Immunology Flashcards
How does the immune system identify harmful organisms
- by distinguishing self from non self proteins
- identifying danger signals (eg from inflammation)
what occurs when the immune system goes wrong?
- allergies
- recurrent infections
- autoimmune disease
- cancer
- transplant rejection
What is veriolation
immunisation where the same organism is admin as the disease–> causing organism but the route of admin is different
eg exposure of an individual to the contents of dried smallpox from an infected patient
What is immunisation
when one disease may protect against another by cross reactive antibodies that neutralise the other infection too
What is the unequal battle between host and pathogen?
pathogens evolve alot faster than hosts, host have to rely upon a flexible and rapid immune response, with a degree on non-specificity
Barriers to infection: SKIN
SKIN- physical barrier (tight packed cells), physiological barrier (low pH), sebaceous glands (secrete hydrophobic oils, lysozymes, defensins, ammonia) low O2 tension, cells undergo renewal
Barriers to infection: MUCOUS
Physiological barrier, secretory IgA, enzymes (lysozymes, defensins, antimicrobial peptides directly killing pathogens, lactoferrin acts to starve invading bacteria of iron) cilia (trap pathogens and revove mucous)
Barriers to infection: COMMENSAL BACTERIA
compete with pathogens for scarce resources and produce fatty acids and bactericidins that inhibit the growth of pathogens
What are first line defences?
physcial barriers
what are second line defences?
immune barriers
what is the innate immune system?
rapid response (0-4h) general response
what cells does the innate imune response involve?
-mast cells
-NK cells
-phagocytes
-complement
these are responsible for acute inflammation and killing of pathogen
what is the adaptive immune response?
slow response (4-96h) unique response- immunological memory
what cells does the adaptive immune response involve?
antigens
Cell components of the immune system?
PHAGOCYTES (neutrophils, monocytes, macrophages, dendritic cells) ingest and kill bacteria, important source of cytokines
LYMPHOCYTES (T cells, B cells, natural killer cells)
EOSINOPHILS, MAST CELLS AND BASOPHILS
Soluble components of the immune system?
ANTIBODIES (immunoglobulins- produced in response to antigens) COMPLEMENT PROTEINS (produced in the liver, critical role in inflammation and defence, complement cascade)
name 3 Haemotopoietic stem cells
Common lymphoid progenitor
Common myeloid progenitor
Common erythoid megakaryocyte progenitor
Common lymphoid progenitor function:
differentiate into lymphocytes
NK/T precursors develop in the thymus
Common myeloid progenitor function:
Differentiate into phagocytes, basophils, eosinophils and mast cells
Common erythoid megakaryocyte progenitor function:
differentiate into platelets and erythrocytes
Mast cells:
- reside in tissues and protect mucosal surface
- degranulates and releases trypsin and tryptase
- gene expression- TNF, chemokines and leukotrines
- fight parasites
- allergic reactions
Basophils and eosinophils:
- circulate in blood
- recruited to sites of infection
- fight parasites
- allergic reactions
Phagocytes:
ingest and kill bacteria and fungi, also clear debris from dead tissue cells and produce cytokines that will promote and acute inflammatory response
Neutrophils:
- circulate in blood
- rapidly recruited to inflammed and infected tissues
- short lives professional killer cells
- PAMP recognition and activation
- active neutrophils produce TNF
PAMP AND PRR
The innate immune system constitutes the first line of defense against invading microbial pathogens and relies on a large family of pattern recognition receptors (PRRs), which detect distinct evolutionarily conserved structures on pathogens, termed pathogen-associated molecular patterns (PAMPs).
how do neutrophils attack pathogens?
Phagocytosis
release of antimicrobial peptides and degradative proteases
generate extracellular traps
what does dead neutrophils+tissue cells+ microbial debri=?
PUS
Lysosomes in neutrophils:
- contain toxic reactive species (oxidative killing), hydrolytic enzymes and acidic pH that makes them good at killing pathogens
Monocytes:
- monocytes are precursors of macrophages
- limit inflammation
- involved in tisue repair and healing
Macrophages:
- reside in tissues
- ingest and kill extracellular pathogens
- clear debris from dead tissue cells
- inflammation
- tissu repair and would healing
- antigen presentation
Dendritic cells:
- immature cels in peripheral tissues
- when in contact with a pathogen they mature and migrate to secondary lympoid tissues
- stimulate adaptive immune response
Natural killer cells:
- large granular lympocytes
- specifically kill tumour and viral infected cells
- can also kill anti-body bound cells
- kill by realsease lytic granules
- release a cytokine gamma-INF which engances macrophage killing activities
T and B cells:
- Mature cells constantly circulate through blood, lymph and secondary lympoid tissues and are activated when they meet a pathogen
- long lived T and B cells are known as memory cells
T cells:
defence agains pathogens
- Helper T cells (regulators of the immune system and activate other immune cells - CD4+)
- Cytotoxic T cells (kill virally infected body cells- CD8+)
B cells:
produce antibodies
What happens in primary lympoid tissues?
site of leukocyte development (bone marrow and thymus)
What happens in secondary lympoid tissue?
site where adaptive immune responses initiate (tonsils, spleen, lymph nodes)
function of lymph nodes?
remove pathogens and antigens from lymph
Direct contact of the immune system?
receptor- ligand interactions
indirect contact of the immune system?
production and secrettion of cytokines
Cytokines
- produced in response to infection, inflammation and tissue damage
- produced in injured tissue cells and activated immune cells
- short half life
- can cause fever via the hypothalamus
- co-ordinate the immune system by modulating cell behaviour
Cytokine signals:
Autocrine signals (for self) paracrine signals (for near by cells) signals for distant cells
Examples of Cytokines
INTERFERONS: anti-viral functions
TNF: tumour necrosing factor, pro-infammatory
CHEMOKINES:control and direct cell migration
INTERLEUKINS:
IL1 AND IL6= proinflammatory
IL2 = T cell proliferation
IL10= anti inflammatory
aim of the innate immue response
acute inflammation and killing of pathogens
Recongition phase in the innate immune response:
PRRs (pattern recognition receptors)
-PRR toll like receptor 4 is found on the cell surface- this find the lipopolysaccharide PAMP
-PRR Detectin 1 is found on the cell surface- find the B-glucans
-PRR NOD2 is found intracellularly- find the muramyl dipeptide
-PRR toll like receptor 7 is found intracellularly- find ssRNA
PAMPs (pathogen associated molecular patterns) (neutrophils uses this for recognition and activation)
Activation phase of the innate immune response:
inflammation and pathogen killin
Pro-inflammatory effects of histamine from mast cell degranulation:
- increased vascular permeability
- vasodilation
- activation of endothelial cells
- pain
Pro-inflammatory effects of tryptase from mast cell degranulation:
-proteolytic enzyme
Pro-inflammatory effects of TNF from mast cell degranulation:
- increased vascular permeability
- activation of endothelial cells
Pro-inflammatory effects of leukotrenes from mast cell degranulation:
- smooth muscle contration
- increased vascular permeability
Pro-inflammatory effects of chemokines from mast cell degranulation:
-attract other innate immune cells
Acute phase reponse:
liver produces acute pahse proteins in repsonse to pro-inflammatory cytokines (IL1, IL6 + TNF)
- increased vascular permeability
- activation of endoethelial cells
- increased neutrophil production and mobilisation
Molecules expressed on active endothelial cells at sites of inflammation:
ACHESION MOLECULES (SELECTINS AND ICAMS)- allow leukocytes to bind weakly to endothelial cells and roll slowly along endothelial surface CHEMOKINES then activate the leukocyte so that they can bind more strongly to the endothelial cell- integrins on the leukocyte then bind to the ICAMs on the endotheilial surface Once inside the cel the leukocytes follow a chemokine gradient to get to the site of infection
Leukocyte adhesion deficency:
rare genetic disease defined by a loss in B2 integrins causing defective transendothelial migratoin. ie leukocytes cannot leave the bood stream and infections cannot be cured
Phagocyte defiency disease:
CHRONIC GRANULOMATOUS DISEASE: recurrent bacterial and fungal infections
Phagocyte defiency disease:
CHRONIC GRANULOMATOUS DISEASE: recurrent bacterial and fungal infections
Complement System
Family of proteins produced in the liver that circulate in the blood
Enter infected and inflamed tissues
3 pathways of the complement system
Classical pathway- antigen-antibody complexes
Lectin pathway- mannose binding lectin (MBL) binds to certain sugars on the pathogens surface
Alternative pathway- amplification loop which causes the spontaneous breakdown of C3–>C3b+C3a (positive feedback)
Functions of the complement system
- Membrane attack complex
- Opsonisation(Coating of microorganisms by immune proteins (opsonins) EG, C3b, CRP, antibodies…Enhances phagocytosis)
- Chemotaxis
- Clearance of immune complexes
- Inflammation
4 complement inhibitors
C1 Inhibitor, Factor I, Factor H and C4 binding
antigens
(communication between pathogen and leukocyte)
Cause adaptive immune response by activating B and T cells
T cells recognise pathogen by
T cell antigen receptor = membrane-bound protein heterodimer (Has alpha and beta chain)
B cells recognise pathogen by
B cell antigen receptor = membrane bound antibody (IgM or IgD) (Has light and heavy chain and disulphide bridges. Membrane bound and soluble proteins)
HLA/ MHC
The human leukocyte antigen (HLA) system or complex is a gene complex encoding the major histocompatibility complex (MHC) proteins in humans. These cell-surface proteins are responsible for the regulation of the immune system in humans.
MHC/HLA proteins display peptide antigens to T cells
Class 1 - expressed on all nucleated cells - present peptide antigens to cytotoxic T cells
Class 2 - expressed only on dendritic cells, macrophages, B cells - present peptide antigens to helper T cells
Stromal cells:
found in B cell zones and trop opsonised antigens
Stromal cells:
found in B cell zones and trop opsonised antigens
Antibodies
- Immunoglobulins
- Produced by B cells in response to an antigen, bind specifically
- Provide defence against extracellular pathogens
- Each heavy and light chain contains a variable region and a constant domain
- Variable regions - antigen binding sites
what antibodies do mothers pass onto their children?
IgG and dimeric IgA
what antibodies found on B cell membranes as B cell antigen receptors
IgM and IgD
Recognition function of antibodies
Binding to antigen mediated by variable region sites
Effector function of antibodies
Clearance mechanisms mediated interaction of Fc constant region with effector molecules (Complement molecules and Fc receptors)
Agglutination
Immune complex formation
antibodies can function as opsonins:
phagocytes have FC receptors and therefore bind to the Fc region of immunoglobulins which are circling the pathogen, enhancing phagocytotic clearnace
antibodies can stimulate NK cells:
have FC receptors too and so bind to antibody bound to the pathogen
antibodies can trigger allergic responses:
mast cells have Fc receptors which bind to Fc on antibody and causes mast cell degranulation
germinal centre
Germinal center are sites within secondary lymphoid organs – lymph nodes and the spleen[1] where mature B cells proliferate, differentiate, and mutate their antibody genes, and switch the class of their antibodies (for example from IgM to IgG) during a normal immune response to an infection.
germinal centre reactions
- B cell proliferation
- Antibody heavy chain switching
- Generation of high affinity antibodies
- Differentiation into Plasma cells and Memory B cells
IL2
helper T cells produce these to increase proliferation of bother helper T cells themselves and Cytotoxic T cells- once helper T cells have migrated to the site of infection and inflammation they are reactivated by marcrophages
Somatic hypermutation
to produce antibodies that recognise the same antigen but with increased affinity, achieved by point mutation made in the heavy light chain gene segments
IgG
is the secondary response to antigens
