1
Q
What is hypersensitivity?
A
overreaction; response to antigens (allergens) leading to damage
2
Q
Autoimmune diseases can be described as…
A
reactions against self
3
Q
HLA issues
A
transplantation, human vs. human
4
Q
Cancer in relation to immune disorders…
A
immune surveillance
5
Q
What are the 4 types of hypersensitivity reactions and what are the times after exposure for clinical symptoms?
A
Type 1 (anaphylactic): occurs in less than 30 mins Type II (cytotoxic): occurs in 5-12 hours Type III (immune complex): 3-8 hours Type IV (delayed, cell medicated or delayed hypersensitivity): 24-48 hours
6
Q
Hypersensitivity requires ____ a ____ _____
A
SENSITIZATION, prior exposure
7
Q
Describe type 1 (anaphylactic) reactions
A
- Prophylaxis is protection
- Localized or systemic
- IgE must trigger mast cells and basophils
- Mast cells and basophils must degranulate to release 3 mediators
8
Q
What are the three mediators released during a type I reaction?
A
- Histamine: pre existing: edema, erythema, mucus
- Leukotrienes
- Prostaglandin
9
Q
What is a mast cell?
A
- Monocyte
- filled w granules
- derives from myeloid lineage
- found in connective tissue
- helps with healing, angiogenesis, immune tolerance
10
Q
What is the key takeaway about mechanism of anaphylaxis?
A
allergen bridges or crosslinks adjacent IgE molecules
11
Q
What is localized anaphylaxis?
A
Causes hives/hay fever and asthma
- Mast cells are in the mucous membranes of upper respiratory tracts
- responsive to antihistamine drugs
12
Q
What are some food allergies many people have?
What are the most common side effects/reactions?
A
Eggs Peanuts Tree nuts Milk Soy Fish Wheat Peas
Hives and GI upset, systemic anaphylaxis and death is possible
13
Q
What is systemic anaphylaxis?
A
- injected or ingested
- bee stings, jellyfish stings
- can result in circulatory collapse and death
- treatment is EPI PEN
14
Q
Skin testing is used to….
A
- determine allergens more precisely
- Allergen in the epidermis w/ pos results gives raised reaction
15
Q
How can anaphylaxis be prevented?
A
- Desensitization injection of Ag
- doses of antigen are gradually increased under the skin
- results in IgG instead of IgE
- IgG intercepts antigen when re-exposed
16
Q
What are type II (cytotoxic reactions)?
A
- IgG or IgM antibodies and complement
- Antibodies react well cell surface antigens
- Complement activation leads to cell lysis
- Macrophages are damaged after they are recruited over several hours
- Include transfusion reactions like ABO, Rh blood and drug induced
17
Q
What are the antibodies of AB blood group?
A
Neither A or anti-B antibodies
18
Q
What are the antibodies of B blood group?
A
Anti A
19
Q
What are the antibodies of the A blood group?
A
Anti B
20
Q
What are the antibodies for O blood group?
A
Anti A and Anti B
21
Q
Individuals with type O blood are more susceptible to what disease?
A
Cholera
22
Q
Populations with low A and AB blood types may be more susceptible in what?
A
Smallpox epidemics
23
Q
Which blood type is less severely affected by malaria?
A
Type O
24
Q
How do antibodies against A and B blood group antigens arise?
A
Presumably in response to microorganisms in ingested foods that have antigenic determinants similar to blood group antigens
25
What is the Rh blood group system?
- either Rh+ or Rh-
- different from blood types in antibodies that react with Rh antigen do not occur naturally in serum of Rh-
- Rh- exposure to Rh+ makes sensitivity
26
What is hemolytic disease of the newborn?
- prevented by artificially acquired passive immunization
- RhoGAM is antibodies to the Rh antigen
- RhoGAM is given to pregnant women to bind fetal red blood cells and keep them from mounting immune response
27
Drug induced cytotoxic reactions...
- drug or other small molecule stimulates immune system as hapten
- second exposure the drug binds to platelets leading to thrombocytopenic purpura , granulocytes causing agranulocytosis and to RBC causing hemolytic anemia
28
What happens in drug induced thrombocytopenic purpura?
1. Drug binds to platelet, forming hapten platelet complex
2. Complex induces formation of antibodies against hapten
3. Action of antibodies and complement causes platlet destruction
29
What is a type II (immune complex) reactions?
- IgG antibodies and antigens form immune complexes that lodge in basement membrane
- Complexes form at certain Ag/Ab ratio
- Complexes passes between vessel endothelial cells and attract neutrophils to release enzymes to cause damage
30
What are type IV (cell mediated) reactions?
- delayed type hypersensitivities due to T cells
- takes time for T cells and macrophages to migrate to the site of stimulating antigen
- cytokines attract macrophages and Tc cells, leading to tissue damage
31
Allergic contact dermatitis
- primary contact makes the T cells sensitized and causes immune response in 7-10 days
- secondary contact causes many active T cells which leads to dermatitis
32
What are autoimmune diseases?
- Clonal deletion of T cells during fetal development in thymus
- Autoimmunity is lack of self tolerance
- Anti self antibodies arise in response to infectious agents like hep C
33
Cytotoxic auto immune diseases
Antibodies react with cell surface antigens
34
Immune complex auto immune diseases
IgM, IgG, complement immune complexes deposit in tissues
35
Cell mediated autoimmune diseases
mediated by T cells
36
How are immune reactions measured?
Quantitatively
37
What is the issue with autoantibodies?
Difficult to define
| -Antibody binding does not define unique molecular signature, antibody can bind to diff. epitopes
38
Why are autoantibodies that cause disease are rare?
Only certain diseases of the immune system generate significant amounts of autoantibodies
39
What type of disease is lupus and rheumatoid arthritis?
Immune complex autoimmune disease
- Lupus causes IC deposits in kidney
- RA causes IC deposits in joints
40
What type of disease is multiple sclerosis and insulin dependent diabetes mellitus?
Cell mediated autoimmune disease
- MS causes immune cells to attack myelin
- Diabetes Mellitus causes cells to attack pancreas
41
Histocompatibility antigens are...
self antigens on cell surfaces
42
What is the major histocompatibility complex?
Genes encoding histocompatibility antigens
- MHC class I on all cells
- MHC class II on immune system cells
43
What is the human leukocyte antigen complex?
MHC genes in humans
| HLA typing or tissue typing for tissue transplants
44
What is HLA typing?
1. anti hla antibodies attach to HLAs on lymphocyte
2. complement and trypan blue are added
3. Cell damaged by complement takes up dye
45
What are some diseases related to specific HLAs?
- MS
- Rheumatic fever
- Addisons disease
- Graves disease
- Hodgkins disease
46
What are some reactions to transplantation?
- Transplants make be attacked by T cells, macrophages and complement fixing antibodies
- Transplants to privileged sites do not cause immune response (cornea, brain, heart valve, fetus)
47
How can transplantation be improved?
Stem cells
- ES cells are pluripotent
- Adult stem cells can be found in many tissues
- iPS cells
48
How are pluripotent stem cells made?
1. Embryo from discarded in vitro fertilized egg
2. Embryo divides repeatedly and makes hollow ball of cells
3. ES stem cells from embryoblast are grown on feeder cells in culture medium
49
An autograft is...
Use of one's own tissue
50
What is an isograft?
use of identical twins tissue
51
Allograft can be described as
use of tissue from another person
52
Xenotransplantation
Use of nonhuman tissue
53
Graft vs. host disease
can result from transplanted bone marrow that contains immunocompetent cells
54
What is immunosupression?
- Prevents an immune response to transplanted tissues
- Cyclosporine and Tacrolimus suppress IL-2
- Mycophenolate mofetil (MMF) inhibits T cell and B cell reproduction
- Sirolimus blocks IL-2
- Basiliximab and daclizumab block IL-2
- (IL-2, Interleukin-2, is a cytokine that is the major growth factor for T cells)
55
What is immune surveillance?
the recognition and removal of abnormal cells by the immune system
56
What to CTL cells do?
Lyse cancer cells
57
What did Willam Coley notice?
that if cancer patients contracted typhoid fever, their cancers often diminished noticably
58
What is Coley's toxin?
endotoxins gram-negative bacteria
stimulates TNF-production by
macrophages
59
Name some immunotherapies for cancer.
-Coley’s toxin - therapeutic
-Vaccines - prophylactic
Human Papilloma Virus (HPV) - cervical cancer
Hepatitis B Virus (HBV) - liver cancer
Feline leukemia (FLV)
-Monoclonal antibodies
Herceptin (Trastuzumab)
a monoclonal antibody that interferes with the Her2/Neu protein, a receptor for FGF signals
60
Tumor necrosis factor, IL-2 and interferons may...
kill cancer cells
61
What do immunotoxins do?
link poisons with a monoclonal antibody directed at a tumor antigen
62
What is congenital immunodeficiency?
Due to defective or missing genes
Example: DiGeorge Syndrome
aka 22q11.2 deletion syndrome
patients lack thymus
63
What is acquired immunodeficiency?
Develop during an individual's life
| Due to drugs, cancers, and infections
64
What is the origin of AIDS?
-HIV evolved from viruses that harmlessly infected monkeys and chimps in Africa, probably during the handling of bushmeat
-Crossed the species barrier into humans in the 1930s
-Patient who died in 1959 in Congo is the oldest
known case
-Spread in Africa as a result of urbanization
-Spread worldwide through modern transportation and unsafe sexual practices
-Norwegian sailor who died in 1976 is the first known case in Western world
65
AIDS in the 80's
1981: In United States, cluster of Pneumocystis and Kaposi's sarcoma discovered in homosexual men in Los Angeles
The men showed loss of immune function, they were immunosuppressed
1983: Discovery of virus causing loss of immune function
66
What is HIV?
primarily infects CD4+ T-cells
it is often spread by dendritic cells
memory T-cells serve as reservoirs for decades
reservoirs exist throughout the body
67
Describe HIV attachement
the viral protein gp120
binds
CD4
as a receptor
with CCR5 or CXCR4
as a co-receptor
68
Active HIV in CD4 T cells
provirus,
integrated into
chromosomal
DNA
69
Active HIV in macrophages
```
macrophages
actively
infected,
producing
HIV viruses
```
70
Latent HIV infection in CD4 T cells
memory T-cells carrying
HIV proviruses are reservoirs inaccessible to treatment
located in
brain, lymphoid tissue, bone marrow, and the genital tract
71
What is phase 1 of HIV infection?
Asymptomatic or chronic lymphadenopathy
millions of viruses in blood in first week
billions of infected cells in first few weeks
symptoms may be just swollen lymph nodes
lasts 3 years
72
What is phase 2 of HIV infection?
Symptomatic; early indications of immune failure
virus replicates at a low level
T-cell decline steadily
some persistent infections
73
What is phase 3 of HIV Infection?
AIDS indicator conditions
| T-cell counts become extremely low, officially AIDS
74
What are the two diagnostic methods for HIV?
-seroconversion takes up to 3 months
HIV antibodies detected by ELISA
HIV antigens detected by Western blotting
-Plasma viral load (PVL) is determined by PCR or nucleic acid hybridization
75
Survival with HIV infection details what?
- anti retroviral chemotherapy
- some may be exposed but not infected (due to mutation in co-receptor CCR5)
- long term nonprogressors
- bone marrow transplants may help cure some
76
Describe HIV transmission
HIV survives 6 hours outside a cell
HIV survives less than 1.5 days inside a cell
Infected body fluids transmit HIV via
77
What are the body fluids that can transmit HIV?
```
Sexual contact
Breast milk
Transplacental infection of fetus
Blood-contaminated needles
Organ transplants
Artificial insemination
Blood transfusion
```
78
Why is there no HIV vaccine if it is a virus?
Not for the lack of trying
Mutation rate of virus in replication
Genetic diversity
Virus exposure to antibodies is brief or nonexistent
Antibody-binding sites hidden by glycosylation
Infected cells not susceptible to CTLs
Latency/Proviruses
Reservoirs in gut, bone marrow (and other places?)
79
mRNA based HIV vaccine
-Using the same mRNA technology used for COVID-19 vaccines, Moderna developed two vaccines for HIV (still in phase 1)
80
HIV chemotherapy
Nucleoside reverse transcriptase inhibitors
Non-nucleoside reverse transcriptase inhibitors
Protease inhibitors
Fusion inhibitors
81
What is HAART?
Highly active antiretroviral therapy
82
How does HAART work?
Combinations of nucleoside reverse transcriptase inhibitors plus
Non-nucleoside reverse transcriptase inhibitor or
Protease inhibitor
83
A cure for HIV/AIDS?
- One adult in Berlin was cured by a combination of antiviral therapy and bone marrow transplant from a person who is naturally HIV resistant (due to a mutant CCR5 co-receptor gene).
- A baby in Mississippi was infected at birth, received a three-drug treatment within hours and was believed to be cured.
84
What is the problem of HIV reservoirs in the body?
The ‘Mississippi baby’ was born to an HIV-positive mother who had not received any treatment during pregnancy. Doctors began treating the child by the time she was 30 hours old, but the family stopped antiretroviral therapy at 18 months. She remained off the drugs for the next 27 months with no signs of the virus in her blood.
Two months shy of her fourth birthday, her pediatricians found her HIV infection had rebounded. The young patient will now face years, if not a lifetime, of antiretroviral therapy. And researchers are now scrambling to determine how this will affect clinical trials aiming to repeat the child's apparent cure.
Microbiology
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