CHAPTER 5: IMMUNITY Flashcards
what are diseases
- a disease is a condition that interferes with the normal functioning of an organism; usually with specific symptoms.
- can be infectious or noninfectious
what are pathogens
- Most microbes are harmless (non-pathogenic) - only about 1% can cause disease
- Most pathogens are species-specific and tissue-specific
- Pathogens are agents that cause diseases in their hosts
- can be extracellular → pathogen in the body but not in the cells yet (innate response)
- can be intracellular → pathogens in the cells (adaptive response)
cellular vs non-cellular pathogens
- cellular: made of cells and can reproduce independently
- bacteria, parasites (worms), fungi, protozoa
- non-cellular: not made of cells and cannot reproduce independently → need the cells of the host to reproduce (hijack)
- viruses, prions
what are antigens
antigens are substances that cause/stimulate an immune response
self vs non-self antigens
- Self-antigens: antigens on cells that are recognised by self-receptors as being part of the same body
- tolerated by the immune system
- Non-self antigens: antigens that do not belong to the body’s own cells
- attacked by immune system
distinguishing self from non-self
- plasma membrane of this immune cells carries:
- self-antigens that identify this immune cell as ‘self’
- cell surface receptors for self-antigens so that this cell can identify and not attack other body cells
- cell surface receptors for foreign antigens so that the immune cell can identify foreign material and signal other immune cells to eliminate it
MHC I vs MHC II markers
- both are located on the outside of cells, anchored to the cell membrane and are specific to individuals.
- MHC-I markers are present on all nucleated cells
(not red blood cells) of the body and present the peptide fragments from inside the cells- they signify if a cell is ‘self’ or ‘non-self’
- if the correct MHC-I marker is not detected, immune cells will cause it to undergo apoptosis.
- MHC-II markers are only found on specific cells in the immune system such as macrophages, dendritic cells, and B lymphocytes
- all involved in antigen presentation → present the antigens from outside the cell.
bacteria
- prokaryotic microbes and their genetic material is double-stranded DNA
- If bacteria multiply in areas they are not normally found they can cause disease
- Intracellular and extracellular
- Symptoms of bacterial infection are often caused by the toxins the bacterium produces
Bacteria can cause disease in humans if:
1. They can enter a person who can act as a host.
2. They have the capacity to reproduce within the host.
3. They act adversely on tissues in their host (exotoxins, adverse enzyme production)
protozoans
- single-celled, eukaryotes
- infection by ingestion of cysts by sexual transmission or insect vectors
- able to multiply in humans, enabling them to survive in a human host while causing disease.
- symptoms: blood, gut and lymphatic system
- Eg. Malaria – bites of mosquitos
- Ingesting contaminated food
fungi
- eukaryotes
- grow from the tips of filaments (hyphae) that make up the bodies of the organisms (mycelia)
- opportunistic pathogens - immune system is weak
- usually external or skin infections
- Eg. Candida albicans - Thrush (oral
candidiasis) - Athletes food – tinea (Trichophyton spp.)
- Eg. Candida albicans - Thrush (oral
parasites (worms)
- (not microbes) can be seen with the naked eye
- transmitted via soil contaminated with human faeces that contains eggs of those worms
- Eg hookworm, roundworms, whipworms
viruses
- comprise of nucleic acid (DNA or RNA) surrounded by one or more coats of protein.
- replicate only within host cell
- viruses cause disease by killing body cells
- to make more viruses, a virus takes over a host cell and uses it as a ‘factory’
- release of viral particles from an infected cell may be by budding or by cell lysis
- infected host cell ‘explodes’ as its plasma membrane disintegrates and viral particles are released into the extracellular fluid from where they can infect other cells.
what is the immune system
the body system that helps resist infections and disease through specialised cells
3 levels of the immune system
INNATE - present from birth, no immunological memory, not acquired
- the first line of defence
- innate
- non-specific
- skin, stomach acid, etc.
- the second line of defence (hasn’t infected cells yet)
- innate
- non-specific
- macrophages, inflammation, complement proteins
- the non-specific cellular and molecular responses to pathogens that have breached the first line of defence and have entered the body.
- The innate immune response is nonadaptable, and does not change during an individual’s lifetime.
ADAPTIVE - more targeted to a specific pathogen
- third line of defence
- acquired (learns and has memory)
- specific
- B cells, T cells, antibodies
- takes time to develop
first line of defence
- physical barriers act to prevent the entry of pathogens
- chemical barriers act to inhibit the growth or development of pathogens and/or act to destroy pathogens
- microbiota barriers act to prevent the growth or colonisation of microorganisms that may be pathogenic.
first line of defence: physical barriers
- intact skin
- skin microbiome
- mucus: traps and prevents entry of pathogens
- earwax
- nostril hair
- acidic environment - digestive, reproductive, and urinary systems
first line of defence: chemical barriers
- destroys pathogens on the outer body surface, body openings, and on inner body linings
- sweat, mucus, tears, saliva (all have enzyme lysozyme that kills pathogen)
- stomach acid - kills pathogens
first line of defence: microbiological barriers
- presence of normal flora
- non-pathogenic bacteria in regions of the body
- inhibits the growth of pathogenic microbes
- also called “commensal bacteria”
- gut contains many microbes [mainly bacteria] which exist in a “mutualistic relationship” with the person.
- prevent the growth of colonies of other species of bacteria by outcompeting them for nutrients and adhesion sites, and secreting antimicrobial chemicals
first line of defence: plant barriers
- plants do not have an immune system comparable to animals, but they have developed structural, chemical and protein-based defences
- cuticle: waxy covering - prevents penetration and virus and bacteria entering
- thick bark
- leaf orientation (horizontal or vertical) - vertical is less susceptible to pathogens
- thorns and spikes
- antimicrobial or antifungal compounds (plants can naturally make this)
- formation of galls
- growing ‘gall’ tissue around the area containing the infective agent to prevent spread to other areas (containing the pathogen)
second line of defence
if the preventative strategies don’t keep the pathogen out, foreign antigens need to be recognized
cells of the immune system
- immune system cells are white blood cells → leukocytes (another name for white blood cells) made in bone marrow
- each has a specific role in defending the body from pathogens and infectious disease
- involved in innate immunity
dendritic cells (phagocyte)
- found in tissues
- reside in and patrol the skin and mucosal surfaces
- can migrate to lymph nodes
- engulf and destroys pathogens by phagocytosis
- antigen-presenting cells that can activate an adaptive immune response
what are phagocytes
- phagocytes (macrophages, monocytes, neutrophils, dendritic cells)
- do not recognize specific antigens but instead recognize patterns on antigens
macrophages (phagocyte)
- found in tissues
- identify and eliminate pathogens by phagocytosis
- antigen-presenting cells that can activate the adaptive immune system
eosinophils
- present in the respiratory, gastrointestinal and urinary tracts
- assist in defending against larger multicellular parasitic agents
- granules with toxic chemicals and induce the degranulation of histamines from mast cells
neutrophils (phagocyte)
- found in blood
- first cells to arrive at the infection site
- attracted to foreign materials by chemical signals
- engulf and destroy pathogens by phagocytosis
- granules in cytoplasm contain antimicrobial agents or enzymes to assist with destruction
process of phagocytosis
- the phagocytes recognize the microbe via a receptor
- the phagocyte engulfs the microbe via endocytosis
- the vesicle containing the microbe fuses with a lysosome
- the lysosome (organelle) empties its digestive enzymes into the vesicle → lysosomes have a lot of digestive enzymes
- the enzymes digest the microbe
- the particles are released from the phagocyte
natural killer (NK) cells
- found in blood/lymph
- kill virus-infected cells
- attack cells lacking self markers - missing/abnormal MHC markers
- have granules filled with potent chemicals
- NATURAL KILLER CELL ACTION: DEGRANULATION
- when an NK cell recognizes an abnormal cell, it releases proteases (enzymes) and perforin
- perforin punches holes in the cell membrane, allowing the proteases to enter
- these trigger apoptosis (destroys it from the inside)
mast cells
- found in tissue - close to the external environment (eg. surface of the skin)
- mediate inflammatory response
- contains chemicals in granules - cytokines, histamine
- histamines increase permeability - in terms of blood vessels
- cytokines attracts other immune cells
humoral innate immunity
- immune response in the ‘humors’ → body fluids
- eg. lymph, blood
- complement proteins
- interferons
- (extracellular body fluids)
- soluble/dissolved in fluid eg. blood, lymph
complement proteins
- inactive enzymes in blood that complement the function of immune cells
- activated when they make direct contact with the molecules on the surface of a pathogen
- complement proteins activate other complement proteins to form a cascade (like a domino effect)
- complement proteins can cause inflammation (acts as chemotaxis), enhance phagocytosis or cause lysis
works against both cellular and non-cellular pathogens
opsonisation (action of complement proteins)
- makes pathogens more susceptible to elimination by phagocytosis
- coat the surface of pathogen cells and the phagocytes have receptors for the complement proteins (bind to the opsonised microbe)
chemotaxis (action of complement proteins)
- movement of cells in response to a chemical stimulus
- small complement peptides that diffuse from the pathogen surface act as chemical signals
- attracting immune cells involved in the inflammatory response to the site of the infection
lysis (action of complement proteins)
- membrane attack complex (MAC) forms on the plasma membrane of the pathogen due to complement proteins
- the MAC inserts into the plasma membrane of the pathogen, producing a pore
- this allows fluid to enter and causes the pathogen cell to swell and burst
interferons
- a group of cytokines (signalling proteins)
- virally infected cells release interferons to prepare neighbouring cells for a possible ’attack’
- the interferon secreted acts as warning signals to nearby cells
- signal change in plasma membrane making entry of virus more difficult (make PM less fluid)
- signals neighbouring uninfected cells to prepare to destroy RNA to reduce protein synthesis
- signal neighboring infected cells to undergo apoptosis
- activates immune cells such as NK cells
inflammation - major weapon of innate immunity
- reaction to an infection/injury/damaged tissue/pathogen
- localised to the site
- prevent the spread of antigen, removes the pathogen and dead cells, restores the tissue to normal (healing)
- results in heat, pain, swelling and redness
process of inflammation
- vascular stage → blood cells
- cellular stage → immune cells
- resolution → normal state restored and inflammation is stopped
vascular stage
- damaged cells release cytokines → attracts neutrophils
- mast cells release histamines → causes capillaries to become permeable (leaky) and wider (vasodilation)
- vasodilation: increases blood flow to damaged area and the increased blood flow produces heat and redness
- permeable: protein-rich fluid (exudate) can escape from capillaries to the infected region
- the exudate causes swelling and the swelling causes pressure on surrounding tissues, stimulating nerve endings→ cause pain
cellular stage of inflammation
- phagocytes are attracted to the site by cytokines → phagocytose antigen
- complement proteins opsonise pathogens → phagocytosis can occur
- platelets travel to the site to block wound → important for clotting
- pus indicates that this stage is occurring
- consists of mainly dead phagocytic cells and other immune cells, dead tissue, dead pathogens
resolution stage
- occurs when the tissue is returned to normal state → infection is under control
- the release of cytokines stop and anti-inflammatory cytokines are released
- resolution occurs when the antigen is removed from the site of infection
- if resolution does not occur, chronic inflammation may occur
lymphatic system
- transport network
- consists of
- lymph
- lymph vessels
- lymph organs
- production and maturation of immune cells
- allows for the process of antigen recognition by T and B cells
roles of components of lymphatic system
- thymus: maturation of T cells
- bone marrow: maturation of B cells (B+ T both made in bone marrow but B stays there and T cells move through the lymphatic system to the thymus)
- lymph nodes: meeting, activation and response
- lymph vessels connect lymphoid organs (transport)
-
spleen: filters blood
- contain B, T, dendritic cells and macrophages
- activation of B and T cells
primary lymphoid organs
- primary tissue where B and T cells are made
- bone marrow
- source of pluripotent stem cells - leukocytes originate (lymphocytes: B and T cells)
- the site of maturation of B cells
- thymus
- thymus is the site where T cells mature after being released from the bone marrow
secondary lymphoid organs
- mature B and T cells are activated
- where antigens presentation occurs (also filter lymph - the fluid)
- lymphoid organs contain lots of lymphocytes → B and T cells
- spleen
- filters blood → clearing of bacteria and/or viruses and worn-out red blood cells
- contains T and B cells
- contained macrophages and dendritic cells
- lymph nodes
- main site of antigen recognition → leading to the adaptive immune response
lymph nodes
- small bean-shaped structures
- the site of ANTIGEN RECOGNITION in which T and B lymphocytes come into contact with their specific antigens → adaptive immune response occurs
- swell when infections occur → number of B and T cells in the lymph nodes increase → this produces the so called swollen glands
maturation of lymphocytes
- activated by meeting their complementary antigens
- antigens presented by macrophages or dendritic cells
- B and T lymphocytes have receptors for only ONE SPECIFIC ANTIGEN
- B cells make antibodies to eliminate pathogens (antibody-mediated)
- T cells eliminate infected or diseased cells (cell-mediated)
how is adaptive immune response initiated
- pathogen enters (first line of defence breached)
- meet at the entry point by phagocytes that engulf and eliminate’
- some of the digested fragments of the antigen are displayed on the MHC II receptors on the surface of dendritic cells or macrophages
- APCs migrate to the lymph nodes and present the antigen to the T helper cells that carry complementary receptors for the antigen
- T helper cells release cytokines
- initiates the adaptive immune response
- humoral B cells
- cell-mediated T cells
- NEUTROPHIL IS NOT AN ANTIGEN PRESENTING CELL BUT CAN UNDERGO PHAGOCYTOSIS
role of helper t cells
- only activated by antigen-presenting cells that present antigen on the MHC II marker
- once active, clone and secrete cytokines which
- help activate cytotoxic T cells (Tc)
- help activate B cells into plasma cells
- help activate macrophages to remove antibody-coated pathogens by phagocytosis
how does antigen presentation occur
- pathogen undergoes phagocytosis
- antigen fragment is presented on the MHC II molecule to helper T cells
- helper t cells have a receptor
what is adaptive immunity
- adaptive immunity involves a specific response against a specific pathogen → with memory retained for future infections
- this immune response is usually only required if an infection is not cleared by the innate response
- specificity: adaptive immune cells (B and T cells) have unique receptors that recognise specific antigens
- immunological memory: remember antigens after primary infection → to enable a more rapid and stronger response in case of future infections
adaptive cell mediated response
- intracellular pathogens
- T cells deliver the cell-mediated immune defences that include the direct elimination of the pathogen-infected cells and other abnormal cells such as cancer cells
- are activated by antigen-presenting cells
- stimulated by Th
- memory T cells
- cytotoxic T cells
humoral response
- extracellular pathogens
- B cells deliver the humoral immune defences by
- secreting antibodies that bind to surface antigens on pathogens and label them for elimination → antibodies also bind to soluble toxins
action of cytotoxic T cells
- cytotoxic T cells recognise virus-infected cells and can also recognise abnormal proteins
- eg. DNA mutations in cancer cells which often results in abnormal MHC-I markers
- this means cytotoxic T cells can target and eliminate cancer cells.
- once activated, T cells recognise the presence of foreign antigens on the surface of body cells by intracellular pathogens
- can be initiated by APC presents antigen using MHC II
- use T helper cells
- cytotoxic T cells proliferate, producing activated cytotoxic T cells and memory T cells through clonal selection and expansion
- memory T cells retain memory of antigens met previously
- clonal selection: Tc cell binds with its antigen in lymph nodes
- clonal expansion: the activated Tc cells divide into many identical copies (clones) all having identical antigen binding receptors
steps in cell-mediated immunity
- APCs display foreign antigen on MHC II marker to specific helper T cells usually within lymph node
- helper T cells undergo clonal selection and expansion
- interleukins (type of cytokine) are secreted by helper T cell to stimulate immature T cells
- upon stimulation by cytokines release by Th cells, cytotoxic T cells proliferate and produced activated cytotoxic T cells and memory T cells through clonal selection and expansion
- cytotoxic T cells destroy the cells through apoptosis
apoptosis by cytotoxic T cells
- if a cytotoxic T cell (has toxic granules) recognises an infected cell it
- releases perforin (a protein that inserts into the plasma membrane and creates pores)
- enzyme (granzyme B) enter via the pore and trigger apoptosis from within the cell
- this ensures that the virus cannot spread
- similar to the action of NK cells but cytotoxic T cells are specific for certain antigens and form memory cells
B lymphocytes role in humoral immunity
- B lymphocytes (cells) are covered in receptors → known as antibodies
- antibodies are membrane-bound or free
- B cells are ‘selected’ when they find an antigen (extracellular pathogen) complementary to the antibody
- most need to be activated by Th cells
- some become memory B cells
- most become plasma cells
clonal selection and expansion in B cells
- clonal selection: B cells bind with its specific antigen in lymph nodes
- clonal expansion: the activated B cells divide into many identical copies (clones) all having identical antigen-binding receptors
memory cells vs plasma cells
- memory cells:
- not active
- ‘lifelong’
- plasma cells:
- active
- short-lived
- secrete antibodies
- each plasma cell can only produce one type of antibody.
events of humoral immunity
- an antigen gains entry to the body for the first time
- comes into contact w/ many naive B cells in the lymph nodes that don’t recognise it
- eventually, the antigen meets a B cell that can recognise and binds to it
- called clonal selection
- helper T cells that have also bound to the antigen release cytokines to activates the selected b cell- the binding of antigen to T helper cells activate the selected B cell to differentiate and proliferate into B plasma cells and B memory cells.
- results in the production of a large number of B cells w antigen-binding receptor antibodies
- clonal expansion
- plasma cells secrete soluble antibodies against the specific antigen
- memory B cells remain in the lymphoid tissue after the infection has resolved
- initiate immune responses more rapidly and stronger upon re-exposure to the same antigen
- produces large amounts of the specific antibody
structure of antibodies/immunoglobulins
- they are antigen-binding proteins made by plasma B cells
- made of 4 polypeptide chains → 2 heavy and 2 light chains (quaternary structure) → constant region (doesn’t vary between antibodies of the same class)
- each antibody has 2 identical specific antigen-binding sites on both sides of the antibody
- variable region is the antigen binding site → differs between antibodies
- located at the end of each arm of the Y shaped molecule
- the variable region gives antibody its specificity for binding antigen
- each antibody can only bind to one specific antigen
- there are billions of antibodies each w a different antigen-binding site
classes of antibodies
- IgG: main antibody in blood
- IgM: first antibody to appear and provides defence until sufficient IgG is formed
- IgA: attaches to the surfaces of mucous membranes
- IgE: stimulates the release of histamine and other chemicals that cause allergies
- IgD: antibody found on B cells
action of antibodies
- antibodies do not directly eliminate antigens
- they can:
- bind to antigens and form a coating that neutralises pathogens by blocking their receptors so that the pathogens cannot attach to healthy body cells and infect them and stop them from functioning neutralisation (common)
- bind to surface antigens to target them for phagocytosis opsonisation
- bind to surface antigens to target them for lysis by complement proteins
- antibodies bind to surface antigens on pathogens to form antigen-antibody complexes → causing them to clump together and be more visible to the immune system agglutination (common)
- precipitation —antibodies bind to soluble antigens, making them insoluble. This causes them to precipitate out of the solution, creating a solid that is much more visible to the immune system. This occurs due to the cross-linking between antigens and antibodies.
- inflammation —antibodies can trigger the release of histamine, causing inflammation. They also activate a complement cascade.
- PIANO acronym
memory B cells
- memory B cells remain in the lymphatic tissue to remember the antigen for future infections
- they initiate immune responses more rapidly and strongly upon re-exposure to the same antigen, producing large amounts of the specific antibody.
- antibody levels peak in the primary response at about day 14 and then begin to drop off as the plasma cells begin to die (low and short-lived)
- there are more memory cells than there were naive B cells for the primary response
- so secondary response: more plasma cells are generated and antibody levels are consequently 100-to-1000 fold higher
what are allergens
- antigens are substances that cause/stimulate an immune response → doesn’t have to be biological (wood splinter)
- pathogens are agents that cause disease in their response
- allergies are caused by an immune response to allergens (antigens)
- allergic reaction is an abnormal overreaction when exposed to an allergen
- usually harmless → some are hypersensitive
- involves the cells of both the innate and adaptive immune system
- not all antigens are pathogens
- allergies are caused by an immune system response to allergens (antigen ) eliciting an allergic response
what is an allergic reaction
- a reaction to a normally harmless substance
- the substance that causes an allergic response is an allergen (not antigen)
- key players in allergic reaction:
- mast cells
- antibodies → immunoglobulin E (IgE) - overproduction of IgE antibodies causes an allergic response
steps in an allergic response
first exposure:
- allergen (eg. pollen) enters into the bloodstream (first exposure)
- B cells- specific to the allergen (bc extracellular) differentiate into plasma cells and make antibodies
- IgE antibodies attach to mast cells
- called ‘PRIMED’ → ready to respond to the allergen
secondary exposure:
- mast cell is primed with IgE antibodies specific for that allergen
- the allergen binds to antibodies on mast cells
- cross-links form→ more than one antibody binds with the allergen (activates more than one antibody)
- histamines will only be released when there is a crosslink (when allergen binds to j one antibody, histamines aren’t stimulated - no inflammation)
- histamine is released from the mast cell
- cytokines are released → attracting more immune cells
- an allergic reaction occurs
- increased blood flow
- increased permeability of blood vessels
- sustains and increases reaction (more histamine can be released)
how can you be immune from a disease
when we have antibodies against an antigen → we won’t develop the disease
sources of antibodies
-
active: own immune system produces long-term immunological memory (produces own antibodies and makes memory B cells)
- secondary response is more enhanced due to memory
- long-lasting
- more effective
- immunity develops over weeks
- eg. infected, vaccine
-
passive: external source, short term, NO immunological memory (made externally so memory B cells aren’t produced) → quicker response eg. get bitten by snake, antivenom injected
- short lasting
- less effective
- immunity is immediate
- eg. from mother, injected vaccine
means of gaining immunity
- can be natural or artificial
-
natural immunity:occurs without deliberate intervention
- infection, mother-child
-
artificial immunity: is created by deliberate intervention and exposure
- vaccine, injection of antibodies
active immunity
- natural
- infection by pathogen-causing agent
- antibodies form with identical antigen binding sites that bind to the antigens
- pathogen destroyed by high amounts of antibodies
- formation of memory cells
- artificial
- deliberate introduction of a disabled pathogen
- eg. injection
- the adaptive immune response is activated to produce the antibodies
passive immunity
- natural
- receives antibodies from a natural source
- eg. breastfed milk →colostrum via the placenta, IgG
- artificial
- provided by injection of antibodies such as antivenom or antitoxins
- eg. clostridium tetani, rabies virus, antivenom (after pathogen enters the body, these are injected)
tonsils
- Have specialised cells called microcells that can trap antigens and present them to macrophages or dendritic cells [APCs] which will then engulf them and take them to the lymph nodes 7 present them to the B & T lymphocytes
infection vs disease
Infection is the invasion and growth of a pathogen in the body
Disease is a condition that impairs the normal functioning of an organ, structure or system of an organism
how does a virus hijack a cell
- Virus adheres and inject viral nucleic acid or is taken up by cell.
- Viral nucleic acid moves to nucleus where it is transcribed.
- Viral mRNA is then translated (USES CELL’S ORGANELLES TO REPRODUCE)
- Viral protein is then packaged
- cell bursts releasing the viruses