IMMUNODEFICIENCIES

Assignment in Immunology

SUBMITTED TO DR. KOHINOOR KAUR

SUBMITTED BY MUSKAN MISHRA

BSC (H) MICROBIOLOGY , 3RD YEAR

• Immunodeficiency, also known as immunocompromisation,
is a state in which the immune system's ability to fight
infectious diseases and cancer is compromised or entirely
absent.

• There are two types of immunodeficiency disorders :

1. Primary or congenital or inherited

2. Secondary or acquired

• Immunodeficiency can be specific or non-specific :

1. Specific = Abnormalities of B & T cells

2. Non-specific= Abnormalities of non specific components
 PRIMARY IMMUNODEFICIENCY
• A number of rare diseases feature a heightened susceptibility to infections from childhood
onward. Primary Immunodeficiency is also known as congenital immunodeficiencies. Many
of these disorders are hereditary and are autosomal recessive or X-linked. There are over 95
recognised primary immunodeficiency syndromes; they are generally grouped by the part of
the immune system that is malfunctioning, such as lymphocytes or granulocytes.

• To date, over 150 different primary immunodeficiency have been identified.

• All are relatively rare.

• Usually present at birth and are usually hereditary.

• Evident during infancy or childhood. However, some disorders (such as common variable
immunodeficiency) are not recognized until adulthood.

• For example X-linked agammaglobulinemia (XLA), common variable immunodeficiency

(CVID), severe combined immunodeficiency (SCID), which is known as alymphocytosis or
“boy in a bubble” disease.
TYPES AND DISTRIBUTION OF PRIMARY
IMMUNODEFICIENCY DISEASES
IMMUNOLOGICAL BASIS OF SOME PRIMARY
IMMUNODEFICIENCY DISEASES
SECONDARY IMMUNODEFICIENCY
• Secondary immunodeficiency disorders happen when an outside
source like a toxic chemical or infection attacks your body.

• The following can cause a secondary immunodeficiency disorder:

severe burns, chemotherapy, radiation, chronic disorders such as
diabetes[diabetes = white blood cells do not function well when
the blood sugar level is high ] or cancer, Drugs, malnutrition.

• Examples of secondary immunodeficiency disorders include: AIDS,

cancers of the immune system, like leukemia immune-complex
diseases, like viral hepatitis multiple myeloma
SOME IMPORTANT IMMUNODEFICIENCY
DISEASES
 SEVERE COMBINED IMMUNODEFICIENCY
(SCID)
INTRODUCTION -BOY IN THE BUBBLE DISEASE

• Severe combined immunodeficiency (SCID) is a primary immunodeficiency

disorder that involves combined humoral and cellular immunity deficiencies. It
is a serious and potentially fatal condition.

• It is caused by mutations in any one of many different genes (eg, for autosomal
recessive forms, Janus kinase 3 [JAK3], protein tyrosine phosphatase, receptor
type, C [PTPRC, or CD45], recombination activating genes 1 [RAG1] and 2
[RAG2]).

• There are various forms of SCID that are

autosomal recessive defects, so for the infant
to be affected with SCID, the same gene must be
mutated on both chromosomes.
• There are 4 different abnormal lymphocyte phenotypes:

1. B cell positive, NK cell negative

2. B cell negative, NK cell positive
3. B cell negative, NK cell negative
4. B cell positive, NK cell positive

• In most forms of SCID, T cells are absent (T-); the number

of B cells and/or natural killer (NK) cells may be low or
none (B-; NK-) or high or normal (B+; NK+), depending on
the form of SCID. However, B cells, even when normal in
number, cannot function because T cells are absent.
Natural killer cell function is usually impaired.
• The most common form of SCID is X-linked. It affects the interleukin (IL)-2 receptor
common gamma chain (a component of at least 6 cytokine receptors) and thus causes
severe disease; phenotype is T- B+ NK-. It results from a mutation in the IL-2 receptor
gamma gene (IL-2RG).

• The 2nd most common form (autosomal) results from adenosine deaminase (ADA)
deficiency purine nucleoside phosphorylase (PNP) genes defect which results is
accumulation of dATP or dGTP, respectively, and cause toxicity to lymphoid stem cells,
which leads to apoptosis of precursors for B, T, and NK cells; phenotype is T- B- NK-.

• The next most common form results from IL-7 receptor alpha-chain deficiency;
phenotype is T- B+ NK+.

• Mutations in recombination activating gene 1-2 (RAG1 or RAG2) represent a T-B-NK+

SCID phenotype.

• Omenn syndrome is another T-B-NK+ SCID phenotype. It typically is the result of one
defective RAG allele and therefore is commonly referred to as atypical SCID, or leaky
SCID. It is an autosomal recessive form of SCID. Frequently the levels of IgA, IgG, and
IgM are low while there is elevated IgE and eosinophilia. These patients usually have a
varying degree of lymphopenia with low numbers of T and B cells and present with
inflammation and lymphadenopathy.
SYMPTOMS

• Most develop pneumonia, persistent bacterial and viral infections,

thrush.
• All infants with this disorder have a severely underdeveloped
thymus gland.
• If not treated, these children usually die before age 1 year.

DIAGNOSIS

• Blood tests are done to measure the number and functioning of B

and T cells.
• Some experts recommend screening all newborns for T-cell
receptor excision circle (TREC) test.
• Use genetic tests to identify the specific mutation causing the
disorder and thus help determine how severe the disorder is.
TREATMENT

• People with this disorder are kept in a protected environment

to prevent exposure to possible infections (called reverse
isolation).
• Treatment with antibiotics and immune globulin replacement
therapy, antibiotics (including P. jirovecii prophylaxis), and
antifungals can help prevent infections but is not curative.
• The only effective treatment is transplantation of stem cells
(for example, from an unaffected sibling with the same tissue
type). If transplantation is done by age 3 months, 96% of
infants survive.
• Gene therapy may be effective, depending on which form of
severe combined immunodeficiency is present.
 DIGEORGE SYNDROME
INTRODUCTION

• DiGeorge Syndrome (DGS) is a primary immunodeficiency disease (PIDD) associated

with susceptibility to infections due to decreased T cell production and function due to
an absent or poorly developed thymus. The thymus is the “school house” where T-
cells are educated to fight infection and prevent autoimmunity. DGS is caused by
abnormal cell and tissue development during fetal growth. In addition to possible
immune system problems, this abnormal development can result in altered facial
characteristics, abnormal gland development (parathyroid or thyroid) or heart defects.
• DGS is a lifelong condition that is typically diagnosed in infancy or early childhood.
Children with DGS differ in the organs and tissues affected, as well as in the severity of
the disease.
• It results from gene deletions in the DiGeorge chromosomal region at 22q11,
mutations in genes at chromosome 10p13, and mutations in other unknown genes,
which cause dysembryogenesis of structures that develop from pharyngeal pouches
during the 8th week of gestation.
• Most cases are sporadic; boys and girls are equally affected.
• DiGeorge syndrome may be

1. Partial: Some T-cell function exists

2. Complete: T-cell function is absent
SYMPTOMS

Signs and symptoms can vary in type and severity, depending on what body systems are affected and
how severe the defects are. Some signs and symptoms may be apparent at birth, but others may not
appear until later in infancy or early childhood.
• Heart murmur and bluish skin due to poor circulation of oxygen-rich blood (cyanosis) as a result of a
heart defect
• Frequent infections
• Certain facial features, such as an underdeveloped chin, low-set ears, wide-set eyes or a narrow groove
in the upper lip
• A gap in the roof of the mouth (cleft palate) or other problems with the palate
• Delayed growth
• Difficulty feeding, failure to gain weight or gastrointestinal problems
• Breathing problems
• Poor muscle tone
• Delayed development, such as delays in
rolling over, sitting up or other infant milestones
• Delayed speech development or
nasal-sounding speech
• Learning delays or disabilities
• Behavior problems
• Autoimmune disorders. People who had poor
Immune function as children, due to a small or
missing thymus, may also have an increased risk of
DIAGNOSIS

• Immune function assessment with immunoglobulin (Ig) levels, vaccine titers, and lymphocyte subset
counts
• Parathyroid function assessment
• Chromosome analysis
• An absolute lymphocyte count is done, followed by B- and T-cell counts and evaluation of lymphocyte
subsets if leukopenia is detected; blood tests to evaluate T-cell and parathyroid function are done. Ig
levels and vaccine titers are measured. If complete DiGeorge syndrome is suspected, the T-cell receptor
excision circle (TREC) test should also be done.
• A lateral chest x-ray may help evaluate thymic shadow.
• Fluorescent in situ hybridization (FISH) testing can detect the chromosomal deletion in the 22q11
region; standard chromosomal tests to check for other abnormalities may also be done.
• If DiGeorge syndrome is suspected, echocardiography is done
• Because most cases are sporadic, screening of relatives is not necessary.

TREATMENT
• Partial syndrome: Calcium and vitamin D supplementation
• Complete syndrome: Transplantation of cultured thymus tissue or hematopoietic stem cells
• In partial DiGeorge syndrome, hypoparathyroidism is treated with calcium and vitamin D
supplementation; long-term survival is not affected.
• Complete DiGeorge syndrome is fatal without treatment, which is transplantation of cultured thymus
tissue or hematopoietic stem cell transplantation. A recent review of thymus transplantation has shown
relatively good results with T cell reconstitution by 5 to 6 months .
 CHÉDIAK-HIGASHI SYNDROME
(BÉGUEZ CÉSAR SYNDROME, CHÉDIAK-STEINBRINCK-HIGASHI SYNDROME)

INTRODUCTION

• Described by Béguez Cesar (1943), Steinbrinck (1948), Chédiak

(1952) and Higashi (1954)
• Rare, autosomal recessive primary immunodeficiency disorder
that involves phagocytic cell defects.
• The syndrome is caused by a mutation in the LYST (lysosomal
trafficking regulator; also known as CHS1) gene. Giant
lysosomal granules develop in neutrophils and other cells (eg,
melanocytes, neural Schwann cells). The abnormal lysosomes
cannot fuse with phagosomes due to defective microtubules,
so ingested bacteria cannot be lysed normally.
SYMPTOMS AND SIGNS

• Clinical findings of Chédiak-Higashi syndrome include oculocutaneous albinism

and susceptibility to recurrent respiratory and other infections.

• In about 80% of patients, an accelerated phase occurs, causing fever, jaundice,

hepatosplenomegaly, lymphadenopathy, pancytopenia, bleeding diathesis, and
neurologic changes. Once the accelerated phase occurs, the syndrome is usually
fatal within 30 months.

• The condition usually results in death of childhood before the age of 10

DIAGNOSIS
• Genetic testing
• Neutropenia, decreased natural killer–cell cytotoxicity, and hypergammaglobulinemia are common. A
peripheral blood smear is examined for giant granules in neutrophils and other cells; a bone marrow
smear is examined for giant inclusion bodies in leukocyte precursor cells.

• The diagnosis of Chédiak-Higashi syndrome can be confirmed with genetic testing for LYST mutations.

• Because this disorder is extremely rare, there is no need to screen relatives unless clinical suspicion is
high.

TREATMENT
• Supportive care using antibiotics, interferon gamma and sometimes corticosteroids

• Hematopoietic stem cell transplantation

• Prophylactic antibiotics can help prevent infections, and interferon gamma can help restore some
immune system function. Pulse doses of corticosteroids and splenectomy sometimes induce transient
remission of Chédiak-Higashi syndrome.

• However, unless hematopoietic stem cell transplantation is done, most patients with Chédiak-Higashi
syndrome die of infections by age 7 years. Transplantation of unfractionated human leukocyte antigen
(HLA)-identical bone marrow after pretransplantation cytoreductive chemotherapy may be curative.
Five-year posttransplantation survival rate is about 60%.
 LEUKOCYTE ADHESION DEFICIENCY
INTRODUCTION

• Leukocyte adhesion deficiency is a primary immunodeficiency disorder that involves phagocytic cell
defects. Inheritance is autosomal recessive.

• Leukocyte adhesion deficiency is caused by deficiency of adhesive glycoproteins on the surfaces of

white blood cells (WBCs); these glycoproteins facilitate cellular interactions, cell attachment to blood
vessel walls, cell movement, and interaction with complement fragments. Deficiencies impair the
ability of granulocytes (and lymphocytes) to migrate out of the intravascular compartment, to engage
in cytotoxic reactions, and to phagocytose bacteria. Severity of disease correlates with degree of
deficiency.

• Three different types of syndromes have been identified:

• Leukocyte adhesion deficiency 1: Deficient or defective beta-2 integrin family

• Leukocyte adhesion deficiency 2: Absent fucosylated carbohydrate ligands for selectins
• Leukocyte adhesion deficiency 3: Defective activation of all beta integrins (1, 2, and 3)
• Type 1 results from mutations in the integrin beta-2 gene (ITGB2), encoding CD18 of beta-2 integrins.
Type 2 results from mutations in the glucose diphosphate (GDP)-fucose transporter gene. Type 3 is
caused by mutations in the FERMT3 gene (11q13.1), which encodes kindlin-3 in hematopoietic cells
SYMPTOMS AND SIGNS
• Begin in infancy.

• Severely affected infants have recurrent or progressive necrotic soft-tissue infections with staphylococcal and gram-
negative bacteria, periodontitis, poor wound healing, no pus formation, leukocytosis, and delayed (> 3 weeks)
umbilical cord detachment. WBC counts remain high even between infections. Infections become increasingly
difficult to control.

• Less severely affected infants have few serious infections and mild alterations in blood counts.
• Developmental delay is common in type 2.

DIAGNOSIS
• Testing for adhesive glycoproteins on the surface of WBCs
• Diagnosis of leukocyte adhesion deficiency is by detecting absence or severe deficiency of adhesive glycoproteins on
the surface of WBCs using monoclonal antibodies (eg, anti-CD11, anti-CD18) and flow cytometry. Leukocytosis
detected by complete blood count is common but nonspecific.
• Genetic testing is recommended for siblings.

TREATMENT
• Supportive care using prophylactic antibiotics and granulocyte transfusions
• Hematopoietic stem cell transplantation
• Hematopoietic stem cell transplantation is the only effective treatment to date and can be curative. Gene therapy,
which is under study, appears promising.

• For patients with type 2 leukocyte adhesion deficiency, correcting the underlying defect with fucose supplementation
should be tried.
• Patients with mild or moderate disease can survive into young adulthood. Most patients with severe disease die by
age 5 unless treated successfully with hematopoietic stem cell transplantation.
 CHRONIC GRANULOMATOUS DISEASE
INTROUCTION

• Chronic granulomatous disease (CGD) (also known as Bridges–Good syndrome, chronic

granulomatous disorder, and Quie syndrome is a Primary immunodeficiency disorder in
which white blood cells of the immune system have difficulty forming the reactive oxygen
compounds (most importantly the superoxide radical due to defective phagocyte NADPH
oxidase) used to kill certain ingested pathogens.This leads to the formation of
granulomas in many organs.CGD affects about 1 in 200,000 people in the United States,
with about 20 new cases diagnosed each year.

• This condition was first discovered in 1950 in a series of 4 boys from Minnesota, and in
1957 it was named "a fatal granulomatosus of childhood" in a publication describing
their disease.The underlying cellular mechanism that causes chronic granulomatous
disease was discovered in 1967, and research since that time has further elucidated the
molecular mechanisms underlying the disease.Bernard Babior made key contributions in
linking the defect of superoxide production of white blood cells, to the cause of the
disease. In 1986, the X-linked form of CGD was the first disease for which positional
cloning was used to identify the underlying genetic mutation.
SYMPTOMS AND SIGNS

• Chronic granulomatous disease usually begins with recurrent abscesses during early childhood, but in a few patients,
onset is delayed until the early teens. Typical pathogens are catalase-producing organisms (eg, Staphylococcus aureus,
Escherichia coli, Serratia, Klebsiella, Pseudomonas, fungi). Aspergillus infections are the leading cause of death.

• Multiple granulomatous lesions occur in the lungs, liver, lymph nodes, and gastrointestinal and genitourinary tracts
(causing obstruction). Suppurative lymphadenitis, hepatosplenomegaly, pneumonia, and hematologic evidence of
chronic infection are common. Skin, lymph node, lung, liver, and perianal abscesses; stomatitis; and osteomyelitis also
occur.

• Growth may be delayed.

• X-linked carriers of gp91 phox chronic granulomatous disease may be asymptomatic or develop various usually less
severe symptoms, including joint pain with a lupus-like syndrome, aphthous ulcers, chorioretinal lesions, and
photosensitivity .

DIAGNOSIS

• Flow cytometric oxidative (respiratory) burst assay

• Diagnosis of chronic granulomatous disease is by a flow cytometric oxidative (respiratory) burst assay to detect oxygen
radical production using dihydrorhodamine 123 (DHR) or nitroblue tetrazolium (NBT). This test can also identify female
carriers of the X-linked form and recessive forms. In these forms, the assay using DHR demonstrates 2 populations of
phagocytes, normal and affected.

• Genetic testing is done to confirm the genetic defect but is not required to make the diagnosis. Siblings are usually
screened using DHR shortly after the diagnosis.

• Hypergammaglobulinemia and anemia can occur; erythrocyte sedimentation rate is elevated.

TREATMENT
• Prophylactic antibiotics and usually antifungals
• Usually interferon gamma
• For severe infections, granulocyte transfusions
• Hematopoietic stem cell transplantation
• Treatment of chronic granulomatous disease is continuous prophylactic antibiotics,
orally twice a day. Oral antifungals are given as primary prophylaxis or are added if
fungal infections occur even once; most useful are

• Interferon gamma may reduce severity and frequency of infections and is usually
included in the treatment regimen. Usual dose is 50 mcg/m2 subcutaneously 3
times a week.

• Granulocyte transfusions can be lifesaving when infections are severe.

• When preceded by pretransplantation chemotherapy, hematopoietic stem cell

transplantation from an HLA (human leukocyte antigen)-identical sibling is usually
successful.

• Gene therapy is under study.

 MODEL ORGANISMS : NUDE MICE
• A nude mouse is a laboratory mouse from a strain with a genetic
mutation that causes a deteriorated or absent thymus, resulting in an
inhibited immune system due to a greatly reduced number of T cells. The
phenotype (main outward appearance) of the mouse is a lack of body
hair, which gives it the "nude" nickname.
• The nude mouse is valuable to research because it can receive many
different types of tissue and tumor grafts, as it mounts no rejection
response. These xenografts are commonly used in research to test new
methods of imaging and treating tumors. The genetic basis of the nude
mouse mutation is a disruption of the FOXN1 gene.
HISTORY AND SIGNIFICANCE

• Nude mice were first discovered in 1962 by Dr. Norman R. Grist at Ruchill Hospital's Brownlee
virology laboratory in Glasgow. Because they lack a thymus, nude mice cannot generate
mature T lymphocytes. Therefore they are unable to mount many types of adaptive immune
responses, including:

1. antibody formation that requires CD4+ helper T cells

2. cell-mediated immune responses, which require CD4+ and/or CD8+ T cells
3. delayed-type hypersensitivity responses (require CD4+ T cells)
4. killing of virus-infected or malignant cells (requires CD8+ cytotoxic T cells)
5. graft rejection (requires both CD4+ and CD8+ T cells)

• Because of the above features, nude mice have served in the laboratory to gain insights into
the immune system, leukemia, solid tumors, AIDS and other forms of immune deficiency as
well as leprosy. Moreover, the absence of functioning T cells prevents nude mice from
rejecting not only allografts, but they cannot even reject xenografts; that is, grafts of tissue
from another species.

• Most strains of nude mice are slightly "leaky" and do have a few T cells, especially as they age.
For this reason, nude mice are less popular in research today, since knockout mice with more
complete defects in the immune system have been constructed (e.g. RAG1 and RAG2
knockout mice).
 MODEL ORGANISMS : SCID MICE
• Mice with severe combined immunodeficiency (SCIDs) are often used
in the research of human disease. Human immune cells are used to
develop human lymphoid organs within these immunodeficient mice,
and many different types of SCID mouse models have been
developed. These mice allow researchers to study the human
immune system and human disease in a small animal model.
DISCOVERY
• The mutation causing SCIDs in mice was discovered by Melvin and Gayle Bosma in
1983 in the CB/17 mouse line.SCIDs occurs in these mice due to a mutation in the
gene for protein kinase, DNA activated, catalytic polypeptide (PRKDC), which plays
a role in repairing double-stranded DNA breaks. This has implications for B and T
cell receptor development, which is dependent upon such double-stranded breaks
and subsequent repairs in order to rearrange V, D, J or V and J segments.

• Mice with SCIDs have lymphocyte progenitors, but these cells are unable to
survive to maturity. This results in a lack of B and T cells in the thymus and in the
secondary lymphoid organs, such as the spleen and lymph nodes. Some SCID mice
are able to produce monocytes, granulocytes, and red blood cells from the
hematopoietic stem cells (HSC) present in their bone marrow. Due to their
immunodeficiency, mice with SCIDs often die young if not kept under extremely
sterile conditions.

• The absence of functional B cells results in an organism that is unable to produce

antibodies. This failure to create antibodies prevents most SCID mice from
rejecting non-self tissues. Some SCID mice are shown to reject skin grafts, so it has
been proposed that this disease arises from a leaky mutation, meaning that some
mice with SCIDs do in fact have a somewhat functional adaptive immune system.
TYPES

• There are many types of SCID mice used by researchers at present.

Some examples include SCID-hu Thy/Liv mice, which are given human
fetal thymus and liver cells, hu-SRC-SCID mice, which are implanted
with human hematopoietic stem cells (HSC), and hu-PBL-SCID mice, in
which human peripheral blood mononuclear cells have been
injected.Each line of mouse has different functional and nonfunctional
cells, making each suited for different experiments.

• In particular, it has been observed that SCID mice with an added

mutation for interleukin-2 receptor common gamma chain (IL2Rγ) are
better able to accept transplantation of human HSC and create human
B and T cells. Studies such as those conducted by Ito et al. have found
that non-obese diabetic (NOD) SCID IL2Rγ mice are even better suited
as models for tissue transplants from non-self organisms due to their
lower rate of rejection of human cells. NOD/SCID IL2Rγ mice have also
been used to study human melanoma.
USE IN RESEARCH
• SCID mice can serve many functions in research, particularly in the study of human
physiology and disease. The study of human physiology in human models is often made
impossible due to ethical limitations, high financial expense, and low availability of model
environments. Furthermore, results gleaned from the study of human cells ex vivo may not
be indicative of their functions in vivo. Due to their immunodeficient state, SCID mice are
able to accept human hematopoietic stem cells harvested from human bone marrow or
thymus. This can lead to the development of human adaptive immune cells, such as B and T
lymphocytes, within SCID mice, and for subsequent study of human cells in vivo.

• SCID mice have allowed for increased research on a wide range of topics, including the
development and pluripotency of human HSC, human-specific diseases and their interactions
with the human immune system, vaccination, and cancer.SCID mice with human immune
cells are able to respond to pathogens such as viruses and create antibodies against them,
which has helped scientists better understand how the human immune system protects
against pathogen infection. For example, they have been used to study Dengue virus and
malaria, as well as to assess the efficacy of drugs that target these diseases.

• It is important to note that the use of SCID mice has been questioned as a model for studying
the human immune system. Some studies have suggested that after a period of time, human
T cells in the immunocompromised mice become anergic, meaning that they no longer
respond to stimuli. Thus, these mice may be able to host a human immune system, but one
that may not be functioning properly.
SCID MICE AND HIV

• Immune compromised mice have become of particular interest for studying

the Human Immunodeficiency Virus (HIV), how it interacts with the host in
human lymphoid organs, as well as how treatments work in vivo.While HIV
normally cannot infect mice,SCID mice have been used to study HIV. Prior to
the use of humanized SCID mice, ape models were used to study HIV due to
their genetic similarity to humans. However, due to the endangered status of
chimps, the cost of maintaining them, and the slight differences between
human and chimp interactions with HIV, humanized mice have been
accepted as a more effective model organism for the study of this disease.

• NOD/SCID mice can be transplanted with human fetal liver, bone, thymus,
and lymphoid cells from blood transplants, leading to the formation of
human immune cells, such as B and T cells, within the mice. These mice are
then infected with the virus and researchers are able to study how HIV
attacks the human lymphocytes and causes acquired immunodeficiency
syndrome (AIDS) over time. Furthermore, humanized mouse models can also
be used to test potential therapies for this disease, including gene-based
therapies.
 CONCLUSION
Nude and SCID mice are transformed into excellent models for
studying human diseases, owing to the immunodeficiency
causing mutations in them and hold great prospect to further
future development.

Immunodeficiencies in humans are extremely risky and can be

fatal.While it is impertive to ensure that the individuals going
through these ailments are given proper medical care and
vigilance, it is equally important to maintain a positive, friendly
and healthy environment around them for their mental well-
being and not adding up to their suffeerings by imparting a
stigma on their condition.
 Refrences
• https://pubmed.ncbi.nlm.nih.gov/29763203
• Kuby Immunology – Richard A. Goldsby |
Thomas J. Kindt | Janis Kuby | Barbara A.
Osborne - 8th edition
• Articles on www.wikipedia.org
• Article on nude and scid mice on https://
www.jax.org/news-and-insights/jax-blog/20
13/july