Immunology Flashcards
What are the two components of the immune system?
White blood cells and soluble (humoral) factors
What are the soluble factors involved in the immune system?
Antibodies, complement proteins, acute phase proteins and cytokines
What are the two types of white blood cell involved in the immune system?
Lymphocytes and phagocytes
What are the phagocytes involved in the immune system?
Neutrophils, monocytes/macrophages, dendritic cells
What are the lymphocytes involved in the immune system?
NKC’s, B cells, T cells (cytotoxic and helper), mast cells, basophils and eosinophils
What are the 4 different types of immunity?
Anti-viral, anti-helminth, anti-intracellular bacterial, anti-extracellular bacterial/fungal
What components are involved in anti-viral response?
Antibodies, NKC’s, cytokines and cytotoxic T cells
What components are involved in anti-helminth immune response?
Eosinophils, basophils, B-cells and antibodies and mast cells
What components are involved in anti-intracellular bacterial immune response?
B-cells and antibodies, cytotoxic T-cells and NKCs
What components are involved in anti-extracellular bacterial and fungal immune response?
Antibodies, neutrophils, macrophages, complement, cytotoxic T cells, NKCs
What are some molecules which are included in the general class of ‘cytokines’?
Chemokines, interferons and interleukins
What do cytokines do?
Modulate behaviour of cells and co-ordinate the immune system
When are antibodies produced and how do they act?
In response to an antigen- they act specifically
What produces antibodies?
Antigen activated B cells
Where do complement proteins come from and what do they do before they are activated?
They are produced in the liver and circulate in the blood as precursor molecules
What happens when an activated complement protein enters an inflamed or infected cell?
It sets off a cascade of complement activation
What do complement proteins promote?
Inflammation
What are NKCs?
Large granular lymphocytes
Where are B and T cells found before the are activated?
Circulating in the blood as inactive molecules until they meet a pathogen
What do B cells do?
Produce antibodies and defend against extra cellular pathogens
What type of pathogen do T cells protect against?
Intracellular pathogens
What do helper T cells do?
Regulate the immune system
What do cytotoxic T cells do?
Kill virally infected cells
Which type of pathogens do basophils, eosinophils and mast cells protect against?
Those which cannot be phagocytosed
What type of cells are eosinophils, basophils and mast cells and what do they produce?
Highly granular cells which produce histamine, heparin and cytokines
What do mast cells do?
Reside in tissues and protect mucosal surfaces
What do basophils and eosinophils do?
Circulate in blood and are recruited to the site of infection by inflammatory signals
What do macrophages do as well as phagocytosis?
Limit inflammation, involved in tissue repair, wound healing and antigen presentation
What do monocytes do?
Circulate in blood, migrate to peripheral tissues and differentiate into macrophages
What are monocytes, macrophages and neutrophils a source of?
Cytokines
What do dendritic cells have a key role in?
Antigen presentation to T cells
What transformation do dendritic cells undergo?
Start as immature cells in peripheral tissues and become mature as they migrate to secondary lymphoid tissues
What happens in primary lymphoid tissues?
Leukocyte (WBC) development
What are examples of primary lymphoid tissues?
Bone marrow, thymus
What happens in secondary lymphoid tissues?
Adaptive immune responses are initiated
What is found in secondary lymphoid tissues?
B cells, T cells and dendritic cells
What are examples of secondary lymphoid tissues?
Spleen, lymph nodes
What is lymphoedema?
Localised fluid retention and tissue swelling caused by a compromised lymphatic system
What can cause lymphoedema?
Parasitic infection, cancer treatments or it can be inherited
What components are involved in innate immune response?
Macrophages, mast cells, complement, neutrophils, NKCs
What type of response does the innate immune system produce?
Rapid (mins-hours), non-specific response
What type of response does the adaptive immune system produce?
Slower (days), specific response
What else does the adaptive immune system do?
Generates immunological memory
What components are involved in the adaptive immune response?
B cells, T cells
What has the function of switching between the innate and adaptive immune systems?
Dendritic cells
What is direct biological communication?
Receptor to ligand interactions
What is the first part of indirect biological communication?
Injured tissue cells and activated immune cells produce cytokines which communicate with the immune system
What is the second part of indirect biological communication?
Virally infected cells produce interferons which puts cells into non-viral state and acts on other immune cells, particularly NKCs
What happens in the recognition phase of the innate immune response?
Innate immune cells recognise and respond to pathogens
What do pathogens express?
Pathogen Associated Molecular Patterns (PAMPs)
What do innate immune cells express?
Pattern Recognition Receptors (PRRs)
Where are PRRs found?
On the surface of the cell and intracellularly to detect intra and extra cellular pathogens
What happens in the activation and effector phase of the innate immune response?
Acute inflammation and pathogen killing
Where do macrophages reside?
Epithelial tissues at sites where pathogens are likely to invade
What is a major function of macrophages in innate response?
Clearance of apoptotic cells
What is an example of an anti-inflammatory mediator released in the innate immune response?
IL-10
What happens if the mechanism of apoptotic clearance fails?
Autoimmune disease
What is degranulation (in terms of mast cells)?
Release of pre-formed pro-inflammatory molecules
What is gene expression (in terms of mast cells)?
Release of new pro-inflammatory molecules
What happens in the acute phase response of innate response?
Changes in the plasma concentration of specific proteins in response to inflammation
What is the acute phase response driven by?
Cytokines
What do CRP, SAP and complement proteins cause?
Prevent spread of infection and act as diagnostic markers
What does fibrinogen do?
Coagulation and wound healing
What do CRP, haptoglobin, manganese superoxidase dismutase and proteinase inhibitors do?
Prevent systematic inflammation
What is the first branch of inflammatory mediators produced by macrophages, mast cells and NKCs?
Nitric oxide, histamine, prostaglandins and leukotrienes
What does the first branch of inflammatory mediators cause?
Vasodilation, increased vascular permeability, smooth muscle contraction
What is the second branch of inflammatory mediators released by mast cells, macrophages and NKCs?
Cytokines- TNFalpha, IL-1 and IL-6
What does the second group of inflammatory mediators cause?
Increased vascular permeability and endothelial cell activation
What is the 3rd group of inflammatory mediators released by mast cells, macrophages and NKCs?
Chemokines
What does the 3rd group of inflammatory mediators lead to?
Leukocyte recruitment and activation
What does acute inflammation cause?
Pain, heat, redness, swelling and loss of function
What do macrophages produce?
TNFalpha, IL-1 and NO
What do mast cells release?
Prostaglandins, histamine, TNFalpha, leukotrienes
What are the adhesion molecules that activated endothelial cells possess?
Selectins (receptors) and ICAMs (ligands)
Where do chemokines come from?
Macrophages and mast cells
What is the first stage of chemotaxis?
Neutrophils bind to selectins and roll along the endothelial surfaces
What is the 2nd stage of chemotaxis?
Neutrophils bind to ICAM-1/VCAM-1 ligands on the endothelium via selectins
What is the 3rd stage of chemotaxis?
Neutrophils change shape and migrate through the endothelial wall to the site of inflammation
What are two structural facts about neutrophils?
They have intracellular granules and a multi-lobed nucleus
What do neutrophils release to immobilise pathogens?
intracellular structures known as NETs
What do NETs do?
Prevent pathogens spreading and facilitate phagocytosis
What is pus made up of?
Neutrophils, NETs, cellular debris and dead bacteria
What is an accumulation of pus known as?
Abscess
What are used to neutralise TNFalpha?
Monoclonal antibodies
What are the four stages of complement function?
1) Pathogen killing
2) Opsonisation
3) Leukocyte recruitment
4) Removal of immune complexes
What defence is complement involved in?
Against encapsulated bacteria
How does complement cause pathogen killing?
C5b binds to the surface of pathogens, it then combines with C6,7,8,9 to form membrane attack complex (MAC) which is inserted into target cell walls to cause osmotic lysis
What does opsonisation do?
Facilitates phagocytosis
What complement protein is involved in opsonisation?
C3b
How does opsonisation facilitate phagocytosis?
Pathogens are coated with opsonsins, phagocytes have opsonin receptors
How do complement proteins cause leukocyte recruitment?
C3a and C5a (anaphylatoxins) promote inflammation by acting directly on blood vessels
Where are T and B cells produced?
Bone marrow
What are the antigen receptors for T cells?
Membrane bound protein heterodimers
What are the antigen receptors for B cells?
Membrane bound antibodies (IgM/IgD)
Where are antibodies found?
Expressed on the surface of B cells and secreted as soluble proteins into extra cellular fluid
What type of polypeptide chains are antibodies made of?
2 Ig heavy and 1 Ig light polypeptide chains
What do they polypeptide chains that make up antibodies contain?
A variable region and a constant domain
What holds the polypeptide chains in antibodies together?
Disulphide bonds
What is the part of the antibody structure that changes with the different types?
Different Ig heavy chain constant regions
What forms the antigen binding site?
Hypervariable regions of the Ig heavy and light chains
Where does adaptive immune response take place?
Secondary lymphoid tissues
Where do mature, antigen specific B and T cells circulate between?
Blood, secondary lymphoid tissues and lymph nodes
What is trapped in secondary lymphoid tissues?
jDendritic cells, pathogens, antigens and debris
What is another name for MHC proteins?
HLA
Where are class I MHC proteins found?
All uncleared cells
What do class I MHC proteins do?
Present peptide antigens to CD8+ T cells
Where are class II MHC proteins found?
Only on professional antigen presenting cells
What do class II MHC proteins do?
Present peptide antigens to CD4+ T cells
What is the differentiation process of forming antibodies?
B cells, plasma cells, antibodies
What do short lived plasma cells do?
Churn out lots of antibodies
What do long-lived plasma cells do?
Reside in bone marrow for low level secretion of specific antibodies (immunological memory)
What role does the variable region of antibodies play?
Involved in recognition function
What role do heavy chain constant regions play?
Involved in effector function, contact region interacts with effector molecules (Fc receptors and complement)
What is an early role of IgM and what does this mean?
B-cell activation therefore it is the first Ig type produced in an immune response
What is the structure of IgM?
Pentamer
Where is IgM found and why?
Only in tissue fluid as it is too big to cross the membrane
What are the other 2 functions of IgM?
Agglutination and complement system activation
What is agglutination?
Immune complex formation (cross linking multiple antigens to produce clumps of antigens) to increase efficacy of phagocytosis
What is agglutination mediated by?
Specific antigen binding
When is IgM produced?
Innate immune response
What is IgG?
The most abundant antibody in human serum, dominant type produced during a secondary response and the best as it has many functions
What are the functions of IgG?
Agglutination, complement system activation, foetal immune protection, neutralisation, opsonisation and NKC activation
How is IgG transported to the foetus?
Directly across the placenta into the foetal blood supply
What does neutralisation prevent?
Pathogens from infecting host cells and microbial toxins disrupting normal cell function
What is opsonisation initiated and mediated by?
Initiated by antigen binding and mediated by Fc receptors binding to the constant region of the heavy chain
What is the function of IgD?
B cell antigen receptor (B cell activation)
Where is IgD found?
Extremely low concentrations in the blood
How abundant is IgA?
Second most abundant form
Where is IgA found?
Monomeric form in serum, dimeric form in secretory fluid
What are the functions of IgA?
Neutralisation and neonatal immune protection
How does IgA protect neonates?
Transported in the colostrum and breast milk to protect the GI tract of neonates
How are false readings of neonatal antibodies common?
Shows maternal ones
What is the function of IgE?
Triggers allergic responses
What do CD4+ T cells secrete?
IL-2
What does IL-2 cause?
Growth factor production and promotes mitosis in T cells
What response are TH1 cells involved in?
Bacteria
What response are TH2 cells involved in?
Helminth and Protozoa
What do T helper cells help activate?
B cells and macrophages
What cells does immunological memory involve?
Memory CD4+ and CD8+ T cells, memory B cells and long lived plasma cells
Describe antibody concentrations in primary response?
IgM first until concentrations of IgG take over
Describe antibody concentrations in secondary response?
Immediate secretion of IgM and IgG but IgG at higher concentrations
What are some examples of opsonins and what do they do?
CRP, IgG antibodies and C3b- mediate opsonisation
What is a key mediator of complement and why?
C3 as it is activated by all 3 pathways
Where is CRP produced?
Liver cells
