Immunology Flashcards
What is the general purpose of the immune system?
Eliminate danger
Without harming the body
Remember the threat
What is meant by immune effector function and why is it important?
Ability to deal with infection without causing harm to the body
Immune response is powerful and cytotoxic so it prevents body cells being killed
What are the main things the immune system fights against?
Pathogens- microorganisms causing disease
Cancer
Viruses
(Commensals- non-harmful bacteria that live in or on the bodies of animals)
How is autoimmune disease caused?
Immune response misidentifying self cells
What is immunological recognition?
Distinction of self from non-self
How is self and non-self cells recognised?
Self- MHC labels body cells to be tolerated by the immune system
Non-self- antigens the immune system recognises as foreign
What is immune memory?
Ability of the immune system to remember antigens from pathogens and mount immune response quicker and more aggressive
What are the two arms of the immune system?
Innate
Adaptive
What is the role of the innate immune system?
Cells and barriers rapidly slowing disease causing processes and invasion
What is the role of the innate immune system?
Always present first defence to pathogenic threats
Recruit adaptive immune cells
How long and how specific is the innate response?
Rapid (minutes) but unspecific
What is the adaptive immune system?
Response by T and B lymphocytes highly specific to pathogen to eliminate disease causing processes
Which arm of the immune system allows immune memory?
Adaptive
How fast and specific is the adaptive immune response?
Slower (upto 5 days) but very specific
How does the adaptive immune system allow immune memory?
Memory lymphocytes stay in the body for a long time and respond to pathogen on reencounter
Where are all immune cells originated from?
Pluripotent haematopoietic precursor cells in the bone marrow
What are haematopoietic precursor cells?
Stem cells capable of differentiating into red and white blood cells
Once formed, where do innate cells reside in the body?
Peripheral tissues where they are likely to encounter their pathogen they are most adapted for
Where do adaptive immune cells reside?
Central lymphoid tissues
Spleen
Lymph nodes
Later mobilised to site of infection
Where do T and B lymphocytes mature and where are they activated?
T- thymus
B- bone marrow
Once matured both travel to spleen and lymph nodes to wait for activation
Why do we need a constant supply of new immune cells in the bone marrow?
Used up or die
What is the general life cycle of an immune cell?
Self renewing haematic precursors are always available in bone marrow as self renewing
Form their immune cell
Mature in bone marrow/thymus
Migrate to periphery/spleen and lymph nodes
Wait until activation by pathogen and carry out rapid effector functions
Die or remain as memory cell
If never activated die as naive cell
What is meant by flavours of immune response?
Immune responses to different pathogens are varied and helped by specialised cell types from innate and adaptive immune repertoire
Define cytokines
Small secreted proteins released by immune cells to allow signalling, interaction and communication
What is the purpose of cytokines?
Help immune cells communicate and tell each other about pathogen and response
What are the common types of cytokines and what are they used against?
Interferons/IFNs- viruses
Interleukins/ILs- produced by white blood cells, many functions
Chemokines- direct immune cells to site of infection
Others- TNFs/tumour necrosis factor family and TGF/transforming growth factor family
How do immune cells respond to detection of presence of non-self on their receptors?
Become activated against that pathogen
What are the two types of innate cell receptors?
Pattern recognition receptors/PRRs
Antibody receptors
What are PRRs?
Receptors that bind general bits or building blocks of cells called PAMPs or DAMPs
Explain what PAMPs and DAMPs are
PAMPs- pathogen associated molecular patterns, fragments of pathogen that join PRRs on innate cells
DAMPs- damage associated molecular patterns, fragments of damaged self cells capable of joining PRRs on innate cells
What are the antibody receptors on innate cells called?
Fc receptors
Define antibodies
Proteins secreted by b cells which bind to antigen to mediate pathogen destruction and enhance innate response
How do innate cells antibody receptors work?
Respond to antibodies produced by the adaptive immune system with different antibodies determining the flavour of response
How does the innate immune system cause antibody production?
Activates B lymphocytes
Define antigen
Protein capable of initiating immune response
Define epitope
Peptide sequence which is part of the antigen protien
What do adaptive immune receptors bind to and why is this useful?
Epitopes
Specificity of epitope allows cells to get much more information about the threat
How do lymphocytes respond to epitopes?
Each lymphocyte has a receptor or one epitope so corresponding lymphocyte rapidly divides to form clones to fight off infection
What is the role of the innate immune system while the adaptive immune cells are undergoing cell division in response to a pathogen?
Helps keep the infection under control
How do T and B cells recognise antigens of pathogens?
Their receptors binding to epitopes presented on antigen presenting cells MHC
Why dont innate cells need to be specific?
Use PRRs to recognise PAMPs and DAMPs which are common across lots of pathogens
Name the non-cellular components of the innate immune system
Physical barriers
Chemical substances
Microbiological
Complement
What are examples of physical barriers of the innate system and how do they help prevent infection?
Epithelial cells are joined by tight junctions in the skin and tract linings
Mucus and fluid flow trap pathogens to be moved out by cilia
How do chemical substances of the innate immune system help prevent infection?
Low pH kills pathogens
Omega 3 and 6 fatty acids on skin protect against bacteria and enhance immune system
Enzymes directly kill pathogens or make them more susceptible to be killed
Antimicrobial peptides are toxic to pathogens
How do the microbiological components of the innate immune system help prevent infection
Commensals take up space and nutrients which prevents harmful bacteria establishing by competitive exclusion
Describe the innate immune system process of complement as defence
Presence of a pathogen activates first protein by binding which triggers activation cascade with the end of the cascade marking pathogens for destruction and proteins directly destroying pathogens by creating pore in the membrane
List the functions of the innate immune cells
Phagocytosis
Degranulation
Antigen presentation
Antibody dependent cellular cytotoxicity/ADCC
What is phagocytosis?
Internalisation of large particles by phagocytotic cells
How does phagocytosis work?
Phagosomes form on membrane and contain pathogenic matter
Fuse with lysosomes inside the cell which contain toxic acids, enzymes and antimicrobial peptides
Pathogenic matter is digested
What is degranulation?
Release of toxic granules to destroy a pathogen
What cells degranulate different infections?
Basophils and eosinophils- parasites
Neutrophils- bacteria and virally infected cells
How is degranulation stimulated?
Antibodies binding to innate cells Fc receptor or the presence of histamine and other inflammatory mediators
What is the role of mast cell granules?
Contain histamine which activates eosinophils to release their granules
What causes allergic reactions?
Eosinophils, basophils and mast cells mistakenly degranulate and allergen
What is antigen presentation?
Processing and presentation of antigens to activate adaptive immune cells
How does antigen presentation work?
Dendritic cells take in bits of pathogen and present its epitopes on its surface to activate T and B lymphocytes
What is ADCC?
Specialised killing of virally infected or cancerous cells by natural killer cells
How does ADCC work?
Antibody recognises and binds to damaged or wrong self cells and marks for destruction
Natural killer cells Fc receptor binds to antibody activating NK cell to degranulate and kill the self cell
Define opsinisation
Process of opsin molecules sticking to molecule to mark for degradation
What is the purpose of opsonisation and how does it work
Makes degranulation and phagocytosis more efficient
Innate cells Fc receptors bind to antibodies on pathogen or complement receptors bind to complement on pathogen
List the different types of innate immune cells
Dendritic cells Macrophages Neutrophils Eosinophils Mast cells Basophils Natural killer cells
How are dendritic cells activated?
PRR binding to PAMPs and DAMPs
What is the role of dendritic cells?
Combat bacteria and viruses
Activate T cells from antigen presentation
Release cytokines
How are macrophages activated?
PRRs binding to PAMPs and DAMPs and Fc receptor binding to antibody
What are the roles of macrophages?
Combat bacteria
Phagocytosis
Antigen presentation for lymphocyte activation
Release cytokines
How are neutrophils activated?
Fc receptors binding to IgG antibodies
What is the role of neutrophils?
First response to site of inflammation
Combat bacteria, parasites and viruses
Phagocytosis and degranulation
How are eosinophils, basophils and mast cells activated?
Fc receptor binding to IgE antibody
What is the role of eosinophils, basophils and mast cells?
Antiparasitics
Degranulation, mast cells contains histamine to enhance innate response
How are natural killer cells activated?
NK receptor, Fc receptor binding to ADCC
Lack of MHC-1 which shows cell is damaged
What is the role of natural killer cells?
Anti-viral and anti-tumour response
Degranulation triggered by ADCC
Why is the adaptive immune system so specific?
Each T and B cell has specific receptor to an epitope and are only activated with they bind
Why does the adaptive immune system take so long to respond?
Have to travel form spleen and lymph nodes to infection
Need to proliferate as only a few present for each epitope
What are the functions of B cells?
Plasma cells produce antibodies during immune response
Memory B cells stay in the body and divide and produce antibodies if pathogen returns
What are the general roles of antibodies?
Neutralise pathogens when secreted by B cells
Activate B cells when stuck to B cell as B cell receptor
What is the structure of antibodies?
Y shaped protein
2 light and 2 heavy chains
Constant region as scaffold for variable region
How many different constant chains are their and what is the purpose?
5
Determine flavour of immune response
Why are their a huge number of variable regions on antibodies?
So their is one for every epitope
List the different antibody subtypes and what their constant chain is
IgM- mu IgG- gamma IgA- alpha IGE- eta IgD- delta
What is the supply to lymph nodes and spleen?
Lymph nodes- lymphatic vessels
Spleen- blood
Where are B cells activated in the spleen and how is it enhanced?
White pulps germinal centres containing CD4+ TH cells to help proliferation
What is the role of the red pulp in the spleen?
Collect and dispose of old red blood cells
What is isotype switching?
Rearrangement of genes which code for antibody proteins to activate production of different antibody classes
What needs to happen in the thymus when T cells are maturing?
Testing to delete any T cells with receptors for healthy self cells
How does T cell testing in the thymus take place?
Thymus presents antigens to bind to T cell receptor which has high affinity to pathogens and none to self cells
Self cells die by apoptosis in thymic selection
Define immune tolerance
Immune cells prevent attack of self tissues
Where does central tolerance take place?
Thymus in T cell development
Describe the structure of T cell receptors
Alpha and beta chain
Constant backbone
Variable receptor binding region
How many variations of T cell receptors variable and constant regions are there?
Variable- billions
Constant- one
What are MHC molecules?
Glycoproteins on the surface of cells that display peptide antigens epitopes
What are the 3 signals of T cell activation?
Signal 1- binding of T cell receptor to epitopes on MHC molecules on antigen presenting cells
Signal 2- co-stimulation by CD80/86 and CD26 produced by antigen presenting cells
Signal 3- cytokines telling T cell the flavour of response
What is the most important signal in T cell activation and why?
Signal 1
Only way to initially activate response, 2 and 3 responsible for producing a strong enough signal to activate T cell
What type of MHC molecules are on antigen resenting cells?
MHC-1 and MHC-2
Describe how antigens get presented on MHC-1 molecules
Antigen is presented from inside the cell to MHC-1 in endoplasmic reticulum
Once binded is transported to surface
What is the role of MHC-1 molecules?
Present self cell antigens to flag to not destroy or presents viral proteins to flag for destruction
Describe antigen presentation on MHC-2 molecules
Antigens are presented form outside the cells and stick to MHC-2 in endocytotic vesicles
Taken to surface to flag for destruction of extracellular pathogen
What do CD4+ t cells respond to and what is their immune role?
Antigens on MHC-2
Activated to fight extracellular pathogens by producing cytokines to trigger innate and B cells
What do CD8+ T cells respond to and what is their immune role?
Antigens on MHC-1
Activated to fight intracellular virus or cancer by killing damages self cells via adaptive response
How does peripheral tolerance take place?
Activation of T cells without CD80/86 co-stimulation
What is the role of chemokines?
Circulate around the body directing immune cells to where to go
How are CD4+ T cells activated?
Antigen presenting cells pick up and present antigen to naive CD4+ T cells causing activation in lymph node
Proliferate and travel to spleen to meet antigen on B cells to help B cells
How are CD8+ T cells activated?
Antigen presenting cells present DAMPs to naive CD8+ T cells to activate at lymph node
Activated CD8+ T cells go to tissues to meet antigen on infected self cells to kill them
What is the function of CD8+ T cells?
Kill damages self cells by releasing toxic granules containing perforin to make holes and granzyme to cause apoptosis
What is the function of CD4+ T cells?
Coordinate immune response using cytokines, not directly eliminating pathogens (known as T helper cells) Help determine B cells what antibody class to produce
What are inactivated CD4+ T helper cells called?
Th0 cells
What are the different phenotypes if T helper cells?
Th1- intracellular pathogen response by helping CD8+ cells kill
Th2- extracellular pathogen response by helping mast cells produce granules
Th17- fungi and bacteria Th2 cant manage
Tregs- switch off immune response when not required or when response is directed to healthy cells
How do vaccinations work?
Shows piece of pathogen or dead pathogen to immune system to generate primary immune response and immune memory
When you meet actual disease immune memory kicks in to prevent illness
What are the requirements of a good vaccine?
Strong enough to produce immune response
Safe- doesn’t cause illness or disease
Protective- prevent illness when exposed to real pathogen
Induces neutralising antibody- essential in preventing infection of new cells
Induces protective T cells- needed along with antibodies
Low cost
Biologically stable
Easy administration
Few side effects
What are the different types of vaccinations?
Live attenuated- live ineffective virus
Inactivated/killed
Toxoid- modified toxin
Subunit- part of protein
What is meant by adjuvant in vaccinations?
Makes vaccine more immunogenic so immune system responds from inducing small amount of damage
Define autoimmunity
Break in immune tolerance allowing immune response to self tissues
Why is peripheral tolerance needed?
Weakly self reactive antigens may escape central tolerance
What are the two mechanisms of peripheral tolerance?
Lack of activation signals 2 and 3
Regulatory T cells
How does lack of activation signals 2 and 3 allow peripheral tolerance?
Weakly self reactive T cells need strong signal 2 and 3 from dendritic cells but this is only provided when they present PAMPs and DAMPs
How do regulatory T cells allow peripheral tolerance?
Produce IL-10 and TGF-beta to turn off immune responses or weakly self reactive T cells
Why are tolerance mechanisms T cell focused?
T helper cells activate B cells so controlling T cells controls B cells
Define hypersensitivity
Group of excessive immune responses to harmless molecules
List the types of hypersensitivity reactions
Type 1- immediate allergy or anaphylaxis
Type 2- antibody mediated reaction
Type 3- antigen-antibody immune complex mediated
Type 4- delayed allergic reaction
Why does type 1 hypersensitivity progressively get worse at each encounter?
First encounter of allergen is mild due to B cells needing to differentiate and class switch to IgE Second encounter means memory cells can rapidly activate to produce lots of IgE and aggressive immune response
How does the type 1 hypersensitivity reaction take place?
Mast cells, eosinophils and basophils produce granules with mediators including histamine producing symptoms
What is the difference between local and systemic type 1 hypersensitivity reaction?
Local- allergy confined to one tissue
Systemic- anaphylaxis
What happens in each stage of a response to a pathogen?
Stage 1- pathogen and innate immunity Stage 2- adaptive immune cell activation Stage 3- adaptive immunity Stage 4- Immune response at tissues Stage 5- regulatory T cells stop immune response
What are the two types of macrophages?
Type 1- IFN-gamma producing
Type-2- IL-4 producing for promotion of healing
What is T cell independent activation?
B cells encounter free antigen which binds to B cell receptor
What is T cell dependent activation?
Activated CD4+ T cells from lymph node present antigen to B cell and produce IFN-gamma to indicate flavour of response
What are the roles of each antibody subtype?
IgM- first produced for general defence
IgA- immunity at mucosal surfaces
IgG- opsonisation and neutralisation against viruses and intracellular bacteria
IgE- eosinophils for allergy and induces mast cell and basophil degranulation
IgD- not understood, found on naive B cells
What is the function of each cytokine?
IL-2- T cell proliferation
IFN-gamma- aid Th1, killing of infected cells
IL-4- aid Th2, allergy and anti-parasitic
IL5- drive eosinophils
IL-10 and TGF-beta- turn off immune response
IL-13- mucous production
