Immunology and Healthcare Theme 1 Flashcards
what is immunology
the study of the body’s defence against infection- allow tolerance of pathogenic infections
what is the importance of immunology
Infections including oral infections are common in individual as they are epidemics of infectious disease. E.g influenza
There are a wide range of clinical conditions (including those with oral manifestations) associated with immune dysfunction.
Rational diagnosis and therapy of disease relies on the understanding of pathogenesis
Vaccination as a key healthcare strategy for both individuals and population
Population disease experience is dynamic
what is the involvement of immunology in gingivitis and periodontitis
Gingivitis- driven by plaque microbiome, presented by acute inflammation. Inflammation Is when the immune system is facing a challenge, redness and swelling.
Periodontitis- chronic associated with tissue destruction. Alveolar bone receded.
what are the symptoms and of inflammation
Symptoms: pain, redness, swelling (increased blood flow) , heat and loss of function.
Causes: chronic infection, autoimmune, hypersensitivity (environmental stimulus), metabolic disorders and immunodeficiency (age and genetic factors).
what is necrotising ulcerative gingivitis (NUG)
Microbial disease (mixed bacterial infection) of the gingiva in the context of an impaired host response
Associated with stress, smoking, HIV & nutritional deficiency
Ulcer- loss of epithelium due to acute infection.
Very painful
Treatment:
- Plaque control (Chlorhexidine, ultrasonics or OHI)
- Metronidazole
what is sjogren’s disease
Autoimmune disease of salivary gland
Inflammation of salivary glands
Infiltration of white blood cells
Swelling in the salivary glands- should be distinguished from abscesses (common) and glandular fever (less common).
what is involved in the pro-inflammatory cytokines stimulate matrix
Diagnosis and therapy rely on understanding the disorder
The ways in which the immune system works. Can stimulate periodontal cells to cause tissue destruction.
Inflammation brings more blood to the region which is good, but in the chronic state the gingival fibroblasts will make MMPs which destroys proteins such as collagen.
Typically this is what a fibroblast does, but when over stimulated the balance tips towards disease.
IL-1 isn’t the only molecule that will stimulate MMP
- E.g . Leptin (present in the inflammatory state)
why is the number of reported cases lower than estimated actual cases
because it is possible to have the virus but not have the actual disease. Asymptomatic.
what are the main functions of the immune system
- Recognition of non-self microbes & viruses
- Effector function (contain/eradicate infection)
- Regulation (appropriate and measured response) -prevent inappropriate immune responses such as chronic inflammation or hypersensitivity
- Memory - immediate and stronger response on second exposure.
what are the features of innate immunity
all multicellular organisms have this. Enhanced by adaptive.
•Rapid response
•Fixed response (rate/intensity always similar)
•Limited number of specificities
•Constant during response
Innate immunity will activate adaptive immunity
Innate will reinforce adaptive -integrated response (i.e. complement system)
what are the features of
Adaptive immunity
- Slow immunity (days to weeks)- requires several cell to cell interactions and processes
- Variable response due to antigen specificity- immune reponse to any macromolecule. It can change and develop.
- Numerous highly selective specificities
- Improve during diagnosis
- Antigen specific, targeted, effective response
what are the innate immunity effector mechanisms and signs and symptoms of this
immediate defenses
- physical, chemical, and microbiological barriers
- complement
- phagocytosis
no signs and symptoms: natural homeostatic function
what are the adaptive immunity effector mechanisms and signs and symptoms of this
Induced defenses:
- cytokines and chemotaxis
- interferon response
- antibodies
- cell mediated immunity
- memory
what can malfunction of the immune response lead to
e.g. persistent or inappropriate inflammation
analysis and manipulation of the immune repsonse are health care strategies
what can cytokines do
induce chemotaxis and an interferon response (cytokine involved in viral infections)
how is the skin a physical barrier to infection
external body surfaces
- keratin-dry barrier to infection
- thick
- cell-cell junctions
- low pH inhibits microbial growth
- lactic acid from sweat glands lowers pH
- fatty acids from sebaceous glands lowers pH
what are the external bod surfaces that are barriers ti infection
skin
nails (keratin)
ducts (fluid flow)
how do bacteria enter when we have a burn
acute infection and serious inflammation. Burns remove epithelium, expose tissue, bacteria gets in, moist surface, vascular damage e.g. Pseudomonas aeruginosa
how do bacteria enter when we have curs/surgery
Staphylococcus aureus (normally on skin, however will penetrate the dermis)
what occurs in acne
infected sebaceous gland ducts/hair follicles- blocked glands
how are the Mucosal surfaces susceptible to infection
airways, GI tract etc, no keratin- epithelial tissue very susceptible to infection.
outline the mucosal defence system
- Mucin = highly glycosylated protein
- Mucin (protein secreted by glands in the epithelium-) + water = mucous
- Secreted by goblet cells
- Ciliated epithelium in airways which traps bacteria/particles
- Cells destroyed by smoking/tobacco or in CF- mucous dysfunctional, particles clogging up trachea and lungs
- Airways infected due to loss of innate immunity
how are the Internal body surfaces (mucosal surfaces) barriers to infection
- Large surface area
- No keratin
- Mucins (form mucus with water): coat microorganisms preventing attachment
- Ciliated epithelium (protection and ejection of large particles)
- Flow of air and fluid
how is saliva a barrier to infection
- Lysozyme: digests bacterial cell walls
* Lactoferrin: removed iron required by bacteria
how is the GI tract a barrier to infection
- Acid environment in stomach, bladder, kidney, bile
* Digestive enzymes inhibit growth
what are Other disorders of compromised physical barriers
- Abnormally thick mucus (e.g. in Cystic Fibrosis) leads to lung infections e.g. P. aeruginosa infection
- Corneal and ear infections upon water exposure (dirty)
- Smoking damages ciliated epithelia in the airways
- Higher rate of sepsis (blood poisoning) after surgery in area of high flora e.g. colon
what is the role of bacteria at mucosal surfaces
- Pathogens can overwhelm host defences and are adapted to do so
- Symbiotic relationship ‘mutualism’
- Can cause disease after trauma e.g. E. coli into blood leading to sepsis and septic shock (sepsis that happens very quickly leading to loss of blood pressure involving acute chronic inflammation- acute shut down of major organs ).
how do Non-pathogenic (commensal) bacteria also protect surfaces from pathogenic infection
- Stimulate colonic epithelial cells giving a balanced state called physiological inflammation
- Dysregulation of this interaction leads to pathology (e.g. Crohn’s disease)
- Compete with pathogens for nutrients, attachment sites and living space
- Fatty acids from propionibacteria (on skin) are toxic to streptococci
how does c difficile cause mucosal injury
colonisation by large numbers of commensal bacteria
antibiotics kill many of these commensal bacteria
c.diff gains a foothold and produces toxins that cause mucosal injury
neutrophils and red blood cells leak into the gut between injured epithelial cells
what are soluble mediators of innate immunity
- Enzymes: lysozyme and phospholipase digest cell walls and membranes respectively (in tears, saliva and phagocytes)
- Complement components: 3 FUCNTIONS lysis, opsonisation (more attractive for phagocytosis) and chemotaxis (movement of WBC in tissues)
- Antimicrobial peptides: gets into bacteria cell membrane and disrupts - cell lysis
what are Antimicrobial peptides (AMPs)
- Defensins disrupt cell membranes via their amphipathicity (have both hydrophilic and hydrophobic properties)
- Made by epithelial surfaces
- Kill bacteria, fungi and enveloped viruses by perturbing their membranes
- Selective action of individual AMPs but some 21 different AMPs made by Paneth cells (intestine at the bottom of crypts- protection) alone
- Neutrophils/Paneth cells - α-defensins
- Epithelial cells - β-defensins
- Broad range of action
What are cathelcidins, histadins and lectins?
•Cathelcidins – family of polypeptides
Found in lysosomes of macrophages and leukocytes
Disintegrates cell membranes of organisms
•Histadins -Produced by salivary glands
•Lectins – carbohydrate binding proteins
Found in foods/nature
Involved in biological recognition & mediate attachment of bacteria/viruses to their targets
what are paneth cells
- Specialised epithelial cells of the small intestine
- Make α-defensins (also called cryptidins)
- Make lysozyme and phospholipase
- AMPs and enzymes kill enteric pathogens
- Important as there is lots of bacteria in and around the gut
what is the Innate immune effector functions I: The complement system
- A group of some 30 blood and tissue fluid proteins
- Proteolytic cleavage of a cascade of proteins (c.f. blood clotting, activation of apoptosis)
- function to directly attack pathogens
- Also, function to mark pathogens for phagocytosis (opsonisation)
- Work with (‘complement’) antibodies
- Stimulates chemotaxis e.g. neutrophils- enter region of acute inflammation.
outline how complement activation works
- alternative pathway- pathogen surface creates lcal environment conductive to complement activation
- lectin pathway- manose binding lectin binds to pathogens surface
3- c-reactive protein or antibody binds to specific antigen on pathogen surface
this is causes complement acitvation
then cleavage of C3 to C3a and C3b - C3b covalently bound to surface components of pathogen
recuritment of infammaotry cells
opsnization of pathogens
perforation of cell membranes
PATHOGEN DEATH
why is c3 important
people lacking it are prone to severe infections
• C3 activates and cleaved into C3A and C3B
• C3B (large) becomes covalently bound to the pathogens surface - complement fixation (tags pathogen for destruction)
• C3A acts as chemoattractant to recruit effector cells
what is the Action of complement 1:
Formation of membrane attack complex with consequent disruption of bacterial outer membrane and bacterial cell death
what is the Action of complement 2
Opsonisation for phagocytosis- antibody binds to bacteria which is encapsulated and activates complement and bonding of C3b to bacteria
bacteria engulfed by neutrophils mediated by fc recpetors and complement receptors
granules fuse with phagosomes, releasing toxic oxygen metabolites that kill bacteria
what are the 2 categories of lymphoid tissues
primary lymphoid tissues
secondary lymphoid tissues
what are the primary lymphoid tissues
bone marrow and thymus
what are the secondary lymphoid tissues
SITE OF IMMUNE RESPONSE
widely distributed in the body
where lymphocytes are activated.
These include: lymph nodes, tonsils, spleen, Peyer’s patches and mucosa associated lymphoid tissue (MALT)
what is the function of red bone marrow
Haematopoiesis – makes white and red blood cells- In bone marrow and periphery
Haematopoiesis driven via cytokine production & stroma
Homeostatically controlled – different branches can be switched on/off depending on demands
Replaced by yellow (fatty) bone marrow that doesn’t undergo haematopoiesis.
what do cytokines do
Cytokine encourage the development of WBCs
Cytokines dictate the type of immune response we get
what does lymph flow rely on
muscular activity – reason why if you are bed ridden accumulation of lymph occurs
what is stroma
connective tissue cells which have a structural/functional role in every organ
what is the function of the thymus
- Train and develop T-lymphocytes (maturity)
- Small bilobed organ above the heart
- Has a connective tissue capsule – defines it as a distinct organ
- Extension of bone marrow
- T-cell maturation- thymus takes the T-cell and fine tunes the maturation of them- key regulators of the immune response.
what do t-cells orignate from
pluripotent haematopoetic stem cell in the bone marrow
what are the 2 mechanisms of WBC production
- lymphoid - lymphocytes
- myeloid line- generates the rest- eosinophils, basophils, monocyte, neutrophils, platelets and erythrocytes)
where are mast cells and macrophages found
aren’t found circulating in the blood – are a result of circulating blood cells differentiating in tissues.
What is the name of the precursor cells which forms platelets and where is it found?
Megakaryocyte- found in bone marrow
What is the function of neutrophils and how can they be identified?
Involved in phagocytosis- engulf bacteria and digest. The granules contain lysosomal enzymes.
Identified by: multi globular nucleus, lobes on nucleus
What is the function of eosinophils and how can they be identified?
Fight parasites and infections
Contains major basic protein (MBP) which is alkaline
Granules appear red
What is the function of basophils and how can they be identified?
Involved in allergic reactions
Contains histamine, heparin and peroxidases
Granules appear blue
what are NK cells
(natural killer) cells – concerned with anti-viral immunity, innate lymphoid cells
what are Innate lymohiud cells (ILC)
look like lymphocytes but are part of the innate system
what cells are part of the adaptive immune response
B cells and T cells are part of the adaptive immune response
outline thymus histology
- Lobular structure
- Fibrous capsule on outside (distinct)- defines boundaries
- Has a cortex and medulla
- Dots – production of WBCs
what occurs in thymus
- Maturation of T cells takes place in the thymus
- Entry of t cells to the cortex, as you go to the inner medullary some T-cells diminish - filter out the t-cells you don’t want.
how can you differentiate between peyers patch and thymus
• Peyer’s patch on tonsils don’t have fibrous capsule
what is secondary lymphoid tissue and its function
- Composed of aggregates of leukocytes (lymphocytes/DCs/macrophages) and stromal cells- support and survival signals
- Capture antigens and antigen presenting cells from sites of infection
- Initiate immune responses i.e. activation and expansion of particular immune cells
what is the role of the spleen in secondary lymphoid tissue
The spleen protects against blood-borne infections-especially encapsulated bacteria- has a well-developed blood supply (cleans blood)
where do lymph nodes appear
Lymph nodes appear at the convergence of lymphatics and protect against tissue infections
where is Mucosa associated lymph tissue (MALT)
airways, GI/urogenitary tract , nasopharynx, thyroid, breast, lung, salivary glands, eye, and skin (exposed to environment - most pathogens will enter body this way).
what is the function of MALT
initiates immune responses to specific antigens encountered along all mucosal surfaces.
MALT inductive sites are secondary immune tissues where antigen sampling occurs and immune responses are initiated
Provide composed of aggregates of lymphoid (lymphocytes/DCs/macrophages) and stromal cells (which provide support and survival signals)..
outline Lymph node histology
follicles- ring like structures
germinal centre where new cells are generated
(see notes for image)
what is the function of the Peyer’s patch of the small intestine and where are they located
- Secondary lymph tissue responsible for maintaining the health of the immune system
- Underneath epithelium is the peyers patch
- have Dendritic cells – very good antigen presenting cells. Activate B and T cells in secondary lymphoid tissues
what is the function of M cells in peyers patches
Between microvilli
take up pathogenic antigens and provides the antigen for the dendritic cells and the peyers patch
outline the histology of peyers patches
Ring of lymphoid cells•
No defined structure/ has surface epithelium
No fibrous capsule- its just the collection of WBC that has collected under the surface
what is the function of the tonsils
Waldeyer’s ring – ring of lymphoid tissue at back of throat (tonsils)
- Provides protection to the back of the throat AND the top of the GI tract
- Common site of infection – tonsillitis - lots of ridges in tonsil area and things get stuck causing acute inflammation.
May lead to tonsillectomy- not as common due to general anaesthetic complications, and we also have good antibiotics.
outline the histology of tonsils
- Have follicles with germinating centre/ epithelium
- Epithelium isn’t wavy like in Peyer’s patch.
- Lots of riges- oppourtinity for collection of food
- No villi so not peyers patch
- Glandular tissue therefore NOT a peyers patch
outline the Immune responses in mucosa-associated lymphoid tissue (MALT)
• Stimulated lymphocytes move between MALT sites rather than in the general circulation
• Similar mechanism in different MALT sites; greater functional importance than internal lymphoid organs
- Massive surface area of mucus membranes (400m2)
- Load of antigen from food, air, natural microflora
how is the MALT protected
• Antibody from activated cells secreted externally- protection of mucosal surfaces
- We swallow bacteria generate immune response in peyeres patches
- cells transport to salivary glands which have plasma cells secreting antibodies into saliva (providing protection against carious bacteria)
Other than the gut, what other anatomical locations have MALT tissue?
Tonsillar tissue and thymus
what do phagocytes do
activate all different types of immune responses (wont have to identify)
what are monocytes and what do they do
Precursor of macrophages.
Circulate blood, enter tissues on infection and develop into macrophages. Kidney shaped and large
what are Macrophages and what do they do
Granular, large cell with an irregular surface. They phagocytose bacteria, virus and fungi - does this to activate t-cells, process that takes place in mucosa and lymphoid tissues.
what are the cells involved phagocytosis
Phagocytes Monocytes Macrophage- Granulocytes Mast cells Dendritic cells
what is the functions of macrophages
multitasker
phagocytosis and cytokine activation
how are macrophages involved in cytokine function
- Responds to the presence of bacterial components by secreting cytokines. They will signal other cells and help in the immune response
- Signal neutrophils and initiate inflammation via cytokines – key trigger of chemotaxis
how are macrophages involved in phagocytosis
•Have a role in presenting antigen (fragments of microorganism which generative adaptive immune responses) and activating T-cells
-Activate acquired immune response
•Act as scavenger cells to clear debris and dead cells – used neutrophils undergo apoptosis and are taken up by macrophage
- Sit in the spleen
what is the function of neutrophils
phagocytose to CLEAR infections
• Part of the myeloid lineage
• A ‘granulocyte’ or ‘polymorphonuclear’ leukocyte
• Short lived effector cells (unlike macrophages)
• Capture, engulf and kill microorganisms
• Rapidly mobilised in the early stages of infection
• Gingivitis- lots of neutrophils in gums – inflammation allows neutrophils to get to the site of infection
• Require a lot of energy – if not healthy susceptible to more infection as can’t supply the energy required to drive these cells
• Contribute to inflammation
what wbc is in the bone marrow and when is it released
neutrophils
released when needed to fight infection
neutrophils travel to and enter the infected tissue, where they engulf and kill bacteria. the neutrophils die in the tissue and are engulfed and degrade by macrophages
- Tissue is red -gingivitis
- Swells
- Neutrophils flood in
- Neutrophils phagocytosed by macrophages
what are the Stages of phagocytosis
- Driven by receptors on neutrophils such as complement Fc.
- Internalised into phagosome
- Phagosome acidified (kills most pathogens)
- Fuses with lysosomes to form phagolysosome
- Neutrophils have primary and secondary granules also which contains additional enzymes and AMPs (go into cell membrane and lyse bacteria)
- Toxic molecules such as nitric oxide and reactive oxygen species (ROS) are also generated
what is the function of dendritic cells
- BEST antigen presenter
- Activate cells and initate immune responses
- Antigen presenting cells (APC)- macrophages, dendritic cells and B-cells
- Take up antigens in the periphery, pass via the lymph node and present antigens to B/T cells
- Phagocytose microorganisms and antigens in tissues
- Purpose to present antigen in the initiation of immune responses in secondary lymphoid tissues (lymph nodes and MALT)
DCs do not have a role in clearance of microorganisms
what is the function of Mast cells
- granules contain histamine which induce muscle contraction/ wheezing
- Signalling cells – aim to get rid of parasites (we don’t need these if we don’t live in africa
- Mast cells mediate hypersensitivity
what are the responses involved in signalling of the effector due to phagocytic recognition of a pathogen
chemotaxis of new phagocytes
interferon response
systemic effects: acute phase response
activation of adaptive immunity
what is the interferon response
specific mechanism to combat viral infections. cytokine produced by immune cells involved in antiviral immunity
what is signalling of the effector response mediated by
distinguish self from non-self
outline the receptor characteristics of the innate immune system
specificity inherited in the genome
expressed by all cells of a particular type e.g. macrophages
triggers immediate response
recognises broad class of pathogens
interacts with a range of molecular structures of a given type
•Innate immunity recognises common structures within bacteria/fungi (i.e. lipopolysaccharide endotoxin)– cannot differentiate between these molecules.
