13- Host Defense Flashcards
What is the innate and adaptive defense?
- Innate defenses: properties of the normal host, non-specific defenses.
- Adaptive defenses: induced by the infection, specific to the pathogen (based on antigens).
- First barriers: (innate defenses) skin
Innate defenses of skin and mucous membrane: normal microbiome? Antimicrobial substances? Innate defenses of the airways?
- Normal microbiome: competes for attachment sites and nutrients, secretes bacteriocin.
- Antimicrobial substances: fatty acids, lysozymes, antimicrobial peptides (AMPs), antibodies (if the host is immune).
- Skin: thick layer of dead cells.
- Mucous membrane: mucus.
Innate defenses of the airways
• Mucous membrane; mucus traps bacteria; ciliated cells remove mucus and trapped bacteria.
Innate defenses of tissues/internal fluids: Second line defense: Complement system? Phagocytes? Inflammation?
- If a pathogen manages to overcome the first line of defenses (skin, mucosa), it will encounter a second line of defenses:
- Complement system: set of proteins that creates pore in the pathogen membrane and induces lysis.
- Phagocytes: cells that take up and digest pathogens.
- Inflammation: general nonspecific response of the innate system to toxins, pathogens and tissue damage.
What is the Complement system? Activation of the classical and alternative pathway? Serum sensitivity?
- Set of blood proteins – also present in tissues – known as complement because they complement the action of antibodies. Proteins: C1, C2, C3, C4, C5, C6, C7, C8, C9.
- Activation by the classical pathway: antibodies.
- Activation by the alternative pathway: microbial cell wall components (polysaccharides, lipopolysaccharide).
- Activation of the complement results in the formation of a membrane attack complex (MAC, made of proteins C5b6789) that causes lysis of some Gram-negatives, no effect on Gram-positives.
- Serum sensitivity: test sensitivity to complement by exposing pathogens to serum (blood without RBC).
Membrane attack complex (MAC)?
Slide 32
- C5b binds C6 and C7
- C5b67 complexes bind to membrane via C7
- C8 binds to the complex and inserts into the cell membrane
- C9 molecule bind to the complex and polymerize
- 1-16 molecules of C9 bind to form a pore i nthe membrane
- membrane lesions- ends on (rings or tubes)
Cell of the immune systems?
Bone marrow steam cell… slide 33
Cell of the immune systems: white blood cells (monocytes, granulocytes, lymphocytes)
– Monocytes: circulate in the blood stream, attracted to inflamed tissues, differentiate into macrophages in tissues, phagocytic. Fixed macrophages in tissues.
– Granulocytes: their cytoplasm contains granules
• Eosinophils, basophils, neutrophils, mast cells
• Neutrophils are phagocytic, also called polymorphonuclear leucocytes (PMNs)
– Lymphocytes:
• B cells: antibodies
• T cells: T helper cells, cytotoxic T cells.
What are phagocytosis?
- Attachment of the organism to the membrane of the phagocyte.
- Ingestion: the organism become enclosed in a phagosome.
- A) Granules (endosomes,
lysosomes) containing hydrolytic enzymes fuse with the phagosome, formation of the phagolysosomes.
B) Oxidative burst: production of reactive oxygen species (ROS).
- Killing and digestion of the
microorganism.
Phagocytosis is carried primarily by neutrophils and macrophages.
What is inflammation? Characteristic signs? Functions?
• Characteristic signs: redness, heat, swelling and pain. Redness and heat are due to
vasodilatation – enlargement of the blood vessels.
Swelling is due to the passage of fluid (plasma) from blood vessels to the tissues – increased vascular permeability
(vasodilatation). Plasma contains antimicrobial proteins.
• Function: inflammation allows the recruitment of immune cells to the site of infection (vascular permeability) and an increase concentration of molecules
(complement subunits and antibodies).
Inflammation Role of Interleukin-1 (Il-1)?
Increase movement of fluid and immune cells to the infection sites.
Activate cells of the immune system (e.g. increase phagocytosis).
What is a fever?
- Macrophages can sense the presence of endotoxins (e.g. LPS), they have specific receptors for it.
- Induce production of fever-producing (pyrogen) signaling molecule: the cytokine Interleukin-1 (Il-1).
• Il-1 acts on the thermoregulatory center of the brain, which in turn causes the
body temperature to increase.
- Temperature higher than 37°C reduce the growth of some pathogens. Death if temperature reaches 44°C .
- Il-1 also activates phagocytes and other cells of the immune system, also cause inflammation.
What is Innate defenses?
• The innate system might be able to contain the infection and clear the microorganisms. – Complement. – Antimicrobial proteins. – Phagocytes (neutrophils, macrophages). – Inflammation (and fever).
What is adaptive defenses?
- During infection, the adaptive defenses are being primed. If the infection is prolonged, adaptive immunity will be called upon to help in the fight against the invading microorganisms.
- Adaptive defenses rely on the detection and response to foreign antigens, molecules of the microorganisms that can be recognized by the immune system.
- Cells of the adaptive immune system: B cells, T cells and antigen presenting cells (APCs: macrophages, dendritic cells; important for activation of the adaptive defenses).
(3: 1. specificity to antigen 2. memory (recognize the antigen) 3. ?)
What are B and T cells?
Population of T cells and B cells.
Virtually, each cell is specific for one antigen.
At the population level, T cells and B cells recognize billions of antigens.
Once activated by the antigen they recognize, T cells and B cells grow and produce copies of themselves. A cell that is specific for antigen X will
produce more cells specific for antigen X. Some cells will differentiate into memory cells, which role is to remember the antigen X.
Antigen specificity is randomly
generated during development of T cells and B cells. Cells that recognize host antigen are destroyed.
What are T-cells? (2 types)
• There are two types of T cells:
– T helper cells (TH): activate B cells and macrophages.
– Cytotoxic T cells (TC): kill host cells that display foreign antigen on their surfaces.
• Population of T cells in the body, each is specific for one antigen.
• APCs (antigen presentation cells) present antigen to Tcells. If the T cell is specific for this antigen, the T cell will become activated and produce interleukin 2 (Il-2).
This induces multiplication and
differentiation into effector T cells and memory T cells.
