- List some features of skin that makes it an effective barrier to infection.
Consists of tightly-packed keratinised cells
Low pH
Low oxygen tension
Sebaceous glands
- What do sebaceous glands produce that has antibacterial effects?
Hydrophobic oils – repels water and microorganisms
Lysozyme – destroys the structural integrity of the bacterial cell wall
Ammonia and defensins – anti-bacterial properties
- Describe the defensive features of mucosal surfaces.
Traps invading pathogens
Cilia promote the removal of mucus
Contains secretory IgA which binds to pathogens and prevents them from attaching to and penetrating epithelial cells
Contains lysozyme and other antimicrobial peptides
Lactoferrin starves invading bacteria of oxygen
- List the cells of the innate immune system.
Polymorphonuclear cells
Monocytes/macrophages
NK cells
Dendritic cells
- List the soluble components of the innate immune system.
Complement
Acute phase proteins
Cytokines and chemokines
- List some key features of cells of the innate immune system.
Identical responses in all individuals
Cells express genetically-encoded receptors (PRRs) that allow them to detect pathogens at the site of infection
Cells have phagocytic capacity
Cells secrete mediators (e.g. cytokines/chemokines) that regulate the immune response
- Name the resident macrophage in the following tissues/organs:
a. Liver
b. Kidney
c. Bone
d. Spleen
e. Neural tissue
f. Connective tissue
g. Skin
a. Liver Kupffer cells b. Kidney Mesangial cells c. Bone Osteoclasts d. Spleen Sinusoidal lining cells e. Neural tissue Microglia f. Connective tissue Histiocytes g. Skin Langerhans cells
- How do macrophages differ from polymorphonuclear cells?
They can process antigens and present them to T cells
- Describe how cells of the innate immune system recognise pathogens.
Pattern-recognition receptors (e.g. TLR) recognise generic motifs called PAMPs (e.g. bacterial sugars, DNA and RNA)
Fc receptors on these cells allows binding to the Fc portion of immunoglobulins thereby allowing phagocytosis of immune complexes
- Which other factors can bind to phagocytes to facilitate phagocytosis?
Complement components (e.g. by binding to CR1)
Acute phase proteins (e.g. CRP)
Antibodies
- Describe the reactions involved in oxidative killing of pathogens within phagolysosomes.
NADPH oxidase converts oxygen into reactive oxygen species (e.g. superoxide and hydrogen peroxide)
Myeloperoxidase catalyses the production of hydrochlorous acid (from hydrogen peroxide and chloride)
- Why do neutrophils die after phagocytosis? What does this form?
Phagocytosis depletes the glycogen stores of the neutrophil resulting in neutrophil death
The accumulation of dying neutrophils forms pus
- Describe the main features of dendritic cells.
Reside in peripheral tissues
Express receptors for cytokines/chemokines
Express pathogen recognition receptors
Express Fc receptors for immunoglobulin
Capable of phagocytosis
Present processed antigens to T cells in lymph nodes to prime the adaptive immune response
- What does a dendritic cell do after phagocytosis?
Upregulate expression of HLA molecules
Express co-stimulatory molecules
Migrate via lymphatics to lymph nodes
- Which receptor is involved in the migration of dendritic cells to lymph nodes?
CCR7
- What is a germinal centre?
Area within a secondary lymphoid organ where B cells proliferate and undergo affinity maturation and isotype switching
- Outline the functions of CD4+ T helper cells.
Recognise peptides derived from extracellular proteins
These peptides are presented on HLA-II (HLA-DP, DQ, DR)
Provide help for the development of a full B cell response
Provide help for the development of some CD8+ T cell responses
- In what form are B cells found in the periphery?
IgM B cells
- What is the early IgM response of B cells?
If the B cell in the periphery engages an antigen it can cause an early IgM response where the cell differentiates into an IgM secreting plasma cell
- What is a germinal centre reaction?
Dendritic cells present an antigen, thereby priming the CD4+ T helper cells
CD4+ T helper cells provide help for B cell differentiation via CD40L: CD40 interaction
This causes B cell proliferation
They undergo somatic hypermutation and isotype switching (from IgM to IgG/A/E)
They will become plasma cells and produce antibodies
NOTE: this process is dependent on CD4+ T helper cells
- Outline the function of antibodies.
Identification of pathogens and toxins (Fab-mediated)
Interact with other components (complement, phagocytes, NK cells) of Immune responses to remove pathogens (Fc-mediated)
NOTE: antibodies are particularly important against bacteria
- How is a secondary response to T-dependent antigens different from the primary response?
Lag time between antigen-exposure and antibody production is decreased (to 2-3 days)
Titres of antibody produced is increased
Response is dominated by IgG antibodies with high affinity
The response is independent of help from CD4+ cells
- Where are pre-B cells found and what do they develop into?
Found in the bone marrow and develop into haematopoietic stem cells
- Outline the classical pathway of complement activation.
Activated by immune complexes
Formation of antibody-antigen complexes results in a conformational change exposing a binding site for C1 on the antibody
This binding results in activation of the cascade
NOTE: this is dependent on antibodies, therefore it requires prior activation of the adaptive immune response (i.e. it does NOT occur very early in the immune response)
