bio - unit 3 aos 3

7A - antigens

• antigens - molecules that are recognized by the immune system, usually found on the surface of cells or pathogens.

  • self antigens - originate inside the body + are found on the surface of cells. they mark the cells of an organism as ‘self’, the immune system recognizes them as their own → no immune response is initiated

  • non-self antigens - originates outside the body. found on the surface of foreign cells or viruses. the immune system recognizes these as ‘non-self’ (foreign) → immune response is initiated.

7A - MHC markers

• in humans, self antigens take the form of MHC (Major Histocompatibility Complex) proteins. they are a group of proteins that are made in the cell and embedded into the membrane of all self-cells

  • class I MHC markers - present on the surface of all body cells that have a nucleus (all except red blood cells).

  • class II MHC markers - present on the surface of antigen-presenting cells (only macrophages and B Cells).

• MHC markers show a high degree of variability between individuals → enables the immune system to distinguish self from non-self material.

• this is because there are 6 main gene loci on our chromosomes that code for MHC markers. each person inherits 2 alleles for each gene locus, and each gene has many possible alleles, (ex. HLA-A has 350) → very unlikely that two individuals have same combination of alleles + therefore very unlikely two individuals have same type of MHC markers. genes:

  • HLA-A - class I

  • HLA-B - class I

  • HLAC - class I

  • HLA-DP - class II

  • HLA-DQ - class II

  • HLA-DR - class II

7A - malfunctions involving antigens

• autoimmune disease - if immune system incorrectly recognize self antigens as non-self antigens → immune system attacks self-cells

• allergies - an overreaction to the presence of an allergen. allergens are antigens that the immune system recognises as non-self, even though they are non-pathogenic and harmless. this unwarranted immune response is called an allergic reaction.

7A - pathogens

• pathogens - sources of non-self antigens that can cause disease. toxins that some pathogens secrete can also act as antigens.

  • cellular pathogens - living organisms with a cellular structure

    • bacteria

    • fungi

    • protozoa

    • nematodes (worms)

  • non-cellular pathogens - don’t have a cellular structure + are non-living

    • DNA viruses

    • RNA viruses

    • prions

7A - cellular pathogen - bacteria

• bacteria - prokaryotic, unicellular organisms that reproduce asexually through binary fission. only some are pathogenic.

• bacteria shapes

  • bacilli - rod shaped

  • cocci - ball shaped

  • spirilli - spiral shaped

• some bacteria have a protective capsule that prevents the bacteria being recognised by the immune system + engulfed by macrophages

• ex. Clostridium tetani causing tetanus

7A - how bacteria cause harm

• pathogenic bacteria - live outside the organism’s cells.

  • most pathogenic bacteria produce toxins to damage/kill cells.

    • exotoxins - secreted by living bacteria and spread through the body

    • endotoxins - part of the cell wall of gram-negative bacteria and are released when bacteria die

  • some bacteria reproduce so rapidly that they crowd other cells

  • some bacteria kill cells outright.

7A - bacteria classification

• gram staining - if bacteria cells have peptidoglycan in cell wall, they are gram positive, and become stained purple. if bacteria cells have lPS, they are gram negative, and become stained pink.

7A - antibiotics

• antibiotics - medications that destroy or slow down the growth of bacteria + are specific for the bacteria. they recognise the cell wall of bacteria.

• antibiotic resistance - however, bacteria can evolve to develop resistance to antibiotics. this can happen quickly as bacteria divide rapidly (in 20 minutes). there are many antibiotic resistance mechanisms.

7A - cellular pathogen - fungi

• fungi - eukaryotic, uni/multi-cellular organisms that reproduce both asexually and sexually, through spore formation. contain long branching filaments called hyphae.

• ex. yeasts, molds. thrush, ringworm

7A - cellular pathogen - worms

• worms - eukaryotic, multicellular invertebrate parasites that reproduce sexually.

• ex. tapeworm

7A - cellular pathogen - protozoa

• protozoa - eukaryotic, unicellular pathogens that reproduce both asexually and sexually. most protists are spread by vectors. ex. plasmodium protist which causes malaria is spread by mosquitoes

• ex. Plasmodium causing malaria

7A - non-cellular pathogen - viruses

• viruses - non-living, non-cellular pathogens composed of a nucleic acid (DNA or RNA) within a protein coat (capsid) + sometimes lipid + protein envelope which protect the nucleic acid. proteins on capsid or envelope. viruses have no metabolic activity + can’t reproduce independently, but contains genetic material that encodes proteins.

• replication - they lack the structures required to reproduce independently → to replicate, they must take over a host cell. viruses have preferred target cells that they enter + replicate in. (more later)

• viruses cause disease by

  • infecting target cells + disrupting their normal function. + direct damage to cells/death → lead to symptoms

  • some DNA viruses can alter the DNA of host cells, leading to the development of cancers

• viruses are continually evolving, and crossing species barriers

• ex. influenzea virus (causes flu), ebola virus (causes ebola)

7A - virus infection

1. attachment - virus attaches to host cell. specific viral proteins detect + attach to specific receptor proteins on the membrane of the target host cell. (virus only affects some cells in the body bc only some cells have the specific receptor).

2. entry - after attachment, virus breaches plasma membrane. three types:

   • membrane fusion - if a virus has an envelope, it can use a protein to puncture the cell membrane, allowing the envelope to fuse with the membrane → capsid enters cell → capsid breaks down by enzyme action, releasing viral genome

   • endocytosis - if a virus doesn’t have an envelope, it can become engulfed in a vesicle by the membrane → virus enetrs through endocytosis → virus exits vesicle → capsid breaks down by enzyme action, releasing viral genome

   • genetic injection - after attachment, some viruses simply inject the viral genome into the cytoplasm of the cell, leaving the rest of the viral structure outside the cell.

3. replication - the host cell’s machinery is taken over, using the inserted viral genome, begins genome replication + protein expression → lots of viral nucleic acids + proteins produced. host cell uses all it’s energy +it’s own amino acids.

4. assembly - viral particles produced are assembled into new viruses.

5. release - assembled viral particles exit the host cell, and continue to infect more cells. three ways:

   • cell lysis - host cell bursts, releasing all viral particles. cell membrane is left ruptured.

   • budding - virus pushes through host cell’s plasma membrane, which is how enveloped viruses aquire their lipid envelope.

   • exocytosis - viruses are packaged into a vesicle, transported to the membrane + exported through exocytosis

7A - plant viruses

• plant viruses are usually transmitted using a vector (usually an insect that feeds on the plant)

• due to the cell wall, a plant virus enters cells using plasmodesmata (channel between cells)

• plants only have one way of dealing with viruses + infections - preventing the virus from entering the plant. ex. waxy cuticle + chemicals. once virus enters, plant tries to prevent spread by dropping leaf

7A - non-cellular pathogen - prions

• prions - non-living, non-cellular pathogens. misfolded proteins that can induce nearby normal proteins to become misfolded. they contain no genetic material.

• prion disease - the protein PrP^c is found in nerve cells, and it’s normal form is not harmful. however, it can spontaneously convert into a different structure. this misfolding turns the protein into the prion PrP^Sc. when these prions interact with normal ones, they convert them into misfolded ones. if this infection spreads, you get prion disease.

• prion disease - all prion diseases result in:

  • a long incubation time (measured in years)

  • a progressive deterioration of brain function resulting in fatality

  • changes in the brain including loss of neurons and development of lesions (holes)

  • there is no immune system response to prion disease, they are also non-treatable and result in death.

7A - infections + diseases

• infection - when a pathogen enters the body and begins to multiply

• disease - when an infection affects the normal function of an organism. only labelled a disease once there are symptoms

  • non-communicable/non-infectious - cannot be transmitted from one individual to another. ex. diabetes, heart disease, most cancers, multiple sclerosis, arthritis

  • communicable/infectious - transmitted from one individual to another

• epidemic - rapid spread of infectious disease within a single population

• pandemic - an outbreak of infectious disease over a wide geographical area, affecting a large number of people

• endemic - present in the population at a constant low level

• host - any organism containing the pathogen

• vector - a living organism that carries and transmits a pathogen from an infected individual to another individual. ex. mosquito, tick

7B - immune system

• immune system - the cells and tissues involved in resistance to infection. the immune system identifies the difference between its own cells (self antigens) and foreign cells + molecules of pathogens (non-self antigens)

  • innate immune system - composed of non-specific defences and responses + doesn’t keep a memory of pathogens. responds to injury + antigens quickly. includes first + second line of defence

  • adaptive immune system - composed of specific defences and responses + keeps a memory of specific pathogens → response to re-infection is faster + larger. includes third line of defence.

• immunity - resistance to infectious disease

7B - the first line of defence

• the first line of defence - consists of 3 types of barriers that prevent pathogens from entering the body. part of the innate immune system.

  • physical barriers - physically block pathogens from entering the body

  • chemical barriers - chemicals that destroy pathogens or inhibit their growth

  • microbiota barriers - competes with pathogen for resources and space, preventing pathogen growth

• plants only have the first line of defence

7B - physical barriers

• physical barriers - physically prevent the entry of pathogens. entry = crossing a membrane

• examples

  • animals

  • mucous membranes + hairs line respiratory tract that trap foreign material, + cilia move pathogen to throat to be swallowed + destroyed

  • intact skin - the outer layer of our skin is dead. this means when viruses land on the dead outer surface of the skin and insert their genome, the cells won’t do anything

  • mechanical defences - sneezing, coughing, diarhea, vomiting, flushing action of tears, flushing action of urine

  • plants

  • cellulose cell wall - thick barrier hard for pathogens to penetrate

  • thick bark

  • presence of thorns + trichomes (small hairs) to deter pathogens + insects

  • formation of galls (abnormal outgrowth of tissue) to prevent the spread of infectionb

  • waxy cuticle on leaves - prevents water accumulation (reduces water-based pathogens) and protects epidermal cells from exposure to pathogens

  • closing of stomata to prevent pathogen invasion

7B - chemical barriers

• chemical barriers - inhibit the growth of or destroy pathogens through the production of chemicals

• examples

  • animals

  • presence of enzyme lysozome in tears + saliva which destroys bacterial cell walls, therefore killing bacteria

  • stomach lining cells secrete strong acids to kill pathogenic bacteria that have been swallowed

  • plants

  • production of chemicals (often toxins) ex. defensins - small peptides that are toxic to microbes + fungi

7B - microbiota barriers

• microbiota barriers - the presence of non-pathogenic bacteria ‘normal flora’ that competes with pathogens for resources and space/adhesion sites, limiting pathogen growth

• these bacteria live in a mutualistic relationship with the person, and the immune system has adapted to not respond to them despite being non-self.

• examples

  • animals

  • bacteria in the digestive tract which prevent pathogenic bacteria from growing by outcompeting them for nutrients and space + also secrete antimicrobial chemicals that prevent growth.

  • bacteria on skin

  • plants

  • non-pathogenic bacteria living in and around roots (ex. citronella oil, peppermint oil) form a barrier against pathogens

7C - the second line of defence

• second line of defence - part of the innate immune system. consists of non-specific responses to pathogens which have entered the body + injury via a variety of cells + molecules.

  • cellular responses

    • phagocytosis

    • natural killer cells (degranulation)

    • eosinophils

    • mast cells

  • non-cellular responses

    • interferons

    • complement proteins

  • both

    • inflammatory response → interactions with third line of defence

7C - leukocytes

• leukocytes (white blood cells) - all immune cells are a type of leukocyte. leukocytes are responsible for protecting the body against pathogens and foreign material. they are found in lymph, blood, lymphatic organs and tissues, and derived from multipotent stems cells in the bone marrow. types to know:

  • mast cell

  • eosinophil

  • natural killer cell

  • phagocytes

    • dendritic cell

    • macrophage

    • neutrophil

7C - mast cells

7C - phagocytes

• phagocytes - leukocytes that engage in phagocytosis, a strategy used to attack extracellular pathogens in tissue fluid or blood. phagocytes include:

  • neutrophils

  • macrophages

  • dendritic cells

• cytokines - phagocytes also release signalling molecules to communicate with the immune system. ex. cytokine, helps protect against pathogens + guide immune cells to site of infection or injury

7C - cellular response - phagocytosis

• phagocytosis - a strategy used to attack extracellular (in space outside cells) pathogens in tissue fluid or blood.

• for phagocytosis to occur, the pathogen must be recognised as non-self. phagocytes have pattern recognition receptors that are complimentary in shape to things they recognise such as: LPS of cell wall in gram negative bacteria, acid on cell wall of gram positive bacteria, glycoproteins on virus envelope, flagella (tail) in bacteria

process

1. pattern recognition receptors on membrane of phagocyte recognise an extracellular pathogen + engulf it through out-foldings of membrane

2. pathogen is completely enclosed in vesicle (phagosome)

3. lysosomes fuse with the vesicle, releasing their toxic chemicals

4. pathogen is digested by lysosome’s chemicals

5. indigestible material is released from the phagocyte by exocytosis

6. if dendritic cell, takes sample, and presents it’s antigens → activates third line of defence

noncellular response - complement system

• complement system - part of the humoral innate immune system. consists of about 30 proteins made in the liver that circulate in the blood in an inactive form. they are activated when they contact bacteria.

• 3 different functions of complement system

  1. opsonisation of bacteria - label bacteria for phagocytes

  2. chemotaxis - complement proteins are activated by contact with bacteria. this involved cleavage of the complement protein. these then diffuse from the bacteria, creating a trail of signals (chemoattractants) which immune cells detect + follow to find the bacteria

  3. lysis of bacteria - membrane attack complex (MAC) is formed from different complement proteins combining together. this puts a hole in the bacteria membrane causing the bacteria to undergo lysis.

cytotoxic cells - eosinophils

• eosinophils contain granules with cytotoxic chemicals that target parasites (ex. worms) that are too large for phagocytosis

• the granules are released when the eosinophil encounters a parasite

• also have a role un allergic reactions and inflammation response

cytotoxic cells - natural killer (NK) cells

• natural killer cells target unhealthy body cells (any cell recognised as pathogen infected or cancerous)

• unhealthy cells lose their MHC I markers. they can no longer be recognised as self

• induce apoptosis, natural cells process

• 2 functions - detecting + apoptosing intracellular viruses + tumour cells

• NK cells check body cells all the time. the NK cell has two receptors which detect wether the cell is healthy or unhealthy

  • healthy - the activating receptor on the NK cell binds to its receptor on the healthy cell + the MHC I marker on the healthy cell binds to the inhibitory receptor on the NK cell. the cell is recognised as ‘self’ and no activation of the NK cell occurs

  • unhealthy - the activating receptor on the NK cell binds to its receptor on the infected cell + the MHC I marker on the infected cell is damaged/missing and cannot bind to the inhibitory receptor on the NK cell. the cell is recognised as ‘non-self’ → starts apoptosis pathway

NK cells - intracellular viruses

• if unhealthy cell detected - the NK cell releases cytokines (to attract phagocytes), perforin and granzymes which enter the cell and cause apoptosis (programmed cell death).

NK cells - tumour cells

• NK cells can also detect cancerous cells and apoptose them. this is because Tumour cells and virally infected cells often overexpress activating ligands on their surface

interferons

• interferons - interfere with virus replication. if NK cell can’t make it in time, cells infected with virus particles secrete interferons which are recieved by neighbouring cells. interferons are a cytokine. interferons act as a signal to nearby cells to prepare in advance for possible viral infection.

• if a cell is going to die from a virus infection and NK cells can’t make it in time, the infected cell will send interferons (type of cytokine) to help neighbouring cells, and interfere with how they function.

signals fir nearby cells

• shut down protein synthesis

• attract NK cells

• change palsma membrane

• tell cells to undergo apotposis

the inflammation response

• when cells and molecules work together, get an inflammation response\

• an early and rapid response to infection (ex. abcteria entering through an open cut)

• usually a short-term response localised to the site of pathogen entry.

• 4 symptoms of inflammation - redness, heat, swelling, pain

• also a response to cell damage by thermal burns, sunburn, frostbite, acid spills onto skin

• purpose

  • to localise and prevent spread of pathogen

  • recruit all cells + molecules needed to eliminate pathogen + remove damaged tissue..

  • + repair damaged tissue

stages

1. vascular stage

2. cellular stage

3. resolution stage

cytokines

• damaged cells release cytokines (general term, many types) that

• cytokines are detected by mast cells, which release histamine

• examples

  • interferons

histamine

functions

• results in vasodilation, so blood flow increases → redness + heat

• results in increased capillary permeability, so fluids enter site of inflammation → swelling + pain

1. vascular stage

• dilation of blood cells

• increased permeability of local capillaries

2. cellular stage

• escape of immune cells from capillaries. dilation of capillaries allows neutrophils to get through capillaries into tissue

• migration of neutrophils to infection site. attracted by cytokines released by damaged cells

• macrophages from nearby tissues arrive next. macrophages release cytokiunes and histaminee to attract more phagocytosise

3. resolution stage

7C - identifying extracellular pathogens

7C - mast cell

• mast cell -

7D - the third line of defence

• adaptive immunity - initiated when an antigen (on a MHC II marker of an antigen presenting cell) is presented to a T helper cell. initiated when innate immunity fails to stop an infection

• slower than innate immunity

• specific to pathogen

• a long-lasting memory is made so if re-infection occurs, the response is quicker.

• involves a humoral immune response + cell mediated immune response

7D - cells of adaptive immune system

• T helper cells

  • humeral

    • Naive B cells

    • B memory cells

    • Plasma cells (Antibodies)

  • cell medicated /cellular response

    • Naïve T cells

    • helper T cells

    • Cytotoxic T cells

    • memory T cells

how B cells vs T cells made

• B cells - mature in bone marrow → matures in bone marrow → goes to lymph nodes

• T cells - T cell precursors are made in bone marrow → migrate to thymus to mature into naiive T cells → migrate to lymph nodes

• lymph nodes - nodules of the lymphatic system where immune cells accumulate

cell mediated response

• T cells are made in bone marrow and mature into naive T cells in the thymus, which then travel to the lymph nodes. every naïve T cell has a different shaped receptor, (randomly made).

• antigen presenting cells - cells which display non-self antigens on their surface MHC II markers, they then bring them to the lymph node, to present the antigens to naiive T cells. dendritic cells and macrophages display antigens after phagocytosis. B cells are also APC.

• adaptive immunity is initiated when the antigens on the APC are perfectly complementary to the receptors of a T helper cell in the lymph nodes. the T helper cell releases cytokines, and then starts dividing (no longer naive), to expand that particular cell type.

7D - stages of cell mediated immune response

• APCs - when pathogens at the site of infection are recognised as non-self, they can be phagocytosed by dendritic cells, macrophages (or B cells?); which are antigen presenting cells. after phagocytosis, the phagocyte will present antigens from the consumed pathogen on their MHC II markers. this APC then travels to a lymph node to interact with the adaptive immune system.

• T cells - T cells are made in bone marrow and mature into naϊve T cells in the thymus, which then travel to the lymph nodes. naïve T cells are always being made, and each has a different shaped receptor, (randomly made).

1. APCs present the antigen to the naϊve T cell population at the lymph nodes.

2. when a naϊve T helper (Th) cell with a receptor that is complementary to the antigen is found, it’s receptor binds to the antigen on the APC → the naϊve Th cell releases cytokines, which activates itself + Tc cells, and produces lots more identical Th cells (clonal expansion), to increase chances…

3. when the naϊve cytotoxic T (Tc) cell with a receptor complementary to the antigen is found (which can take several days), it’s receptor binds to the antigen on the APC. this first naϊve Tc cell does nothing once binded. it must be activated, which is done when a Th cell binds to the same APC, and secretes cytokines (explains why Th cells undergo clonal expansion, to increase chances of binding to the APC with the Tc cell).

4. When the Tc cell + a Th cell binds to the APC, the Tc cell is activated, and undergoes clonal expansion, producing more Tc cells (which no longer require activation by Th cells) and also memory T cells.

5. Tc cells travel to the site of infection. there they recognise infected host cells (most often virally infected), due to Tc’s receptor complementary to the antigen presented on pathogen’s MHC class I marker. Tc cell induces apoptosis of infected cells through the release of perforin and granzyme, or by releasing death ligand.

6. memory T cells remain in the lymph nodes, and are activated if they bind to the APC in the future, quickly activating adaptive immune system and producing lots of Tc cells.

7D - humeral response

• 2 ways

  • APC (which has phagocytosed pathogen + displaying it’s antigens on the MHC II markers) goes to the lymph nodes, presenting the antigens to naive B cells. it binds to the B cell with complementary receptors. T helper cells activate the B cell (using cytokines) → B cells then undergo clonal expansion + differentiation

  • when there is enough antigen buildup in the body, pathogens themselves (presenting antigens on their class I markers) can find their way to naive B cells in the lymph nodes, and binds. the B cell acts as an APC. it phagocytoses the pathogen, and displays it’s antigens on their MHC II markers. the B cells get activated by Th cells → B cells then undergo clonal expansion + differentiation

• activation of a B cell results in:

  • producing plasma cells - plasma cells stay in the lymph nodes, but they produce specific antibodies that are released from the lymph node and travel around the body, and bind to the antigen.

  • producing Memory B cells - stay in the lymph node. activated if they bind to the antigen in the future.

antibodies

• antibodies are proteins. they are made from more than one amino acid chain, they contain primary, secondary, tertiary, quaternary and quintenary structures

• each type of antibody is made from a selected plasma cell

• each antibody has a unique antigen-binding site that can recognize and bind to just one specific antigen.

functions of antibodies

• neutralisation - bind to antigens on pathogens and block pathogen receptors from attaching to and infecting body cells

• agglutination - antibodies bind together with antigens forming antibody-antigen complexes, to hold them in place, so phagocytes can easily come and phagocytose them all

• immobilisation - the antibodiy-antigen complexes formed have restricted movement through the body

• opsonisation

• activation of compliment proteins

antibody structure

• variable region - site where specific antigen binds. on an antibody, the variable region on each arm is the same.

• constant regions -

7D - classes of antibodies

• IgG - breastmilk, placenta

• IgE - allergies

• IgD

• IgM

• IgA

7D - stages of humeral response

allergies

• allergy - a substance in the environment that is harmless to most people but causes some people’s immune systems to react abnormally

• allergic responses involve both specific and non-specific immune systems

• allergen - a substance that causes an allergic reaction. many allergens are small, highly soluble proteins present on the surface of dry particles, food substances, pharmaceutical drugs and plant products

the allergic reaction

sensitisation

1. the body is exposed to a potential allergen. ex, you inhale pollen and it lodges in the mucous membrane of the airway

2. cells of the immune system identify antigens on this pollen as non-self and an immune response is activated

3. specific antibodies against the antigens are produced by plasma cells

4. the IgE antibodies on allergen attach to surface receptors of mast cells. these mast cells are primed with antibody. the next exposure to the allergen will cause an allergic reaction.

activation of mast cells

• next exposure to the allergen results in primed mast cells (have IgG antibodies on surface)

  • binding to the allergen and

  • causing degranulation of mast cells (releasing of chemical mediators, including histamine)

7E - the lymphatic system

• the lymohatic system is a transport network that:

  • transprots immune cells throughout the body

  • is where antigen recognition by lymphocytes occurs

  • returns fluid that seeps out of the circulatory system back into blood

  • provides a place for lymphocytes to mature

• primary lymphoid oragns - bone marrow and thymus. sites where lymphocytes (B cells and T cells) mature

• secondary lymphoid oragns - lymph nodes and spleen. site where mature B cells and T cells are activated by meeting complementary antigens.

8A - specific immunity

• specific immunity - using antibodies to resist specific diseases. antibodies do neutralisation, aggutiration, opsinisation.

  • active immunity - antibodies produced in the person’s body. B cells, plasma, B memory. lifelong protection against antigen.

    • natural active - pathogens enter the body naturally

    • artificial active - the pathogen is introduced into the body as a vaccine

  • passive immunity - antibodies from another organism enter the person’s body.

    • natural passive - antibodies enter a person naturally. ex, antibodies cross the placenta into the fetus

    • artificial passive - antibodies are injected into a person

8A - aquiring immunity

active immunity - Creates memory cells for long-lasting protection.

passive immunity - Immediate protection, but no memory.

vaccines - Contain inactivated/weakened pathogens or antigenic fragments to stimulate adaptive immunity.

8B - emergence of pathogens

8C - controlling pathogen spread

8D - immunotherapy