Immunology - Immune Response/Physiology Flashcards
What are the stages of a normal innate response?
- Phagocytes are produced in the bone marrow and released into the blood
- Endothelial cells express adhesion molecules
- Phagocytes stick to the blood vessel wall and migrate into the tissue
- Phaogcytes engulf the micro-organisms
- Phaogcytes kill the micro-organisms through oxidate and non-oxidative killing
- Neutrophils die after phagocytosis and form pus
- Macrophages are activated and use cytokines for cell-cell communication (predominantly with T cells)
What are three consistutive, non-specific barriers to infection?
- Skin
- Mucosal surfaces
- Commensal bacteria
How does skin act as a barrier to infection
- Tightly packed keratinised cells physically limits colonisatioin by micro-organisms
- Physical factors (e.g. low pH, low oxygen tension)
- Hostile wall with sebaceous glands (hydophobic oils repel water + micro-organisms, lysozyme destroys bacterial cell wall, ammonia and defensins = antibacterial)
How do the mucosal surfaces act as a barrier to infection?
- Secrete mucous = traps invading pathogens (secretory IgA prevents bacteria/virus attachment to cell membrane, lysozyme kills invading pathogens, lactoferrin starves bcteria of iron)
- Cilia directly trap and remove mucous, assited by physical manoeuvres (sneezing/coughing)
How do commensal bacteria act as a barrier to infection?
- Compete with pathogenic micro-organisms for scarce resources
- Produce fatty acids that inhibit growth of many pathogens
What aspects are part of the innate immune system?
Cells:
- polymorphonuclear cells = neutrophils, eosinophils, basophils
- monocytes + macrophages
- natural killer cells
- dendritic cells
- granulocytes
Soluble components:
- complement
- acute phase proteins
- cytokines + chemokines
How do cells generally work as part of the innate immune system?
- Express receptors for cytokines/chemokines (detect inflammation)
- Express pattern recognition receptors (detect pathogens)
- Phagocytosis / oxidative + non-oxidative killing
- Secrete cytokines + chemokines (regulate inflammation)
What is the role of polymorphonuclear cells / granulocytes in the innate immune system?
- Produced in bone marrow
- Rapid migration to site of injury
- Express Fc receptors for Ig (detect immune complexes)
- Release enzymes, histamine, lipid mediators of inflammation from granules
What is the role of monocytes/macrophages in the innate immune system?
- Monocytes produced in bone marrow, circulate in blood + migrate to tissues where they differentiate into macrophages
- Present processed antigens to T cells
- Name dependent on tissure (e.g. Kupffer cell = liver, osteoclast = bone, langerhans cells = skin)
What is the process of oxidative killing?
- NADPH oxidase complex converts oxygen to reactive oxygen speces (e.g. hydrogen peroxide)
- Myeloperoxidase catalyses production of hydrochlorous acid (from hydrogen peroxide and chloride)
- Hydrochlorous acid = effective oxidant and anti-microbial
What is the process of non-oxidative killing?
- Release of bactericidal enzymes (lysozymes + lactoferrin) into phagolysosome
- Enzymes present in granules (each has unique antimicrobial spectrum = broad coverage against bacteria + fungi)
What is the role of the neutrophil in the innate immune system
Death of the phagocyte
- Phagocytosis depletes neutrophil glycogen reserves (energy expensive) which leads to cell death
- As cell dies, residual enzymes released causing liquefaction of close tissue
- Assumulation of dead/dying neutrophils forms pus
- Extensive localised formation of pus causes abscess formation
What is the role of the natural killer cell (cytotoxic lymphocyte) in the innate immune system?
- Present within blood + migrates to inflamed tissue
- Expresses inhibitory receptors for self-HLA molecules (prevents inappropriate activation by normal self)
- Expresses range of activating receptors (e.g. natural cytotoxicity receptors) that recognise heparan sulphate proteoglycans
- Cytotoxic
- Secrete cytokines to regulate inflammation
What is the definition of cytotoxic?
Kills “altered self”, malignant or cirus infected cells which lack inhibitory signals
What is endocytosis facilitated by and what does it do?
Opsonisation = Opsonins act as bridge between pathogen and phagocyte receptors
- Abs bind to Fc receptors
- Complement components bind to complement receptors
- Acute phase proteins