I&I Flashcards
Name the 4 groups into which microbes can be classified
Viruses
Bacteria
Fungi
Parasites
Name the 2 types of parasite
Protozoa and helminths
Name 5 properties of viruses
1) They have a DNA or RNA core within a protein capsid made of capsomeres.
2) They have a helical, cubic or more complex arrangement
3) They have no cytoplasm
4) They may have an envelope derived from the host cell
5) They have membrane-bound attachment proteins
What is meant by the phrase ‘viruses are obligate intracellular organisms’?
Viruses must invade cells in order to replicate inside the cell
Name 3 viral causes of upper respiratory tract infection
Rhinovirus, influenza and RSV
Name 2 viral causes of gastroenteritis
Norovirus (SRSV) and adenovirus
Name 2 viral causes of rashes
Varicella zoster virus and measles
Name the virus responsible for meningitis
Enterovirus
What’s a healthcare associated infection?
An infection commonly acquired in hospital
Name 10 properties of bacteria
1) Prokaryotic cells
2) Haploid DNA
3) No nucleus
4) Usually have a rigid cell wall outside the cytoplasmic membrane
5) Circular DNA
6) No histones
7) No introns
8) No mitochondria
9) No membrane-bound organelles
10) Reproduce by binary fission
What’s the difference between strict aerobes and facultative aerobes?
Strict aerobes can only grow in free oxygen. Facultative aerobes can also grow in the absence of oxygen
What are the 2 main morphologies of bacteria?
Cocci (spherical) and rods/ bacilli (cylindrical)
Describe gram stain and how it divides bacteria
Gram positive bacteria stains blue. Gram negative bacteria stains red
What are the 2 factors that determine whether bacteria is gram positive or gram negative, and which is which?
The thickness of the peptidoglycan layer, and the presence or absence of an outer lipid membrane. Gram positive bacteria have a thick peptidoglycan layer and have no outer lipid membrane. Gram negative bacteria have a thin peptidoglycan layer and have an outer lipid membrane.
What bacteria commonly causes a UTI?
Escherichia coli
What bacteria commonly causes pharyngitis?
Streptococcus pyogenes
What bacteria commonly causes skin and soft tissue infection?
Streptococcus aureus
What bacteria is commonly responsible for causing post-operative wound infection?
Staphylococcus aureus
What bacteria is commonly responsible for causing ventilator-associated pneumonia?
Pseudomonas aeruginosa
Name 6 properties of fungi
- Eukaryotic
- Haploid or diploid DNA
- Mono- or polynucleate
- Have a rigid chitinous wall outside the cytoplasm
- May be multicellular or single cell or filamentous form.
- May be dimorphous
How do teleomorphous fungi reproduce?
Sexually
How do anamorphous fungi reproduce?
Asexually
Name 5 properties of parasites
- Single celled
- Single or multiple nuclei
- Haploid DNA
- Morphology varies throughout their life cycle
- May have flagella
What are helminths?
Helminths are multicellular parasitic worms which can be microscopic or visible to the naked eye. A lot of helminths don’t cause harm to humans.
What are protozoic parasites?
Single-celled eukaryotes which feed on organic material
Name the 4 components of blood
Plasma fluid, red blood cells, white blood cells and platelets
What are the most common type of RBC?
Erythrocytes
Describe the structure of RBCs
RBCs are biconcave discs which do not contain DNA, RNA, mitochondria or a nucleus
What is anaemia?
A condition in which there is a deficiency of red blood cells or of haemoglobin in the blood, leading to weariness and pallor
What are the 2 most common types of WBC?
Neutrophils and lymphocytes
Why are WBCs colourless?
They do not contain any haemoglobin and so have none of the Fe2+ ions that make RBCs red
What’s another name for a white blood cell?
A leukocyte
Name 2 properties of neutrophils
Neutrophils are polymorphonuclear, as they have irregular, multi-lobed nuclei
Neutrophils are granulocytes because they have prominent cytoplasmic granules
What’s the function of neutrophils?
Neutrophils are the first line of defence against pathogens. They phagocytose and kill bacteria and fungi
What’s the function of lymphocytes?
Lymphocytes are the main mediators of adaptive immunity. They produce antibodies and kill virus-infected cells.
What are the 2 types of mononuclear cells
Monocytes and lymphocytes
What are 2 properties of mononuclear cells?
They have large, regular nuclei and lack granules
What’s the function of monocytes?
Monocytes phagocytose dead cells and pathogens. They present antigens to T cells. Eventually, they become tissue macrophages which remove dead cell debris and attack microorganisms
What’s another name for platelets?
Thrombocytes
How are platelets formed?
Platelets form when cytoplasmic fragments of megakaryocytes (very large cells in bone marrow) pinch off into the circulation as they age
Name 3 properties of platelets
- No nucleus
- Membrane-bound
- Contain granules
What’s the function of platelets?
Platelets are responsible for causing blood clots (primary haemostasis) to form a platelet plug and stop bleeding
Where are mature blood cells produced?
Mature blood cells are produced from stem cells in the bone marrow
What are the components of blood plasma?
Water, salts, proteins (such as albumin), clotting factors, metabolites, carbohydrates, ions and lipids
What cations does plasma contain?
Na+, K+, Ca2+, Mg2+ and H+
What anions are present in plasma?
Cl-, PO4 3-, SO4 2-
What is serum?
Serum is the fluid left after blood clotting
What’s the most abundant protein in plasma?
Albumin (>90% of plasma protein)
What’s the difference between plasma and serum?
Plasma contains the clotting agent fibrinogen, while serum does not
How is blood important to transport?
Blood carries oxygen and nutrients to tissues and moves CO2 and other waste products. Blood also carries hormones from their source to their sites of action
How many polypeptide chains is haemoglobin made of?
2 alpha globin chains and 2 beta globin chains. All 4 carry a ham molecule
How does oxygen associate with haemoglobin?
Oxygen binds reversibly to the iron atom in each haem molecule via a coordinate bond
What does pulse oximetry measure?
Pulse oximetry measures the colour of someone’s haemoglobin and determines if the patient is hypoxic
How many Hb molecules are there in each RBC?
About 300,000,000
What is the function of an eosinophil?
Eosinophils kill parasites and are involved in allergic responses
What’s the function of a basophil?
Basophils make up less than 0.5% of WBCs. They’re involved in allergic responses and inflammation. Basophils contain heparin, a naturally-occurring blood-thinner, so they prevent blood clotting. Basophils release histamine to help in allergic reactions
What’s an immunoglobulin?
An immunoglobulin is an antibody, acting against pathogens to protect the body from infection
What’s a complement protein?
A plasma protein that can be activated directly by pathogens or indirectly by pathogen-bound antibody, which causes opsonisation and killing of bacteria
What is fibrinogen?
Fibrinogen is a major plasma protein that gets converted into fibrin in clot formation, to reinforce the primary platelet plug
How’s blood involved in homeostasis?
Blood maintains a pH of 7.4. Blood distributes heat around the body. Blood controls the distribution of water and solutes to tissues. Plasma pH, ion concentrations and protein concentrations must be kept within safe limits
What’s the average life span of RBCs?
120 days
What’s an approximate value for total blood volume in an adult?
Around 5 litres
What’s an approximate value for average plasma volume in an adult?
Around 40 ml/Kg
What the average haematocrit levels in men and women? (haematocrit level is the ratio of RBC volume to total blood volume)
For men, normal haematocrit level is 45%-52%
For women, normal haematocrit level is 37%-48%
What’s the function of albumin?
Albumin regulates the oncotic pressure of blood by binding water, cations, fatty acids, hormones, bilirubin, thyroxine and pharmaceuticals
What is a microbiome?
The microbiome is defined as the collective genomes of the microbes that live inside and on the human body
Define symbiosis
A relationship between 2 or more organisms that live closely together.
What is commensalistic symbiosis?
One organism benefits and the other is neither harmed nor helped
What is mutualistic symbiosis?
Both organisms benefit from the relationship
What are the 2 types of mutualists?
An obligate mutualist cannot survive with out its partner, while a facultative mutualist can survive alone
What is parasitic symbiosis?
Where one organism benefits and the other (the host) is harmed.
Commensals are also sometimes referred to as the ‘______ _____’, which may vary at different sites of the body.
normal flora
What bacteria make up the normal flora of the skin?
Staphylococci and corynebacteria, coliforms, enterococci
Rather than infecting the host, what do commensal microbes do?
Commensal microbes colonise the host. This isn’t the same as infection, as infection implies that harm is done
What is opportunistic infection?
Commensal microbes do no harm in healthy individuals, but if the host’s defences are weakened, the commensals may infect the host
Some organisms that are commensals at one site in the body can be pathogenic at another site. Give an example
Staphylococcus aureus is a commensal in the nasal cavity, however if it gets into post-operative wounds, it acts as a pathogen and causes infection
Name 6 sites which are generally sterile, having no normal flora
- The lower respiratory tract
- Blood
- Bone, joint and subcutaneous tissue
- Female upper genital tract
- Urinary tract
- CNS, including CSF and the eyes
What’s the name of the commensal on the skins outer surface
Staphylococcus epidermidis
What happens if staphylococcus epidermidis infects an intravenous line?
It causes a blood stream infection
What word describes highly pathogenic microbes?
Virulent
What’s a saprophyte?
A plant, fungus or microorganism that feeds off dead or decaying organic matter
Name 3 routes of spread of infection
- Airborne/ droplet pathogens can get into the respiratory tract
- Pathogens can get into the GI tract via food and water
- Pathogens can get into the body via breaks in the skin
Describe herpes simplex virus
Herpes simplex is between 120-300nm in diameter. It has an envelope with a nucleocapsid inside. In between the nucleocapsid and the envelope there’s a tegument. Herpes simplex cannot be seen under a microscope. It stores its genetic information as DNA.
What do herpes simplex type 1 and 2 infect?
Herpes simplex type 1 generally infects the mouth, while type 2 tends to infect the genitalia
What virus causes chicken pox?
Varicella zoster virus
What virus causes glandular fever?
Epstein Barr virus
Describe adenovirus
Adenovirus has no envelope and stores its genetic information as DNA. It has different serotypes which can cause eye infection, respiratory infections or gastrointestinal infection
Describe papillomavirus
Papillomavirus has no envelope and stores its genetic information as DNA. It causes warts and cervical cancer
Describe HIV
HIV has an envelope and stores its genetic information as RNA
What’s rotavirus?
A small, non-enveloped virus which causes diarrhoea
Describe ebola
Ebola is an RNA virus which is enveloped and can be transmitted from person to person via direct contact with blood or bodily fluids
How does ebola infect people?
Ebola enters the body through mucus membranes, breaks in the skin or parenterally, and can infect many different cell types. The virus migrates from the initial site of infection to the lymph nodes, then to the liver, spleen and adrenal glands
What’s acute inflammation?
An initial rapid response to injury. A non-specific innate immune response.
What are the 5 purposes for acute inflammation?
- Alert the body
- Limit spread of infection or injury
- Protect an injured site from infection
- Eliminate dead cells
- Create the conditions required for healing
What are the 5 R’s of acute inflammation?
- Recognition of injury
- Recruitment of leukocytes
- Removal of injurious agent
- Regulation
- Resolution/ repair of affected tissue
What are the 5 signs of acute inflammation?
Redness Swelling Heat Pain Loss of function
What 3 vascular events occur in acute inflammation?
Vasodilation
Increased blood flow to the injured area
Increased vessel permeability
What is the overall vascular effect of acute inflammation?
Leukocytes and plasma proteins exit vessels and enter the inflammation site to deal with infection
What is inflammatory exudate?
The fluid that causes the swelling associated with acute inflammation
What’s inflammatory exudate made of?
Water, salts, small plasma proteins (fibrinogen), inflammatory cells and RBC’s
What is a pyrogen?
A substance which induces a fever
Name 2 endogenous pyrogens
IL-1, IL-6, TNF-a
What are exogenous pyrogens?
Pyrogens from outside the body
Name 2 systemic changes from acute inflammation
Fever and neutrophilia
What does G-CSF stand for and what does it do?
Granulocyte-colony stimulating factor is a major extracellular regulator of haemopoiesis and more specifically neutrophil production
In rare cases, what can systemic inflammatory reactions lead to?
Sepsis, a form of SIRS
What vascular events occur in acute inflammation?
Vasodilation in the area in response to histamine and serotonin released by injured cells, macrophages and mast cells. The vasodilation means there’s more blood flow to the area. There’s also increased vessel permeability
What forms pus?
Dead neutrophils
What is transudate?
Fluid that leaks from blood vessels due to altered osmotic/ hydrostatic pressure, without any change to vessel permeability
Name the 5 steps of neutrophil recruitment
- Margination and rolling
- Integrin activation by chemokines
- Firm adhesion to the endothelium
- Transmigration through the endothelium into tissue
- Chemotaxis to the inflamed site
Name the 3 adhesion molecules involved in neutrophil recruitment
Selectins
Integrins
Immunoglobulin superfamily cell adhesion molecules (CAMs)
What are selectins and what do they do?
Selectins are CAMs which are expressed by activated endothelium and mediate the rolling of neutrophils
What are the 3 types of selectin and what’s the difference?
P-selectin is preformed by granules
E-selectin is induced by IL-1 and TNF-a
L-selectin is expressed by leukocytes
How do selectins mediate neutrophil rolling?
Selectins bind to ligands protruding from the surface of neutrophils in low affinity interactions. This means blood flow breaks the bonds, so neutrophils bind then detach easily, are pushed along by blood, then bind to another selectin etc. This is the rolling process along the endothelial cells of the blood vessels
Explain integrin activation by chemokines
Neutrophil rolling slows them down, so they have a lot of endothelial contact. Neutrophils express integrins (LFA-1) which are in a low affinity configuration, so they don’t bind to ligands. Activated endothelial cells produce and bind to chemokines, which bind to receptors on neutrophils. When chemokines bind to neutrophils, integrin is activated and becomes a high affinity configuration
What do activated integrins do?
Integrins bind to ligands on the endothelium. These ligands are ICAM-1 and VCAM-1. They’re induced by IL-1 and TNF-1 cytokines.
Describe the firm adhesion of neutrophils to the endothelium
The binding of integrins to ligands on the endothelium means neutrophils become firmly adhered to the endothelium
Describe neutrophil transmigration and chemotaxis
Neutrophils migrate through inter-endothelial spaces, passing through vessel walls and entering tissue. They migrate (chemotaxis) through tissue towards the inflamed site. A gradient of chemoattractants produced at the site of infection or damage guides the migration in tissues.
Name the 4 chemoattractants involved in neutrophil chemotaxis
Bacterial components
Chemokines (IL-8)
Complement components (C5a)
Leukotriene B4
How long do neutrophils live for in tissues?
6-24 hours
How long do monocytes live for in tissues?
24-48 hours
What reactions are eosinophils involved in?
Allergic reactions or reactions to parasitic infections
What reaction are lymphocytes involved in?
Reactions to viral infection
Name the 4 mechanisms of pathogen destruction by neutrophils
Release of granular content
Phagocytosis
Generation of reactive oxygen/nitrogen species
Formation of Neutrophil Extracellular Traps (NETs) (netosis)
What are neutrophil extracellular traps?
Neutrophil extracellular traps are a mesh of nuclear content (chromatin) which trap microbes and contain anti-microbial molecules
What’s a mast cell and what does it do?
Mast cells are located in tissues, close to blood vessels. The granules contain inflammatory mediators. The main role of mast cells is hypersensitivity type I (allergy), and dealing with parasites
What do macrophages do?
Macrophages are monocytes in the blood which carry out efficient phagocytosis and killing of microbes. They secrete inflammatory factors (cytokines) which lead to inflammation
What are dendritic cells?
Dendritic cells are found in the skin,mucosa and tissue. They capture microbes, phagocytose them, then present antigens to T cells
Via what patterns do immune system cells recognise pathogens from body cells?
Pathogen Associated Molecular Patterns (PAMPs)
What are PAMPs?
Structures shared by groups of related microbes and which are only present on pathogens, never on host cells. Without PAMPs, we would not be able to carry out immune responses to pathogens
How do phagocytes recognise pathogens?
Pattern Recognition Receptors (PRRs), which are receptors present on phagocytes and other cells such as those of the epithelia, which recognise PAMPs and can therefore detect foreign invaders or damaged host cells
What are the different classes of PRRs?
Toll-like receptors (TLRs) C-type lectin receptors (CTLRs) NOD-like receptors (NLRs) RIG-like helicase receptors (RLRs) Scavenger receptors
What is opsonisation?
A process in which microbes are coated with opsonins, which makes them more easy to phagocytose
How is a phagosome formed?
Rearrangement of the actin cytoskeleton and remodelling of the membrane
What are the 4 different enzymes involved in oxygen-independent pathogen decomposition?
Proteolytic enzymes (cathepsins)
Lysozymes
Lactoferrin
Defensins
Describe the oxygen-dependent mechanism for phagocytosis
Once the pathogen is in the phagolysosome, the phagocyte is activated and the NADPH oxidase system is activated. Oxygen gets converted into superoxide anions. Microbes are killed by oxidising radicals
How can some pathogens sabotage phagocytosis?
By blocking phagocyte attachment, blocking engulfing, blocking destruction or by killing phagocytes with toxins
What does cellular immunity involve?
Phagocytes and NK cells
What does humour immunity involve?
Complements, pattern receptors, enzymes and cytokines
Describe adaptive immune response to new infection
The response is slow, selects for specific signals and generates memory
Where are naïve T lymphocytes made and sent?
Made in the bone marrow and sent to the thymus gland
What is central tolerance/ negative selection?
The process of eliminating any developing T or B lymphocytes that are reactive to self (recognise self-antigens as foreign microbes)
What does central tolerance ensure?
That the immune system does not attack self-peptides
What’s the secondary mechanism to ensure that T and B cells are not self-reactive once they leave primary lymphoid organs?
Peripheral tolerance- this is distinct from central tolerance in that it occurs once developing immune cells exit primary lymphoid organs, prior to their export into the periphery
What’s the exogenous antigen pathway?
Antigens get processed in proteasomes into small peptides, then get presented with MHC class II molecules on the cell surface. A T helper cell recognises the presented antigen and attaches to the MHC class II molecule. The CD4+ T helper cell ‘licences’ the APC, detaches, releases cytokines and looks for a B cell
What is the endogenous antigen pathway?
Viral antigens are presented on MHC class I molecules’ cell surface. CD8+ T cells recognise the antigen and become cytotoxic. They then begin to make cytokines. This is promoted via prior CD4+ licensing.
What molecules do CD4+ molecules recognise?
MHC class II molecules
What molecules do CD8+ molecules recognise?
MHC class I molecules
What does MHC stand for?
major histocompatibility complex
What does B cell activation initiate?
Proliferation and the synthesis of some memory cells.
What is the first antibody made?
IgM
What do plasma cells create?
Monoclonal antibodies specific to the antigen of the pathogen
What recognises an antigen presented by a professional APC?
A B cell
What does a B cell that’s recognised an antigen release?
Chemokines that attract T helper cells
What does protease cleavage of an antibody generate?
2x Fab- antigen binding fragments
1x Fc- crystallisable fragment
What’s the function of the Fc constant region of an antibody?
Binding to receptors on phagocytes and activating complement
What is an antibody made of?
2 identical light polypeptide chains and 2 identical heavy chains, which have carbohydrates that are attached to them during their assembly in the Golgi body. The 4 chains are held together by non-covalent interactions and by disulphide bridges
What are the 5 Ig classes (isotypes) determines by the Fc sequence?
IgM IgD IgG IgA IgE
What is the most common class of antibody?
IgG (75%)
What immune responses make IgG antibodies?
Secondary responses
What is IgG good at?
Activating complement via the classical pathway
How does IgG induce phagocytosis?
IgG acts as an opsonin
What does IgM become a few days after its release?
IgM becomes IgG by changing its DNA in a process called Ig switching
Name 2 cytokines that signal to drive specific Ig switching
IL-5 and TGF-B permit IgA expression
What can IgM become?
IgM can become IgD, IgG, IgA or IgE, but cannot switch back to IgM
Natural immune responses are polyclonal. What does this mean for B-cell clones and Ig’s?
Multiple clones of B cells are generated, and more than 1 Ig is synthesised
Via what 3 ways does an immunoglobulin fight infection?
By opsonisation
By activating complement
By coating a pathogen to neutralise it
What’s the most abundant class of immunoglobulin in external secretions (milk, sweat, tears, saliva etc)?
Secretory IgA
What is IgA useful in?
The first line of protection at external surfaces. It initiates localised mucosal response different from more general circulating immune responses
When does IgE have a useful function?
In response to parasitic worms (helminths). It activates eosinophils via Fc receptor binding.
What are the weaknesses of IgA
Opsonisation and complement activation
What does over-response by IgE cause?
Anaphylactic shock
What’s the concentration of IgE in circulation like?
Normally low
What’s the concentration of IgD like in circulation?
Extremely low
Describe the structure of IgMs
IgMs are the largest antibody isotype and are usually pentameric, although they can be hexameric
Why is IgM found very little in the interstitium even though its mainly present in serum?
Due to its size, it cannot diffuse well out of blood vessels
What is chronic inflammation?
A long-lasting inflammatory response which may follow acute inflammation, or may have a slow, insidious onset. Chronic inflammation causes significant tissue destruction and attempts to repair the tissue result in fibrosis
What immune cells are involved in chronic and acute inflammation?
In chronic inflammation, adaptive immune responses involving macrophages, fibroblasts and lymphocytes are the main response, while in acute inflammation, mainly neutrophils and monocytes are involved
What are the mediators of chronic and acute inflammation?
Chronic inflammation- adaptive cytokines (IFN-gamma)
Acute inflammation- histamine, IL-1, TNF-a
What is the onset time for chronic inflammation?
Days-weeks
What’s the onset of acute inflammation?
Minutes-hours
What are macrophages derived from?
Monocytes in the blood which are recruited at the site of inflammation before differentiating
What are the tissue resident macrophages in the liver?
Kupffer cells
What are the tissue resident macrophages in the brain?
Microglial cells
What are the tissue resident macrophages in the lungs?
Alveolar macrophages
What role do macrophages do in tissue repair?
They released growth factors for tissue repair
How do macrophages recruit lymphocytes against chronic inflammation?
They produce TNF-a and IL-1 cytokines
How are eosinophils involved in response to chronic inflammation?
They’re involved in infections with parasites and IgE-mediated allergic reactions
What produces interferon-gamma (IFN-g) and what does it do?
IFN-g is produced by T cells and NK cells. It activates macrophages, increasing microbicidal activity
What are the 4 types of chronic inflammation?
Non-specific chronic inflammation
Autoimmune chronic inflammation
Chronic supparative inflammation
Chronic granulomatous inflammation
When does non-specific chronic inflammation tend to develop?
When acute inflammation fails to eradicate the causative agent.
What is autoimmune chronic inflammation?
When immune response to self-antigens causes insidious and progressive onset chronic inflammation
Name an example of chronic autoimmune inflammation?
Rheumatoid arthritis
What is chronic supparative inflammation?
Persisting supparative inflammation (pus-forming inflammation) that starts as acute purulent inflammation caused by Pyogenic Bacteria
What leads to abscess formation?
When fibrosis walls off a focus of acute inflammation so there’s a localised collection of purulent inflammation.
What are the 3 areas of an abscess?
A central area of necrotic leucocytes and tissue cells, a neutrophil zone and a fibrotic area
When does chronic granulomatous inflammation usually develop?
When the causing agent can’t be eradicated
What’s a granuloma?
A mass of granulation tissue, usually produced in response to infection or inflammation
What do granulomas consist of?
Macrophages, lymphocytes, fibroblasts and necrotic tissue in some cases
What does macrophage fusion form?
Multinucleate giant cells
How are the nuclei of a giant cell arranged?
Horseshoe arrangement
What tissue is repaired after chronic inflammation?
Parenchymal and connective tissue is repaired, while surface epithelium is healed
What does replacement with connective tissue mean?
Scar formation
What 2 ways can skin wounds heal by?
Primary and secondary intention
What are the conditions for primary intention healing of skin wounds?
The injury must be limited to the epithelial layer. The repair is by regeneration
What’s the first step of primary intention healing?
Coagulation is activated and a clot fills the wound. The external surface of the clot dehydrates and a scab forms
What happens after around 24 hours into primary intention healing?
Neutrophils infiltrate the wound margins and proteolytic enzymes are released, which clear debris and microbes
What happens in the 24-48 hour period of primary intention healing?
Epithelial cells migrate and proliferate at the wound edges, depositing ECM components and meeting in the midline beneath the scab
What happens by day 3 of primary intention healing?
Macrophages replace neutrophils and granulation tissue starts to invade the wound space. Macrophages clear cell debris
What happens by day 5 of primary intention healing?
Granulation tissue fills the wound with neovessels and oedema
What happens by the 2 week point of primary intention healing?
Fibroblast proliferation and collagen deposition continue, there’s vessel regression, and inflammatory infiltrate is reduced
What happens by the 1 month point of primary intention healing?
There’s scar formation from connective tissue, with no, or very few, inflammatory cells. The epidermis is normal. Dermal appendages are destroyed by incision.
When would secondary intention healing be used?
When there is more extensive tissue loss with the skin wound
What is secondary intention healing like compared to primary? (3 points)
The clot is bigger due to larger wounds.
There’s more exudate
Inflammation is more intense
What makes the scar bigger?
Granulation tissue is more extensive
Describe the scar formed from secondary intention healing
The scar is avascular and pale. It’s made of fibroblasts and dense collagen
What lymphocytes are involved in cellular immunity?
T lymphocytes
What lymphocytes are involved in humour immunity?
B lymphocytes
Th cells express what glycoprotein?
CD4
What are the 3 classes of T cells?
Th cells
Cytotoxic (CTL) T cells
Treg cells
What glycoprotein do CTLs express?
CD8
What’s the role of Th cells?
Activate macrophages and help B cells to produce antibodies
What’s the role of CTL cells?
Kill cells infected with microbes and kill tumour cells
What’s the role of T regulatory cells?
Inhibit or suppress the function of other T cells and control immune responses and tolerance
When do T cells recognise and become activated by antigens?
Once the antigens have been processed and presented by APCs
How do antibodies neutralise the extracellular microbes and toxins they bind to?
They prevent the binding of antigens to receptors or cells and block their entry or effects on cells
How do antibodies eliminate microbes?
Opsonisation to increase phagocytosis
Name 2 antigen presenting cells
Dendritic cells and macrophages
How do APCs activate T cells?
APCs process antigens into peptides, which bind to MHC molecules. The APC then presents the peptide-MHC complexes to activate T cells
What MHC class presents the antigenic peptides for CD4+ helper T cells?
MHC class II
What MHC class presents the antigenic peptides for CD8 CTLs?
MHC class I
What do gamma delta T cells recognise, which means they’re not MHC restricted?
Antigens that are not displayed by MHC class I or II
What’s a peptide binding cleft?
A groove in an MHC molecule that holds a peptide to be presented to T cells
Describe the steps of antigen recognition by CD4+ T cells (extracellular pathogens)
Antigen is taken up into vesicles in an APC via phagocytosis. The antigen is processed in endolysosomes into peptides. MHC class II produced in the ER is transported to endolysosomes, where it’s loaded with processed peptides. The peptide-MHC II complexes are displayed on the APC surface. CD4+ helper T cells can scan peptide-MHC II complexes on APCs
Describe antigen recognition by CD8+ T cells (intracellular pathogens)
Viral proteins are released in the cytosol, which are processed by proteasomes into peptides. The processed peptides are transported to the ER, where they’re loaded onto MHC I. The peptide-MHC I complexes are displayed on the cell surface and CD8+ CTLs scan the peptide-MHC I complexes
What 5 types of T cells are involved in cell-mediated immunity?
Th1 (CD4+) Th2 (CD4+) Th17 (CD4+) CTL (CD8+) Treg cells
What’s the role of Th1?
Help phagocytes to kill ingested microbes
What’s the role of Th2?
Help eosinohils/ mast cells to kill helminths
What’s the role of Th17?
Defence against bacteria and fungi
What’s the role of CTLs?
Kill cells infected by microbes that grow freely in the cytosol
What’s the role of Treg cells?
Inhibit immune responses
What’s the main cytokine in Th1-mediated response?
IFN-gamma
What are the 2 roles of IFN-gamma in Th1-mediated immune response?
To activate phagocytes for destruction of intracellular pathogens.
To stimulate IgG antibody production, increasing phagocytosis
What bacterium can block phagosome-lysosome fusion to prevent phagocytosis?
Mycobacterium
What are the 2 signals Th1 has that induce macrophage activation?
Signal 1- contact-mediated signals (CD40L-CD40)
Signal 2- soluble signals (IFN-gamma)
What do contact-mediated signals ensure?
That only the infected macrophage will receive help from Th1 cells (specificity)
Describe Th2-mediated immune response
Th2-mediated responses are responses against infections with helminths. Th2 cells help B cells produce antibodies to opsonise helminths and activate eosinophils and mast cells to destroy the helminths
Why aren’t helminths phagocytosed?
Helminths are too large to be phagocytosed and have a thick coat resistant to microbicidal activities of macrophages
What are the 3 Th2 cytokines?
IL-4, IL-5, IL-13
How do IL-4 and IL-13 aid the Th2-mediated immune response?
They stimulate IgE production, which opsonises helminths. Eosinophils can bind to the Fc of IgE
How does IL-5 aid the Th2-mediated immune response?
IL-5 activates bound eosinophils to kill helminths. The release of granule content by degranulation in eosinophils can destroy tough integument in worms
What do CTLs do for CD8+ CTL-mediated immune responses?
CTLs eliminate intracellular microbes, mainly viruses, growing in the cytosol. CTLs also kill microbes that escape from phagosomes into the cytosol, such as mycobacterium
Why aren’t healthy cells targeted by CTLs?
Killing by CTLs is antigen-specific and contact-dependent
What’s the function of the cytolytic protein perforin?
To form pores for the delivery of granzymes
What’s the function of cytolytic proteins granzyme A, B and C?
Initiate apoptosis by activating caspases
