- The DNA from mature B cells has been rearranged resulting in the removal of some DNA
- millions of different types of antibodies can be produced due to the rearrangement of the DNA during B cell development
- once mature each B cell leaving the bone marrow displays a different antibody on its cell membrane which acts as an antigen receptor
- any B cell that recognises self antigens undergoes apoptosis
What is the colonal selection of antibody production?
An antigen reaches the lymph nodes and comes into contact with naive B cells that do no recognise it,
Eventually the antigen meets a specific B cell that can recognise and bind to it. This is called colonal expansion
-When a specific B cell binds to a foreign antigen this B cell is activated it replicates rapidly and produces a large clone of cells Clonal expansion,
-Cells produced in this way will all contain the same genetic material and produce the same antibody
-these cells differentiate into plasma cells or effector cells me produce the same kind of antibody
How do cloned antibodies help destroy pathogens?
- Agglutination of pathogen, antigen to antibody complex is formed
- Pathogen is immobilised
- Then macrophages (phagocytes) engulf the antigen antibody complex and digest it
What are memory cells?
B cells also reproduce to form B memory cells which have the same antigen to antibody specificity as the parent B cell but survive for several years rather than the few days of a plasma cells.
- If the second infection of the same pathogen containing the same antigen occurs, B memory cells react faster and more vigorously than the initial B cell reaction to the first infection
- The immune system responds so quickly that the person shows few, if any symptoms
What are the steps of humoral immunity (b cell activation and antibody production)?
- Any B cell with a specific antigen receptor on its cell membrane (i.e an antibody bound to the cell membrane) binds to an antigen on a pathogen. The B cell also ingests the pathogen and then displays the pathogen’s antigen with its MHC 2 on its cell membrane.
- An effector T helper cell then binds to the B cell displaying the specific antigen on its MHC 2 with its matching antigen receptor.
- Binding between these two cells caused the T helper cell to secrete interleukins that stimulate B cell Clonal expansion. The B cells reproduce many times by mitosis producing many clones of the B cell
- The B cells differentiate into plasma cells and memory cells
- Plasma cells secrete antibodies which are specific for the antigen of the pathogen
- Antibodies bind to the antigen on the pathogen (or foreign molecules) in the extracellular fluid forming antibody-antigen complexes which are recognised by phagocytes that then engulf and destroy the complex.
What are helper T cells?
- Have receptors that detect specific antigens displayed on MHC class II which are found on macrophages dendritic cells and B cells
- Also have cell surface markers called CD4 which aids in binding to forge in antigens
- Produce cytokines such as lymphokines and interleukins which induce activated B or T cells to divide and give rise to effector cells and memory cells
- Lymphokines stimulate macrophages to engul invading cells more Rapidly
- without helper T cells B cells and Tc cells would not be stimulated and without B cells stimulated, antibodies would not be produced.
How are T helper cells activated?
- In the tissues a dendritic cell (or macrophage) phagocytose and destroy the pathogen
- The dendritic cell then acts as an antigen presenting cell. Antigens from ten pathogen are combined with MHC2 and sent to the cell membrane and displayed as antigen-MHC complexes
- The dendritic cell migrates to the lymph nodes
- A t helper cell with matching MHC2 antigen receptor and binds to the MHC 2-antigen complex on the antigen-presenting fell
- This binding stimulated the dendritic cell to secrete interleukins which stimulate clonal expansion of the Th cells producing effector Th cells and memory T helper cells. Th cells also secrete interleukin that stimulate its own Clonal expansion.
- An effector Th cell then binds to a B cell displaying the specific antigen on its MHC 2, with its matching antigen receptor
- Binding between these two cells causes the Th cell to secrete interleukins that stimulate B cell Clonal expansion
- The effector T helper cells also secrete interleukins that stimulate Clonal expansion of activated Tc cells.
What are suppressor T cells?
- Regulatory T cells
- regulate the action of lymphocytes which suppress the action of phagocytes and slow the production of antibodies and cytotoxic G cells.
- Turn off the immune response when no more antigen is present
What are cytotoxic T cells?
- Have receptors that detect specific antigen that have been presented on MHC class 1 of infected body cells.
- Cytotoxic T cells (TC) kill body cells that have been infected with a virus, therefore, they destroy eukaryotic cells.
- They recognise an infected body cell by the viral antigen presented on the MHC class I left outside the cell, aided by their surface markers TCR.
- TC cells kill the infected cell by releasing powerful cytotoxins, such as perforins, that punch holes in the membrane of the cell and the contents spill out.
- Like B cells, cytotoxic T cells will only divide with a signal from the helper T cell.
What are the steps in the cell mediated response?
- A dendritic cell in the tissues phagocytose a pathogen e.g. a virus. The cell packages some of the viral peptides with its MHC 1 forming a MHC 1-antigen complex and migrates to the lymph nodes.
- A cytotoxic T cell with a matching T cell antigen receptor binds to the dendritic cell at its MHC 1–antigen complex. The dendritic cell secretes cytokines and clonal expansion of the specific Tc cell occurs.
- Effector T helper cells secrete interleukins that also stimulate division and differentiation of the cytotoxic T cells into effector and memory cells.
- The effector cytotoxic cells then migrate to the tissues.
- Meanwhile, a body cell infected with the same virus signals ‘infection’ by displaying the antigen of the virus with its MHC 1.
- The effector Tc cells recognise the infected cell using their MHC1-antigen receptor. Binding results in the Tc cell secreting perforins that punch holes in the membrane and other cytotoxins which induce apoptosis and cell death of the infected cell.
- The cytotoxic T cell can then attack other infected cells.
