Infection and Inflammation Flashcards
List points in the viral replication cycle where the immune system can act.
Some defensive strategies of the immune
system are directed against free virus particles, destroying them directly or neutralising their ability to infect cells. Other strategies are directed at the infected cells, either blocking virus replication, or killing the infected cells.
Outline the antiviral effects of antibodies and the antigenic variation of the influenza virus.
- The antibody can block the binding ability and therefore the entry of the virus to cells by attaching to their antigens. They also activate intracellular degradation via TRIM21. TRIM21 can trigger ubiquitination of the virus to target it for degradation by proteasomes.
- An antibody and a complement of proteins can damage enveloped viruses and carry out opsonization for phagocytosis.
Describe the sequence of innate and adaptive defence mechanisms employed against intracellular viruses.
Antibodies cannot enter the cytoplasm of the cells if not already bound to the virus upon its entry into the cell. Production of cytokines, particularly interferons, natural killer cells and the T-mediated killing of infected cells all work together synergistically to fight the infection.
Outline the production and activities of type I interferons.
Interferon-interferon receptor reaction between the surfaces of other cells introduces an antiviral state. Enzymes are activated which bring about resistance to viruses, such as degrading viral mRNA and inhibiting protein synthesis.
Describe the recognition of infected target cells by CD8 cytotoxic T cells.
Some proteins in the virus are degraded, and the polypeptide is bound to the HLA Class I protein. This complex is expressed on the surface of the infected cell and acts as a target for recognition by a cytotoxic T cell that is specific to that viral peptide. The cytotoxic T cell then kills the infected cell.
Describe the recognition of target cells by natural killer (NK) cells (large granular lymphocytes).
- antibody-dependent cellular cytotoxicity. NK cells have Fc gamma receptors on their surface, so can be a target for recognition for antibodies specific to an antigen.
Explain how NK cells distinguish target cells to be killed from normal cells that should not be killed.
The NK mechanism of target cell recognition depends on the fact that the NK cells contain two types of receptor molecules. When the virus binds, a positive signal is sent to the NK cell to kill the virus. The use of two receptors stops normal cells being killed, as the second receptor sends a dominant inhibitory signal.
Describe the processes of target cell killing by NK cells and cytotoxic T cells.
Killer cells have granules in their cytoplasms called perforins and granzymes, which are secreted onto the surface of target cells.
Perforins perforate the membranes of the target cells. Water moves in, leading osmotic lysis. Perforins also allow granzymes to enter the cytoplasm of the target cell, activating the cell’s caspase enzymes, which activate endonuclease enzymes, which induce apoptosis of the target cells.
Killer cells can also express fas ligand on their surface, which binds to the protein as if it is expressed on the target cell, leading again to programmed apoptosis via caspase and endonuclease enzymes. Killer cells also produce type 2 interferon (IFN-), that has anti-viral activity and enhances HLA class I and class II expression.
Outline the functions of skin and describe how skin structure facilitates these.
protection - against UV light, infection, keratin
waterproof - the sensation of touch, temperature and pressure, phospholipid
thermoregulation - vasodilation/constriction, erector pili muscles, hair follicles
metabolism - synthesis of vitamin D3, fat is energy store.
Describe the structure and contents of the layers of the skin: epidermis, dermis and hypodermis, including the blood supply
epidermis - stratified squamous, forms keratinocytes
dermis - connective tissue formed of fibroblasts, collagen I, elastin, blood, nerves and receptors. It is divided into the papillary and the reticular dermis
hypodermis - formed of adipose tissue and main blood supply
Describe the detailed structure and cell types of the epidermis of skin and relate them to their functions, including the processes of keratinisation and pigmentation
Keratinocytes - formed of stratified squamous keratinising epithelial cells and produces keratin.
Melanocytes - pigment synthesising cells responsible for skin and hair colour.
Langerhans cells - communicate with the immune system.
Merkel cells - neuroendocrine function.
Outline some pathologies arising from defects in skin structure
albinism, vilitigo, basal cell/squamous cell carcinoma, melanoma, epidermolysis bullosa
Explain the purpose and structure of the skin appendages, glands and sensory organs
sensory nerve endings - responsible for deep pressure and vibration.
meissner’s corpuscle - rapidly adapting mechanoreceptors for light touch and pressure sensation.
ruffini corpuscle - mechanoreceptors, and is used in the stretching of the skin.
efferent nerve endings - control vessel diameter and blood flow and send information to sweat glands and arrector pili muscles.
Eccrine sweat glands are a dermal-subcut junction of all skin and produce sweat. The ducts open onto the skin surface and have a role in thermoregulation.
Apocrine sweat glands are localised on the axilla/groin and are used in scent production. They open into hair follicles above the sebaceous duct. They are functional at puberty.
Explain how skin structure varies with function in different parts of the body; recognise and explain the difference between thick and thin skin
Thin skin is present in most locations. This epidermis has less well defined rete ridges, a thinner keratin layer, and lots of eccrine glands. Thick skin is present on the fingertips and soles of feet. It is characterised by thick epidermis and thick keratin layer, well developed rete ridges, and lots of eccrine glands, with no hair.
Hairy skin is present on the scalp, axilla and groin. It has a thin epidermis, lots of hair follicles and sebaceous glands. In curly hair, the follicles are oblique. Lots of apocrine glands in the axilla and groin.
To describe how cells adapt to changes in their environment
maintain homeostasis, atrophy, involution, metaplasia, hypertrophy, hyperplasia
To establish the possible outcomes of inflammation
resolution, repair (fibrosis/scarring), chronic inflammation, or abscess formation
To define the capacity of different tissues to regenerate and repair
Labile cells can resolve damage.
Stable cells are capable of regeneration and so can resolve or scar.
Permanent, non-dividing cells will always scar and have a consequent loss of function.
To describe the process of tissue resolution and repair and the differences between them
Resolution arises from damage to parenchyma in labile or stable tissues. The damaging stimulus is removed, and inflammatory cells, mediators and exudate are introduced. Injured cells are replaced by regeneration, and this restores normal function. There is minimal or absent evidence of damage.
Repair arises from damage to parenchyma and stroma (or in the brain or muscle). The damaged tissue is replaced with connective tissue. Formation of granulation tissue and scar tissue occurs. The tissue is remodelled for strength and lacks the functional capabilities of the damaged tissue.
To describe the process of wound healing in relation to skin
inflammatory phase - acute inflammation and the arrival of macrophages which produce growth factors for the next phase occurs.
proliferative phase - granulation tissue is formed, building tissue to fill the wound. Fibroblasts secrete matrix components, growth factors to stimulate angiogenesis, and epithelial cells to regrow over the wound.
remodelling phase - remodelling/organisation of the matrix takes place to develop appropriate tissue architecture for the function of the tissue. Due to the action of fibroblasts laying down collagen and collagenases breaking down collagen to orientate for maximal tensile strength. Wound contraction and decreased vascularity follows.
To list mediators of the repair process
growth factors, which are hormone-like molecules that stimulate proliferation, differentiation and the maturation of cells. In healing they attract endothelial cells and fibroblasts and therefore have a role in angiogenesis and the production of the extracellular matrix.
To consider examples of scarring causing disease (fibrosis)
Pathological fibrosis occurs where repair is the problem. In the liver, this is cirrhosis. In the lung, this is interstitial fibrosis, such as asbestosis.
Outline different social-cognition models of health behaviour change including the Health Belief Model and the Theory of Planned Behaviour.
Health Belief Model - useful to help to predict, understand and address non-adherence to treatment. It is better at predicting initiation of health protective behaviours (such as screening) than reducing health risk behaviour (such as smoking)
Theory of Planned Behaviour - idea of perceived behavioural control. It suggests what constraints might be on a person to stop them from doing a particular behaviour, intentions don’t always turn into actions.
Understand the role of patient motivation and self-efficacy in behaviour change.
people are influenced by factors in their life when it comes to undertaking health behaviours
Apply psychological theory to the design of individualised interventions to improve patients’ health-related behaviour.
The health belief model ensures people understand threat, minimise barriers, increase cues to action and increase self-efficacy. The planned behaviour model thinks about people’s resources and opportunities, and what normative beliefs they might have.
We must understand how a person’s societal norms might influence their ability to complete the behaviour. Social cognition also plays a role.
Apply Motivational Interviewing approaches to health-related behaviour change.
Motivational interviewing is a type of counselling that is patient centred that acts to explore and resolve ambivalence about behaviour change. It is useful for people who are unmotivated and unprepared for change. It is not as useful for people who are already motivated to change. The idea is to increase motivation, and then make a commitment to change.
Defining health beliefs and culture
Culture is an umbrella term which encompasses the social behaviour and norms found in human societies, as well as the knowledge, beliefs, arts, laws, customs, capabilities and habits of the individuals in these groups.