Immunology Flashcards
What are cytokines?
Family of secreted proteins, cell growth, differentiation, activation
Immune system- cell trafficking, immune tissue/organ development
Tailoring of immune response
C
What are chemokines
• Subset of cytokines -8-12kDa - small proteins
• Immune system- cell migration, chemotaxis
Tailoring of immune response
What are the three way cytokines and chemokines can act?
Autocrine, Paracrine and endocrine action
What is Pleiotropy?
Act on more than one cell
What is redundancy?
More than one cytokine produces same response
What is synergy?
Two or more cytokine act together to enhance response
What is antagonism
Two or more cytokine act opposingly
Describe the cascade that occurs when cytokines/ chemokiness bind to membrane bound receptor
Protein phosphoryl HSCs- recruits STAT to JAK- phosphorylateS STAT - causes STAT to break off - go into nucleus and activates transcription
What ae chemokines function
Chemokines functions
* Inflammation
* Metastasis
* Wound healing
* Angiogenesis
* Lymphoid organ development
* T-cell subset development
* Lymphocytes trafficking
* Cell recruitment (chemotaxis)
What is a C chemokine?
Have on disulphide bridge between two cysteines
What is CXC chemokine?
Two cysteines molecules- causes disulphide bridge to form but amino acid between cysteines
What is CX3C?
Has three amino acid between cysteines
What is an interferon? What are three types?
IFN-A , b and y
Interferes with viral replication- subset of cytokines
Enhances phagocytes activity of macrophages
What is the interferon mode of activity?
Interferon mode of active-
Intracellular components- identify viral parts of cell- recruit interferon- bind to other cells in that area to protect other cell against virus- get signalling cascade- production of inactive enzymes that interfer with viral replication process- inactivated enzymes become active against that virus.
* When goes wrong can be catastrophic
What is a zymogen?
An inactive precursor
Name the order of molecules involved in pathways? In discovery?
C1,4,2,3,5,6,7,8,9,
Is a the smaller fragment of larger fragment?
What is the exception?
Smaller fragment
C2
What are the two primary cells involved in phagocytosis?
Neutrophil
Macrophage
What are pseudopods?
Projections to engulf pathogen
What are Toll-like receptors (TLRs)>
Toll-like receptors (TLRS)
10 tlrs in humans
* Single pass transmembrane receptors
* Leucine rich extracellular domain
* Homon or hetero diners
* Immune and non-immune cells
* Recognise conserved molecular patterns
What TLRS work through MYD88 pathway?
All expect type 1
What tell our immune cells what is dangerous and what is foreign?
Foreign- PAMPs
Danger- DAMPs
What are the three major components of the lymphatic system?
Lymphatic system that runs parallel to blood vessel
Three major component of lymphatic system
* Lymph- watery fluid that originates from blood plasma and circulate the lymphatic vessels
* Lymph vessels and nodes- networked of vessels that recirculate lymph fluid and 6-700 lymph nodes that act as checkpoints
* Lymphoid organ- thymus and bone marroq( pimay, spleen, tonsils, peters patch, mucosal associate lymphoid tissues (MALTs) (secondary)
Where does T-lymphocytes mature?
Thymus
What removes blood born pathogens?
Spleen
What are the lines of defense in immunity?
1st barrier - physical- skin acid, bile, mucus
2nd - innate immune response
3rd adaptive immune response
Where do immune cells develop?
Bone marrow
What is the functions of the immune system?
Functions of immune system
* Recognises- what is self and non self- what is causing damage
* React- Need to do something about the cells- destroy, repair,
* Regulate- need to switch immune system on and off - when thing go wrong have chronic inflammation
* Remember — Vaccination- t and B -lymphocyte0 once encountered pathogen for first time- remember how to deal with it
What are two phases after the Barrie’s have been beaten?
Innate phase- immediate action performed mediators, kill, weaken or mark pathogen
Early induce phase- sensin, recruitment, inflammation
How does the body work initially to get rid of the pathogen?
Urinate and sneeze - get rid of pathogen
Tears- contain enzymes- breakdown stuff that land in the eye
Salivary gland - enzymes
How is the stomach altered to fight bacteria?
Low PH, digestive enzymes, mechanical flow
How is the small intestine altered to fight pathogens?
Chnage in pH from acidic to 8
Digestive enzymes
Antimicrobial peptides
Fluid flow
How is the large intestine altered to fight pathogens?
Large intestine
* Microbiome
* Antibiotics produced
* Expulsion of faeces
How are lungs adapted to fight pathogens?
Lungs
* mechanical flow
* Coughing/ sneezing
HOW IS THE MUCociliary escalator adapted to fight pathogens?
Mucociliary escalator
* Co-ordinated movement of cilia
* Moves mucus and foreign particles up airway
What are neutrophils?
> 60% OF BLOOD leukocytes
Recruited to tissue
Phagocytes - eating of pathogens
Defences against bacteria and fungi
What are Eosinophil?
<5% of blood leukocytes
Also tissue resident
Defense against parasites
Implicated in allergy
Describe the basophil?
<1% of blood leukocytes
Defense against parasites
Immune modulation
What are monocytes?
Monocytes- 2-A10% blood leukocytes
Phagocytosis
Bacterial killing in blood
What are dendritic cells?
Dendritic cells- link between innate and adaptive immunity
* Primarly tissue resident cells
* Tiny percentage in blood
* Guardians at potential entry points
* Phagocytose to present antigens
* Link to adaptive immunity
What are natural killer cells?
Natural killer cells
Highly aggressive 5-10% lymphocytes
Anti-cancer, anti-viral, cell-cell killing, immunoregulatory effects
What is inflammation?
What is inflammation?
A Non-specific, localised and complex biological response of tissues to harmful stimuli:
* Pathogens
* Damaged cells
* Irritants
Involves
* Blood vessels
* Immune cells
* Molecule mediators
What is the function of inflammation?
Role of inflammation:
Function:
* eliminate initial cause of injury
* Removal of necrotic cells/tissues
* Initiate repair and recovery
* Protective mechanism
potentially harmful process:
What is harmful to microbes can be harmful to surrounding tissue
What are the signs of inflammation?
Cardinal signs of inflammation
* Localised to reaction to injury
* 4 characteists
1. Rubor (redness)- Increased blood flow to site of injury
2. Tumour (swelling) - accumulation of fluid at site of injury - vasodilation
3. Calor (heat)
4. Dolor (pain) - release of chemicals e.g histamine/ bradykinin
5. Added 5th- functio laesa- loss of function - multiple causes- immobilisation
What is mast cells?
They first encounter pathogens when enters the body- release chemical etc such as histamines
What does the release of nitric oxide do?
Vasodilation but also killing ability
Describe leukocytes adhesion deficiency. How many types are there?
Leukocytes adhesion deficiency
* three type LAD1/2/3
* Rare 1 in 1,000,000 births
* Delayed umbilical cord sloughing
* Defects in neutrophil adhesion
* Recurrent bacterial infections
* Mutations in ITGB2 gene- encodes integrins subunit
* Leukocytes arrests impaired Nodiapedesis
* Bacterial infections progress unchecked
What are the possible pathways after acute inflammation?
Resolution
Abscess
Chronic inflammation
Fibrosis- loss of function
Describe the acute phase response?
Fever (temp >37.8 degress Celsius
• increased blood pressure/ heart rate
• Chills
• Anorexia
• Isolates person so don’t have opportunity to spread diseases
What are neutrophilia for?
Bacterial
What are lymphocytes for?
Viral
What are eosinophilia?
Parasitic/ allergy
Describe chronic inflammation?
Chronic
* Slow onset (weeks/months)
* Long duration (months/ years)
* Predominantly monocytes/ lymphocyte driven
* Necorosis, fibrosis, angiogensis
What are naive Cells?
Naive cells- have been matured but naive as not yet. Encountered cognate antigen- not activated- when do become activated- cytokine may be produced- direct rest of immune response around.
CD8- direct cell to cell killing-
B-cell produce antibodies
What are the type of receptors found on antigen presenting cells?
MHC class I (all nucleated cells)
MHC class II (only APCs)
Describe T-lymphocytes
Present with TCR- T-cell receptor unique antigen recognition structure
Expressed on plasma membrane of T-cels only
T-cells only recognise antigen via TCR when presented by MHC class i or II
Describe B lymphocytes
BCR presenting- b-cell receptor unique antigen recognition strucuture
Expressed on plasma membrane as BCR and in plasma as antibody.
BCR/Ab can recognise free antigen. MHC not needed
What do CD4 cells do?
Cytokine production
What do CD8 cells do?
Cell death
What do B cells do?
Antibody production
What happens when one has never been exposed to a virus before? Such as coronavirus?
Novel virus > no antigen-specific cells or antibodies > develop antigen-specific cells and or antibodies
List the features of immature dendritic cells
low mHC II expression, low pro inflammatory cytokine secretion, increased phagocyte capacity, low CCR7 expression, low glycolysis
List the features of mature dendritic cells
high mHC II expression, high pro inflammatory cytokine secretion, decreased phagocyte capacity, high CCR7 expression, high glycolysis
What does CCR7 do
mature dendritic cells, drives their chemotaxis to the lymph nodes, enhance endocytosis and increase survival
DESCRIBE THE INNATE IMMUNITY
ADAPTIVE IMMUNITY- OVERVIEW
Innate immunity
* Rapid onset (minutes)
* Relatively non-specific
* Germline encoded cell surface and soluble protein- inherited from portents
* Cellular and hum oral component
* Inflammatory mediators directly/ indirectly toxic to pathogen
What expresses both CCL19 and CCL21
stroma cells in the lymph node
What are the 3 signals that cause the T cells to be educated on a threat
signal 1 = MHCII and TCR interaction, causes activation
signal 2 = CD80 and CD28 interaction, causes survival
signal 3 = secretion of cytokines, causes differentiation
What cell type does MHCII and MHCI bind to
MHCII = CD4+ TCR
MHCI = CD8+ TCR
What is MHC class I?
endogenous peptides, intracellular pathogens, all nucleated cells, resents to CD8+ cells
What is MHCII class II?
exogenous peptides, extracellular pathogens, APCs, present to CD4+ cells
What does CD28 co stimulation drive
NT-AT or AP1 or NF-B production which regulates the activity of T cells
What does PD1-co-inhibition result in
T cell activation, proliferation and survival
Describe adaptive immunity?
Adaptive immunity
* slow deployment (7-10 days)
* Targeted response
* Tailor made, highly specific anitgen receptors (somatic rearrangement)- depends where you grew up etc
* Diversity, clonality and memory
* T and b lymphocytes express antigen receptors
What expressed CCL21
afferent lymphatic vessels
What types of cell present MHC class II?
Only professional antigen presenting cells
What are the professional APCs?
Macrophages, dendritic cells, b cells
What is the functions of antibodies?
Antibody functions
* neutralisation
* Opsonisation- coat
* T-cell recruitment
* Activation o complement system
* Innate immune cell recruitment
* Phagocytosis
* Agglutination
How do dendritic cells respond to so many different signals
they have many receptors on their surface
How do dendritic cells migrate to an area of infection
down a chemotactic gradient
What do dendritic cells do when they are activated
migrate to lymph nodes to educate T cells to mount immune response
How do dendritic cells leave the lymph nodes
through the efferent vessel
What does the influence of pre-pro-b cell influenced by?
CXCL12
What cause change from stromal cell to pro-B cell?
IL-7
Where do the final maturation of b -lymphocytes take place?
Outside the bone marrow
What happen in the p follicle to immature b cells that recognise self antigens?
Removed by apoptosis before negative selection is reached
Once in the follicle, T cell undergo a process similar to positive selection. What is this?
B cells reside and needs to receive a combination of signals in order to survive
Describe the process of b cells reside and maturation?
Process of b cells reside and maturation:
* regulates BCR construction
* Ensure each cell has one specificity
* Remove auto-reactive b-cells
* Passes functional b cells to the periphery
* Provide a site for antibody production
* Activated b-cells return to bone marrow
What is the primary way b cells can become activated?
T-cell dependent activation - where cd4+ cell activated by a dendritic cells and has co simulatory molecules
During t-cell dependent activation what is the three cell fates possibel?
Plasma cell
IgM memory cell
Germinal centre differentiation
What is the primary out of b-cells?
Production of antibodies
Name the strucutes that make up antibodies
Heavy chain
Light chain
Hinge region
Constant region of light chain
Variable region of light chain
Constant region of heavy chain
Variable region of heavy chain
Antigen binding site
What are the 5 different classes of antibodies?
IgG, IgE, IgD, IgA, IgM
Describe IgD antibody
IGD
* 0.2% serum immunoglobulin
* Co-expressed on surface of mature, naive b lymphocytes
* Provides activation signals to b-cells
* Might play a role in respiratory defence by activating basophils and mast cels
* Potential role, therefore in allergy
Describe IgM antibody
IGM - can exist as a monomore- often b cells that recognise recpetor on naive cells- 5 immunoglobulin subunits joined at fc end of molecule by J chain
Describe IgG antibody
IGG
* Most abundant serum immunoglobulin
* 4 subclasses IgG1,2,3,4
* Ig1 and IgG3 bind to Fc receptors on phagocytes- oposinsation
* IgG3 mos effective complement activator
* IgG1,IgG3 and igG4 convey passive immunity to foetus
Describe IgA antibod
• makes up about 10% of serum immunoglobulin
• Dominant form in external secretion e.g tears saliva
• Central role in barrier immunity
• Greatest amount of antibody produced daily compared to all other classes
• Binds bacterial/viral antigen and prevents attachment to mucosal cells (Fc region locked)
Describe IgE
• least abundant serum immunoglobulin except in allergy
• Binds Fc receptors on blood basophils and tissue mast cells
• Crosslinking of receptors
• Induces release of pharmacologically active mediators e,g histamine via degranulation
DESCRIBE the complementarity determinant region
Complementarity determinant region
* Three in each of heavy and light chain- CDR1,CDR2,3- CD3 most variable
* Egion between domains-are less variable ae called framework region -
* Amino acid sequence in viable region/ domains determine specificity
* Sequence variability occurs in clusers called CDRs, CDR1, CDR2, CDR3
*
What is class switching?
A mechanism which b cells can hinge the production of antibodies from one to another
Describe differences between BCRs and TCRs
BCRs
* recognises free antigen
* Membrane bound or soluble
* Strong interaction with antigen
* Alternative RNA processing produces membrane and soluble forms
TCR
* Only recognises anitgen in context of MHC
* Membrane bound only
* Weaker interaction with antigen
What is the 12/23 rule
Between heptamer and monomer ther 12 or 23 BPH sequence
What is somatic hypermutation?
B cells randomly mutates its immunoglobulin region to produce a molecule with greater affinity for antigen
What are DN cells in T cell formation
double negative, no CD4 or CD8 expression
What are DP cells in T cell production
double positive, express both CD4 and CD8
What are SP cells in T cell formation
single positive, either CD4 or CD8 expression
Where do haematopoetic precursors derive
the bone marrow
What happens if a T cell recognises MHC too strongly
undergoes negative selection to prevent autoimmunity
What is positive selection
T cell recognises MHC and self, expresses MHC class I and II
What is the role of aire and fezf2
Aire = promotes expression of tissue-specific antigens in the thymus, allowing T cells to be tested for reactivity against a range of self-antigens
Fezf2 = works alongside Aire to expand diversity of self-antigens presented during negative selection, improving tolerance to self
What are the roles of Tregs
Deprives other cells of IL-2 which is needed for their sirvival so results in a reduced immune response
Kill effector T cells using cytotoxic molecules
Secrete cytokines which inhibit activation and proliferation of other T cells
Suppress APCs reducing their ability to present antigens and activate other immune cells
Prevent autoimmune diseases
What is anergy and what causes it
T/B cells are alive but unable to respond to antigen
Eg, if signal 1 happens without signal 2 or engagement of inhibitory receptors like CTLA-4 and PD1 which block activation signals
What are the CD4+ T helper subsets
Treg = suppress immune response
Th17 = extracellular pathogens
Th2 = helminth infections, activates eosinophils
T-bet = cell mediated immunity, intracellular pathogens, activates macrophages
Tfh = regulates affinity maturation of germinal B cells
What are memory T cells - what activates them, where are they found and what are the 2 types
Have long lived memory
Activated by B cells, DCs and macrophages (naïve T cells rely on DCs)
Distributed throughout the body = lymph nodes, circulating tissues, organ specific residents
Different sub types of memory cells with distinct functions
CD8 memory cells more prevalent than CD4 memory cells
