Innate and Adaptive Immunity Flashcards
(106 cards)
1
Q
Immune response - process
A
- Microbe penetrating body epithelia aka skin
- Neutrophils - 1st to infection site
- Monocytes differentiate into macrophages
- Macrophages utilizing surface receptors PRRs - that recognize and bind to pathogen.
- Macrophages activated and secrete cytokines and hemokines - causes inflammation
- Cytokines - >’s permeability of Bvs, increases adhesive properties of bvs - initiate inflammation
2
Q
Which cells are first to infection site?
A
Neutrophils
3
Q
In step 6 of immune response, cytokines are activated by macrophages thereby causing inflammation, what else triggers inflammation?
A
Complement ;
• Complement coats microbial surfaces with fragments that are recognised and bound by phagocytic receptors on macrophages
4
Q
Cytokines and complement fragments cause circulating neutrophils to migrate to site of infection, cytokines attract them there. (T/F)
A
False; Cytokines and complement fragments cause circulating leucocytes to migrate to site of infection, chemokines attract them there.
5
Q
List cells involved in Adaptive Immune System
A
B cell, T cell, Antibodies, CD4+ T cell, CD8+ T cell, gamma delta T cell, Natural killer T cell
6
Q
Functions of Adaptive Immune System:
A
- Recognition of specific “non-self” Ags among “self” Ags
- Elimination of specific pathogens or pathogen-infected cells
- Development of an immunologic memory – quicker elimination of pathogen upon reinfection
7
Q
Main cells of Adaptive Immune System
A
T and B cells
B cell receptor is membrane bound
8
Q
Adaptive Immune System - role
A
Generates large numbers of preexisting receptors expressed on lymphocytes, that can identify essentially any Ag
9
Q
Three molecule groups specifically recognize foreign Ag (adaptive immune sys) , what are they?
A
T cell receptor (TCR)
B cell receptor (BCR)
Major Histocompatibility Complex (MHC)
10
Q
Major Histocompatibility Complex (MHC) - cluster of genes in humans is?
A
Human Leukocyte Ag (HLA) in humans
11
Q
The MHC molecule is always bound to the Ag presenting cell surface (T/F)
A
True
12
Q
The TCR is always bound to the T cell surface and recognises Ag and MHC (T/F)
A
True
13
Q
Antigen - define
A
a substance recognised by receptors of the adaptive immune system
Majority of antigens are proteins
14
Q
How are antigens classified?
A
Can be classified via how they induce an immune response and their origins
15
Q
Immunogen - define
A
Animmunogenis an antigen or any substance that may be specifically bound by components of the immune system (antibody, lymphocytes).
16
Q
Haptens - define
An example of Haptens is viruses, what does this imply for the host immune response?
Hapten conversion to Immunogen - how?
Haptens introduced to mouse - outcome
Carrier protein introduced to mouse - outcome
Hapten + carrier protein introduced to mouse - outcome
Some antigens have low immune power, how is this combated?
Which factors influence antigen immunogenicity? A Foreignness of antigen; B Molecule weight of antigen C Host's inheritance D Host's age E Adjuvant
A
Haptens are small molecules that elicit an immune response only when attached to a large carrier such as a protein.
Since Haptens are too small to initiate an immune response, the body will not show any signs and symptoms
If a Hapten stays in the body for a long time, mutations can occur in the Hapten causing it to eventually bind to a carrier protein forming a hapten-carrier protein complex, which allows it to become Immunogenic since the size of the molecule is large.
Haptens introduced to mouse - No antibodies
Carrier protein introduced to mouse - Antibodies produced against carrier protein
Hapten + carrier protein introduced to mouse - Antibodies produced against haptens
Adding adjuvants to antigens can increase the immune response by increased attraction and uptake to APCs.
A, B, E
17
Q
Diff between an antigen and a hapten
A
Anantigenis a complete molecule that can trigger an immune response by itself whereas
Ahaptenis an incomplete molecule that cannot trigger an immune response by itself.
18
Q
Tolerogen - define
Foreign antigens/ Heteroantigens -
Self antigens/ Autoantigens -
1st, 2nd, 3rd lines of defense
State of unresponsiveness of immune system to antigens is?
State of unresponsiveness of immune system to self antigens is?
What happens if self tolerance fails?
How are immune responses to self antigens prevented in human body?
Tolerogen - define
What happens if the molecular form of tolerogen is changed?
Tolerogen - MoA
A
Tolerogen - A foreign antigen that suppresses immune response, or produces immune tolerance.
Heteroantigens - Not part of human body
Autoantigens - Body cells
1st line - skin + mucous membranes
2nd line - Inflammation, fever, innate immune cells
3rd line - T cells, B cells, APCs
Immune tolerance
Self tolerance
Autoimmunity (immune cells attack itself)
Antigen that invokes a specific non-responsiveness due to its molecular form.
If molecular form is changed, tolerogen can become an immunogen.
Instead of inducing the immune system to be active, the tolerogen binds to the antigen receptor of the lymphocytes in order to suppress it.
19
Q
T lymphocytes are derived from
A
Haemopoietic stem cells in BM
20
Q
T lymphocytes mature in
A
Thymus
21
Q
T lymphocytes express TCRs on surface (T/F)
A
True
22
Q
T lymphocytes does not require action of APCs to recognise specific Ag (T/F)
A
False; T lymphocytes require action of APCs to recognise specific Ag
23
Q
How are T cells activated?
A
T cells are activated when they encounter antigenic peptide fragments bound to MHC molecules
24
Q
What happens during and after T cell activation?
A
- Ag-MHC complex activates TCR
- T cell secretes cytokines
- T cells differentiates into CD8+TC or CD4+TH cells
25
CD8+ T cells - main function
Primarily involved in destruction of cells infected by foreign entities
26
How are CD8+ T cells activated?
Activated by TCR interaction with peptide-bound MHC I molecules.
• Activated via Ag on APC and co-stimulatory signal or Ag on a nonAPC target cell and cytokines from CD4 T cells
27
Result of CD8+ T cell activation
• Clonal expansion – effector cells – utilize perforin, granzyme and granulysin
28
Most effector cells/mature T cells die – few retained as memory cells – subsequent infection (T/F)
True
29
Function of CD4+ T helper cell
Primarily involved in establishing and maximizing the
immune response
-- Direct other cells to perform immune task
30
CD4+ T helper cell is activated by?
TCR interaction with peptide-bound MHC II
| molecules
31
MHC I is found where?
nucleated body cells (not red blood cells)
32
MHC II is found where?
antigen presenting cells
33
Antigen is in MHC molecule (T/F)
True
34
T cells can recognize when antigen is on APC (T/F), if true what does it mean for CD4+ and CD8+ molecules?
T cell recognizes MHC II (CD4+)
| T cell recognizes MHC I (CD8+)
35
BCR - antibody bound to membrane of B cell (T/F)
True
36
Antibody = soluble immunoglobulin (T/F)
True
37
Dendritic cells, B cells, Macrophages - professional APCs (Use MHC I) T/F
False; they use MHC II
38
Function of APCs
They present antigenic peptides
39
Why are professional APCs the molecules responsible for presenting antigenic peptides when when nucleated cells have MHC which is recognized by T cells?
Nearly all nucleated cells have MHC I. They have MHC I so they can present to a T cell.
Thus professional APCs are ones whose role is to present antigens.
40
How do antigens present in MHC molecule?
When virus enters cell, various processes in cells produce peptides, these peptides can present on cell surface. Antigen peptide moved to surface on MHC molecule.
41
Why would we want these nucleated cells to present to CD8 T cell?
Depends on where the antigens are found
i.e. location with respect to cell
Ag can be inside or outside cell
Pathogens inside cell:
Viruses - interested in nucleus where dna replication occurs
Bacteria - Brucella abortus, Listeria monocytogenes, Chlamydia trachomatis, Mycobacterium tuberculosis, Salmonella enterica - outside
T cell can't enter cells
so MHC I is on cell surface so it can present antigens to the cytotoxic T cell whose main purpose is to kill cells.
42
Function of CD4+ T helper cell
Primarily involved in establishing and maximizing the
immune response
• Direct other cells to perform immune tasks
43
CD4+ T helper cell is activated by?
TCR interaction with peptide-bound MHC II
| molecules
44
Once T cell becomes activated, many events occur as a result, what are these events?
Can signal naive T cell to be activated
Can signal macrophage/ any other dendritic cells to be activated
Can signal B cells to mature to plasma cells
Can signal NK cells to beome activated and kill infected cells
45
Two types of T cells - name them
CD8 cells - cytotoxic cells
| CD4 cells - helper cells
46
Activation of CD4 T cells is important for beginning of response in cell mediated immunity (T/F)
If true, what cells would be important to T cell activation?
True; APCs
47
Types of APCs
Dendritic, macrophage, B cell (produces antibodies)
48
Macrophages are a type of APC involved in T cell activation, how are MHCs involved with macrophages and T cells?
Macrophage engulfs bacteria, degrades into fragments and loads these fragments onto MHC II.
Then MHC II showcases the fragments to T cell.
49
1st step of T cell activation - outline
1. MHC II forms a complex with TCR -- T cell can recognize the pathogen fragments on MHC II as non self
50
2nd step of T cell activation - outline
2. Costimulatory rxns required to confirm this binding of MHC II and TCR
- B7 from macrophage and CD28 receptor on T cell interactions
- CD40 from macrophage and CD40 ligand from T cell
- CD4 from T cell will place the MHC II and TCR in the perfect orientation
Costimulation - enhancement of previous signal
51
3rd step of T cell activation - outline
3. Chemical signalling
After these rxns macrophage releases chemicals
i.e. IL-12. Receptors on T cell recognizes IL-12, genes will be transcribed and RNA translated
52
4th step of T cell activation - outline
4. IL-12 causes T cell to produce receptor on T cell surface called IL-2 receptor and T cell produces IL-2 which acts on ITSELF -- known as autocrine signalling
53
5th step of T cell activation - outline
Also produces Il-1 which converts naive T cells into helper T cells
Interferon gamma which acts on macrophage and signals to bring more macrophages to signal more T cells
54
All immune responses have a call and response action so cells usually respond back to each other (T/F)
True
55
Why do the T cells remain in the thymus for a bit?
T cells need to be trained in thymus then can go into circulation. From the T cells multiple cells will be produced.
56
B cell class switching - define
Class switching is the process whereby an activated B cell changes its antibody production from IgM to either IgA, IgG, or IgE depending on the functional requirements.
57
Effector B cells - define
Effector B cells are called plasma cells and secrete antibodies
58
What does T cell activation cause in B cells?
Clonal expansion – effector cells – release cytokines –
activities including B cell class switching and affinity
maturation
59
What is the fate of B cells after clonal expasion?
Most effector cells die – few retained as memory cells –
| subsequent infection
60
Types of CD4+ T helper cells
Why does the body need diff types of T helper cells?
• TH1
•-- Intracellular/virus infection occurs. DCs/macrophages secrete IL-12 and present the peptide fragments to naive T cells in lymph node.
Once IL-12 signal is recognized, it stimulates naive T cell to become TH1.
The TH1 cell now:
- secretes interferon gamma (IFN-γ) which activates macrophages
- interferon gamma also stimulates production of antibodies that promote phagocytosis since they act as complement proteins (enhance phagocytosis by opsonization)
- also TH1 secretes IL-2 which stimulates growth and differentiation of T cells
• TH2
•-- Parasitic infection occurs and APCs secrete IL-4, APC presents antigen to naive T cell which differentiates into TH2 cell.
TH2 Secretes:
IL-4 - stimulates B cells to produce IgE antibodies
IL-5 - activates mast cells and eosinophils
IL-13 - stimulates mucus production in intestines
Parasite too large for phagocytosis, MoA involves:
1. IgE antibodies coat parasite surface
2. Mast cells and eosinophils have receptors for Fc regions of the antibodies, so they bind to Fc region
3. Parasite killed by granule enzymes secreted by mast cells and eosinophils
4. Mucus secretions are to promote parasite expulsion from gut
– IgE producing B cells, mast cells and eosinophils
• TH17
•-- Infection involving fungi and extracellular bacteria present. IL6 and transforming growth factor beta (TGF-beta) are produced by innate immune cells.
T cell recognizes antigens from pathogens presented on dendritic cell.
IL6 and TGF-beta induce tranformation of T cell into TH17
TH17 does the foll:
- Secretes IL17 which recruits neutrophils to infection site
- IL22 and IL17 stimulate epithelial cells to promote antimicrobial peptides that resist invasion
(Patients lacking gene for IL17 are more susceptible to bacterial and fungal infections)
• T-regs
Limit the tissue damage caused by immune response once a pathogen has been eradicated and suppress T cell response.
Prevents autoimmunity - communicate with other immune cells and help to stop their effector functions
Produces IL10 (suppress macrophage) and TGF-beta (induce generation of Treg cells) which help inhibit inflammation and immune response
```
• Follicular TH cells
•-- Involved in class switching and affinity maturation
- Produces IL-21 which guides B cells to make appropriate antibodies (class switching) to combat infection
```
Body encounters diff types of pathogens that infect diff parts of body and diff cells. E.g. helminths are too large to be phagocytosed and mycobacteria get ingested by phagocytes but resist phagocytosis. T helper cells will signal diff immune cells to help eliminate the pathogen.
61
Intracellular pathogens - name
Mycobacteria, viruses , protozoa
62
Initiators of response for intracellular pathogens - name
IL-12 secretion by Macs and DC, IFN-γ secretion by NK cells
63
Responding T cell to initiators of response for intracellular pathogens\
TH1
64
Clonal expansion - explain
In clonal selection, an antigen is presented to many circulating naive B and (via MHC) T cells,
and the lymphocytes that match the antigen are selected to form both memory and effector clones of themselves.
This mass production is termed “clonal expansion,” in which daughter cells proliferate into several generations of clones of the original parent cells.
65
```
Most effector cells die – few retained as memory cells –
subsequent infection (T/F)
```
True
66
TH1 - role
• IFN-γ production; Ab production by B cells
67
TH2 - role
• IL-4, IL-5, IL-13 production – IgE producing B cells, mast cells and eosinophils
68
TH17 - role
• IL-17, IL-22 production – defense against Fungi and extracellular bacteria
69
T-regs - role
• Limit/suppress Immune System – role in autoimmunity
70
Follicular TH cells - role
• Involved in class switching and affinity maturation
71
Types of CD4 Th cells
Th1, Th2, Th17, T-regs, Follicular Th cells
72
Gamma delta (γδ) T cells - explain
Gamma delta (γδ) T cells are the prototype of ‘unconventional’ T cells and represent a relatively small subset of T cells in peripheral blood.
Gamma delta cells are lipid based so doesn't need MHC I or II whilst alpha beta T cells are protein based
- defined by expression of (TCRs) composed of γ and δ chains. This sets them apart from the classical and much better known CD4+ helper T cells and CD8+ cytotoxic T cells that express αβ TCRs.
- Do not need APCs to function, can interact with all unbound antigens
- Believed to be first line of defense, acting faster than alpha-beta T cells
73
In the thymus, T cells diversify and undergo selection processes which are?
• Positive selection
• Permits survival of only those T cells which TCRs are
capable of recognising self-MHC molecules
* Negative selection
* Eliminates T cells that react too strongly with self-MHC or with self-MHC plus self peptides
74
T cell
B and T lymphocytes arise from a common ancestral cell—lymphoid progenitor or common lymphoid precursor-2 (CLP-2). ... During the development of T- and B-cell lines in the organs of the central immune system (thymus and bone marrow) they begin to express various cell surface markers.
75
T cell lineage - Ontogeny
➢ Common lymphoid precursor leaves the bone marrow and migrates through the bloodstream
to the thymus.
------ Thymocytes early in development lack detectable CD4 and CD8, and are referred to as double-negative (DN) cells or T cell precursor. DN cells can become T cells, NK cell, Dendritic cell or B cell.
--------------------------------------------------------------------------------------
➢ These DN Pre-T cells differentiate into ɣδ DN Pre-T cells and ⍺β DN Pre-T cells.
ɣδ DN Pre-T cells leave the thymus to populate lymphoid tissue and epithelia.
➢ Most DN thymoctyes progress down the ⍺β developmental pathway.
They stop proliferating and begin to rearrange the TCR β-chain genes, then express the β chain.
➢ β chain combines with the pre-T ⍺ chain and the CD3 group to form the pre-TCR.
➢ The pre T cell advances to the double positive (DP) stage, as a Pro-T cell with the expression CD4 and CD8 correctors and the rearrangement of ⍺ chain genes to form the ⍺β TCR.
➢ DP thymocytes expressing ⍺β TCR-CD3 complex develop into immature CD4+ TH cells or CD8+ TC cells.
76
What are HSCs?
Hematopoietic stem cells (HSCs) are the stem cells that give rise to other blood cells via haematopoiesis.
77
B cells arise from?
HSC
78
B cells roles
```
• Can recognize free Ag directly
• Upon activation, undergo proliferation and
differentiation
• Plasma cells
• produces Abs
• undergo apoptosis once inciting agent is eliminated
• Memory B cells
• Major role in humoral immune responses
```
79
Humoral immunity response to whole antigen in circulation
1. Antigen --> engulfed by macrophage
2. Fragments of antigen --> presents on macrophage and macrophages becomes APC
3. APC --> activates Helper T cell
4. Helper T cell can differentiate into B cell and cytotoxic T cell
80
Humoral immunity response to free antigen/piece of antigen e.g. bacteria flagella
1. Free antigen is recognized by B cells
| 2. B cells turn into plasma cells which produce antibodies
81
Cell mediated immunity response to whole antigen inside normal cell
1. Antigen is recognized by cytotoxic T cell
| 2. Cytotoxic T cell kills infected cells
82
Humoral and cell mediated immunity response to whole antigen in circulation for the 1st time
Helper T cells and B cells would be changed to memory cells if infection is experienced for the first time since the immune sys will have to make memory cells
So we will have memory helper T cells and memory B cells.
83
Abs bind to Ags, destruction occurring via ?
* pathogen & toxin neutralization
* Classical complement activation
* Opsonisation promotion
84
• Ag-Ab complexes are cleared by?
Complement cascade
85
Properties of antibodies
Proteins that react specifically with the Ag that
stimulated their production.
Very specific, binding only on a particular Ag
Possess high affinity i.e. bind Ag very strongly
Are ~ 20% of plasma proteins
During electrophoresis, Abs are separated into the γzone – referred to as the gamma globulin fraction of
serum.
86
What is primary function of Ag and what does this cause?
Primary function is to bind Ag
Can result in the inactivation of a pathogen
Opsonization (make pathogen more recognizable to immune cells)
Complement activation
87
B cell activation process
An effective signal for B cell activation involves two distinct signals induced by membrane events
Occurs via two different pathways dependent on the nature of the Ag.
Antigens that can activate B cells in the absence of direct contact with TH cells are thymus independent (TI) antigens.
TI-1 Ags are mitogens - polyclonal B cell activators that are able to activate B cells regardless of the antigenic specificity e.g. LPS
TI-2 Ags activate by extensively cross-linking the mIg receptor and engaging several BCRs e.g. polymeric proteins - bacterial flagellin
Response to TI Ags is generally weaker, with no memory cells and a low level of class switching
88
Diff btw T cell and B cell activation
T cell activation responsible for humoral and cell mediated immunity while B cell activation is responsible for cell mediated immunity.
89
B cells role in antibody production
Can produce antibodies which are attached to B cell receptors
90
Antibody variable region purpose
Variable region - rxn with antigen
91
Somatic hypermutations in antibodies
Mutations occur in variable regions called somatic hypermutations. Since there are mutations the antibodies have diff variable regions so they can each bind to diff antigens.
92
CD40 is present on surface of all APCs (T/F)
True
93
Special T cells can identify B cells (T/F)
True
94
An effective signal for B cell activation involves two distinct signals induced by membrane events (T/F)
Occurs via two different pathways dependent on the nature of the Ag. (T/F)
True
| True
95
Antigens that can activate B cells in the absence of direct contact with TH cells are
thymus independent (TI) antigens
96
TI-1 Ags (Thymus independent antigens) are mitogens - define mitogen
polyclonal B cell activators that are able to
| activate B cells regardless of the antigenic specificity e.g. LPS
97
TI-2 Ags activate by B cells by?
extensively cross-linking the mIg receptor and
| engaging several BCRs e.g. polymeric proteins - bacterial flagellin
98
Response to TI Ags is generally (stronger/weaker?), with no memory cells and a (high/low?) level of class switching
Response to TI Ags is generally weaker, with no memory cells and a low level of class switching
99
T independent antigens structure
Repeating structures that cross link the BCR or cross link PRRs and BCR
100
T cells do not participate in response to T independent antigens, what does this mean for class switching?
No class switching will occur, only IgM will be produced
101
Why can't class switching occur for T independent antigen immune response?
CD40 ligand on T cell must interact with CD40 on B cell to induce class switching and T cells aren't participating
102
What will happen to the B cells without T cell assistance?
The B cells will proliferate into plasma cells which will secrete only IgM antibodies
103
What will happen to the B cells without T cell assistance?
The B cells will proliferate into plasma cells which will secrete only IgM antibodies and some IgD
104
TI-1 Ags (Thymus independent antigens) are mitogens - define mitogen
polyclonal B cell activators that are able to
| activate B cells regardless of the antigenic specificity e.g. LPS
105
TI-2 Ags activate by B cells by?
extensively cross-linking the mIg (membrane bound immunoglobulin) receptor and engaging several BCRs e.g. polymeric proteins - bacterial flagellin
106
Are host cells recognized by the innate or adaptive immune system?
No, however host cells can express substances on receptors such that when immune system cells bind their phagocytic actions are inhibited
