1
Q
Lymphocytes can be divided into three major populations —
A
- T cells,
- B cells,
- natural killer (NK)
2
Q
produce cytokines that contribute to
immunity by stimulating B cells to produce antibodies, assisting in killing tumor cells
or infected target cells, and helping to regulate both the innate and adaptive immune
response.
A
T cells
3
Q
% of T cells
A
61-80%
4
Q
does not directly recognize the antigens of microorganisms or
other living cells but recognizes when the antigen is present on the surface of an
antigen-presenting
A
T lymphocyte
5
Q
10-20%: End product of activation is antibody
A
B cell
6
Q
NK cell %%
A
10-15%
7
Q
Referred to as HUMAN LEUKOCYTE ANTIGEN (HLA)
A
MHC Molecules
8
Q
MHC Molecules Referred to as
A
HUMAN LEUKOCYTE ANTIGEN (HLA)
9
Q
Molecular basis for T cell discrimination of self from non-self
A
MHC Molecules
10
Q
Found on the SHORT ARM of CHROMOSOME 6 at BAND 21
A
MHC Molecules
11
Q
MHC Molecules found on ?
A
SHORT ARM of CHROMOSOME 6 at BAND 21
12
Q
Gene product of MHC molecule found in?
A
WBC
13
Q
Allows for an IMMUNE RESPONSE to DIVERSE IMMUNOGENS
A
MHC Molecules
14
Q
Second only to the ABO antigens influencing the survival or graft rejection of
transplanted organs
A
MHC Molecules
15
Q
Considered the MOST POLYMORPHIC SYSTEM
A
MHC Molecules
16
Q
different individuals have different MHC alleles resulting in immune system
recognizing variation
A
Polymorphism
17
Q
different variations of MHC molecules
A
Alleles
18
Q
Main Function:
* Bring antigen in the body to the surface of cells for recognition by T CELLS
* T cell activation – occur only when antigen is combined with MHC molecules
A
MHC Molecules
19
Q
3 Classes of MHC Molecules
A
- Class 1
- Class 2
- Class 3
20
Q
Class 1 Molecules Loci (Classical)
A
HLA-A
* HLA-B
* HLA-C – Not expressed in the surface of cells
21
Q
Class 1 MHC Not expressed in the surface of cells
A
HLA-C
22
Q
Class 1 MHC Non-Classical
A
HLA-E
* HLA-F
* HLA-G – expressed in trophoblast cells
23
Q
HLA-G Non-Classical MHC 1 expressed in?
A
Trophoblast cells
24
Q
Present antigen to:
CD8+ T cells – triggering a cytotoxic reaction
A
Class 1 Molecules
25
Function:
* Associate with foreign antigens, such as:
Viral proteins, tumor, parasitic antigens
Synthesized WITHIN a host cell
ENDOGENOUS pathway for antigen presentation
Class 1 Molecules
26
Class 2 Molecules Major Class II
* HLA-DP
* HLA-DQ
* HLA-DR
27
Loci of Class 2 MHC
D region
28
Class 2 Molecules Non-Classical Class II
* HLA-DM
* HLA-DN
* HLA-DO
29
Only found on:
* B cells
* Monocytes
* Macrophages
* Dendritic cells
* Thymic epithelium
MHC 2 molecules
30
MHC 2 molecules are only found on, what are these cells?
Only found on:
* B cells
* Monocytes
* Macrophages
* Dendritic cells
* Thymic epithelium
31
Present antigen to:
* CD4+ T cells
helper cells involved in antibody production
regulate the interaction between helper T cells and ANTIGEN PRESENTING
CELLS
MHC 2 molecules
32
Function:
* Associate with foreign antigens taken into the cell from the OUTSIDE
* EXOGENOUS ANTIGEN PRESENTATION
MHC 2 molecules
33
Code for the:
* C4A
* C4B
* C2
* B complement proteins
* Cytokines
o Tumor necrosis factor
Class 3 Molecules
34
Class 3 Molecules code for the?
Code for the:
* C4A
* C4B
* C2
* B complement proteins
* Cytokines
o Tumor necrosis factor
35
Secreted proteins that have an immune function, but they are not expressed on cell surfaces, as
are class I and II
Class 3 Molecules
36
* Mainly present peptides that have been SYNTHESIZED WITHIN the cell
* They present it to CD8+ (Cytotoxic) T cells
* If antigens is recognized as being foreign, cytokines are released causing destruction of
the target cell
Class I Restriction
37
Mainly BINDS EXOGENOUS PEPTIDES
* Present these to CD4+ helper T cells which then secrete cyotkines that cause an antigen
ACTIVATED B CELL to PROLIFERATE and PRODUCE PLASMA CELLS to make
ANTIBODIES against the ANTIGEN.
* Significant in BACTERIAL INFECTIONS
* Significant in the presence of other material that is ENDOCYTOSED by cell
Class II Restriction
38
Class I MHC Molecule Cellular Distribution
All nucleated cells
39
Class I MHC Molecule Structure
One a chain and B2 microglobulin
40
Class I MHC Molecule Classes
ABC
41
Class I MHC Molecule Size of peptides bound
8-11 amino acids
42
Class I MHC Molecule Nature of peptide binding cleft
closed at both ends
43
Class I MHC Molecule Interaction with T cells
Presents endogenous antigen to CD8+ T cells
44
Class II MHC Molecule Cellular Distribution
B cells
Monocytes
Macrophages
Dendritic Cells
Thymic Epithelial Cells
45
Class II MHC Molecule Structure
A chain and B chain
46
Class II MHC Molecule Classes
DP
DQ
DR
47
Class II MHC Molecule Size of peptides bound
13-18 amino acids
48
Class II MHC Molecule Nature of peptide binding cleft
Open at both ends
49
Class II MHC Molecule Interaction with T cells
Present exogenous antigen to CD4+ T cells
50
Main Role of Class I and II Antigen
Presentation
Bind peptides within cells→ Transport them to the plasma membrane →T cells recognize them
51
Attack cells from the OUTSIDE
Bacteria
52
Attack cells from the INSIDE
Virus
53
ROLE of HLA
Successful organ transplant
Paternity Testing
HLA typing
54
HLA typing is also useful in:
Forensic medicine
anthropology
Basic research in immunology
55
Process of eliminating/rejecting foreign
antigen
APC dendritic cells → present T lymphocytes (CD4+ cells/T helper cells) → Function T helper
cells: → CD4+ cell helps CD8+ cells to destroy bacteria or antigen that are present within the
cell → stimulate B cells → B cells when activated – trigger plasma cells → plasma cells will
produce antibody → destroy bacteria
56
ENDOGENOUS PATHWAY SIMPLIFIED
1. Endogenous antigen within cytosol is degraded by proteasome
2. Peptide transported into Endoplasmic Reticulum by TAP
3. Alpha chain of Class 1 MHC binds to B2-microglobulin
4. Alpha chain of Class 1 binds to peptide
5. Peptide-class 1 MHC transported to Golgi Complex and then to cell surface
6. Class 1 MHC peptide binds to CD8+ T cells
57
Exogenous Pathway SIMPLIFIED
1. Class 2 MHC binds invariant chain to block binding of endogenous antigen
2. MHC complex goes through Golgi Complex
3. Invariant chain is degraded, leaving CLIP FRAGMENT
4. Exogenous antigen taken in and degraded and routed to intracellular vesicle
5. CLIP fragment exchanged for antigenic peptide
6. Class 2 MHC antigenic peptide is transported to cell surface
7. Class 2 MHC peptide complex bind to CD4+ T cell
58
Mechanism Endogenous Pathway Class 1
1. Virus enters the cell and produce its own antigenic protein
2. Antigenic protein enters proteasome
a. Proteasomes: degrades antigenic protein into peptides
3. In RER has attached Ribosomes
4. Ribosomes: synthesize/produce MHC class 1 molecules (Incomplete structure only
alpha chain; no beta 2 microglobulin)
5. MHC class 1 will bind to Calnexin
a. Calnexin: chaperon molecule that allows the binding of incomplete MHC 1 into
beta 2 microglobulin
6. After MHC class 1 is complete (binded alpha and beta 2 microglobulin) it will produce
2 chaperon molecules which stabilizes the structure of MHC class 1
a. ERp57 (Endoplasmic Reticulum protein 57)
b. Calreticulin
i. FUNCTION: blocks the antigen binding site of MHC class 1 molecules
and stabilizes the structure of MHC class 1
7. Once MHC class 1 is stabilized, it will leave the RER by TAPASIN (chaperon
molecule)
8. The peptides from the proteasome will be transported by TRANSPORTERS
ASSOCIATED with ANTIGEN PRESENTATION/PROCESSING
9. Once the MHC is close to the peptides, ERp57, Calreticulin, TAPASIN, will be
degraded
10. Once degraded, peptides will now bind to MHC class 1
11. MHC class 1 together with peptides will now travel to the golgi apparatus and the GA
have VESICLES which will be the pathway of MHC with peptide (MHC class 1
molecules with peptide complex) to be presented to the cell surface
12. MHC class 1 will interact to CD8+ molecules
13. CD8+ has its own receptor (T cell receptor, CD8 receptor) which will check if the
complex is MHC class 1
14. Once confirmed it will trigger cytokines to kill the virus
59
Mechanism Exogenous Pathway Class 2
1. Ribosome in the RER will produce MHC class 2 molecule
2. MHC class 2 molecule has a protein (Invariant chain; symbol Ii)
a. Invariant chain: stabilizes and protects the binding site of Class 2 molecule
3. Phagolysosome will be degraded to peptides
4. The peptides will be transported in the vesicles
5. Class 2 molecules will go out the RER with Invariant chain (complete structure) and go
through the Golgi Complex to meet with peptides
6. Once they meet, Invariant chain will be degraded and the degraded Invariant chain will
form into CLIP FRAGMENT (Class II invariant chain peptide)
7. Clip fragment: blocks the antigenic site of Class 2 MHC; Clip Fragment will exchange
location with the peptides for the class 2 molecules and peptide to combine
8. Once they combine, they will be presented to the cell surface where MHC peptide
complex meets/binds to CD4+ cells of T helper
9. CD4+ cell has its own receptors (T receptor and CD4 Receptor)
10. These receptors will confirm if it is MHC class 2
11. If confirmed, the CD4+ cells will release cytokines to TRIGGER B CELL to produce
PLASMA CELLS to KILL ANTIGEN
IMMUNOSERO PRELIM
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