[M] Lec 01: MHC and Transplantation Flashcards
1
Q
Refers to:
- Belong to the host
- Normally, do not evoke an immune response while inside our body
- Autoantigens should not trigger antibody production or else it can lead to autoimmune disease wherein the body will produce
antibodies against self-antigens
A
Autoantigens
2
Q
Refers to cell antigen
A
Autoantigens
3
Q
Refers to:
o From other members of the host’s species
o Capable of producing an immune response
o Example: Human to human
A
Alloantigens
4
Q
Refers to antigens coming from the same species
A
Alloantigens
5
Q
Refers to:
- From other species
- Heterophile antigens
A
Heteroantigens
6
Q
Refers to:
- Exist in unrelated plants or animals but are either identical or closely related in structure
- Antibody to one will cross react with antigen of the other
A
Heterophile Antigens
7
Q
Refers to:
- Present on the red cells of sheep, horse, guinea pig, dog, cat, mouse, fowl, bacteria
A
Forssman antigen
8
Q
Antigens are presented by APC in _______. ______ can ony recognize and respond to antigens when the antigens are combined with MHC molecules.
A
T cells
9
Q
MHC is also referred to as ______________
A
Human Leukocyte Antigens (HLA)
10
Q
These are cell surface glycoproteins which allow immune system to differentiate self from nonself/foreign substances
A
MHC
10
Q
MHC for
- Rats
- Mouse
A
- RT1
- H-2
11
Q
Gene location for MHC
A
Short arm of chomosome 6
12
Q
T or F: Class 3 is not important for antigen presentation because only Class 1 and Class 2 are expressed on the cells
A
True
13
Q
MHC classes
- Present in all nucleated
- Present in APC
- Not important for antigen presentation
A
- Class I
- Class II
- Glass III
14
Q
Enumerate the MHC Class III antigens
A
C4, C2, Factor B, TNF, heat shock proteins
15
Q
T or F: Though RBCs and platelets are anucleated, they still contain Class I because it is vital for immune response
A
False uto-uto
16
Q
T or F: For blood transfusion, we take into consideration the MHC and the blood type (ABO and Rh)
A
False (we do not consider MHC)
17
Q
T or F: MHC Class I has exogenous pathway of antigen presentation
A
False (Endogenous)
18
Q
Refers to:
The type of antigen presented by MHC Class 1 is intracellular antigen
Example: viral antigens, tumor antigens, and certain parasitic antigens
A
Intracellular anitgens
19
Q
What type of cells are intracellular antigens presented to?
A
CD8+ cells or T cytotoxic cells
20
Q
MHC Class I presentation
These intracellular antigens are presented to CD8+ cells or the T cytotoxic cells
T cytotoxic cells will release __________ that will lead to apoptosis which will result to having fragments and products of apoptosis that will activate the T cells leading to the formation of activated T cells and memory T cells
A
Perforins and granzymes
21
Q
Described as serologically defined antigens
A
Class I proteins
22
Q
Enumerate the Class I proteins
A
HLA-A, HLA-B, HLA-C, HLA-E, HLA-F, and HLA-G
23
Q
Class I proteins that are not used for recognizing/classifying
A
HLA-E, HLA-F, and HLA-G (Nonclassical Class 1 Antigens)
24
The glycoprotein dimer of MHC Class I is made up of two noncovalently linked polypeptide chains such as?
Alpha chain and B2 Microglobulin
25
In Class I MHC, how many alpha chains are there?
3
26
Glycoprotein dimer
1. Where the antigen will stick in the MHC molecule
2. Where the T cell receptor of CD8+ cells react
A. A1
B. A2
C. A3
1. A and B
2. C
27
Alpha chains
1. Peptide binding sites
2. Reacts with CD8 cells
1. A1 and A2
2. A3
28
Refers to:
Unique for MHC Class 1
Only present in MHC Class I molecules; therefore
Does not penetrate cell membrane
Essential for proper folding of α chain
B2 Microglobulin
29
Gene location of B2 microglobulin
Chromosome 15
30
T or F: MHC molecule is polymorphic, so as B2 microglobulin because it is a part of the molecule
False (B2 microglobulin is not polymorphic uto-uto ka teh)
31
MHC Class I
Inside the cell, after the α chain is synthesized, it binds first to 1.)__________ (to maintain/stabilize the folding) before the α
chain attaches to b2 microglobulin.
Once α chain attaches to
b2 microglobulin, the 1.) __________ disappear → will become 2.)___________ → they will then bind to α chain after it is attached to b2 microglobulin
1. calnexin and Erp 57
2. calreticulin and tapasin
32
Refers to the transport protein of MHC Class I proteins that helps antigen enter the endoplasmic reticulum
TAP 1 and TAP 2
33
MHC Class I
Inside of ___________ is where the antigen and MHC molecule meets
MHC molecule will be transported into the surface to go out of nucleated
cell until it binds to the receptor of _______ cells
1. Endoplasmic reticulum
2. CD8+ / T cytotoxic
34
Pathway of antigen presentation in MHC Class II
Exogenous
35
Refers to:
* Present in APC
* Presented to CD4 cells
MHC Class II
36
Best APC
Dendritic cells
37
T or F: Islet of Langerhans are macrophages, therefore they contain the MHC Class II for antigen presentation of CD4
False
38
Class II Proteins
1. Lowest in concentration
2. Highest in concentration
3. Most pleomorphic
1. DP
2. DR
3. DR B gene
39
Nonclassical Class I Antigens/Proteins
1. Helps in loading peptides
2. Function not known
3. Modulates antigen binding
1. HLA-DM
2. HLA-DN
3. HLA-DO
40
MHC Class II components
1. Heterodimers
2. Invariant chain
3. CLIP
41
Heterodimers in MHC Class II proteins include which two noncovalently linked chains?
a. α chain (α1 and α2)
b. β chain (β1 and β2) `
42
MHC Class II
1. Peptide binding sites; open structure
2. Binds with CD 4 cells; T cell binding site
1. α1 and β1
2. β2
43
To protect and cover the antigen binding site to prevent unnecessary binding of antigen to MHC class II while it is being synthesized inside of antigen presenting cell (APC)
A. CLIP
B. Invariant chain
C. Both
D. Neither
C
44
The major histocompatibility complex is very effective in infection; however, in terms of ______________, the major histocompatibility complex is strict
Transplantation
45
The genes coding for MHC and HLA are inherited following the rule of ___________
Mendelian genetics
46
Match
1. Myasthenia gravis
2. Ankylosing spondylitis, Reiter’s Disease, Neisseria-Gonococcal Infection
3. SLE, Addison’s Disease, Graves Disease, IDDM
4. Rheumatoid Arhtritis, IDDM
5. Hashimoto's Thyroiditis
6. Multiple Sclerosis
A. B8
B. B27
C. DR3
D. DR4
E. B7 and DR2
F. DR5
1. A
2. B
3. C
4. D
5. F
6. Es
47
Define
1. Healthy organ or tissue transplanted
2. Individual that provides the graft
3. Individual in whom the graft is placed
1. Graft
2. Donor
3. Recipient or Patient or Host
48
Two major types of transplant
Solid organ
Bone marrow / hematopoietic stem cell
49
1. Most immunogenic organ
2. Least immunogenic
3. No immune response (ocular immune privilege)
1. Bone marrow
2. Liver
3. Cornea
50
Refers to when the eyes have an immune mechanism protecting them from foreign substances, wherein despite an infection, antigen presenting cells (APCs) do not easily enter the eyes.
Immune tolerance
51
1. Transfer between two genetically different individuals of the same species
2. Transfer from one area of the body to another area of the body of the same individual
3. Transfer between two individuals of different species
4. Transfer between two genetically identical individuals of the same species
1. Allograft
2. Autograft
3. Xenograft
4. Isograft
52
Autograft
1. Burnt skin → skin from one area to another may be used
2. Blood vessels are derived from the legs and will be used to connect blocked arteries from the heart (in order to bypass the blocked artery)
3. Cartilage from other parts of the body will be placed in the nose
1. Skin gaft
2. CABG
3. Rhinoplasty
53
In isograft, what is probably the best donor?
Twin or sibling
54
First recipient of pig's heart aka the first successful xenograft
David Dennett (2022)
55
Two types of immune system reconition
Direct Allorecogniton
Indirect Allorecognition
56
Match
1. Recipient T cells bind and respond directly to foreign (allo) HLA proteins on graft cells
2. Uptake, processing, and presentation of foreign HLA recipients APC to recipient T cells
A. Indirect allorecognition
B. Direct allorecognition
1. B
2. A
57
Recognition that refers to:
* Recognition of foreign antigen
* Predominant role in induction of alloantibody and chronic rejection
Indirect allorecognition
58
Types of transplant rejection
Hyperacture, acute, chronic
59
Match
1. Occurs days to months; there are no Ab yet, the recipient will have to synthesize them first
2. Minutes to hours after transplantation; presence of preformed antibodies against the donor's graft
3. Occurs months to years; due to graft arteriosclerosis and proliferation of smooth muscle cells
A. Hyperacute rejection
B. Acute rejection
C. Chronic rejection
1. B
2. A
3. C
60
Rejection that refers to:
* Preformed antibodies of the recipient against the donor’s graft
* Antibodies and complement are involved → leading to lysis
* Incompatibility caused by ABO Ag, HLA/MHC, Endothelial Ag
Hyperacute rejection
61
Result of hyperacute rejection
Ischemia and necrosis
62
Rejection that refers to:
* T cells and antibodies are involved in acute rejection
* Mediated by cellular alloresponse (ACR) or by donor-specific antibody also known as antibody mediated response (AMR)
* Antibody and complement → transmural necrosis and inflammation
Acute rejection
63
Type of cells involved in acute rejection
CD4 cells
64
Result of acute rejection
Transmural necrosis and inflammation
65
Rejection that refers to:
* Most significant cause of graft loss after the first-year post-transplant because it is not readily amenable to treatment
* Delayed-type hypersensitivity reaction to foreign (antigens of the donor) HLA proteins
* Alloantibody production
Chronic rejection
66
Chronic rejection is due to ____________ and _____________
Graft arteriosclerosis and proliferation of smooth muscles
67
Chronic rejection
State whether characteristic of chronic rejection or predisposing factor
1. Reperfusion injury
2. Prolonged cold ischemia
3. Progressive fibrosis and scarring
4. Narrowing and thickening of the vessel lumen
5. Toxicity
6. Acute rejection episodes
1. Predisposing factors
2. Predisposing factors
3. Characteristic
4. Characteristic
5. Predisposing factor
6. Predisposing factor
68
T or F: In Hyperacute, Acute, Chronic Rejection — both antibodies and cells against the donor cells are involved hence there is a complement activity
True
69
Refers to
* Under Type 4 Hypersensitivity reaction
* Mediated by mature T-cells:
* Occurs when lymphoid cells from the donor in the graft mounts an immune response against the host’s MHC molecules
Graft vs Host Disease
70
Match
1. Occurs within the first 100 days after transplant
2. Occurs beyond 100 days after transplant
A. Acute GVHD
B. Chronic GVHD
1. A
2. B
71
Prevention for GVHD
Immunosuppressive therapy
T-cell reduction (purification of donor’s graft)
72
In TA-GVHD, what reacts against the HLA antigens of the patient?
Donor's Immunocompetent T cels
73
T or F: If the patient is immunocompromised, the patient cannot counterattack the T cells of the recipient, leading to TA-GVHD
False (the donor*)
74
Major prevention of TA-GVHD
Irradiated blood
75
In organ and tissue transplantation, the minimum requirement is limited to _____________ ONLY
ABO Blood Type
76
HLA Typing is composed of which two components?
Phenotyping and genotyping
77
Tests under phenotyping (HLA)
Complement Dependent Cytolysis/ Cytotoxicity Test
Mixed Lymphocyte Reaction Test
78
Tests under genotyping (HLA)
o PCR with sequence specific PCR: most common
o PCR-SSOP
o Sequence-based Typing: gold standard
79
Genotyping gold standard
Sequence-based Typing
80
Match
1. For HLA Antibody screening (AB detector); detect presence of HLA
2. Tests for Allo recognition and determine whether the T cells of the patients will react ot the HLA proteins in the donor's cells
A. Mixed Lymphocyte Culture
B. Microlymphcytotoxicity Test
1. B
2. A
81
Refers to:
* This is a test for Class 1 MHC molecules
* Detect the presence of Human Leukocyte Antigens such as:
o HLA-A, HLA-B, HLA-C, HLA-E
* Sample: Patient’s Lymphocytes for HLA Typing
Microlymphcytotoxicity Test
82
Sample used in Microlymphcytoxicity Test
Patient's lymphocyte
83
Familiar the reagents used in Microcytotoxicty test
o Anti-sera containing Anti-HLA Antibody
o Complement Reagent from Rabbit Serum
o Eosin Red or Trypan Blue Dye
84
Familiarize the major steps in HLA screening/typing (Microlymphocytotoxicity Test)
1. Addition of anti-HLA typing sera
2. Addition of complement reagent (rabbit serum)
3. Addition of dye (eosin or trypan blue)
85
Positive result in Microcytotoxicity Test
Uptake of dye (colored cells)
86
What does the uptake of dye mean in Microcytotoxic Test?
Presence of HLA Ag in the lymphocytes
87
Match the ASHI grading
1. 21% to 50% cell death; weak positive
2. 51% to 80% cell death; positive
3. 11% to 20% cell death; doubtful negative
4. 81% to 100% cell death; strong positive
5. Unreadable
6. 0% to 10% cell death; negative
A. 1
B. 2
C. 4
D. 6
E. 8
F. 0
1. C
2. D
3. B
4. E
5. F
6. A
88
Refers to:
Blastogenesis Reaction
A direct test for Allo recognition to determine whether the T-cells of the patients will react to the HLA proteins or MHC present in the donor’s
cells
Determine Class II Compatibility between donor and recipient
Mixed Lymphocyte Culture
89
Specimen used in Mixed Lymphocyte Culture
o Live Recipient’s Lymphocytes
o Donor Lymphocytes
90
Familiarize the steps for Mixed LymphocyteC Culture
1. Recipient and patient's lymphocytes are incubated
2. Addition of radio-labeled thymidine
91
In Mixed Lymphocyte Culture, this is added to quantify the blastogenesis reaction or the proliferation of the patient's T-cells
Thymidine
92
Positive result in MIxed Lymphocyte Culture
Increased reactivity or thymidine uptake
93
What does a positive result in Mixed Lymphocyte Culture mean?
* High reactivity (high cell proliferation)
* High chance of graft rejection
* The greater the amount of reaction in the recipient responder cells, the more foreign are the MHC class of donor cells
94
Three other tests for HLA
1. HLA Antibody Screening
2. Crossmatching
3. ELISA
95
Other tests for HLA
1. Confirms the absence of donor specific antibody
2. Aids in the diagnosis of antibody-mediated rejection
3. Substitute for Complement Dependent Cytotoxicity (CDC) based HLA Antibody Testing
4. Assess the effectiveness of therapy for antibody-mediated rejection
A. HLA Antibody Screening
B. Crossmatching
C. ELISA
1. B
2. A
3. C
4. A
96
Most sensitive method for detecting donor-specific antibody
Flow Cytometric Crossmatch
