1
Q
why is immunology important?
A
- helps decide what medications or vaccines to use for infectious diseases or cancers
- autoimmune disorders: self turns against self
- allergies: we overract to something harmless
- cancer: immune cells already target some masses + other treatments include immune checkpoint inhibitors, CAR T cells
2
Q
CAR-T cells?
A
- patients T cells are modified to express CAR (receptors) that can recognize and kill cancer cells
- then put back into body
- artificial receptor to recognize tumor antigens
- retroviral or transposons used to transfer genes into patient or donor T cells
- CART T can be used against B cell leukaemias and lymphomas
3
Q
immune checkpoint inhibitors?
A
- t cells made to re attack cancer cells, “unmasked”
4
Q
adaptive immune system?
A
- adaptive has evolved over the years
- organisms that live longer have fewer but more specific immune cells
- slower, but memory response is rapid
- hi specificity
- dependent on MHC
- requires B cells and/or t cells
5
Q
purpose of CD4 cells? “4” functions
A
- also called helper T cells
- white blood cells that are needed for start of immune response
- detect infection and signal for other cells
- activate b cells, assist CD8 cells
- memory cell formation
- secrete cytokines and help other cells do the same
6
Q
what do B cells do? and CD8 cells?
A
- B cells make antibodies
- CD8 kill infected cells
7
Q
what do MHC proteins do?
A
- display antigens on t cells
- identitiy markers as self
- help trigger adaptive immune response by helping to identify foreign cells
8
Q
what is antigen?
A
- anything that can be recognized by immune system
- like vaccines or antigens, self antigens lead to autoimmune disorders
9
Q
innate immunity? e.g.?
A
- e.g. TLR, complement, lysozyme
- rapid, but low specificity
- doesn’t require MHC, B cell, T cell
- works with adaptive immunity in vertebrates
- developed over generations/inheritance of traits
10
Q
lysozymes?
A
- found in tears, muscous surfaces
- digests microbes before they’re a threat
- always being secreted
- low specificity
11
Q
complement?
A
- series of blood born proteins, involved with microbes and pathways
- part of innate immune system
- helps antibodies and phagocytes to destroy pathogens
- promotes inflammation, phagocytosis, and membrane attack complex
12
Q
classical pathway?
A
- C1 binds to IgM antibody
- C4 cleaved and C4b-C2b formed
- converted into C3
- cleaved by complement
- trigger immune response
13
Q
lectin pathway?
A
- C3 converstase formed by complement
- C3b leads to phagocytosis/acts as opsonin
- C5b, C6-9 forms membrane attack complex (MAC)
14
Q
alternative pathway?
A
- continous surveillance against pathogens
- triggers by C3 tick over
- C3 convertase
- C3bBb formed
- spontaneous hydrolysis of C3 leads to deposition of C3b on microbe surfaces
- pathogen lysis can occur with C5b, C6-9 (MAC) or C3b (phagocytosis)
15
Q
Complement inhibitors? what happens with HIV?
A
- possessed on our cells to protect us from complement attack
- or else it would lead to lysis of RBCs
- there are many receptors for complement
- as HIV buds off it takes many proteins, MHC, and complement receptors from the host cell
16
Q
how is immune system turned on by danger?
A
- microbial invasion to regions with a lot of leukocytes and TLR triggers inflammation
17
Q
what are TLR? activated by what?
A
- commensals and pathogens activate them
- some of the first pathogen receptors discovered in fruit flies
- recognize flagellum, bacterial DNA, or bacterial membranes
- lead to immune system stimulation
18
Q
what are commensals? pathogens?
A
- commensals are generally kept out by physical and chemical barriers
- needed for development and recruitment of immune cells to later protect against pathogens
- oppotunistic pathogens: don’t cause disease/harm unless immune system is compromised
- igA in gut is produced against them
19
Q
what are pathogens?
A
- act to supress immune system
- intrinsically invasive
- igA in gut is produced against them
20
Q
what are dendritic cells?
A
- most potent of antigen prosenting cells
- protrusions are good for capturing antigens
- found in skin, major organs, blood, areas of inflammation
- carry antigen into lymph nodes for surveillance by T cells (engage with t cells)
- display fragments of pathogens
21
Q
order of events?
A
- dendritic cells activate CD4 helper t cells
- CD4 helper t cells activated CD8 and B cells
- CD8 is cytotoxic and can kill viral or cancer cells via apoptosis
- B cells produce antibodies to neutralize or tage microbes for destruction + memory B cells
22
Q
how do immune cells sense microbes?
A
through PRR
23
Q
how does TLR signal induce inflammatory gene expression?
A
recognize microbial components
24
Q
how does the innate and adaptive system co-operate?
A
25
what are pattern recognition receptors? (PRR)
- recognize pathogen associated molecular patterns (PAMPs) e.g. bacterial DNA
- recognize damage associated molecular patterns (DAMPs)
- subset of PRR is Toll-like receptors
26
cellular location of TLR?
present on plasma membrane and endosome
27
effect of TLR signaling?
- increases cytokine secretion and phagocytic ability
- more pathogens can be cleared
- costimulator molecule expression induced on Antigen Presenting Cells e.g. dendritic cells
- better T cell stimulation and memory responses
28
how does TLR signaling occur?
- ligand binds
- adapter molecules recruited
- dimer forms
- transcription factor activated
- inflammatory gene transcription occurs
29
Major histocompatibility complex (MHC)? where are they expressed?
- Proteins that present peptides for T cell stimulation
- Expressed at cell surface
30
What are the 2 classes of MHC? What cell types are they found on? Antigen presenting cells have which MHC?
- MHC Class I = all nucleated cells
- 9-10 amino acid long peptide
- MHC Class II = antigen presenting cells, dendritic cells, B cells, monocytes, macrophages
- 11-15 amino acid peptide
- APC has both
31
Endogenous peptides vs exogenous peptides?
- endogenous are generated in cytoplasm and bind to newly synthesized MHC-I
- exogenous are generated in acidic vesicles and bind to newly synthesized MHC-II
32
What does polymorphic MHC I and II mean?
- mutations that result in alternative forms of genes
- useful because they allow different peptides to bind
- positions of these polymorphisms are confined to peptide binding sites
33
what does a stable MHC I and II require?
- requires peptide bound to antigen binding groove
- non-peptide bound MHC are either recycled from cell surfcae or don't reach it
- in absence of infection 100% of MHC is loaded with self peptide
34
steps of T cell activation?
1. T-cell receptor binds to a peptide held by MHC
(CD4+ T cells bind to Class II, CD8+ binds to MHC Class I)
2. Costimulation, 2nd signal occurs (CD28 interacts with T cell and CD80 interacts with on APC)
3. Cytokines are released to promote t-cell proliferation
35
what is serial triggering with MHC-TCR?
- MHC-TCR interactions are weak and have a hi on and off rate
- one MHC can serially trigger hundereds of TCR molecules
- increases efficiency of antigen presentation (esp. for rare MHC/peptide complexes)
36
Why is costimulation needed for T cells?
- to activate T cell and prevent unresponsiveness
- induce proliferation and production of cytokines (IL-2)
- anti-apoptosis
- signal 1: TCR recognizes MHC/peptide + signal 2: costimulation with CD28 and CD80
37
what T cells expand during an immune response?
just antigen specific T cells
38
what is TCR structure restricted to recognizing?
self MHC
39
what do dendrites bind to in lymphatic system? how does activation occur?
- naive T cells that enter
- T cells become activated when they encounter foregin antigens (need two signals anc costimulation too)
40
similarites between B and T cell receptors?
- antibody and T cell receptor both have antigen binding sites
- and highly diverse/variable regions
- capable of binding with a lot of things
41
where are T cell precursors produced? migrate to where? TCR rearrangment occurs where?
- bone marrow
- blood
- thymus
42
what results when T cell precursors with TCR genes become rearranged?
- mature, clonal populations displaying distinct antigen receptors
43
what is clonal selection?
- selective expansion of lympocytes that interact with antigen
44
what is thymic selection?
- thymic stroma (epitherlial cells) expresses MHC I and II
- developing thymocytes (immature T cells) are tested for ability to bind to self MHC
44
what are developing T cells screened for?
- their ability to bind to MHC in thymus
45
what are the 3 thymocyte TCR interactions with MHC self peptide? what does it result in?
- No binding = death by neglect
- moderate binding = positive selection (survival)
- hi binding = death
46
escape from central tolerance?
- autoreactive T cells can escape if self antigen is expressed at low levels in the thymus
- autoimmunity may result if self antigen is expressed at higher levels in the periphery
47
most polymorphic gene we possess? what does this mean?
- MHC
- structures differ greatly between people
- useful mutations in MHC for greater diversity microbbiral peptides to be bound to presented to T cells
48
what needs to happen with MHC to prevent transplant rejection?
- donor/recipient should be perfectly matched
- polymorphisms can result in T cells reacting to other peoples MHC
-
49
what are the different types of transplants?
- autologous (self + self)
- syngeneic (self + identical, twins)
- allogeneic (non-identical members of the same species)
- xenogeneic (diff species)
50
what does isotype switching do?
- changes function of B cell but not antigen specificity
51
what are antibody variable sequences the result of?
- DNA rearrangments
- germline sequences for antibody proteins that can't be expressed until rearranged
52
how does antibody germline sequence get rearranged? results in what?
- B cells do this
- mini genes present, reffered to as variable genes all together
- results in production of unique antibodies in most B cells
- generates diversity within individual B cell clones
- DNA joins together messy
53
antigen-specific B cells are 10,000x better at...
- taking up a specific antigen and presenting a peptide from it to a CD4 helper T cell
54
memory B cells express what? plasma cells don't express what?
- BCR
- don't express BCR
55
how is isotype switched out in mature B cells?
- antibody produced
- some genes looped out (permenant)
- others produced
56
B cell tolerance?
- checked to determine if they bind self antigen
- check is performed while B cell is immature
- immature B cells that bind self antigen die via apoptosis
57
IgG?
- enters tissues readily, crosses placenta
- monomer
58
IgA?
- serum form (monomer)
- secretory is for mucosal protection (dimer)
59
IgM?
- complement activation
- pentamer
60
IgE?
- parasites/allergy
- monomer
61
IgD?
- unknown
- monomer
62
what cells make antigen specific B cells during an immune response?
- only antigen specific
63
hinge region of antibody?
- connects heavy and variable chain
- disulfide bond between constant and variable parts
64
binding with small antigens?
- can be hard to generate antibodies against
65
class switching?
- need help from T cell to recognzie native antigen
- 2 signals including presenting peptide on MHC class II
66
how is cell division asymmetric during the immune response?
- more memory cells are generated
- B cell receptor expressed by the memory cells and antibodis as transmembrane receptor
- sensors for if something goes wrong
67
clonal selection?
- selective expansion of lymphocytes that interact with antigen
- can then become activated and undergo extensive cell division
68
how do only B cells bearing correct BCR recieve T cell help?
- B cells that bind antigen through BCR are 10,000x more effective at presenting antigenic-peptide/MHC-II to the correct T helper cell of non specific B cells
69
cytotoxic t lymphocytes?
- serial killers of tumor cells
- can engage, disengage, and kill more virus infected cells
- require activation of apoptotic pathways in target cells
70
how does cell death occur with CTL and infected cell?
- the virally infected cell displays viral-peptide in MHC I
- encounters antigen specific CTL
71
what are the CTL's 1st weapons? what do they each do?
- perforin: forms a polymeric, cylinderical structure in lipid bilayer of target cell
- granzyme: enters target cell via perforin pore, it's a protease that cleaves target cell proteins to initiate apoptosis
72
what is CTL's 2nd weapon? does what?
- CD95 ligand
- binds to CD95 on target cell to initiate apoptosis
73
natural killer cells?
- detect altered MHC expression
- respond to missing self
- activation and killing of target cells occurs with low or absent expression of MHC-1
74
what happens when a virally infected target cell without MHC I encounters CTL?
- no killing
- so NK cell responds
75
neonatal tolerance?
- predispose to tolerance because early life APCs and lympocytes have weak costimulation
- central tolerance is higly active
- can respond to pathogens but...
- thershold for activation is higher and system defaults to tolerance unless strong danger singals are present
76
what is central tolerance?
- eliminates immature T and B lymphocytes that are autoreactive while they mature in
- in bone marrow for B cells
- in thymus for T cells
77
peripheral tolerance?
- lack of co-stimulation from dendritic cell leads to immune tolerance
- danger activated DC provide 2 signals for T cell activation
- leads to immature dendritic cell
MICROBIO
flashcards
Decks in class (6)
# Cards
