Transplant Immunology and Immunodeficiency disease Flashcards
(104 cards)
1
Q
What is Hypersensitivity
A
Altered immunologic response to an antigen resulting in disease and damage to a host
2
Q
Types of Hypersensitivity
A
Allergy
Autoimmunity
Alloimmunity
3
Q
What is an allergy
A
deleterious effects of hypersensitivity to environmental (exogenous) antigens
4
Q
what is Autoimmunity
A
Disturbance in immunologic tolerance of self-antigens with damage to self tissue
5
Q
what is Alloimmunity
A
Immun reaction to tissues of another individual
6
Q
How is Hypersensitivity characterized
A
by the immune mechanism
7
Q
Types of Hypersensitivity
A
Type I
Type II
Type III
Type IV
8
Q
type I hypersensitivity
A
IgE mediated
9
Q
Type II hypersensitivity
A
Tissue-specific reactions
10
Q
Type III hypersensitivity
A
Immune complex mediated
11
Q
Type IV hypersensitivity
A
Cell mediated
12
Q
When the Immune system reacts with antigens on the tissue of other genetically dissimilar members of the same species
A
Alloimmunity
13
Q
When the Fetus expresses parental antigens not found in the mom
A
Transient neonatal alloimmunity
14
Q
What are the types of Alloimmunity
A
Transient neonatal alloimmunity
Transplant rejection
Transfusion reactions
15
Q
What is MHC essential for
A
Antigen presentation to T cell
16
Q
What do T cells look for
A
Foreign antigens
17
Q
Self MHC + foreign Ag
A
T cell response
18
Q
Self MHC + Self Ag
A
No t cell response
19
Q
Where is MHC expressed
A
it is expressed or can be induced to be expressed on nearly every nucleated cell in the body
20
Q
MHC I in response to Virus
A
Viruses can infect virtually any nucleated cells so MHC I fnction to alert the CD8+ T cells
21
Q
what does MHC expression tell the immune system when it sees a self cell
A
it says, yo don’t fuck this cell up, its you.
22
Q
What is a key factor in determining tissue match for transplant donors and recipients
A
MHC
23
Q
Specificity of MHC
A
Many different pepetides can bind within the MHC binding cleft with broad specificity
24
Q
Binding rate of PEptides to MHC
A
Slow on and Slow off rate
25
Do MHC molecules discrimate from self and foreign peptides
NO
26
what determines which peptides bind and how peptides bind to MHC
MHC haplotypes of an individual
27
what is MHC also known as
HLA (human Leukocyte antigen)
28
how many alleles for MHC genes are there
Highly polymorphic (10^13 combinations) as the most polymorphic gene in the human genome
29
problem with MHC being highly polymorphic
Hard to find transplant donors even under 1st degree relatives
30
How are MHC alleles expressed
Concomitantly
31
the set of MHC alleles on an individual chromosome
MHC haplotype
32
What can the MHC haplotype influence
how an individual responds to certain pathogens
Susceptiblity to certain diseases
Transplant success
33
Different types of transplant rejection classified according to time
Hyperacute
Acute
Chronic
34
how does Hyperacute graft rejection occure
Immediately due to preexisting antibody to the antigens on teh graft
35
Commonality of hyperacute graft rejection
rare
36
How does Acute GRaft rejection occure
Cell-mediated response against unmatched HLA antigens
37
When does Chronic Graft rejection occur
Months or years
38
what is the cause of Chronic GRaft rejection
Inflammatory damage to endothelial cells of vessels due to a weak cell-mediated reaction against minor HLA antigens
39
what is the result of Hyperacute rejection
Complement activation
endothetlial damage
Inflammation
thrombosis
40
what is the result of an acute rejection
Parenchymal cell damage
Interstitial inflammation
Endothelialitis
41
what is the result of ionchronic rejection
Chronic DTH reaction in vessel wall
Intimal smooth msucle cell proliferation
Vessel occlusion
42
who is at risk for Graft-Versus-Host (GVH) Disease
Immunocompromised individuals (not a problem in Immunocompetent people)
43
what are the T cells capable of in grafts
They are mature and capable of cell-mediated destruction of tissues in the recipient
44
What are Transfusion reactions
Antibodies agisnt blood group antigens
45
how are a and B blood antigens expressed
Codominant
46
what antibodies do people have in response to a or B blood type
antigens to antibodies to whatever they lack
47
how are anti-a and anti b antibodies produce
Made by similar antigens on naturally occuring bacteria in the intestinal tract
48
what class are antibodies for A and B blood type
IgM
49
Universal donor
O blood type
50
Universal acceptor
AB blood typ
51
history of Immunodeficiency discription
```
Hippocrates: 400 bc
Da Vinci: 1510 AD
Traygdon Wilsmyth: 1770
Louis PAstuer: 1880
Ogden Bruton: 1950
```
52
what was the first primary immunodeficiency disease to be described
Bruton Agammaglobulinemia
53
What did Colonel Ogden Bruton note
1952, absence of Immunoglobulins in a boy with a history of pneumonias and other bacterial infections
First physican to provide specific immunotherapy for X linked disorder by administering intramuscular injections of IgG
54
Types of Immunodeficiencies
PRimary/Congenital Immunodeficiencies
| Secondary/acquired immunodeficiencies
55
What are Primary/Congenital immunodeficiencies
Genetic defects that result in an increased susceptibility to infection
56
when do Primary/COngenital Immunodeficiences manifest
In infancy and Childhood
57
How many people have Primary or congenital immunodeficiencies
1:500 in the US
58
what do Secondary or acquired Immunodeficiencies develop as
```
As a consequence of:
Malnutrition
Disseminated Cancer
Treatment with immunosuppressive drugs
Infection of cells of the immune system
```
59
how common are Toll-Like receptors
Conserved across widely diverse species
60
What can Primary immunodeficiency disorders affect
one+ components of the immune system
| T, B lymphocytes, NK cells, Phagocytic cells and complement proteins
61
Immunodeficiencies from Primary Immunodiciencies may result from what
Defects in leukocyte maturation, activation from defects in effector mechansisms of innate and adaptive immuntiy
62
what is the principle consequence of an immuno-deficiency
INcreased susceptibility to infection
63
What determines the nature of the infection due to an immunodeficiency
Depends on the componenent of the immune system that is defective
64
Deficient humoral immunity results in
Increased susceptibility to infection by pyogenic bacteria
65
other name for X-linked Agammaglobulinemia(XLA)
Bruton's Agammaglobulinemia
66
What is XLA
All antibody isotypes are very low (not even IgM or IgD)
Circulating B cells are absent
PRe-B cells are present in reduced numbers in bone marrow
67
What happens to the tonsils and lymph nodes due to XLA
Tonsils are usualy very small
| Lmph nodes rarely palpable due to lack of gerinal center
68
Thymus changes due to XLA
Architecture is normal b/c t-cell dependent areas of spleen and lymph nodes
69
Why do boys with XLA remain healthy for the first 6-9 months of life
Maternally transmitted IgG antibodies
70
What happens after a while for guys with XLA
Get a lot of extracellular pyogenic organisms infections
71
What is the defect due to XLA
Loss of function of Bruton Tyrosine Kinase
72
Roll of Bruton Tyrosine Kinase
Pre-B cell expansion and maturatio into Ig-expressing B cells
73
What characterizes X-linked immunodeficiency with Hyper-IgM
Low serum IgG, IgA, and IgE
| High levels of polyclonal IgM
74
When do patients with Hyper-IgM become symptomatic
after the 1st or second year of life with recurrent pathogenic infections
75
How are patients with XLA different than that of Hyper-IgM
Hyper IgM patients have lymphoid hyperplasia
76
What is the defect in X-linked immunodeficiency with hyper-IgM
Loss of CD40 ligand (CD154) that is expressed on helper T cells
77
What does Loss of CD40 ligand (CD154) lead to
Prevents the T cell from co-stimulating antigen-specific B cells (through CD40)
B cells are not signalted be the T cell to go through isotype sqitching and only produce IgM
78
How to treat immunodeficiencies for humoral immune response
Routine -- prophylactic antibiotics and/or gamma-globulin therapy
79
What results in increased susceptibility to viruses and other intracellular pathogens
Deficient Cell-mediated Immunity
80
How to treat defects associated with deficient T cell responses
It is very hard to treat
81
How long can people live with Defects in T-cell function
Not long, rarely past infancy or childhood
82
Commonality of X-linked Recessive Severe Combined Immunodeficiency disease
Rare
83
What is a Severe combined Immunodeficiency
A rare, fetal syndrome characterized by profound deficiencies of T- and B-cell function
84
what is the most common form of Severe combined Immunodeficiency(SCID)
X linked SCID(XLSCID)
85
When do people present XLSCID
Within the first few months of Life
86
Symtpoms of XSCID in early life
Diarrhea, pneumonia, otitis, sepsis, cutaneous infections
87
growth of someone with XLSCID
may be normal initially, but extreme wasting usually develops after infections and diarrhea begins
88
What do people with XLSCID often have
Persistent infections due to opportuistic organisms (candida albicans, pneumocysits carinii, varicella, measles, parainfluenzae, cytomegalovirus, ebv)
89
Can infants with XLSCID get grafts
Lack the ability to reject foreign tissue and therefore are at risk for GCHD
90
when can GVHD ocure in XLSCID
when maternal T cells cross into fetal circulation while the SCID infant is in utero
91
What cells do XSCID patients lack
They have few or no T cells and NK cells
92
What cells do XSCID patients have a lot of
B cells ( don't produce immunoglobulin normally, even after T cell reconstitution by bone marrow transplantation)
93
what are the aims of current treatments for Immunodeficienceies
1. Minimize and control infections
| 2. replace the defective or absent components of the immune system by adoptive transfer and or transplantation
94
What is valuable for agammaglobulinemic parients to save their lives
Passive immunization with pooled gamma globulin
95
what is the treatment of choice for various immunodeficiency disease
Bone marrow transplantation
96
Successfulness of Bonemarrow transplantation
it can treat SCID and other similar diseases
97
Short lived Cellular reservoir of HIV
CD4+ T cells for the first phase of decay with a half life of 1 day
98
Productively infection long lived cells for HIV
Monocytes and macrophages for the second phase of decay with a half life of 2 weeks
99
Productively infected resting memory cells for HIC
Resting/memory CD4+ cells as the 3rd phase of decay greater than 50 years
100
Progression of HIV
Primary infection of cells in blood, mucosa
Infection established in lymphoid tissues (lymph node)
Acute HIV syndrome, spread of infection throughout the body
Immune response
Clinical latency
AIDS
101
Acute HIV syndrome with spread of infectionthroughout the body
Viremia
102
Immue response to HIV effectiveness
PArtial control of viral replication
103
What happens during the Clincial latency of HIV
Estblishment of Chronic infection
Virus trapped in lymphoid tissues by folicular dendric cells
low level viral production
then more microbial infections leads to increased viral replicaion
104
what happens with AIDS
Destruction of Lymphoid tissues
| Depletion of CD4+ T cells
