Immunology Flashcards
Innate Immunity - cells responsible for innate immunity
macrophage - phagocytosis and activation of bactericidal mechanisms, antigen presentation
neutrophil - phagocytosis and activation of bactericidal mechanisms
mast cells - ease of granules containing histamine and other active agents
NK cells - release lytic granules that kill some virus-infected cells, through recognition by downregulation of MHC-I
Sequence of Acute Inflammation
- tissue damage causes release of vasoactive and chemotactic factors that trigger a local increase in blood flow and capillary permeability 2. permeable capillaries allow influx of fluid (exudate) and cells 3. phagocytes migrate to site of inflammation 4. phagocytes and antibacterial exudate destroy bacteria
Phagocytes in the body
brain - microglia
lungs - alveolar macrophages
liver - kuppfer cells
blood and bone marrow - macrophages
kidneys - mesangial phagocytes
skin and mucosa - langerhans cells
macrophage activation
releases cytokines IL-1, 6, 8, 12 and TNF-alpha.
Cytokines released by T-cells
All T cells - IL-2 and IL-3
Th1 - IF-gamma
Th2 - IL-4, IL-5, IL-10
Functions of Interleukins
[Hot T-bone stEAK]
IL-1: fever
IL-2: stimulates T cells
IL-3: stimulates bone marrow
IL-4: stimulates IgE production
IL-5: stimulates IgA production
IL-6: stimulates aKute-phase protein production
IL-8: Major chemotactic factor for neutrophils
(Clean up on aisle 8)
IL-12: Activates NK cells and induces differentiation of CD4 cells into Th1
Function of Interferons
IFN-alpha/IFN-beta: Part of innate response, INTERFERE with viruses, causing apoptosis
IFN-gamma: Secreted by NK cells in response to IL-12. Activates other NK cells and macrophages to kill. Increases MHC expression and antigen presentation by all cells.
Complement
A series of 20 plasma proteins activated by foreign cells or antibodies to those cells. They lyse bacteria, promote phagocytosis, and promote inflammation.
Opsonins
Proteins that coat pathogens so phagocytes recognize and ingest them. These could be antibodies, acute phase proteins, and complement proteins.
Acute phase response
Refers to the response of the liver to inflammation. Is triggered by the release of TNF-alpha, IL1, IL6, and IL8 from neutrophils and macrophages. Liver produces acute-phase reactants, most notably C-reactive protein, to support the immune system in many ways. Major component of innate immune response.
Eosinophils
Phagocytic, primary cell involved in allergic and parasitic invasion. Stimulate histamine release from mast cells and basophils.
Mast cells and basophils
Immune cells that function to detect foreign substances in tissue spaces; initate local inflammatory responses
Mast cells: Bound IgE stimulates degranulation & release of mediators -> immediate hypersensitivity (allergic rxn). Mast cells release: Activators (vasodilation and vascular permeability), spasmogens (bronchial smooth muscle contraction), and chemoattractants (e.g. cytokines).
T Cells
Cells that recognise processed antigens,
Created in bone marrow, matures in thymus
T-cytotoxic cells - CD8+, MHCII
T-helper cells - CD4+, MHCI
Th1 - Maximizes the killing efficacy of the macrophages and the proliferation of cytotoxic CD8+ T cells. Also promotes the production of opsonizing antibodies. (IgG, IgM and IgA, not IgE)
Th2 - Stimulates B-cells into proliferation, to induce B-cell antibody class switching, and to increase neutralizing antibody production. (IgG, IgM, IgA and IgE)
MHC I
A, B, and C types, with further subtypes. Displays peptides from intracellular proteins. Recognized by CD8 T cells. Expressed by all nucleated cells.
Cytoplasmic proteins are broken down by the proteasome complex, peptides exported to the ER, bound to MHC I, then MHC I with peptide is transported to the cell surface. (Attached within ER)
MHC II
DR, DP, DQ types, with further subtypes. Displays peptides from extracellular proteins. Recognized by CD4 T cells. Only expressed by professional APCs.
Exogenous proteins are taken up by endocytotic processes, degraded by proteases within uptake vesicles, bound to MHC II, then displayed at the cell
surface. (Attached outside of ER, remains in vesicle)
Immunoglobulin structure
Inner heavy chain, outer light chain, linked by disulphide bonds in the hinge region. The Fc domain contains the C terminus of the heavy chain and is either attached to the B cell or freely floating. The Fab domain contains the N terminus, consists of both chains, and is termed the “variable region”.
Immunoglobulin function
Neutralization, opsonization, and antibody-dependent cell mediated cytotoxicity (ADCC) on NK cells
IgG - Most common (75%), found in serum/tissue fluids, produced in secondary immune response, can cross placenta and provide passive immunity to newborns
IgM - Primary immnue response Ig, mainly confined to vascular pool, binds with low affinity and high avidity due to pentameric structure, potent activator of complement pathway. multimeric
IgD - Most obscure Ig, no known functions, found on surface of new B cells
IgA - Functions as a neutralizing antibody, found in the gut and secreted fluids, usually occurs as a dimer with a secretory component that is synthesized by epithelial cells, can be transported across epithelial surfaces. multimeric
IgE - Located along blood vessels and just beneath epithelial surfaces, binds to mast cells via Fc receptors and cross linking upon second exposure leads to allergic response
Function of dendritic cells
Reside in tissues, capture antigens and move to lymph nodes upon activation via PAMP receptors, present MHC II/peptide complex to naive T cells
Reason for Ig diversity
- Somatic recombination of VDJ gene segments
- Pairing of heavy and light chains
- Somatic hypermutation
- Junctional diversity
X-linked agammaglobulinemia
epidemiology: 1:250,000 in population, only male, usually appears 4-5 months
Aetiology/pathophys: Absence of BTK gene, B cells can’t differentiate
Diagnosis: No class of antibodies present, absence/reduction of spleen, tonsils, adenoids, peripheral lymph nodes
Confirmed from abnormally low or absent B cells, T cell count may be elevated.
Clinical features/consequence: Recurrent infections, diarrhoea, staph
Treatment: No cure, commonly treated with IVIg, antibiotic therapy and nutritional supplements
Severe combined immune deficiency (SCID)
Epidemiology: Aus 0.15:100,000 incidence. X-linked males only, autosomal recessive males and females equally. patients present around 3mth, age at diagnosis 6mth
Aetiology/pathophys: Mutation of common Y chain of IL receptors encoded on X chromosome - X-linked
adenosine deaminase deficiency builds up enzymes, inhibits lymphocyte proliferation - autosomal recessive
Clinical features: Profound abnormalities in T-cell, B-cell and NK cell functions, paediatric emergency. FTT, multiple and severe recurrent infections (particularly resp)
Diagnosis: clinical features + fever, dehydration, increased RR, absent lymphatic tissue. Hallmark = lymphopenia
CBC, total serum Ig levels, lymphocyte count and function
Consequences: severe opportunistic infection with viral, fungal and bacterial sources. If not treated = death
Treatment: IVIg, Bone marrow transplant, gene therapy
DiGeorge Syndrome
Epidemiology: 1:4000-6000, sexes equally affected, no ethnic predisposition, detected in infancy but late presentation is possible
Aetiology/pathophys: parents with DGS, deletion of one copy of 22q11.2 causes decreased levels of TBX1 which is a key transcription factor for development of pharyngeal arches. No thymus - failed T cell maturation
Clinical features: hypoplastic/absent thymus and parathyroid glands. T cell deficiency, cleft lip and palate, mild dysmorphic facial features, cardiac anomalies (truncus arterioles, Tetralogy of fallot)
Diagnosis: abnormal T cell cound, low serum calcium, low serum Ig, abnormal CXR and ECG. fluorescence in situ hybridisation to confirm DGS
Consequences: long term heart defect, increased risk sinopulmonary infections, risk schizophrenia
Treatment: IVIg, thymic transplant, adoptive transfer of mature T cells
Common Variable Immune Deficiency (CVID)
epidemiology: 1:50,000. 1M:1F. can become evident any time 0-40yrs
Aetiology/pathophys: Lack of B cells (failed development), defect in B-cell expression in surface molecules, defecits in second messenger and translocation pathways in B cells
Clinical features: low levels of most/all Igs, lack of B cells and plasma cells capable to produce Igs, frequent bacterial infections, splenomegaly, lymphadenopathy
Diagnosis: decreased/absent IgA and IgD, decreased IgM, test for circulating T and B cell function
Consequences: recurrent infections, auto-immune phenomena, possible malignancy.
Treatment: IVIg
Chronic Granulomatous Disease
Epidemiology: usually inherited in x-linked recessive, 90% males, 1:160,000-1,000,000. Typically occurs at a young age, may have late onset
Aetiology/pathophys: Impaired phagocyte function. Defects in NADPH oxidase enzyme complex that generates ‘respiratory burst’. Inability of phagocytes to kill
Clinical features: recurrent bacterial and fungal infections, skin infections, pneumonia, spleen/liver/gingival abscesses, granulomas
Diagnosis: nitroblue tetrazolium test - in CGD, patients are unable to oxidise NBT to insoluble blue formazan. Dihydrorhodamine test: principles are similar to NBT. CBC: anemia, high level of circulating neutrophils. Quantitative Ig test: all increased
Consequences: intracellular survival of ingested bacteria leads to granuloma formation in lymph nodes, skin, lungs, liver, GIT and bones
Treatment: aggressive and prolonged broad-spectrum antibiotic therapy, antifungal therapy, bone marrow transplant or haemopoietic stem cell transplant may be successful
