Immunology Flashcards
Significance of low oxygen tension on skin
Good against aerobic microbes
Main immunoglobin found in mucous
sIgA, prevent attachment and penetration of epithelial cells
Enzymes in mucous
Lysozyme, defensins, antimicrobial particles directly kill pathogens. Lactoferrin starve invading bacteria
What are bactericidins
Produced by commensal bacteria which can cause lysis of other bacteria
What is humoral immunity
Immunity mediated by soluble macro-molecules found in extracellular secretions and fluids such as antibodies, complement system proteins, cytokines
What are cytokines
Small proteins and peptides that modulate behaviour of cells and co-ordinate the immune system
Different long lived tissue macrophage
Kupffer cell - Liver
Alveolar macrophage - Lung
Mesangial cell - Kidney
Microglial cell - Nervous system
What are polymorphonuclear cells
Neutrophils
Main role of natural killer cells
Detect and kill tumour cells and virally infected cells
Also kill antibody-bound cells/pathogens
Main function dendritic cells
Phagocytose, process and present antigen on surface
What are primary lymphoid tissues
Sites of leukocyte development - Thymus and Bone Marrow
What cells do immune cells derive from
Hematopoietic stem cells
What are secondary lymphoid organs
Sites where T and B cell become activated by antigen
Adenoid, tonsil, lymph node, spleen, peyer’s patch in small intestine, large intestine
What comprises the adaptive immunity
B cells, T cells, antibodies
What cells acts as a link from innate to adaptive
Dendritic cells
Example of anti-viral cytokines
Interferon alpha, beta released by virally infected cells
How does recognition occur in innate immunity
Pathogen Associated Molecular Pattern on pathogens are recognised by Pattern Recognition Receptors on innate immune cells
PRR for lipopolysaccharide found on gram negative bacteria
Toll-like receptor 4
PRR for beta-glucans (Fungi)
Dectin - 1
PRR for ssRNA (Virus)
Toll-like receptor 7
Which cells are best at phagocytosis
Macrophage, Neutrophils and Dendritic cells
What cell release pro-inflammatory mediators
Natural killer cells release Interferon Gamma that activate macrophage
How is Natural Killer Cell response mediated
NK cells contain inhibitory receptor that doesn’t affect cells with normal MHC Class-1. Also activated by interferon alpha/gamma
How is phagocytic capacity of macrophage increased
By natural killer cells releasing Interferon gamma
What is a hallmark in inflammation
Neutrophillia
What are acute phase proteins
Proteins whose plasma concentration increase or decrease in response to inflammation, eg: C-reactive protein and complement proteins
What can increase C-reactive protein be indicative of
Marker for inflammation, production increased by the liver in infection/inflammation
What pro-inflammatory mediators increase vascular permeability and cause vasodilation
Nitric oxide, Prostaglandins, Leukotrienes, Histamines
Which vessels does margination occur in
Venules
Which has tighter bond, with Selectin or ICAM/VCAM
With Selectin
What is Diapedesis
Neutrophils squeeze through endothelial cells
Neutrophil killing mechanisms
Phagocytosis, degranulation, NETs
Mechanism of neutrophil phagocytosis
Anti-microbial proteins and enzymes, reactive oxygen species
What is Neutrophil Extracellular Traps
Neutrophils release their intracellular structures and immobilize and phagocyte pathogens
Why is pus yellow-green in colour
Neutrophil release enzymes that require Iron
Pathways in complement system
Classical, mannose-binding lectin pathway, alternative
Initial step in complement cascade
C3 - C3b (Amplification loop) + C3a
How does spontaneously broken down C3 stabilise
C3 breaks down into C3a and C3b. C3b produced near bacterial with carbohydrate or protein ligand get attached and stabilized. This C3b further amplifies the cascade
Classical complement pathway
The classical complement pathway is initiated by antigen-antibody complexes with the antibody isotypesIgGandIgM. Following activation, a series of proteins are recruited to generateC3 convertasewhich cleaves theC3 protein. TheC3bcomponent of the cleaved C3 binds to C3 convertase (C4bC2a) to generateC5 convertase which cleaves theC5protein. The cleaved products attract phagocytes to the site of infection and tags target cells for elimination by phagocytosis. In addition, the C5 convertase initiates the terminal phase of the complement system, leading to the assembly of the membrane attack complex (MAC). The membrane attack complex creates a pore on the target cell’s membrane, inducing cell lysis and death
What part of the immune system is important against encapsulated bacteria
Membrane attack complex, forms a pore and causes osmotic lysis of pathogen
What is opsonisation
Coating of pathogens by humoral factors such as C3b, C-reactive protein, IgG/IgM to facilitate phagocytosis
What part of complement system are anaphylatoxins
C3a and C5a
CD4+ vs CD8+ T cells
CD4+ T cells - Regulate entire immune system
CD8+ T cells - Kill virally infected cells
PAMPs vs Antigens
Limited number of PAMPS common to different pathogens
Antigens are unique to individual species
Receptors in T cells
Membrane bound alpha-beta heterodimer
Receptors in B cells
Membrane bound antibody (IgM or IgD)
Structure of antibodies
Two Ig heavy and two Ig light polypeptide chains help by disulphide bond
What forms antigen binding site
Hypervariable regions of heavy and light chains
How does adaptive immune system recognise millions of different antigens
Antibody heavy and light chains are encoded by segmented genes in haematopoietic cells. Random arrangement of these gene segment occurs in development of B cells
Where does adaptive immune response occur
In secondary lymphoid tissue
How do naive B and T cells enter lymph nodes
Transendothelial migration from high endothelial venules
Function of dendritic cells
Immature state in peripheral tissue
Phagocytose antigens partially
Travel to secondary lymph nodes
Antigen presentation to T cells here
How do dendritic cells express co-stimulatory molecules
By inflammatory cytokines such as Tumour Necrosis Factor alpha
Do dendritic cells have PRR or MHC
Both
What gene complex encodes MHC
Human Leucocyte Antigen (HLA)
MHC Class 1 vs 2
MHC Class 1 are expressed on all nucleated cells, present peptide antigen to CD8+ T cells
MHC Class 2 expressed on professional antigen presenting cell, present to CD4+ T cells
How many signals do T cells need for activation
Two, one if antigen specific between TCR and MHC
Second is non-antigen specific between TCR and co-stimulatory molecules
What trap opsonised antigens in lymph nodes
Stromal cells with opsonin receptors
How many signals does B cell require
Two, BCR + antigen and T follicular helper cell or PRR + PAMP
Second, multiple BCR’s engaged
What cells can B and T cells differentiate into
Effector or memory cells
What are plasma cells
Fully differentiated B cells that secrete antibodies
Possible B cell pathway after activation
Differentiate into short lived plasma cells that secret low affinity antibodies (or)
Cluster to form a germinal center and undergo clonal expansion to produce long lived plasma cells with high affinity antibodies and memory B cells
What antibodies are found in humans
IgA, IgD, IgE, IgG and IgM
Functions of IgM
B cell antigen receptor (activate B cell)
Agglutination (Immune complex formation)
Complement system activation
First antibody produced in immune response
IgM, pentamer in plasma and secretory fluids
What is agglutination
Action of antibody cross-linking multiple antigens producing clumps of antigens. By IgM and IgG
Increases efficacy of microbial elimination
Functions of complement system activation
Pathogen killing
Pathogen opsonisation
Leukocyte recruitment and inflammation
Removal of immune complexes
How do antibodies cause complement system activation
Antigen binding to IgM and IgG causes a conformational change, Planar to Staple form of IgM
This exposes multiple binding sites for C1, first component of classical activation pathway
Most abundant antibody in the body
IgG
Functions of IgG
Agglutination Complement system activation Foetal immune protection Neutralisation Opsonisation NK cells activation
What antibody provides foetal immune protection
IgG antibody
How do antibodies neutralise pathogens
Binding prevents pathogens from infecting host and prevent microbial toxins from disrupting normal function
How does opsonisation work
Cells such as neutrophils and macrophage contain Fc receptors that bind to IgG antibodies bound to antigen
How does IgG activate NK cells
IgG opsonise the pathogen. NK cells have CD16 Fc receptors and degranulate upon cross linking with the IgG
Function of IgD
B cell activation in monomeric membrane bound
Second most abundant antibody
IgA
Functions of IgA antibody
Monomeric form in serum-B cell activation
Secretory dimeric form in secretory fluids -
Neonatal defence and neutralisation (mucus)
What antibody is found in colostrum
IgA
Functions of IgE
Allergic response - Degranulation of mast cells through Fc receptor binding to IgE
Large intracellular pathogens - Parasites
How are antibodies of same specificity but different Ig classes produced
B cells can switch Ig heavy chain constant region gene segment but retain Ig heavy and light chain gene hypervariable segment
What cell secrete cytokines to cause T cell differentiate
Dendritic cells secrete cytokines
Does dendritic cells have MHC Class 1 or 2
Both
How do effector T cells help T cells respond
T helped cells secrete IL-2 to drive further proliferation and differentiation of helper T cells. IL-2 also drives differentiation of CD8+ T cells into cytotoxic T cells
How do T helper 1 cells help macrophage
Th1 cells leave lymph node, travel to infected tissue site
Here, they are activated by macrophages in antigen specific manner. Th1 cells then release INF gamma to hyper activate macrophages
How do effector Tfh cells help B cells
Effector Tfh cells are re-stimulated by co-stimulatory molecules. These cause B cells to clonally proliferate. Tfh secrete cytokines that stimulate germinal centre response
Imporant of germinal centre response in B cells
Differentiation into antibody secreting plasma cells and memory cells
High affinity antibodies generated
Ig heavy chain switching
What do CD8+ T cells differentiate into
Cytotoxic T cells, kill infected host cells
How do cytotoxic T cells kill infected cells
By recognising and inducing apoptosis
How does restoration after immune response occur
Macrophage release anti-inflammatory cytokines such as IL-10 that induce tissue repair and revert to a anti-infammatory state
Main coreceptor used by HIV virus
CCR5 usually on CD4 T cells
What causes immune suppression by HIV infection
HIV affects CD4+ cells which get overwhelmed eventually, leading to immune depression
What is pyroptosis
A highly inflammatory form of programmed cell death that occurs during infection with intracellular pathogen like HIV. Infected cells recognize danger signs, release pro-inflammatory cytokines, swell, burst and die
