Infection and Immunity - 3 - Flashcards in University Pharmacy

Why do we need an immune system?

To control the micro-organisms in the body (most organisms are commensal due to humans having an immune system)

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What is innate immunity?

Systems that you are born with, usually functional throughout life course until you die, prior exposure to micro-organisms is not required

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What is adaptive immunity?

Allows us to adapt to changing conditions to allow us to overcome an infection (micro-organisms can evolve and overcome the immune system in order to be successful/virulence factors). Higher vertebrates have evolved an adaptive immune system

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What is the first line of defence? (1)

Epithelial surface, skin surface/barrier, has microflora, harsh environment, washing of epithelial surface controls normal microflora (e.g. tears, mucus in respiratory system, cilia, sebaceous secretions, Zn in sperm etc)

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What is the first line of defence? (2)

Presence of other commensal micro-organisms also seen as innate immunity e.g. lactobacilli in vagina. Virulence factors - attachment and adhesion (cannot do this if other organisms are present)

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How can micro-organisms overcome the first line of defence? (1)

Micro-organisms can break through epithelial surface on the skin. Consequence of damage to barrier - alerts immune system that invade is present

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How can micro-organisms overcome the first line of defence? (2)

Pathogen evolved to damage host then alert immune system, pathogen gains access to more prosperous region but results in damage to barrier

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How does the human immune system distinguish pathogens from human tissues? (1)

In humans proteins are produced to allow survival in niche. In a pathogen, proteins are also produced to allow survival in their niche. Immune system can recognise primary sequence of protein (amino acid sequence)

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How does the human immune system distinguish pathogens from human tissues? (2)

If the immune system recognises the amino acid sequence for protein in human (self). If the immune system doesn't recognise the amino acid sequence for protein in pathogen (non-self)

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How does the human immune system distinguish pathogens from human tissues? (3)

Despite having enzymes between human and pathogen with the same function, the immune system can recognise the difference (different amino acids)

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The innate immune system is divided into which two systems?

Humoral (involves soluble proteins) and cell-mediated (involves using cells)

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Describe features of humoral factors (1)

Presence of bacteria results in the activation of the alternative complement pathway (sometimes fungi, not viruses). C3 protein (produced in liver in small amounts all the time/innate, produced/broken down cycle) breaks down to for C3a and C3b

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Describe features of humoral factors (2)

In the absence of bacteria (proteolytic lysis of proteins, cycling). Presence of bacterium - C3b attaches in bacterium surface, cell surface structures (PAMPs), C3b coats surface of bacterium (opsonisation)

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Describe features of humoral factors (3)

Cascade occurs. C3 and C3b combine to form C3 convertase enzyme (catalysis/hydrolysis of C3 to C3a and C3b, more C3b produced, more opsonisation occurs). Amplification of humoral response. C3 convertase stabilised by properdin

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Describe features of the cell-mediated response (1)

Next part of innate response. Neutrophils (long lived), monocytes (short lived due to maturing into macrophages) produced in bone marrow, passed into bloodstream. Macrophage lodged in secondary lymphoid tissue, strategically placed in the body

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Describe features of the cell-mediated response (2)

Become in contact with micro-organisms (8 sites e.g. alveolar macrophage, Kupffer cells/vaccine delivery). Neutrophils/macrophages (phagocytic cells) detect/engulf invading bacteria

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Describe features of the cell-mediated response (3)

Phagocytic cells will detect/engulf anything non-self (e.g. transplanted organs - different surface proteins, cancer cells - different surface structure)

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How does the innate immune response distinguish between a bacterium and a normal cell?

Bacterial cells are covered with C3b

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Describe features of phagocytosis (1)

Phagocytic cells have a C3b receptor on their surface (engulf anything coated with C3b). Phagolysosome produced, release contents, kill/degrade bacteria, oxygen dependent - generate toxic free radicals

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Describe features of phagocytosis (2)

Oxygen independent - degrade micro-organism in cellular debris

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What is the next step after phagocytosis?

Depends on the phagocytic cell (neutrophil, macrophage)

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How are neutrophils attracted to sites of infection?

Follow chemical gradient to site of infection (produced by C3a - which is produced by C3 convertase). Can pass through blood vessels in tissue/cross biological barriers. Target for C3b (PAMPs)

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PAMPs can cause which proteins to be produced as a result of infection?

Simulating acute phase proteins (e.g. mannose binding lectin and CRP - amplify the innate response by opsonisation). Infection - more C3 needed (stimulate CRP). Phagocytosis (presence of debris in liver stimulates acute phase proteins, more C3/CRP)

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Describe features of the acute inflammatory response

Mast cell degranulation at the site of infection, triggered by C3a being present (above a certain concentration), granules contain cytokines (e.g. histamine - inflammatory effect), other proteins can cause mast cell degranulation

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Give examples of the signs and infections of inflammation (infection)

Vasodilation, capillary permeability (allows neutrophils to get to site of infection), bronchoconstriction. Heat, swelling, redness, pain, loss of function

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How can micro-organisms overcome macrophage degranulation?

Degrade surface C3b, prevent fusion of granules, resist degradation

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Describe the innate immune response to Gram-negative bacteria (1)

E.g. E.coli (need to overcome phagocytosis and next step in cascade in order to survive/be successful). C3b binds to C3 to form C5 convertase (converts C5 into C5a and C5b). C5a has same effect as C3a (mast cell degranulation, chemogradient)

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Describe the innate immune response to Gram-negative bacteria (2)

On surface of Gram-negative organism, C5b bound (magnet for other proteins to join C6/7/8/9 - bound to C5b), complex of proteins forms a pore in the membrane (membrane attack complex - causes cell lysis)

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Describe features of the membrane attack complex

Gram-negative cell wall and membrane diameter are large compared to the membrane attack complex (only needs to reach a certain portion to cause cell lysis). But lack of knowledge about how the membrane attack complex works

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Describe the innate immune response to viruses (1)

Cells get infected with virus (requires host cell to replicate). Infected cell produces cytokines (interferons alpha/beta - protect uninfected cells). All cells have MHC I associated with them (recognised as self)

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Describe the innate immune response to viruses (2)

Viral cells stop producing MHC I due to infection (recognised as non-self). NK cells recognise cells which don't have MHC I/infected cells). MHC II (super antigens, APC cells involved). Humoral and cell-mediated responses for viral infection

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What are the five main features of the innate immune response?

Physical barriers, chemical barriers, inflammation, phagocytosis and NK-cells

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Infection and Immunity - 3

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