Acute inflammation Flashcards
What are the signs of inflammation (4)
- Rubor - redness
- dolor - pain
- calor - heat
- tumour - swelling
What is inflammation (2)
- A complex, coordinated response to damage or pathogen
- Orchestration of cell movement, activation and death via direct cell:cell contact and soluble mediators
what does innate immunity involve (4)
- 0-12 hours
- Epithelial barriers
- phagocytosis
- Complement & NK cells
what does adaptive immunity involve (3)
- 0-5 days
- B lymphocytes → clonal expansion → antibodies
- T lymphocytes → clonal expansion → antibodies
What happens in 1º Adaptive response (7)
- Naive T and B lymphocytes come into contact with antigen-presenting cells (recognition phase)
- Clonal expansion
- Differentiation - day 7
- resulting in antigen-producing cell and Effector T lymphocytes (activation phase)
- Humoral immunity and cell-mediated immunity result in the elimination of antigens (effector phase) - day 14
- Apoptosis (decline [homeostasis])
- Surviving memory cells (memory) - day >30
What happens in 2º Adaptive response (4)
- Naive B cells → antigen X B cell - week 1-2
- Activated B cells (Primary antigen X response) - week 3-4
- Memory cells & Naive B cells → Antigen X and Antigen Y - week 5-8
- Secondary antigen X response and primary antigen Y response = activated B cells - week 8-12
what is the adaptive immune system (5)
- longer lasting inflammation
- Specific
- Primary and secondary
- T and B cells
- Memory
How is the adaptive response controlled (3)
- Adaptive response can be variable - Th1/Th2/Treg, IgG/IgE
- Response determined by innate immune cytokine production
- DCs programmed to induce Th responses - IL-33, IL-23, TSLP (epithelial cell derived)
what is the innate immune system (6)
- ancient, evolutionary conserved response
- immediate response to barrier breach
- Non-specific, inborn recognition (PRRs)
- no memery
- Interacts with potentiates and adaptive immune response
- rarely malfunctions
what are the innate recognition molecules (6)
- collectins
- Mannan biding lectins
- Ficolins
- C-reactive proteins
- Toll-like receptors
- Lipopolysaccharide receptor
what are the innate cells (4)
- Neutrophils
- Mononuclear cells
- Natural Killer cells
- Eosinophils
what are the innate soluble components (2)
- Complement
- Interferons
what are the barriers for immunity (3)
- Epithelial layers - prevent microbial entry
- defensins/cathelicidin - microbial killing
- intraepithelial lymphocytes - microbial killing
What are the circulating effector cells (3)
- Neutrophils - early phagocytosis and microbial killing
- Macrophages - efficient phagocytosis and microbial killing, secretion of cytokines that stimulate inflammation, resolution via apoptotic cell phagocytosis
- NK cells - lysis of infected cells, activation of macrophages
what are the circulating effector proteins (3)
- Complement - microbial killing, opsonisation of microbes, activation of leukocytes
- Mannose-binding lectin (collectin) - opsonisation of microbes, activation of complement (lectin pathway)
- C-reactive protein - opsonisation of microbes, activation of complement
what are the cytokines (6)
- TNF, IL-1, chemokines - inflammation
- IFN-α, -β - resistance to viral infection
- IFN-γ - macrophage activation
- IL-12 - IFN-γ production by NK and T cells
- IL-15 - proliferation of NK cells
- IL-10, TGF-β - control of inflammation
what are the barriers to infection (9)
- lysozyme in tears and other secretions
- removal of particles by the rapid passage of air over turbinate bones
- Mucus, cilia
- Skin - physical barrier, fatty acids, commensals
- Low pH and commensals of the vagina
- stomach acid
- rapid pH change when going to the intestines from the stomach
- Commensals in the large intestine
- flushing or urinary tract
what are the outcomes of barrier breaches (3)
- pathogen destruction
- phagocyte activation
- inflammation
what happens during barrier breaches
cells of the innate immune system use recognition molecules - PRRs
how is there protection from adherence to epithelium (3)
- normal flora
- local chemical factors
- phagocytes (especially in lung)
how is there protection from local infection (penetration of epithelium) (3)
- would healing induced antimicrobial proteins and peptides
- phagocytes and complement destroy invading microorganisms,
- activation of gamma, beta and T cells
how is there protection from local infection of tissues (3)
- complement phagocytes, cytokines, NK cells
- activation of macrophages
- dendritic cells migrate to lymph nodes to initiate adaptive immunity
how is there protection from adaptive immunity (3)
- clearing infection by specific antibody
- T-cell-dependent macrophage activation
- cytotoxic T cells
how are leukocytes recruited (4)
- Rolling
- Tethering (integrin activation by chemokines)
- stable adhesion
- diapedesis (migration through endothelium)
How do PPRS work
Pattern Recognition Receptors (PRRs) recognise pathogen-associated molecular patterns (PAMPs) and recognise Damage associated molecular patterns (DAMPs)
how do phagocytes bind microbes (2)
- directly with cell surface PRRs
or - indirectly via soluble PRRs
What are PRR engagement outcomes (3)
- immobilise pathogen and phagocytosis
- activate host cell
- remove damaged tissue & promote wound healing (sterile inflammation)
What are PAMPs examples (4)
- LPS
- Mannose
- fmlp
- N-acetyl glucosamine/N-acetylgalactosamine
- Non-sialylated sugars
what are PRRs examples (3)
- Toll-like receptors (TRLs)
- Scavenger Receptors
- Opsonins
What are scavenger receptors (2)
- Involved in binding - modified low density lipoproteins, some polysaccharides, some nucleic acids
- Internalisation of - bacteria, apoptotic cells
What are opsonins (4)
- Bind target microbes or apoptotic cells
- Increase ‘attractiveness’ if target cell for phagocytosis
- Augment response to targets (bacteria, fungi, apoptotic cells)
Examples: complement, collectins, surfactant proteins A and D, ficolins
What are soluble defence mechanisms (4)
- Interferons
- Microcidal molecules
- Complement
- Cytokines
What are interferons (2)
IFN-alpha/beta - antiviral, target many cells, increase MHC I
IFN gamma - Th1 pro-inflammatory, target many cell types, activate macrophage
what are microbiocidal molecules (3)
- Collectins and ficolins
- Pentraxins
- Complement
What are collectins and ficolins (2)
- Recognise sugars on microbes and apototic cells
- MBL; ficolin -H, -L, and -M
What are pentraxins (3)
- familty of pentameric proteins
- CRP ans SAP
- recognise phospholipids on microbes and apoptotic cells
What are cellular defence mechanisms (3)
- Phagocytosis - macrophages, neutrophils, dendritic cells
- NK cell responses
- Intestinal gamma/beta/T cells
What happens during Phagocytosis (7)
- chemotaxis and adherence of microbe to phagocyte
- ingestion of microbe by phagocyte
- formation of a phagosome
- fusion of the phagosome with a lysosome to form a phagolysosome
- digestion of ingested microbe by enzymes
- formation of residual body containing indigestible material
- discharge of waste materials
What are the two types of phagocytosis (2)
- Take up microbes - immune response
- take up necrotic or apoptotic cells - initiation of inflammation, resolution of inflammation, maintenance of homeostasis
What are the phagocytosis outcomes (2)
- Inflammatory mediator release - cytokines/chemokines, oxidative burst (reactive oxygen species), lipid mediators (leukotrienes/prostagladins)
- Inflammation - pain, heat, redness, swelling, vascular permeability, cell recruitment and activation, resolution
What is resolution (5)
- once threat is gone
- remove recruited immune effector cells
- apoptosis is a controlled form of cell death
- anti-inflammatory
- altered cytokine expression
