Immunology - Introduction Flashcards
what barriers does the skin have to infection?
- tightly packed keratinsed cells
- physiological factors (low pH, low oxygen tension)
- sebaceous glands (hyrophobic oil repel water/micobes, lysozyme destroys cell walls, ammonia has anti-bac properties)
what barriers does the mucosal surface have to infection?
- secreted mucous (physical barrier, secretory IgA which prevents attachment into epithelia, lysozyme, lactoferrin starves bacteria of iron)
- cilia (trap and remove pathogens)
what does the commensal bacteria barrier do?
- compete for resoures
- produce fatty acids and bactericidins to inhibit growth
what are the different cells of the innate immune system?
- polymorphonuclear cells (neutrophils, eosinophils, basophils)
- monocytes and macrophages
- NK cells
- dendritic cells
what are the soluble components of the innate immune system?
- complement
- acute phase proteins
- cytokines and chemokines
what are the features of the cells of the innate immune system?
- identical in all individuals
- cells express receptors that allow them to detect and home to sites of infection
- express PRR to detect pathogens at site of infection
- phagocytic capacity to engulf pathogen
- secrete cytokines and chemokines to regulate immune response
where are polymorphonuclear cells produced and where do they go?
- produced in bone marrow
- migrate rapidly to site of infection
what do polymorphonuclear cells express?
- receptors for cytokines and chemokines to detect inflammation
- PRR to detect pathogens
- express Fc receptors for Ig (to detect immune complexes)
what do polymorphonuclear cells do?
- capable of phagocytosis/ oxidative and non-oxidative killing (esp neutrophils)
- release enzymes, histamine, lipid mediators of inflammation from granules
- secrete cytokines and chemokines to regulate inflammation
where are mononuclear cells present?
monocytes produced in bone marrow
circulate in blood to migrate to tissues
differentiate into macrophages
what do mononuclear cells do?
- capable of phagocytosis/ oxidative and non-oxidative killing (esp neutrophils)
- secrete cytokines and chemokines to regulate inflammation
- present processed antigen to T cells
what are macrophages called in the liver?
Kupffer cells
what are macrophages called in the kidney?
mesangial cells
what are macrophages called in the bone?
osteoclast
what are macrophages called in the spleen?
sinusoidal lining cell
what are macrophages called in the lung?
alveolar macrophage
what are macrophages called in the neural tissue?
microglia
what are macrophages called in the connective tissue?
histiocyte
what are macrophages called in the skin?
langerhans cells
what are macrophages called in the joints?
macrophage like synoviocytes
how are phagocytes recruited?
- cellular damage and bacterial products = local production of cytokines and chemokines
- cytokines activate vascular endothelium = enhanced vascular permeability
- chemokines attract phagoyctes
how are microorganisms recognised?
- PRRs recognise PAMPs
- Fc receptors bind to Fc portion of Ig to allow for recognition
what is the purpose of opsonisation?
- facilitates endocytosis
- opsonins act as a bridge between pathogen and phagocyte receptor
what are the 2 microbial killing mechanisms?
- oxidative killing
2. non oxidative killing
what are the steps to oxidative killing?
- NADPH oxidase converts oxygen to oxygen radical
- superoxide dismutase converts radical to hydrogen peroxide
- myeloperoxidase converts this with Cl- to hydrochlorus acid (HCOl)
what happens in non-oxidative killing?
- release of lysozyme and lactoferrin into phagolysosome
- enzymes present in distinct specific granules
describe the formation of pus
- phagocytosis depletes neutrophils glycogen reserves
- neutrophil death
- as cell dies, enzymes release and liquify local tissues
- accumulation of dead/dying neutrophils = pus
where are NK cells present?
within blood and migrate to inflamed tissues
kills altered self or virus infected
what do NK cells express?
- inhibitory receptors for self-HLA molecules to prevent mal activation by normal self
- a range of activator receptors
what is the function of NK cells?
- integrate signals from inhibitoru and activator receptors
- secrete cytokines to regulate inflammation (promote dendritic cell function)
where do you find dendritic cells? what do they represent?
reside in peripheral tissues
represent innate-adaptive transition
what to dendritic cells express? purpose?
- cytokine/chemokine receptors to detect inflammation
- PRRs to detect pathogens
- Fc receptors for Ig to detect immune complexes
what are the functions of dendritic cells?
- capable of phagocytosis (following this the DC mature)
- upregulate expression of HLA molecules
- express costimulatory molecules
- migrate via lymphatics to lymph nodes (mediated by CCR7)
- present processed antigen to T cells in lymph nodes to prime adaptive response
- express cytokines to regulate immune response
what are the components of the adaptive immune system?
- humoral immunity (B lymphocytes, antibodies)
- cellular immunity (T lymphocytes = CD4, CD8)
- soluble components (cytokines and chemokines)
what are the characteristics of the adaptive immune response?
- wide repertoire of antigen receptors
- good specificity (detects small difference in molecule structure)
- clonal expansion (appropriate cells will proliferate during infection)
- immunological memory
what are the primary lymphoid organs and what do they do?
organs involved in lymphocyte development
- bone marrow: T and B cells derived, B cells mature
- thymus: T cells mature
what are secondary lymphoid organs and what do they do?
sites of interaction between naive cells and microorganisms
- spleen
- lymph nodes
- MALT
describe the process of T lymphocyte maturation?
- arise from haematopoetic stem cells
- exported as immature cells to thymus
- undergo selection
- mature T lymphocytes enter circulation and reside in secondary lymphoid organs
what do CD8+ T cells recognise?
recognise peptides presented by HLA class I molecules
what do CD4+ T cells recognise?
recognise peptides presented by HLA class 2 II molecules
how does selection and central tolerance of T cells work?
- low affinity for HLA (not selected to avoid inadequate reactivity)
- intermediate affinity for HLA (positive selection, around 10% of cells)
- high affinity for HLA (negative selection to avoid autoreactivity)
what decides how T cells differentiate?
- intermediate affinity for HLA class I = differentiate as CD8+ T cell
- intermediate affinity for HLA class II = differentiate as CD4+ T cell
what are the 3 different types of T lymphocytes?
- CD4+ Helper cells
- CD8+ Cytotoxic Killer cells
- T cell memory
what do CD4+ Helper cells do?
- recognise peptides presented on HLA class 2 molecules
- immunoregulatory functions via cell-cell interactions and expression of cytokines
- provide help for developing full B cell response
- provide help for developing some CD8+ T cell response
what do CD8+ cytotoxic cells do?
- specialised cytotoxic cells that kill cells directly (perforin and granzymes, expression of Fas ligand)
- recognise peptides derived from intracellular proteins (from HLA class 1)
- secrete cytokines
- important in defence against viruses and tumours
wgat do T memory cells do?
- response to successive exposures to antigen is quicker and bigger than first exposure
what are the CD4+ T cell subsets?
Th1 Th17 Treg TFh Th2
what do Th1 cells do?
help CD8 T cells and macrophages
secrete IFN gamma, IL-2, IFN alpha, IL10
what do Th17 cells do?
help neutrophil recruitment
enhance generation of autoanitbodies
secrete IL-17
what do T reg cells do?
express Foxp3 and CD25
IL-10/TGF beta expressing
what do T follicular helper cells do?
promote germinal centre reactions and differentiation of B cells into IgG and IgA secreting cells
what do Th2 cells do?
secrete IL4, IL5, IL13, IL10
allergy (IL-4)
helper T cells
how does central tolerance work in B cells?
- no recognition of self in bone marrow = survive
- recognition of self in bone marrow = negative selection to avoid autoreactivity
describe the steps to B lymphocyte activation?
- B cell receptor binds to antigen
- some B cells mature to plasma cells (secrete IgM)
- if signalled from CD4+ T cells, B cells rapidly proliferate
what happens to B cells to improve specificity?
- isotype switching to IgG, IgA, IgE (needs CD40)
- somatic hypermutation to generate high affinity receptors
what part of the immunoglobin determines the antibody class?
heavy chain
what is the function of antibodies?
- identify pathogens/toxins
- interact with other components of immune response (complement, phagocytes, NK cells)
what are the features of the secondary immune response (B cell memory)?
- lag time between antigen exposure to antibody production is decreased
- more antibodies produced
- response dominated by IgG antibodies of high affinity
- may be independent of help from CD4+ lymphocytes
what is the complement system?
> 20 proteins
produced in liver
present as inactive molecules in circulation
when triggered, enzymatically activate each other in biological cascade
what are the 3 pathways in which complement can be activated?
- classical pathway
- mannose binding lectin
- alternative pathway
describe the classical pathway
antibody + C1 –> C2, C4 –> C3
changed antibody site exposes C1 binding site
C1 binding to antibody activates cascade
antibody-antigen immune complexes
describe the mannose binding lectin pathway
MBL –> C2, C4 –> C3
binding of MBL to microbial cell surface CHO
direct stimulation of classical pathway
not dependent on acquired immune response
describe the alternative pathway
PAMP –> C3
C3 binds to bacterial cell wall components (e.g. LPS)
involves factors B, I, P
not dependent on acquired immune response
which is the major amplification step in the complement cascade?
C3
what happens when complement is activated?
- inc vascular permeability and cell movement
- opsonisation of immune complexes
- opsonisation of pathogens (promote phagocytosis)
- active phagocytes
- promote mast cell and basophil degranulation
- form MAC (via C5-C9) to punch holes in membrane
