Immunology Flashcards
Immunology
The study of the immune system - an important part of the body’s response to infection.
‘Immunology is the study of the immune system and is a very important branch of the medical and biological sciences. The immune system protects us from infection through various lines of defence. If the
immune system is not functioning as it should, it can result in disease, such as autoimmunity, allergy and
cancer.’
The Nature of Infection
Infection describes when an organism replicates inside the body, resulting in disease.
Infection can occur within cells (e.g. viruses), whilst some replicate in organs (e.g. the gut)
Causative Agents of Infection (and Examples of Resulting Diseases)
Pathogen Definition:
‘Any small organism, such as a virus or a bacterium that can cause disease’.
Pathogens: Bacteria, Viruses, Fungi, Prions, Protoctists and Parasites
Bacteria
Bacteria are prokaryotes and often causes illness due to the toxins they produce as a result of their metabolism. Bacterial infections are treated by antibiotics, but bacteria are becoming increasingly resistant to antibiotics.
Examples:
• Chlamydia
• Gonorrhoea
• Tuberculosis
Viruses
Viruses are akaryotes because they are not proper cells. Many treatments that work against cellular pathogens will not work with viruses. Antibiotics are not effective against viral infections. SARS-CoV-2, the coronavirus that causes COVID-19, has recently become the best known virus.
Examples:
• Common Cold
• Mumps
• Measles
Fungi
Fungal infections can be from unicellular fungi (e.g. yeast) or multicellular fungi. Other fungal skin infections include toenail fungus and athlete’s foot. Fungal infections are known as mycoses in medicine.
Example:
• Yeast Infection (Thrush)
Prions
Prions are non-living pathogenic proteins which can act as an infectious organism. The mutant form of a prion protein, when ingested, can cause normal prion proteins to change shape. This causes damage to the nervous system and eventual death.
Example:
• Creudtzfeldt-Jakob disease (CJD)
Protoctists
Protoctists are eukaryotes and usually unicellular (but some simple multicellular forms exist). Examples include protozoa, algae and slime moulds. Some varieties causes diseases.
Example:
• Malaria
Don’t confuse the pathogen (Plasmodium) with the Anopheles mosquito that transmits the pathogen
Parasites
Parasites are organisms which live off another organism either external (ectoparasites) or internal (endoparasites). They can be multicellular (e.g. nematode worms which infect the digestive system). They can also include protozoa (e.g. causing toxoplasmosis).
Example:
• Toxoplasmosis
Toxoplasmosis is caused by Toxoplasma gondii, a parasitic protoctist. Many multicellular parasites can also cause infections, particularly in developing countries
Glossary terms in the innate immune system
• Self/Non self
• Major Histocompatibility complex/ Human leukocyte antigen (MHC/HLA)
• Antigen
• Inflammation
• Mast Cells
• Histamine, Cytokines
• Vascular permeability
• T regulatory cells (Tregs)
• Phagocytosis
• Macrophages and Neutrophils and dendritic cells
• Phagolysosome
• Antigen Presenting Cells (APC)
The immune system
Our bodies are really well prepared to prevent pathogens from gaining entry – this is non specific immunity.
Non specific immunity includes:
• Skin – a barrier to penetration
• Stomach acid – ‘disinfects’ food through destruction of pathogens
• Mucus – to prevent pathogens from attaching to cells
• Phagocytosis – white blood cells that engulf and destroys pathogens
• Fever – creates conditions that are not favourable for growth
• Inflammation – brings white blood cells to the site of injury or infection
• Lysozyme- antimicrobial enzyme found in tears, salvia, human milk and mucus
• Complement system – proteins in the blood that to alert your immune system
How do we know what is foreign in the body?
• Our bodies do have a mechanism that allows them to recognise our own cells and molecules (self) and foreign matter (non self)
• Each cell in our body has specific proteins on its surface that show the immune system that they belong in our bodies - Human leukocyte antigens (HLA) – also known as the Major Histocompatibility Complex – MHC).
• Your HLAs are genetically determined and are unique to each individual - they are coded for on chromosome 6 (224 genes) so we can recognise self or non self material and respond
HLA genes in practice – transplantation
• The HLA genes determine an individual’s tissue type, which varies from person to person as HLA genes have many possible variants.
• If you require a transplantation, tests are carried out to try and get a perfect match, or as close as possible match, between the HLA genes of the donor and those of the recipient to reduce the risk of the
transplanted organ being rejected.
• Individual HLA genes are inherited from your parents. Variants in the HLA genes are associated with more than 100 diseases, including infectious diseases like HIV, and some cancers.
• Some autoimmune conditions, including diabetes and multiple sclerosis, are also linked to specific variations in the HLA
The basics of immunity
• The function of the immune system to allow the body to recognise the difference between self and non self material.
• Any molecule that the body is able to identify as non self is known as an antigen.
• Antigens stimulate an immune response
• *In autoimmune conditions the body mistakenly recognises self material as an antigen so produces an immune response as well
Inflammation and immunity
• One of the first responses to an injury is inflammation. The inflammatory response (inflammation) occurs when tissues are injured by bacteria, trauma, toxins, heat, or any other cause.
1.) Mast cells secrete histamine that is a cell signalling compound that causes other cells to react
2.)Histamine increases blood flow in capillaries and causes them to become permeable (vascular permeability) so fluid (causing swelling) and leukocytes leave the capillary and go to the site of injury
3.) Histamine causes cells to release other chemicals such as cytokines which stimulate the immune system and promote phagocytosis and other immune responses
4.) T regulatory cells stop the immune response when it is no longer needed which removes these symptoms so the swelling, redness and temperature decreases at the site of injury (negative feedback loop).
Types of cells
Types of leukocytes can carry out phagocytosis and secrete chemicals that increase immune activity;
• Neutrophils – Short lived - destroy pathogens completely then die (pus)
• Macrophages – long lived - display the antigens of the pathogen on the surface on the MHC – this is known as an antigen producing cell
• Dendritic cells – ingested material is taken to lymph nodes and then display the antigens of the pathogen on the surface on the MHC – this is known as an antigen producing cell
Phagocytosis – phagocytes and macrophages
• If the physical or chemical barrier to infection in breached then the white blood cells are next in line.
There are two types – phagocytes and lymphocytes.
- Phagocytes track the pathogen through attractants such as chemicals or dead/damaged cells –
chemotaxis - Phagocytes have receptors on their surface that attach to the pathogen
- Phagocytes then ingest (through endocytosis) forming a phagosome inside the cell, this merges with a
lysosome creating a phagolysosome containing lysozymes that hydrolyse the pathogens cells wall and
destroy the pathogen. - The soluble products and dissolved in the cytoplasm of the phagocyte and any digestion products are expelled from the cell through exocytosis.
- In some phagocytes – macrophages - the MHC is then presented on the surface of the phagocyte.
These cells are known as antigen presenting cells. (APC)
Extra knowledge
• Pathogens that invade the body may be engulfed by cells that carry out Phagocytosis. One types of cell that can do this is the Macrophages The pathogen is engulfed through the process of endocytosis and forms a vesicle called a phagosome.
• The vesicle called the phagosome the merges with another vesicle called the lysosome, forming a new vesicle called a harose the pathose destroy cel that arme then neutrophils then die and form puss.
• However, macrophages don’t destroy the pathogen completely they present the antigen on its surface in a structure called the Major Histocompatibility complex which then triggers other parts of the immune system.
Key terms in the specific immune system
• Lymphocytes
• T cells – two main types: T helper (TH), T cytotoxic/killer (TC/K)
• T cell receptors (TCR)
• Activated TH cell
• Cell mediated immunity
• B cells – two main types: Plasma cells, memory cells
• B cell receptors (BCR)
• Activated B cell
• Humoral immunity
• Antibody
• Perforin
• immunoglobulins
Specific immunity
• There are two types of lymphocyte involved in specific response.
T Cells:
• These mature in the Thymus gland and are associated with cell mediated immunity which involved body cells.
• The two main types are T Helper (TH) and T cytotoxic/killer cells (TC/K).
• T helper cells have CD4 receptors
• T cytotoxic cells have CD8 receptors
• Their role is also to reactivate B cells after activation by a specific pathogen in the past
B cells:
• These mature in the bone marrow and are associated with humoral immunity (antibodies that are present in body fluids or plasma).
• The majority form clones of plasma cells that secrete antibodies into the into the blood but some form memory cells that provide the secondary immune response
Humoral immunity – B cells
• This type of immunity involves antibodies and as they are soluble in water they travel in the humours (fluids of the body) – lymph and blood plasma.
• B cells with the appropriate antibodies for many pathogens are present from birth (or through exposure – naturally through infection or artificial through vaccination
• B cells are specific to each antigen and it can take a long time to match the right antibody to the pathogen (like a jigsaw) so it is not as quick as cell mediated immunity which is turn is not as quick as inflammation and phagocytosis
B cell action
• Just like T cells, B cells can also be activated but by bonding to antigens that have not been processed.
• However they can only bond with antigens that they have a specific receptor for.
• This is different to T cells who need the antigen processed by an APC first.
• Once activated they have create memory cells and plasma cells
Following B cell activation
The B Cell clones then develop into one of two types of cell:
Plasma cells:
• These cells secrete antibodies into the blood plasma which lead to the destruction of the antigen in different ways. These cells produce thousands of antibodies a second but only live for a few days. This is the primary immune response.
Memory cells:
• Some of the B cells (just like T cells) become memory cells that do not produce antibodies but continue to stay in the body for decades. When they are activated they rapidly produce plasma cells and more memory cells and this provides the secondary immune response
Cell-mediated immune response
- Pathogens are engulfed and hydrolysed by a Macrophage and present the pathogens MHC on its surface.
- CD4 or CD8 Receptors on a specific T Cells bind to the macrophage presenting the antigens
- This attachment activates the T cells to divide rapidly by mitosis and form a clone of genetically identical cells. The cytokines are proteins that activate other T cells
- The cloned T cells then:
- Can become a memory cell ready to combat the specific pathogen again with the matching CD4 receptor.
- Stimulates B cells to divide and secrete their antibodies.
- Stimulates phagocytosis by further phagocytes.
- Activates cytotoxic T cells (TC cells) or killer T cells (TK cells) that produce a protein called perforin that makes holes in the cell membrane so destroys infected cells
Humoral immunity
- When an antigen enters the body there will be a B cell for that antigen that engulfs (though endocytosis) the pathogen because it has a BCR receptor on its surface that matches the antigen so binds.
- The B cell then presents the antigen on its surface (APC) where T helper cells bind to it and activate it.
- The B cell then divides by mitosis and form a clone of identical B cells that then produce the antibody specific to that antigen (plasma cells) and memory cells that support secondary immune response
Antibodies in more detail
• Antibodies are proteins produced by B lymphocytes in response to a specific antigen which binds with the antigen aiding its destruction.
• They consist of four polypeptide chains and are Y shaped.
• They are called immunoglobulins (There are five types - IgG, IgM, IgA, IgD, and IgE) – the mix and levels can be used in diagnostic tests
This occurs in four main ways:
1. Agglutination – causes pathogens to stick together for phagocytes
2. Complement activation – destroy plasma membrane of the pathogen
3. Toxin neutralisation – bind to toxins preventing them affecting cells
4. Opsonisation – binding causes them to be consumed to phagocytes
Antibodies structure
• The four polypeptides have a constant region that is the same for all antibodies and a variable region that is specific to each antigen.
• This produces the antigen-antibody complex.
• Each binding site is a specitic 3D shape that binds directly to the 3D shape of the antigen.
• Mutations can affect the antigen shape so previous antibodies may not fit so well or at all reducing immunity.
Antibody types of functions
IgA-Found in body secretions such as breast milk, and salvia –prevents antigens crossing epithelial cells crossing into deeper tissues
IgD-Made by B cells and displayed on their surfaces. Antigens bind here which activates the B cell
IgE-Found on cell membranes and activate the inflammatory response
IgG-Largest and most common – can cross placenta and attacks many pathogens
IgM-Produced in large amounts in the primary response – activates the compliment system (20 proteins in blood that activate when present of a APC to attract immune cells and also destroy bacterial cells walls)
Vaccination
• Vaccines contains antigens that trigger immunity but do not cause disease.
• Immunity - the ability of the body to resist an infection by a pathogen.
• So vaccination is the deliberate administration of antigens that have been made harmless after being obtained by from a disease causing pathogen.
• This is artificial active immunity as opposed to being naturally exposed which is natural active immunity. We can also use mRNA vaccines too
• Passive immunity is when the person does not make the antibodies themselves so transfusion or
Memory cells and immunity
• Long lived memory B cells provide longer term immunity because they are retained in the lymph nodes after the infection has passed.
• By producing antibodies more rapidly and in greater numbers after the primary response so a stronger response is mounted to the pathogen on re- exposure and less of the disease develops
Immunological memory from B cells
• This is the reason why catching certain diseases twice is so unlikely.
• For example, there is only one strain of the virus that causes measles, and each time someone is re infected with this virus, there is a very fast secondary immune response so they do not get ill.
• However, some infections such as the common cold and influenza are caused by viruses that are constantly developing into new strains.
• As each strain has different antigens, the primary immune response (during which we often become ill) must be carried out each time before immunity can be achieved
Antimicrobial resistance
Definition - ability of a microorganism to survive exposure to antimicrobial agents (for example antibiotics)
‘Antibiotic stewardship’ is the effort to measure and improve how antibiotics are prescribed by clinicians and used by patients. Improving antibiotic prescribing and use is critical to effectively treat infections, protect patients from harms caused by unnecessary antibiotic use, and combat antibiotic resistance’
Impact of antimicrobial resistance:
• overuse of antibiotics has reduced the overall effectiveness
• overuse has led to the emergence of new strains of microorganisms increase in super bugs (for example MRSA and Clostridium difficile)
How do bacteria become resistant?
• A person become ill and is prescribed an antibiotic
• They fail to complete the course or complete the course but remain ill (so the most hardy bacteria remain and replicate)
• They return to their GP and are prescribed more of the same antibiotic
• The strongest bacteria left in the body are less effected by the antibiotic or through mutation during replication have acquired resistance to the antibiotic so continue to replicate in the presence of an antibiotic.
• Plasmids within bacterial cells can carry the genes for resistance which are they passed between generations.
• If they pass the resistant bacteria onto someone else the bacteria will continue to be resistant to that antibiotic
