Immunity Flashcards
What is innate immunity?
Innate immunity is the rapid response to infection (within hours). It is a fixed response with limited specificity to pathogens
Which cells are involved in innate immunity?
Neutrophils, eosinophils, basophils (granulocytes), Macrophages (monocytes)
What makes up the innate immune response?
Barriers (skin), antimicrobial peptides and the complement system
Describe the complement proteins
They are within the bloodstream as soluble proteins. There is 30 different complement proteins which are inactive until they are in the presence of a pathogen
Describe the classical pathway of the complement system
The classical pathway is antibody dependant/independant. Complement proteins are released from the liver into the bloodstream, and when a pathogen is presence this causes a cascade of activation, which leads to complement proteins binding to antigens on the pathogen surface (opsonization), which allows for the pathogen to be engulfed by a macrophage.
What is the alternative pathway?
a classical dependent/totally independent pathway. Complement proteins Form a Membrane attack complex and fluids leak from the surface of a pathogen, leading to lysis of the pathogen.
What makes up the induced innate immune response?
phagocytosis, cytokines, toll like receptors and natural killer cells
Describe the function of toll like receptors
Toll like receptors are found in immune cells and are plasma bound receptors which initiate and promote the immune response
Which toll like receptors form dimers?
TLR2&6, TLR2&1
Which toll like receptors do not form dimers
TLR 3,7,8,9
What happens after dimerization?
TLR 2&6 on the outer membrane of immune cells recognise petidoglycans of bacteria and bind together to form a dimer. This activation leads to a cascade of events. Activation of transcription factors.
What are the different transcription factors activated by toll like receptors?
AP-1, IRF, NfKB
What is the function of activator proteins?
Activate genes in DNA to form RNA, which form proteins for cell signalling, which leads to differentiation, proliferation and apoptosis
What is the function of IRF? (interferon regulatory factors)
To activate genes in DNA to produce specific RNA which is translated into interferons. They are produced in response to viral infections. Signal to other cells to up their defence
What is the function of NfKB?
To stimulate genes that transcribe for DNA to make cytokines, which promote inflammation. TNFa induces apoptosis.
What is the difference between the bacterial innate immune response and the viral innate immune response?
Bacteria innate imune response involves different toll like receptors (1,2,4,5,9). Induces phagocytosis (macrophages and neutrophils)
Viral innate immune response involves TLR 3,7,8,9. Interferons, NK cels
What is the function of NK cells?
Natural killer cells are part of the viral immune response. Viral infection triggers interferon response after TLR activation. Interferon drives the proliferation of natural killer cells, which produce cytotoxic effector cells, effector NK cells kill virus infected cells by inducing apoptosis.
What is adaptive immunity?
Specialised response to infection, involving antibodies (B cells and T cells)
Describe the structure of an antibody
Antibodies are secreted from B cell receptors. They are Y shaped, and have a 4 polypeptide chain structure. They have 2 identical light and heavy chains. They have a variable and constant region. The binding of the heavy and light chains produces 6 hypervariable loops, and forms the antigen binding site
How many antigens can one Ig bind?
2
What is the specific function of the IgM antibody?
First antibody to be produced, gives the primary response to infection in defense of tissues and to prevent septicaemia.
What is the specific function of the IgG antibody?
To give the secondary response to infection, which is more specific and stronger. Protects the foetus during pregnancy
What is the specific function of the IgA antibody?
This antibody can be passed on via maternal milk/placenta
What is the specific function of the IgE antibody?
Allergies - activation of mast cells and dendrites
Do antibodies protect against extracellular or intracellular bacteria?
Extracellular, they cannot work against intracellular bacteria as they cannot pass the blood brain barrier
What is are the three different antibody-bacterial functions?
Neutralisation, opsonization and complement activation
What is neutralization?
Antibodies bind to bacterial toxins, to attract the macrophage which leads to the toxins being ingested and destroyed
what is opsonization?
Antibodies bind to bacteria and make it more appealable to the macrophage, which ingests the bacteria and leads to apoptosis
what is Complement activation and what happens to the pathogen?
Complement proteins are activated, which leads to lysis of the pathogen and ingestion by the macrophage
What are the 3 different antibody-antiviral functions?
- Neutralise free virus and prevent entry to cells. Antibodies coat the virus and inhibit attachment
- opsonise to increase phagocytosis
- Activate the complement leading to lysis (holes in the membrane)
When are B cells activated and antibodies produced?
In the presence of an antigen
What happens in the primary response?
Mature B cells in the absence of an antigen leave the lymph tissue and recirculate. Naive B cells encounter an antigen in secondary lymph tissue which leads to specific B cells being activated by helper T cells, which proliferate and differentiate into plasma cells, secreting the IgM antibody and fighting the infection.
When are memory cells produced?
In the primary response
What happens in the secondary response?
Upon the second exposure to the same antigen, memory B cells are rapidly activated and produce a quicker and stronger response to the infection
Describe some features of MHC class 1
MHC class I glycoproteins are present in all nucleated cells. They present antigens that originate from the cytoplasm, presenting 8-10 amino acid peptides. They present the antigen to cytotoxic T cell lymphocytes, bind to CD8 co-receptors on cytotoxic T cells.
Describe some features of MHC class 2
MHC class II glycoproteins are only present on specialised antigen presenting cells, including macrophages that engulf foreign particles, dendritic cells and B cells that produce antibodies. They present antigens that originate outside the cell of foreign bodies. They present 14-18 amino acid peptides to helper t lympocytes and bind to CD4 coreceptor molecules on helper t cells.
What happens in response to MHC class I
Bind to T cell receptors on cytotoxic CD8 cells, which kill infected virus cells
What happens in response to MHC class II
Bind to T cell receptors on CD4 helper t cells and activate them (Th1,2,17,h)
What is the function of TH1?
Activate macrophages and cytotoxic t cells
What is the function of TH2?
Support antibody production particularly class switching to IgE
What is the function of TH17?
Active against extracellular bacteria and funghi
What is the function of TFH
To support B cell maturation, stimulate IgM production during the primary response and support isotype switching during the secondary response.
What is the function of TFH
To support B cell maturation, stimulate IgM production during the primary response and support isotype switching during the secondary response.
What happens on activation of CD8+ T cells
Signals antigen presenting cells to increase co-stimulatory activity, to kill infected cells
What is the difference in the adaptive immune response between bacterial and viral cells?
Bacterial and viral infection have the same B cell response, but in bacterial infection, TH1 and Th17 are produced, whereas viral involves Cytotoxic T cells and TH1 mostly
How can pathogens avoid the immune response?
Concealment of antigens, antigenic variation, immunosuppression, resistance to the immune response
What ways does concealment of antigens occur?
Intracellularly: pathogens inhibit antigen presentation by MHC class I Privileged sites: hiding dormant in the CNS Uptake of host molecules: cloak effect
How does antigenic variation occur?
Antigenic shift via mutation or drift via recombination
How does infliuenza avoid the immune response?
antigenic variation
What kind of antigenic variation produces a worse illness?
Antigenic shift, as there is no crossover protection
How does immunosuppression occur?
Shielding or inhibition of opsonisation, inhibition of the inflammatory response, induction of T regulatory cells which inhibit antigen presenting to T cells.
How does immunosuppression occur in HIV?
CD4 T cells are blocked
What are the different types of hypersensitivity reactions?
Type I, II, III, IV
Which hypersensitivity reactions are antibody mediated (immediate)?
Type I-III
Which hypersensitivity reactions are cell mediated (Delayed)?
Type IV
What happens in a Type 1 sensitivity reaction?
Within 30 minutes, upon the first exposure to an allergen, antigens activate Th2 cells which leads to the stimulation of IgE class switching in B cells and the production of IgE. IgE binds to mast cells and repeat exposure to the allergen leads to mast cell release of mediators such as histamine.
Which antibody is involved in a Type I reaction?
IgE
What conditions are associated with Type I reactions?
Allergic rhinitis, eczema, drug allergies
What happens in a Type II sensitivity reaction?
Within minutes to hours, cell or matrix/cell surface receptor antigens activate the complement system.
Which antibody is involved in a Type II reaction?
IgG on cell surface
What conditions are associated with Type II reactions?
Some drug allergies such as penicillin
What happens in a Type III sensitivity reaction?
Within 3-8 hours, soluble antigens activate the complement system and phagocytes.
Which antibody is involved in a Type III reaction?
IgG (extracellular)
What happens in a Type IV sensitivity reaction?
Takes 3-5 days develop abd is not due to antibodies. Caused by protein antigens such as gluten and induces a T-Cell response.
Which antibody is involved in a Type IV reaction?
They are not, a T cell response is induced.
What conditions are associated with Type IV reactions?
Th1 - macrophage activation: allergic contact dermatitis
Th2 - igE production: chronic asthma
ctl - cytotoxicity: graft rejection
What happens when mast cells degranulate?
When mast cells degranulate, cell mediators such as histamine are released
What is Type IV sensitization?
Happens 1-2 weeks after the primary contact, involves antigen presenting cells such as macrophages. Chronic Type 1 reactions can become Type IV reactions mediated by Th2 cells
How does immunological memory work?
Immunological memory uses memory cells during the primary immune response
Why is there usually 2 doses of vaccine required?
Because the first dose stimulates the primary response mediated by B cells and T cells, to produce memory cells. The second dose stimulates the secondary immune response by memory B and T cells
What are the different types of vaccination?
Live attenuated secreted toxins conjugated killed/inactivated subunit RNA
What is a live attenuated vaccine and give an example?
Mutant form of live virus/bacteria that grows poorly in humans. Gives better protective immunity as the virus can replicate real infection. They are fragile, and should not be given to children with weakened immune systems.
EXAMPLE: MMR vaccine
What is a killed/inactivated vaccine and give an example?
Virus particles which are unable to replicate in humans because they have been treated chemically or physically. You will always need multiple doses/booster
EXAMPLE: Polio, Hep B
What is a secreted toxin vaccine
Secreted toxin vaccines involve purifying bacterial toxins and treating them with formalin to destroy their toxic activity. Inactivated toxoids have sufficient antigenic activity to provide protection against disease
What is a Conjugated vaccine
Conjugating bacterial polysaccharide to tetanus/diphtheria. Use capsule to escape CD4/TFH
Produce highly specific IgG antibodies which leads to complement fixation and killing of bacteria.
What is a subunit vaccine
Only one part/subunit of the virus rather than the full virus is injected
What is an RNA vaccine and give an example?
mRNA vaccines use mRNA created in a laboratory to teach our cells how to make a protein—or even just a piece of a protein—that triggers an immune response inside our bodies
EXAMPLE: COVID-19 vaccine
What is the new vaccine for meningitis B based on? How does it work?
Reverse immunology. FHbp prevents activation of the complement. Antibodies with ant FHbp induced with vaccination block FHbp inhibitory functions and allow activation of the complement cascade
What is passive vaccination and when is it indicated?
IM/IV injection of antibodies. Indicated for the prophylaxis of infectious disease, to prevent symptoms, protect during incubation period, treat antibody deficiences
What is active vaccination and when is it indicated?
iM/IV/SC, introducing the antigen to stimulate a specific response. Indicated as usual vaccines are.
What is the purpose of adjuvants and what must they do?
Additional components of vaccines which increase the immunogenicity. Important in subunit vaccines. Must provide appropriate immune response but not induce a response against themselves, but be stable with long shelf, biodegradable, cheap to produce, and reduce vaccine cost.
What is the purpose of excipients?
Additives in vaccines to prevent microbial contamination or to stabilise vaccines. Can potentially cause allergic reactions.
What makes a good vaccine?
SAFE: vaccine itself must not cause illness or death
PROTECTIVE: vaccine must protect against illness resulting from exposure to live pathogen
GIVES SUSTAINED PROTECTION: protection against illness must last for years
INDUCES NEUTRALISING ANTIBODY: essential to prevent infection
INDUCES PROTECTIVE T CELLS
PRACTICAL: low cost/dose, stability, easy administration, few side effects
What is the purpose of the vaccine delivery system?
Protects vaccine from being degraded, a good delivery system can be used to make a prolonged release formulation.
What are the different routes of administration of vaccines?
Injection
Intranasal
oral
pros and cons of injection delivery
prevent person to person transmission, produce a sytstemic response but they are painful, expensive and they do not mimic pathogen route of entry
pros and cons of mucosal vaccination (intranasal/oral)
Produce antibodies in the usual route of delivery but provide less organ protection
