Immunity and Infection Flashcards
What is the innate immune response?
Non specific defence mechanism
Host uses immediately/within several hours after exposure to antigen
What are 4 characteristics of the innate immune response?
Born with it
V fast
Responds same way each time
Induces + directs acquired/adaptive immune response
What enzyme is in tears, sweat and saliva that protects body and what does it do?
Lysopzyme
Destroys bact walls
What antibacterial compound does the skin produce and what bact is it active against?
Psoriasin
E coli
What is primary cilia dyskinesia?
Can’t make cilia/ cilia x move
Recurrent lung infections
What is PAMP?
Pathogen Associated Molecular Patterns
What 2 features must PAMP have?
Present in microorganism, x host
Essential to survival of pathogen
What is the PAMP in:
a) Gram negative bacteria?
b) Gram positive bacteria?
a) Lipopolysaccharide (LPS) in cell wall
b) Lipoteichoic acid in cell wall
What is PRR?
Pattern Recognition Receptor
What are the 3 types of PRR?
Collectins
Toll-like receptors
Nod-like receptors
What are 2 regions of collectins?
Collagen like region - interacts effector prts immune system
Lectin region - binds sugar molecules on surface of pathogen e.g. mannose
What do these toll-like receptors recognise?
a) TLR 3
b) TLR 5
c) TLR 9
a) Double stranded RNA
b) Flagellin in bact
c) Unmethylated CpG DNA in bact
What does NOD stand for?
Nucleotide Oligomerization Domain
Where are complements synthesised and when?
Liver
In response to inflammation
What is the key complement protein and what enzyme activates it?
C3
C3 convertase
What are 3 ways complements are activated?
Classical
Alternative
MB-lectin
How are the 3 complement activating pathways triggered?
Classical - antigen-antibody complex
MB-lectin - mannose residue on pathogen
Alternative - pathogen spontaneously activates
What molecules are formed from the cleavage of C3?
C3a - smaller
C3b - larger
What does C3a do?
Diffuse away from site of infection
Binds C3a receptor in macrophage + neutrophils
Recruits them to site of infection
What does C3b do?
Coats pathogen - opsonization
What is the MAC and what does it do?
Membrane Attack Complex
Makes pore that inserts ==> bact cell wall, destroy by lysis
What protein is MAC activated by?
C3
What is the difference between macrophage and monocyte?
Monocyte - In bloodstream
Macrophage - In tissue
Name 3 features of monocytes/macrophages
Mature from circulating monocyte
Large no in GI tract, lung, liver, spleen
Relativ long lived
Name 2 features of neutrophils?
Only in blood
Short lived
What reactive intermediates are in neutrophils and what are they involved in?
O2 intermediates
Respiratory burst
What enzyme reduces O2 to make O2 radicals?
NADPH oxidase
Form hydroxyl radicals + hypochlorite
What is the effect of reactive O2 and N2 intermediates on bacteria?
DNA damage + alterations to bacterial membranes
Why are O2 radicals regulated and how?
X specific to bacterial cells so can damage host cells
Rapid conversion to harmless products
What reactive intermediates are in macrophages?
N2 intermediates
Equation for formation of NO radicals + enzyme?
O2 + L-arginine ==> L-citrulline + NO radicals
NO synthase
What are the most potent activators of NO synthase?
Interferon gamma
Tumour necrosis factor
What molecules do cytokines activate in the innate immune response?
IL-1 (interleukin 1) IL- 6 (interleukin 6) TNF alpha (turnover necrosis factor alpha)
What is the role of chemokines?
Promote inflammation by enabling cells to adhere to surface of blood vessels + migrate to infected tissue
What are the 2 type 1 interferons and when are they produced?
IFN alpha
IFN beta
Produced in response to virally infected cells
What does pleiotropic mean in context of chemokines?
When 1 chemokine receptor can bind >1 chemokine
Name 3 features of natural killer cells?
Kill virally infected cells + tumour cells
Response to TNF alpha, IL-12
Produce IFN gamma
Name 2 functions of critical cytokines
Activate macrophages
Upregulate MHC molecules
What do critical cytokines do with IL-12?
Stimulate differentiation of CD4 Th1 cells
What are the antigen presenting cells in body?
Macrophages
B cells
Mature dendritic cells activate T cells
What is the T cell receptor made up of and how many antigen binding sites does it have?
Alpha and beta chain - heterodimer
1
What is the B cell receptor made up of and how many antigen binding sites does it have?
2 identical heavy chains
2 identical light chains
2
How quicky does the innate immune response act?
Within 96 hours
How quickly does the adaptive immunity response act?
1st exposure (Primary response): 12 days 2nd exposure (Secondary response): 5-7 days
What 3 regions make up the antibody heavy chains and how many different options for each?
Total diff combos for heavy region?
Variable - 48
Diversity - 27
Joining - 6
48 x 27 x 6 = 7776
What 2 regions make up the antibody light chains?
Total diff combos for light region?
Variable
Joining
340 variants
What is the total no of variants for antibody (heavy + light chain combined)?
Name?
7776 x 340 = 2, 643, 840 variants
Combinatorial diversity
What is junctional diversity?
Joining of diff regions in antibody chains x precise
Nucleotides added + removed during rearrangement
Where are
a) B cells
b) T cells
developed with gene rearrangement?
a) Bone marrow
b) Thymus
What is another name for antibodies?
Immunoglobins
What are the 2 types of light chains in antibodies?
Kappa/Lamda
What are Fc receptors?
Paired constant region segments
What are 4 functions of antibodies?
Neutralise toxins + viruses
Opsonise pathogens
Activate complement cascade
Agglutinates particles
What are 3 features IgG?
Good at opsonization
Antibody-dependant Cellular Cytotoxicity
4 subclasses of IgG
How is a IgA dimer formed?
2 monomers joined by J chain
How do you measure specific IgG?
Measurement of antibody titre in serum in response to a vaccine
How many binding sites does a IgA dimer have and what can they do?
4
Agglutination + neutralisation
Retention of antigen by adherence to mucus
What is the 1st antibody made in the immune response?
Pentameric IgM
How many binding sites does pentameric IgM have and what is this called?
10 binding sites
High avidity
What cells have receptors for IgE?
Mast cells
What type of antibodies do people with allergies have a higher concentration of?
IgE in serum
What cells can improve their specificity for antigens?
Only B cells
Where are germinal centres found?
Secondary lymphoid tissues contain zones of dividing B cells
What is affinity maturation of B cells?
B cells mutate immunoglobulin variable region genes by somatic hypermutation
High affinity variants are selected
What 2 types of cells leave the germinal centre?
Memory cells
Plasma cells
What are the 2 locations plasma cells migrate 2 and what antibodies do they produce?
Intestines ==> IgA
Bone marrow ==> IgG
What is 1 feature of bone marrow plasma cells?
V long lived
Secrete protective antibodies for lifetime
What is a chimeric MA?
Mouse MA engineered so variable region of heavy region of heavy + light chains associated mit human contact regions
What is the ending for chimeric MA?
-ximab
What is an example of a chimeric MA?
Function?
Rituximab
Antibody to CD20 receptor, present in B cells
Targets B cells for killing, remove from circulation + lymphoid tissue
Effective against B cell lymphoma + rheumatoid arthiritis
What is a humanised MA and what is the ending?
Prts of variable region that contact antigen are from mouse
-zumab
What is an example of a humanised MA?
Function?
Omalizumab
Specific to IgE
Treat moderate-severe asthma
What is the ending of fully human MA?
-umab
What is an example of a human MA?
Function?
Adalimumab
Specific to TNF alpha
Treat inflammatory diseases
What is plasmapheresis?
Plasma separated from blood cell
Replaced mit another solution e.g. saline/albumin
/ treated + returned to body
What bonds holds together the light and heavy chains in antibodies?
Disulfide bonds
What is the name of the antigen encoded by MHC genes?
Human Leukocyte Antigens (HLA)
What does MHC stand for?
Major Histocompatibility Complex
Name 3 features of MHC I
Single chain
Associate non-covalently to beta-2 microglobulin
Endogenously expressed on all nucleated cells
Name 2 features of MHC II
Alpha-beta heterodimer
Expressed on specialised antigen presenting cells
What type of proteins do
a) MHC I molecules
b) MHC II molecules
present?
a) Endogenous proteins
b) Exogenous proteins
Name 5 features of T Cell receptors (TCR)
Heterodimer 2 chains joined by disulphide bridges 2 subtypes alpha-beta, gamma-delta Consists of variable + constant domains TCR genes undergo rearrangements from germline before translation
What type of T cells interact with MHC I molecules?
CD8+ (Cytotoxic T cells)
What type of T cells interact with MHC II molecules?
CD4+ (Helper T cells)
What occurs in signal 1 during T cell response?
TCR (T cell receptor) encounter antigen presenting cell bearing MHC receptor
What occurs in signal 2 during T cell response?
Co-stimulation
CD28 receptor on T cell binds to CD80/86 on antigen presenting cell (APC)
What are the 4 diff types of cells CD4+ cells can differentiate into and in response to what?
Th1 - Viruses + intracellular pathogens
Th2 - Extracellular parasites
Th17 - Extracellular parasites + fungi
Treg- Modulate immune response (Regulatory T cell)
How do Th1 T cells help immune response?
IL-2 helps CD8+ T cells to proliferate
IFN-gamma helps macrophages