Immuno 1: Immune Response To Infection/primary Immune Deficiencies 1 Flashcards
List 4 ways in which the skin is able to act as a barrier to infection ?
tightly packed keratinised cells
Low PH
Low oxygen tension
Sebaceous glands- hydrophobic oils, lysosymes, ammonia, defensins
List 4 ways in which the mucous membrane acts as a barrier to infection ?
Secretory IgA in the mucous- prevents bacteria from attaching and penetrating
Lysosymes
Lactoferrin- starves bacteria of iron
Cilia- actively traps and removes bacteria
Which receptors allow cells of the innate immune system to recognise pathogens ?
PRRs - pattern recognition receptors
List 3 polymorphonuclear cells ?
Neutrophils
Eosinophils
Basophils
How do Neutrophils detect immune complexes ?
They have Fc receptors for the Immunoglobulin (antibody) in the complex
Give one example of how neutrophils and Macrophages differ in function ?
Macrophages can also phagocytose pathogens but they are able to process the antigen and present the antigen to T cells
Give 2 examples of PRRs ?
Toll like receptors
Mannose receptors
Give 3 examples of opsonins ?
Antibodies
Complement
Acute phase proteins - CRP
Give 2 examples of enzymes involved in oxidative killing of pathogens ?
NADPH oxidase - converts oxygen into reactive oxygen species
Myeloperoxidase- catalysts the production of HCL acid
Give 2 examples of enzymes involved in non-oxidative killing of pathogens ?
Lactoferrin
Lysozyme
What is pus ?
Collection of dead and dying neutrophils in infected tissues
Which inhibitory receptors stop NK cells from destroying self cells ?
HLA receptors
Which activating receptor causes NK cells to become cytotoxic ?
Heparan sulphate receptors
Which chemokine receptor mediates the migration of dendritic cells into the lymphatics to lymph nodes ?
CCR7
What is the role of Dendritic cells ?
They reside in peripheral tissue and can phagocytose pathogens.
They then migrate into the lymphatics and present the processed antigen to T cells to prime the Adaptive immune system.
Where does lymph re enter the circulation ?
Thoracic duct
How do NK cells recognise infected cells ?
The infected cell (e.g dendritic cell )will down-regulate inhibitory molecules such as HLA and up-regulate activatory molecules such as modified pathogen antigen.
The NK cell can now recognise the cell as altered cell and starts cytotoxic killing
List 2 organs that are considered primary lymphoid organs ?
Bone marrow
Thymus
Where does T cell maturation occur ?
Thymus
Where do B cells undergo affinity maturation and isotope switching ?
Germinal centres
Give 3 examples of secondary lymphoid organs ?
Lymph nodes
Spleen
MALT- mucosal associated lymphoid tissue
What does the TCR do ?
Recognises peptide presented by the target or antigen presenting cell (APC)
Which T cells recognise peptide presented by HLA Class 1 ?
CD8+ T cells
Which T cells recognise peptide presented by HLA Class 2 ?
CD4+ T cells
Which T cells are thought to be associated with Autoimmune disease ?
Th17 T cells
Give 2 ways in which CD8+ T cells cause cytotoxic killing of cells infected by intracellular pathogens e.g viruses
Perforin (forms a pore into cell ) and granzyme
Express Fas Ligands
Which T cells express Foxp3 and CD25 ?
T reg cells
Which T cell helps in B cell maturation ?
Tfh cells (follicular helper)
What is somatic hypermutation ?
The variable region of the B cell antibodies / receptor are edited
What are the 3 pathways of complement activation ?
Classical
Alternative
MBL- mannose binding leptin
How is the classical complement pathway activated ?
Immune complexes
How is the MBL complement pathway activated ?
MBL binds to a microbial carbohydrate such as mannose
How is the alternative complement pathway activated ?
Bacterial cell walls components bind directly to C3z
What triggers the formation of the MAC (membrane attack complex) ?
activation of C3 convertase (common pathway of all 3 complement pathways)
how do commensal bacteria inhibit growth of pathogens
compete with pathogenic bacteria for scarce resources
produce fatty acids and bactericidins that inhibit growth of pathogens
list cells of the immune system
PMN cells
monocytes and macrophages
NK cells
dendritic cells
list soluble components of the immune system
cmplement
APP
cytokines and chemokines
what are the roles of PMN cells
express receptors for cytkines/ chemokines to detect inflammation
express PRR - to detect pathogens
express Fc receptors for Ig - to detect immune complexes
capable of phagocytosis + oxidative/ non oxidative killing
release enzymes, histamine, lipid mediators of inflammation from granules
secrete cytokines and chemokines to regulate inflammation
what are the roles of cytokines and chemokines in phagocytes recruitment
cytokines - activate vascular endothelium enhancing permeability
chemokines - attract phagocytes
how are microorganisms recognised by phagocytes
PPRs like TLLs and mannose receptors recognise generic motifs known as PAMPs
Fc receptors on these cells allows them to bind to the Fc portion of immunoglobulins allowing phagocytes to recognise immune complexes
what is the role of opsonins in phagocytosis
forms a bridge between the pathogen and the phagocytes receptors
complement components can bind complement receptors
APPs also promote phagocytosis
how is a phagolysosome formed
pathogen taken up into a phagosome
fuses with a lysosome
killing of the pathogen via oxidative and non-oxidative methods
how do phagocytes die
phagocytosis depleats glycogen reserves in the neurtophil
causes neutrophil death
accumulation –> pus
how do NK cells work
express inhibitory receptors for self HLA
express activating receptors including those that recognise heparan sulphate proteoglycans
what are the roles of dendritic cells
reside in peripheral tissues express PRRs express Fc receptors capable of phagocytosis following phagocytosis, densritic cells: - upregulate expression of HLA molecules express co-stimulatory molecules migrate via lymphatics to LN (mediated by CCR7)
how are microorganisms recognised by phagocytes
PPRs like TLLs and mannose receptors recognise generic motifs known as PAMPs
Fc receptors on these cells allows them to bind to the Fc portion of immunoglobulins allowing phagocytes to recognise immune complexes
what is the role of opsonins in phagocytosis
forms a bridge between the pathogen and the phagocytes receptors
complement components can bind complement receptors
APPs also promote phagocytosis
how is a phagolysosome formed
pathogen taken up into a phagosome
fuses with a lysosome
killing of the pathogen via oxidative and non-oxidative methods
how do phagocytes die
phagocytosis depleats glycogen reserves in the neurtophil
causes neutrophil death
accumulation –> pus
how do NK cells work
express inhibitory receptors for self HLA
express activating receptors including those that recognise heparan sulphate proteoglycans
what are the roles of dendritic cells
reside in peripheral tissues express PRRs express Fc receptors capable of phagocytosis following phagocytosis, densritic cells: - upregulate expression of HLA molecules express co-stimulatory molecules migrate via lymphatics to LN (mediated by CCR7)
what are the components of the adaptive immune system
humoral immunity - B lymphocytes and antibodies
cellular immunity - T lymphocytes
soluble components - cytokines and chemokines
list the functions of antibodies
identification of pathogens and toxins (Fab mediated)
interact with other components of immune respones to remove pathogens (Fc mediated)
especially involved in defence against bacteria
describe T lymphocyte maturation
CD4+ recognises peptides presented by HLA class II CD8+ recognises peptides presented by HLA class I intermediate affinity = positively selected
features of CD4+ (T helper cells)
recognise peptides derived from extracellular protiens
peptides presented on HLA class II molecules (HLA-DR - DP, DQ)
help for the development of a full B cell response
provide help for development on some CD8+ responses
list subsets of CD4 T cells
Th 1 - helps CD8+ T cells and macrophages Th17 - helps neutrophil recruitment T reg - IL-10/TGF beta expressing TFh - follicular helper Th2 - helper
features of CD8+ cytotoxic T cells
recognise peptides derived from intracellular proteins presented on HLA class I (HLA A-B-C-)
kills cells directly - perforin and granzymes, expression of fas ligand
secrete cytokines
important against viral infections and tumours
descibe what happens when B cells encounter an antigen
early IgM response -differentiates into an IgM secreting plasma cell
In germinal centre:
- dendritic cells prime CD4+ T helper
- CD4+ cells provide help for B cell differentiation
- mediated by CD40L:CD40
- with help of CD4+ cells, B cells proliferate
- undergo somatic hypermutation and isotope switching (from IgM to IgG/A/E)
difference with B memory cells
lag time between antigen exposure and antibody production is decreased
titres of antibody produced is increased
response dominated by IgG antibodies of high affinity
what is complement
20+ tightly regulated, linked proteins
made by liver
in circulation as inactivated molecules
when triggered, they activate a biological cascade
what are the 3 pathways in complement activation
classical (C1,2,4): activated by immune complexes, forming antigen antibody complexes causes a conformational change - exposes the binding site for C1) - activates the cascade
mbl (C2,4): activated by direct binding of MBL to microbial cell surface carbohydrates, directly stimulates the classical pathway involving C2+ 4 NOT 1)
not dependent on adaptive immune response
alternative: directly triggered by binding of C3 to bacterial cell wall components
not dependent on adaptive response
involves factors: BIP
(final common pathway C5-9 –> MEMBRANE ATTACK COMPLEX)
what are the roles of complement
increase vascular permeability opsonisation of immune complexes opsonisation of pathogens activation of phagocytes promotes mast cell/ basophil degranulation punches holes in bacterial membranes
cytokines vs chemokines
cytokines = small protein messengers
immunomodulatory function
autocrine and paracrine dependent action
eg IL2,6,10,12,TNF a, TGF b
chemokines = subset of cytokines
direct recruitment/homing of leukocytes in an inflammatory response
CCL19 + CCL21 are ligands for CCR7 and important in directing dendritic cell trafficking to lymph nodes
