Immunology Flashcards
What is the immune system?
An organised system of organs, cells and molecules that work together to protect the body against disease.
What is the immune system important for?
to protect the body against infections, inflammatory disease and cancer.
What are pathogens?
micro-organisms that cause disease
What are lymphocytes?
primary lymphoid organs that produce white blood cells.
What are the 2 primary lymphoid organs?
Thymus
Bone marrow
What is the function of the thymus?
contain white blood cells called T cells and whilst they develop, it ensures they do not react to themselves.
What is the function of bone marrow?
Contains stem cells that then go on to become innate and adaptive immune cells
What are the 2 secondary lymphoid organs?
Spleen
Lymph Nodes
What is the function of the spleen?
initiates immune responses against blood-bone pathogens
What is the function of lymph nodes?
they initiate other immune responses and filter lymph fluid from the blood and tissues
What are lymph nodes?
are abundant and located along lymphatic vessels,
What are the 3 layers of defense for the immune system?
chemical and physical barriers
Innate arm
Adaptive arm
What are the 2 layers of the skin?
epidermis and dermis
What does the epidermis contain?
dead cells, keratin and dentritic cells
What is the function of the epidermis?
Phagocytic immune cells which are constantly being renewed
What is the dermis?
a think layer of connective tissue, collagen and blood vessels
What immune cels are found in the dermis?
phagocytic
What is the chemical defense for the skin?
antimicrobial peptides
What are antimicrobial peptides?
defensins which form pores in microbial cell membranes, lysozymes which break down bacterial cell walls, sebum which has a low pH and salt which is hypertonic
What is the purpose for the skins chemical defense?
can kill microbes or provide non-optimal conditions for growth and function.
What is the mucous membrane?
defense barrier found in ocular, respiratory, oral, urogenital and rectal parts of the body.
What makes up the mucous membrane?
1-2 layers of tightly packed, constantly renewed epithelium with goblet cells.
What are goblet cells?
produce mucous
What is the mucociliary escalator process?
mucous catches debris, cilia move mucous, and thus debris, up to the pharynx where it is swallowed and excreted
Where is cilia found?
mucous membranes in the trachea and uterine tubes
What is the innate defense?
already in place, consisting of the surface barriers and internal defenses.
What is the adaptive defenses?
improve and develop as the response goes on and consists of humoral immunity – B cells and cellular immunity – T cells
What is the repsonse time of innate and adaptive defenses?
innate is rapid
adaptive is slow
What is the specificity of the innate and adaptive defenses?
innate is low
adaptive is high
What is the memory of the innate and adaptive defenses?
innate has no memory
adaptive is long-term specific
Can the innate and adaptive defenses develop/adapt?
innate is fixed
adaptive is variable
What is an example of innate immunity?
Skin, mucous membranes.
Phagocytes, inflammation, fever, natural killer cells, antimicrobial proteins.
What is an example of adaptive immunity?
B cells, T cells
What is the % make up of blood?
55% plasma and 45% formed elements
What is plasma made up of?
proteins
What are formed elements consisting of?
platelets, leukocytes and red blood cells
What are the 3 lineages of blood?
Erythroid
Myeloid
Lymphoid
What are the 3 lineages derived form?
hematopoiesis of bone marrow stem cells
What are Erythroid?
red blood cells
What is Myeloid?
granulocytes, monocytes, dendritic cells, platelets (innate)
What is Lymphoid?
B and T cells (adaptive)
What are granulations?
type of myeloid blood cell that contains granules
What are examples of granulations?
neutrophils and mast cells
What are neutrophils?
type of granulocyte that makes up 75% of leukocytes present in the body.
What is the function of neutrophils?
phagocytic cells that digest foreign materials and cells
What happens to the number of neutrophils int he blood during infection?
increases
where are mast cells?
line mucosal surfaces
What is the function of mast cells?
release granules that recruit more WBCs to damaged tissue
What do phagocytic cells consist of?
monocytes, macrophages and dendritic cells
Where are monocytes found?
in blood
What is the phagocytic ability of monocytes?
low
What is the function of monocytes?
when they leave the blood and enter tissues they develop into macrophages
What is the phagocytic ability of macrophages?
high
What is the function of macrophages?
can be remain in tissues or migrate between them. also have the ability to release chemical messengers and to inform T cells about pathogenic microbes
Where are dendritic cells found?
in the blood and epithelial tissue in low numbers.
What is the function of dendritic cells?
initiating the adaptive immune responses.
What is the migration of immune cells?
travel through the blood, in which they can leave to enter tissues. They can also be carried in the lymph by lymphatic vessels and drained into lymph nodes, where immune responses can be initiated
How do innate cells recognise pathogens?
pathogen-associated molecular patterns
What is pathogen-associated molecular patterns?
building-blocks of pathogenic organisms
In viruses what can the building blocks be?
ssRNA and dsRNA
in bacteria what can the building block be?
lipopolysaccharides, endotoxins and lipoteichoic acid found in the cell wall, flagellin from flagella, or unmethylated CpG DNA
Where are toll-like recpetors found?
either on the cell membrane or in the cell in phagolysosomes
What is the function of toll-like receptors?
bind PAMPs and send signals to the nucleus to regulate gene transcription
When do fevers occur?
when the pyrogen interleukin-1 (IL-1) is released by immune cells after ingesting bacteria
What does a fever cause?
re-setting of the thermostat to an abnormally high temperature of above 37°C.
What is the inflammatory response?
- Tissue-resident cells release chemical signals that attract more cells to injury site.
- Neutrophils enter blood from the bone marrow and travel to injury site.
- Neutrophils cling to the capillary wall.
- Tissue-resident cells release chemical signals that dilate blood vessels, making the capillaries leaky.
- Neutrophils enter the injury site, following the chemical signal, by squeezing though the leaky capillary wall.
What are the stages of phagocytosis?
- Phagocyte comes into contact with pathogens/debris and adheres to it.
- Pseudopod forms around and engulfs the particle, forming a phagosome.
- Lysosome fuses with phagosome, forming a phagolysosome.
- Lysosome enzymes and toxic compounds break down pathogens.
- Indigestible and residual material removed from the phagocyte via exocytosis.
Where are Pathogens and debris are broken down in ?
phagolysosome
What are the properties of the phagolysosome?
acid environment, contains reactive oxygen and reactive nitrogen intermediates, as well as enzymes such as proteases, lipases and nucleases
What does the complete cascade involve?
9 proteins/protein complexes that act in sequence to clear tissues and blood of pathogens,
What are the 3 pathways for the complete cascade?
classical
alternative
lectin
What is the classical pathway?
occurs when an antibody bound to a pathogen binds a complement.
What is the alternative pathway?
occurs when a pathogen directly binds a complement to its surface or one of its components.
What is the lectin pathway?
occurs when a carbohydrate component of a microbe binds complement.
3 pathways converge to undergo amplification via …
C3 convertase
What is C3 convertase?
enzyme complex
What are the 3 outcomes from the complement cascade?
label
destroy
recruit
What is the label outcome?
involves opsonisation which is the coating of a microbe with an antibody or with complement fragment C3b.
What is the destroy outcome?
involves the formation of the membrane attack complex (MAC) aided by C9. This forms pores in bacterial cells, leading to cell death
What is the recruit outcome?
involves C3a and C5a degranulating mast cells which release inflammatory mediators such as proteins that recruit phagocytes to the site
What is antigen sapling and presentation?
> dendritic cells are present in major organs
the phagocytose antigen and process it down to peptides
DC migrate from organs to draining lymph node
They present peptides on MHC to other white blood cells.
What is adaptive immunity?
> DC present peptides on MHC to T cells
CD4 T cells help B cells make antibody
CD8 T Cells become cytotoxic and kill virus infected cells and cancer cells
What is an antigen?
Anything that has the potential to be recognised by the immune system
What is a foreign antigen?
anything from the outside
What is an auto-antigen?
may be recognised in autoimmune disorders
What is the purpose of antigen uptake?
Clearance of pathogens for presentation of T cells
Why did phagocytes evolve?
to keep remnants of pathogens and display these to other cells of the immune system
What immunity do invertebrates have?
innate
What immunity do vertebrates have?
Innate and adaptive
What is MHC expression?
MHC-1 presents endogenous antigen and is expressed on all nucleated cells.
MHC-2 presents exogenous antigen expressed only on antigen presenting cells
What is MHC-1 antigen precessing?
Antigenic proteins are degraded to peptides in cytoplasms. peptides are imported into endoplasmic reticulum. peptide loading of MHC-1 takes place in the ER
What is MHC-2 antigen processing?
Antigenic proteins are degraded in acidic phagolysosome. peptide loading of MHC-2 takes place in phagolysosome
What is an antigen presenting cell?
cells that link the innate immune repsonse with T cell and B cell responses
How do APC’s work?
Take up proteins from pathogens and process them into antigens
Where are APC’s found?
all over the body
What are the best APC’s?
dendritic cells
What are T cells?
lymphocytes that are specific for a particular organsim
How to T cells work?
they get activated by APC’s and then proliferate and make cytokines an cytotoxin molceules
What can T Cells destroy?
pathogens
What can T cells help?
other immune cells destroy pathogens
What are the 2 types of T cells?
CD4 and CD8 T cells
What is immune response?
- Pathogen infects a tissue site
- DC live in the tissue sites and see the pathogen 1st
- DC process the pathogen into antigenic peptides and load them onto MHC
- DC with antigenic peptides move to the local lymph node
- T cells live in the lymph node and meet up with the DC
- T cells activate and make cytokines or become cytotoxic
- B cells in the lymph node activate and make antibodies
What is the MHC 1 processing for endogenous antigens?
Antigenic proteins are degraded in cytoplasm and peptide loading of MHC-1 takes place in the ER
What is the MHC 2 processing for endogenous antigens?
Antigenic proteins are degraded in acidic phagolysosome and peptide loading of MHC-2 takes place int he phagolysosome
Where are T cells developed?
Bone marrow and then to thymus
What happens to T cells in the bone marrow?
they are produced
What happens to T cells in the thymus?
Make T cells be able to recognise antigen and not destroy themselves
What is the thymic gene rearrangement?
Immature T cells rearrange the variable parts of their TCR gene in the thymus. it is random so that each of the T cells have a unique TCR thus creating diversity
What do CD4 T cells recognise?
peptide antigen in context of MHC-2
What do CD8 T cells recognise?
peptide antigen in context of MHC-1
What are T cells that have not been activated?
Naive
What are activated T cells known as?
Effector cells
What are effector cells function?
> Kill infected cells
Make cytokines
Support antibody production
remember the antigen for next time
What are memory T Cells?
the formation of effector T Cells and then T cell activation
How long do memory T cells remain in the body for?
Long time
What is the difference between memory and naive T cells?
memory t cells become effector cells again much quicker than naive T cells do for the first time
What are B Cells?
lymphocytes that secrete antibodies
What are plasma cells?
Activated B cells that secrete antibody
What are the primary lymphoid organs for B cells?
bone marrow and thymus
What are the secondary lymphoid organs for B Cells?
lymph nodes and spleen
What are the 2 chains involved in the B cell receptor structure?
Heavy and light chains
How are B Cells activated?
BCR cover the surface of the B Cell in which antigens bind to
What happens when B Cells are activated?
the B cell becomes a plasma cell and secretes antibodies
What are the functions of antibody?
> Neutralisation
Opsonisation
Complement activation
What is viral neutralisation?
cover up pathogen so it cannot get into anything that it doesn’t need to
What is opsonisation?
Antibody binds to the antigen then the phagocytes can recognise it as something that needs to be destroyed, therefore, increases the process of phagocytes
What is activation of complement?
Makes holes, includes antibodies. By them binding to the surface, they provide a site fore the compliment proteins to bind and work
What are the Antibody Isotypes?
IgM IgG IgA IgE IgD
What is the distribution of IgM?
> First Ig class produced after initial exposure to antigen > Expressed on naive B cells
What is the function of IgM?
> Very effective in activating complement targets
Extracellular Bacteria
acts as antigen receptor
What is the distribution of IgG?
> Most abundant Ig class in blood
What is the function of IgG?
> Opsonises/neutralises > Only Ig class that crosses placenta: provides passive immunity > Targets virus/bacteria
What is the distribution of IgA?
> Present in secretions such
> Monomeric form in blood
What is the function of IgA?
> defence of mucous membranes
present in breast milk
Confers passive immunity on nursing infant
Targets virus/bacteria
What is the distribution of IgE?
> present in blood in low conc.
What is the function of IgE?
> immunity to multicellular parasites
activates mast cells that blow up parasites
allergic reactions (down side)
What is the distribution of IgD?
> Expressed on naive B cells
What is the function of IgD?
> can act as antigen receptor (BCR)
> Specific function is unknown
What is the result of stimulation of B cells by antigen and help from T cell?
differentiation into plasma cells and a small number of stimulated B cells form a pool or memory cells
How long do memory cells persist for?
Years in blood and lymph
Do memory B cells secrete antibody?
no
How do memory B cells respond to seeing the same antigen?
rapidly - become a plasma cell
What is the primary immune response?
naive B cells
How long does the primary immune response take?
7-14 days
How many antibodies are secreted in the primary immune response?
Low amounts - mainly IgM
What does the secondary immune response rely on?
Memory B cells
How fast is the secondary immune response?
2-3 days
How many antibodies are produced in the secondary immune response?
Higher amounts
How fast is innate immunity?
Rapid
Is innate immunity specific?
no
does innate immunity have memory?
no
What is innate immunity important for?
response against bacterial pathogens
What are the chemical and physical barriers to bacterial attachment and invasion in the skin?
> dead cells and keratin
Salt - osmotic control
Sebum - trapping and pH
What are the chemical and physical barriers to bacterial attachment and invasion in the airways?
> Mucus - trapping
> Beating cilia moves trapped bacteria up tot he throat where they are swallowed
What are the chemical and physical barriers to bacterial attachment and invasion in the gut?
> constant flow of fluids
stomach acid
digestive enzymes
bile
What do lysozyms do?
Break binds between the glycopeptides
What happens if the bacteria makes it fast the first defence?
- Leukocytosis
- Margination
- Diapedesis
- Chemotaxis
What is leukocytosis?
Neutrophils enter blood from bone marrow
What is Margination?
Neutrophils cling to capillary wall
What is diapedesis?
Neutrophils flatten and squeeze out of capillaries
What is chemotaxis?
Neutrophils follow chemical trail
What are the events of phagocytosis?
- phagocyte adheres to pathogens or debris
- Phagocyte forms pseudopods that eventually engulf the particles, forming a phagosome
- Lysosome fuses with the phagocytic vesicle, forming a phagolysosome
- Toxic compounds and lysosomal enzymes destroy pathogens
- Sometimes exocytosis of the vesicle removes ingestible and residual material
What are the 3 pathways of complement activation?
Alternative pathway
Classical pathway
lectin pathway
What are the 3 outcomes of complement cascade?
label
destroy
recruit
What is the label (opsonisation) outcome?
coating a microbe with antibody and/or complement fragment C3b
What is destroy outcome?
Microbes coated with C3b are phagocytosed and assembly of MAC complex causes lysis
What is the recruit outcome?
Complement proteins act as peptide mediators of inflammation and recruit phagocytes
How fast is adaptive immunity?
slow
Is adaptive immunity specific?
highly
Does adaptive immunity have memory?
yes
What is adaptive immunity essential for?
the fight against intracellular pathogens such as viruses
What are the key stages of microbial pathogenesis?
- Adherence to host cells
- Invasion of host tissues
- Replication within host tissues
- Disease causing damage to host tissue
What are the phases of adaptive immunity?
Antigen recognition Lymphocyte activation Effector phase Decline Memory
How is the virus captured and presented in to the adaptive immune system?
Loads of viral capsids on the MHC II and locked out on the surface of the DC. Also locks some of the pieces of capsid and loads it onto MHC I
What is the model used for clonal selection/expansion?
Key and lock
How do cytotoxic T cells synthesise special proteins that specifically kill the virally infected host cell?
The infected host cell lets the cytotoxic cell know its infected by presenting the viral antigen on the cell surface using MHC I
How does the antibody producing ‘plasma cells’ develop to from b cells
- Unprocessed antigen to attach to the BCR
2. Helper T cell attaches to processed antigen presented by the APC cell MHC II.
What is neutralisation?
When antibodies cling to the sides of the virus
What is opsonisation?
Bind to microbes and make them more tasty
What is complete activation
alternative, lectin and classical pathways. classical is a potent activator of the compliment system
What are the 2 components of vaccines?
- antigen
2. adjuvant
What is adjuvant in vaccines?
helps to enhance the immune response against the antigen
What is the antigen in vaccines?
the specific molecule that the immune system may recognise
What are the three stages of progression of RA?
- initiation phase, an amplification phase
- chronic inflammatory phase
- tissue injury
What is the isotype found in allergic reactions?
IgE
What is the sequence of events in immediate (type 1) hypersensitivity?
> Exposure to the allergen
Antigen activation of the THC cells and stimulation of IgE class switching B cells
production of IgE
Binding of IgE to FccR on mast cell
Repeat exposure to allergen
Activation of mast cell: release of mediators
What cells do SCID not have?
B and T cells