IM1: Introduction to Immunology Flashcards
1. What are the cellular components of the immune system 2. How do these component interact and communicate
Define immunity
Ability of an organism to resist disease
Define antigen
Molecule that can bind and be recognised by an antibody or T cell to generate antibodies
Define antibody
Protein produced by plasma cells with specific shapes complimentary to a specific antigen
Define an antigen determinant (epitope)
The smallest part of an antigen that is recognised by T/B cells as foreign to which antibodies can bind (an antigen has many epitopes)
Define a hapten
Extremely small antigen determinants that can react with antibodies but are unable to stimulate an immune response without being combined to a larger molecule e.g. protein
Define immunogenicity
Any molecule that can induce an immune response
Define a receptor
A molecule that has at least one recognition site to which a molecule can bing - the molecule it recognises is the determinant
Define specificity
The ability to distinguish the identity of the determinant which is recognised
What is SCID
Severe combined immune deficiency
When someone is born without an immune system due to lack of lymphocytes and this causes
- recurrent bacterial, viral and fungal infections
- these are more severe and less responsive to treatment
- bone marrow transplants are needed to replace immune functioning
How do host organisms know there is an infection
- Pattern recognition receptors (PRRs) = expressed by cells of the immune system
- Pathogen-associated molecular patterns (PAMPs) = conserved structures expressed by pathogens
Outline the innate immune inflammatory response
- Macrophages encounter pathogen in tissue
- Release cytokines (communicate with nearby cells)
- Release chemokine (attract cells from distance)
- Cytokines increase blood vessel permeability
- Chemokine attract neutrophils and macrophages
- Neutrophils and macrophages phagocytose pathogens and clean debris
Physical signs of inflammation
Redness, Heat, Swelling, Pain, Loss of function
Chronic = tissue damage/loss Acute = resolution and healing
List features and cellular components of the innate immune system
- Rapid response (0-12h), non-specific, no memory
- Localised pathogens + preventing spreading
- Activates adaptive immune response
- neutrophils
- macrophages
- dendritic cells
- NK cells
Cytokines, chemokine, cytotoxic granules
Role of macrophage
- Phagocytosis
- Tissue-resident
Role of neutrophil
- Phagocytosis
- Form neutrophil extracellular traps (NETs)
- Short-lived
Role of dendritic cells
- Antigen presentation
- Active adaptive immunity
Role of NK cells
They recognise malignant and virally infected cells and kill them
MHC Class I is a self-antigen for which expression is down regulated in virally infected cells and tumours - this is recognised by NK cells
They don’t have antigen specific receptors but kill those lacking the self-antigen
What are the cells of the adaptive immune system and what is this important for
B cells
CD8+
CD4+
T helper cells
This is important for specificity and immunological memory
How is specificity achieved in adaptive immune response
- Each lymphocyte has one type of receptor recognising one antigen
- An antigen will only activate lymphocytes with the right receptor = COLONAL SELECTION
- These lymphocytes divide and daughter cells express the same receptor = CLONAL EXPANSION
What are the functions of the adaptive immune system
- slow response (>4days)
- develops after exposure to antigens
- it is specific and has memory
- 2 parts = cell-mediated (t-cells), and humoral (b-cells)
What are the four classes of pathogen
- Extracellular bacteria, parasites, fungi
- Intracellular bacteria and parasites
- Intracellular viruses
- Extracellular paralitico worms
What is the significance of the immune system
- vital role in inflammation
- maintains constant environment
- acts against infections
- resolves pathology/ contributes to it (gingivitis)
Role of eosinophil
Ending allergic reactions and parasitic infection
Role of basophil
Bilobed nucleus
Secrete histamine
Inflammation mediators
Role of mast cells
Release histamine
Role of monocyte
Transform into macrophages to perform phagocytosis
Role of lymphocyte
Most important in adaptive immunity
T/B cells
Role of T cells
Role in cell-mediated immunity
Produced in bone marrow and mature in thymus
- Helper T-cells = help B cells make antibodies
- Cytotoxic T-cells = kill virally infected cells
- Regulatory cells = regulate immune response
Role of B cells
Role in humoral immunity
Produced and matured in bone marrow
Antigen producing cells
First line of defence
Non-specific and barriers to entry
- skin
- muco-cilliary escalator
- coughing, sneezing, vomiting reflex
- flushing of blood, saliva and urine
- pH of stomach and vagina
- commensal bacteria in colonisation resistance
- bile and sebum
- lysozyme in saliva and tears
Second line of defence
Non-specific
- Pathogens recognised as they have antigens
- Immune response causes engulfing by phagocytic cells
- PRRs recognise PAMPs (e.g. mannose receptors)
- Cytokines and chemokine released causing local inflammation
- Inflammation and cytokines cause immune cell recruitment to the area
Third line of defence
Adaptive immune response = specific
- APCs show material to T cells to stimulate response:
- Dendritic cells and APCs mature after engulfing pathogens
- Pathogens are carried to lymph nodes via lymphatics and presented to T cells
- T-cell becomes - helper (activates B-cells)/ cytotoxic
- B-cells remain in peripheral tissues until signal is received
- Antigen binds to BCR and is internalised, digested and complexed with MHC II molecules on B-cell surface
What is required in the thymus dependant mechanism
Interaction of B-cells with Helper T-cells to form the MHC II complex on B-cells enabling it to act as a APC to T-cells
TCRs on helper T-cells bind to antigen-complex MCH II then this works as a secondary activation signal to B-cells
What is required in the thymus independent mechanism
Few antigens can directly provide B-cell activation signals but these include
- some bacterial wall components (LPS)
- antigens containing highly repetitious molecules (flagellin)
What are the functions of antibodies
- Neutralise toxins and viral activity
- Immobilise microorganisms
- Agglutinate bacteria
- Bind bacteria adhesions (prevent them binding to receptors)
- Kill infected cells by antibody dependant cellular cytotoxicity (ADCC)
- Mast cell activation
What is the complement system
A system that enhances the removal of microorganisms by antibodies or phagocytes - they are a group of plasma proteins that coat bacteria
What does the complement system result in
- recruitment of inflammatory cells
- opsonisation of pathogens
- killing of pathogens
What activates the complement system
- Classical pathway = antigen-antibody complexes
- MB-lectin pathway = lectin bound on pathogens binds to mannose receptors
- Alternative pathway = phagocytes recognise pathogenic surfaces and activate complement cascade
What are the different types of immunoglobulins
These are antibodies are there is a different isotope of antibody to any given antigen
- IgM, IgG and IgA = infection response
- IgE = hypersensitivity and allergy
- IgD = unknown, found on maturing B-cells
What are the constant regions of different antibodies
- IgM = pentameric (first Ab produced in immune response)
- IgG = monomeric (main Ab in serum immune response)
- IgA = monomeric (low serum levels, high dimeric in secretions)
What are the 4 subsets of CD4+ T cells
- TH1
- TH2
- TH17
- Tregs
What is the role of TH1
Coordinates immune response against intracellular microbes (bacteria) by producing + secreting molecules which alert and activate other immune cells
What is the role of TH2
Coordinates immune response against extracellular pathogens (helmiths, parasitic worms) by alerting B cells, granulocytes and mast cells
What is the role of TH17
Produce IL-17 = signalling molecule that activates immune and non-immune cells to recruit neutrophils
What is the role of Tregs
Regulatory T cells = monitor and inhibit other T cells preventing adverse immune activation and maintaining tolerance/ prevention of immune response against the body’s own cells and antigens
What is the role of cytokines
immune cell growth, activation, IG class switching
What is the role of colony stimulating factors
Interleukins = context specific instructions with activating/inhibitory response
Interferons = immune cell activation
- type 1 - mediate antiviral immune response
- type 2 - mediate antibacterial response
What is the role of chemokines
Made in specific sites of infection to attract immune cells
TNF (tumour necrosis factor) is a family of chemokine stimulating immune cell proliferation and activation of inflammatory responses
Why are anti-TNF drugs used for autoimmune diseases
Because they prevent stimulation of TNF which causes immune cell proliferation and activation of inflammatory response
What is the role of TLRs
Toll-like receptors = expressed on innate immune cells (macrophages and dendritic cells) and located on cell surface/intracellular compartments
They recognise general microbial patterns which is essential for innate immune-cell activation and inflammatory responses
What is the role of BCRs and TCRs
B-cell receptors = expressed on adaptive immune cells and secreted as antibodies to neutralise pathogens
Have potential to recognise anything due to their random generation
They are highly specific
Same for T-cell receptors but these are only found on the cell surface
What are MHCs
Major Histocompatibility Complexes (HLAs = human leukocyte antigen) these function as carriers to present antigens on cell surfaces
What are MHC Class I proteins
These present viral antigens and are expressed by all cell types except RBCs
What are MHC Class II proteins
These are only expressed by antigen-presenting cells (DC, macrophages) and are important for presenting antigens to CD4 T-cells
These are varied and include both pathogen and host derived molecules
What is the role of MHC proteins
Signal weather a cell is host/foreign
Everyone has a unique set of inherited MHCs
MHC/HLA proteins are matched for oran donation to prevent rejection
How do complement proteins function
Once activated they stick to a pathogen, recruiting and activating more complement proteins - they assemble to form a pore/hole which is punched into the pathogen causing it to leak and die
It acts as a signalling molecule to alert immune cells and recruit them
