Immunity Flashcards
immune molecules that mediate immune responses
complement, cytokines and antibodies
cytokines
immune messenger hormones (IFNs, ILs, TGFs and chemokines which are chemoattractants)
complement cascade
sequence of soluble blood proteins/ enzymes that are cleaved downstream, 3 pathways by which it can be stimulated, all of which converge at the stage producing the enzyme C3 convertase, which cleaves the protein C3 into C3a and C3b.
myeloid immune cells
- Neutrophils
- Monocytes
- Macrophages
- Mast cells (in tissue)
- basophils (in blood)
- eosinophils
[part of innate immune system]
lymphocytes
- T lymphocytes
- B lymphocytes
- Plasma cells
- Natural killer cells
[mainly part of adaptive immune system- apart from NKCs]
neutrophils
most abundant, good at killing, recruited rapidly to the scene, very short lived, chief constituent of pus, IL-8 stimulate their production in bone marrow
non-phagocytic immune cells
basophils and mast cells
why do mast cells and basophils release heparin and histamine from granules?
causes vasodilation
[mainly part of innate immune system]
macrophages
good at killing if activated, reside in tissue, involved in tissue healing, clearance of dead cells & metabolism
which immune cells are involved in allergic and anti-parasitic reactions?
Mast cells (in tissue), basophils (in blood), eosinophils
C3a (anaphlatoxin) function
increases the inflammatory response, stimulating mast cell degredation
C3b function
acts as an opsonin on cells
C5b function
along with other cascade products produces a membrane attack complex (MAC), this forms a small pore in the membrane of a pathogen so water rushes in and ions out, leading to lysis which kills the cell
classical pathway of complement activation
only occurs when there are antibodies present specific to foreign antigen
mannose binding lectin pathway of complement activation
activation through binding of mannose (or similar carbohydrates) by mannose binding lectin on bacteria
alternative pathway of complement activation
complement component C3 is spontaneously activated and binds to nearby membranes and bacteria to activate complement as they lack control proteins on surface to prevent activation
types of T lymphocytes
- Cytotoxic T cells (CD8+ T cells) kill infected or mutated cells
- Helper T cells (CD4+ T cells) produce cytokines for other cells to respond to, organises body’s immune response
NK cells
provoke apoptosis in cells missing MHC I markers
plasma cells
activated B lymphocytes, produce antibodies
where are T cells made?
thymus
where are B cells made?
bone marrow and then mature further in spleen
primary lymphoid organs
bone marrow and thymus
secondary lymphoid organs
lymph nodes, spleen, tonsils, Peter’s patches in gut
maturation of B cells in bone marrow
Hematopoietic stem cells → pro B cells → pre B cells → immature B cell
what do lymphatic vessels drain into?
the lymph nodes at the junctions where the adaptive immune system scans the fluid for pathogens and initiates a response if necessary
what does the lymphatic system drain into?
the blood via the thoracic duct
thymus
gland between the sternum and lungs that is only active until puberty after which it begins to shrink and become replaced by fat
what are leukocytes derived from?
bone marrow stem cells
where are B cells located
lymphoid follicles
how do T and B cells enter and leave lymph nodes?
via blood vessels and leave via efferent lymphatic vessels found in the central medullary region
APCs
antigen presenting cells,
how do naive CD4 helper T cells mature?
APCs present antigens to them via MHC Class 2, this binding triggers maturation and stimulated cytokine release
types of APC
dendritic cell (main), macrophage, B cell
first line of defence in immune response
are physical barriers like skin, epithelia and mucous membranes
MHC (major histocompatibility complex)
a protein coded for by the human leukocyte antigen (HLA) gene and located on chromosome 6
General function- presenting antigens to adaptive immune system.
MHC Class 1
found on all nucleated cells apart from neurons, presents endogenous antigens (antigens within host cells) to cytotoxic T cells
how do NK cells recognise and kill viral cells?
viruses downregulate production of MHC Class 1 so NK cells bind to the cells and kill it via apoptosis
what prevents NK cells from killing every cell?
inhibitory receptors that bind to MHC Class 1
innate immune system
- Infection or necrosis releases PAMP and DAMP signals and also activates basophils, mast cells and resident macrophages- non-specific phagocytes fully activated by IFNy from other macrophages, NKs or T-helper cells
- These signals bind to PRRs (toll like receptors, C-type lectins or nod like receptors) on phagocytes, stimulating chemotaxis of neutrophils and releasing inflammatory mediators (cytokines)- IFNs, ILs, TNFs and kinins
- Neutrophils phagocytose debris/pathogens and IL-8 stimulates their production in bone marrow, pseudopodia extend around the pathogen to meet it in a phagosome, this fuses with a lysosome to give a phagolysosome which actively pumps in H ions to activate acid proteases such cathepsins
- PAMPs and DAMPs activate the complement cascade causing extravasation, opsonisation and MACs
- Use of NETs on parasites/fungi as a last resort
2 components of acquired immune response
humoral (B cells) in fluid and cell mediated (T cells) in tissues
epitope
part of antigen that immune cell recognises
what do linear T cells recognise?
proteins so must have the antigen presented to them
B cell recognition
B cells recognise soluble antigens in fluid and produce antibodies to clump the pathogen, to prevent binding to host receptors which would allow entry to host cells
BCR structure
Y shaped receptor with a heavy chain and 2 light chains with variable regions with antigen binding sites on the end of light chains.
TCR structure
alpha chain and a beta chains with antigen binding sites at the end of both chains
somatic hypermutations
When a B cell is activated, it proliferates and during this it undergoes a high rate of mutation → largely driven by substitutions of single bases in the heavy chain of the BCR and variable V region of light chain
junctional diversity
extra/fewer nucleotides at VDJ regions
combinatorial diversity
different combos of V,D,J
BCR- difference combinations of heavy and light chains
TCR- different combos of alpha and beta chains
somatic recombination
random pairing of V, D and J regions in BCRs and TCRs
negative selection in B cell development
B cells that react too strongly to self antigens are deleted
positive T cell selection
any lymphocyte which bind weakly to MHC molecules undergo apoptosis which ensures all T cells can recognise MHCs
negative T cell selection
medullary dendritic and epithelial cells present self-antigens to lymphocyte and those which bind strongly to them are forced to undergo apoptosis
MHC Class 2
present on specialised APCs only, present endogenous antigens by CD4 (helper) lymphocytes
what do TI IFNs produced by NK cells do?
message an anti-viral state to nearby cells- prevents viral proliferation
what do specialised APCs do?
take up the antigen, present it on an Class II MHC and upregulate cytokine production. They drain into the lymphatics and present to CH4 (helper) cells in the lymph nodes (call this signal 1).
signal 2
CD4 cells then send a co-stimulatory signal back to APCs, signifies them recognising the foreign antigen and allows immune response
why do CD4s release cytokines?
to direct B cells, CD8s and APCs
how to CD8s induce apoptosis in infected cells?
them using the Fas death ligand or perforin and granzyme- both stimulate caspase cascade
why are memory T cells produced?
to mount a faster 2nd response if re-infection occurs
humoral immunity
BCRs complementary to a specific antigen detect it and present it on a Class II MHC. Co-stimulation form activated T helper cells activates the B cells which divide to produce many clones. These either differentiate into plasma cells (also called immunoglobulins)- produce antibodies or memory cells which remain in the bloodstream long after infection so that the 2nd response is faster if the pathogen re-enters, antibodies can also activate complements
T cell immunity compared to humoural immunity
antibodies can be generated directly after antigen detection response will be faster but less effective
immunoglobulin types
IgM, IgA, IgD, IgE, IgG
IgA
- Fc alpha
- Dimer
- Neutralisation and flushing mucosal pathogens
- Most abundant in mucosal tissues
IgD
- Monomer
IgE
- monomer
- mast cell, basophils and eosinophil activation in allergy
- on surface of mast cells
- deals with allergy reactions and dealing with helminths
IgG
- monomer
- neutralisation
- opsonises pathogens or phagocytosis
- complement activation
- ADCC
- Can cross placenta
- Abundant in extra-mucosal tissues
- Four subclasses: IgG1, IgG2, IgG3, IgG4
IgM
- pentamer
- first to be released and not very specific
- neutralisation
- complement activation
- primarily in blood
ADCC (antibody dependant cell mediated cytotoxicity)
antibodies bind to surface antigen presented by an infected cell (opsonisation without phagocytosis), NKs and neutrophils release cytotoxic granules containing perforin, granzyme and TNFalpha which induced apoptosis in a cell
class switching
T cell signals to activated B cell to produce a different class of antibody (probably be CD40L from the helper T cell binding to the CD40 receptor on the B cell), the B cell will produce IgM first but will undergo gene rearrangement ot produce a different one (IgG, IgA or IgE)
why can’t class switching occur in T independent activation?
only IgM will be produced
affinity maturation
helper T cells select those activated B cells which have been mutated to produce antibodies with the highest affinity for an antigen to survive as a plasma cell or memory B cell, lower affinity ones are rejected and die
T independant activation
the additional signals will come from microbes, cytokines and APCs. This activation will cause the B cell to produce IgM
what is T cell dependant activation in response to?
protein antigens like viral proteins which bind to BCRs and allow them to get degraded by lysosomes. The peptides from the internal proteins of the virus are exposed and can be loaded onto MHC Class II to be presented on the B cell surface. At this point a helper T cell will recognise the presented peptide via it’s TCR and provide co-stimulation to the B cell.
what enzyme plays a role in somatic hypermutation and class switching?
activation-induced cytidine deaminase
Type 1- IgE mediated hypersensitivity mechanism
Ag induces induces cross- linking of IgE bound to mast cells with release of vasoactive mediators
Symptoms:
- Vasodilation due to histamine ect. - hypotension, oedema
- Bronchoconstriction (histamine, bradykinins)
Treatment is symptomatic: adrenaline, beta agonists, IV fluids, corticosteroids
examples of type 1 hypersensitivity
[anaphylaxis], hay fever, eczema
type 2- Ab-mediated cytotoxic hypersensitivity
Ab directed to cell surface IgG or IgM mediates destruction by phagocytosis, ADCC or complement-mediated lysis
type 3- immune complex mediated hypersensitivity
IgG/M complexes induce mast cell degranulation via FcgRIII
type 2 hypersensitivity examples
Blood transfusion reactions, Rhesus reactions, Graves disease, myasthenia gravis
type 3 hypersensitivity examples
Arthus reaction, Serum reaction, systemic lupus erythematosus
type 4- T cell mediated hypersensitivity
Delayed type, TH1 cells release cytokines that recruit and activate macrophages
type 4 hypersensitivity examples
Tubercular lesions, contact dermatitis
autoimmunity
type II, immunity misdirected at healthy tissues,
characteristics: chronic disease with relapse & remission, clinical symptoms shaped by nature of immune response
Genes for MHC Class 1
A/B/C
genes for MHC class 2
DP/DQ/DR
regions in BCRs
light chain= VJ
heavy chain= VDJ
regions in TCRs
alpha chain= VJ
beta chain= VDJ
peripheral tolerance
Activation of lymphocytes requires multiple signals or cells become anergic
immune regulation by
T-regulatory cells (Tregs)
central tolerance
- Deletion of self reactive T cells in the thymus
- Deletion of self reactive B cells in the bone marrow
