AUTO IMMUNE DISEASES AND IMMUNO DEFICIENCY DISEASES

Immunity:
Immunity is defined as the capacity of the body to resist pathogenic agents.It resists
the entry of different types of foreign bodies like bacteria, virus, toxic substances
etc.
Types:
• Innate Immunity –
1. First line of defense
2. Without Antigenic specificity
• Acquired immunity –
1. Second line of defense
2. With Antigenic specificity
Sub types:
1. Humoral : Resist by Production of Antibodies
2. Cellular : Resistance mediated by T lymphocytes
Cells of Immune System :

Functions of Immune System:

• Recognition of self from non- self
• Mounting a specific response against non – self
• Memory of what was early recognised as non- self
• Antibody formation
• Cell-mediated reactions

Derangements of Immune system

 IMMUNO DEFICIENCY DISEASES:

• Primary immuno deficiency diseases – Genetic or Developmental

abnormality of Immune system

• Secondary immuno deficiency diseases – Acquired suppression of

immune system

PRIMARY IMMUNO DEFICIENCY DISEASES:

1. Digeorge Syndrome – Thymic Hypoplasia
DiGeorge syndrome is a T-cell deficiency that results from failure of development
of the third and fourth pharyngeal pouches. The latter give rise to the thymus, the
parathyroids, some of the C cells of the thyroid, and the ultimobranchial body.
Thus, individuals with this syndrome have a variable loss of T cell–mediated
immunity (resulting from hypoplasia or lack of the thymus), tetany (resulting from
lack of the parathyroids), and congenital defects of the heart and great vessels. In
addition, the appearance of the mouth, ears, and facies may be abnormal. Absence
of cell-mediated immunity is caused by low numbers of T lymphocytes in the blood
and lymphoid tissues and poor defense against certain fungal and viral infections.
The T-cell zones of lymphoid organs—paracortical areas of the lymph nodes and
the periarteriolar sheaths of the spleen—are depleted. Ig levels may be normal or
reduced, depending on the severity of the T-cell deficiency.
It results from a deletion that maps to chromosome 22q11
Treatment:
- Anti Pneumocystis
- Anti fungal Prophylaxis
- Immunoglobulin replacement
- Human stem cell transplantation
2.Various Immunoglobinopathies – B Cell defect:
a) Bruton's X linked agammaglobulinaemia – Defective differentiation from PreB
to B cells
b) Autosomal recessive agammaglobulinaemia – Defective differentiation from
PreB to B cells
c) Ig A deficiency - Defective Maturation of Ig A synthesising B cells
d) Selective deficiency of Other Ig Types – Defective differentiation from B cells to
specific Ig synthesising plasma cells

Treatment
- Immunoglobulin replacement

3. Severe combined immuno deficiency (SCID)

Severe combined immunodeficiency (SCID) represents a constellation of
genetically distinct syndromes, all having in common defects in both humoral and
cell mediated immune responses. Affected infants present with prominent thrush
(oral candidiasis), extensive diaper rash, and failure to thrive. Some patients
develop a morbilliform rash shortly after birth because maternal T cells are
transferred across the placenta and attack the fetus, causing GVHD. Persons with
SCID are extremely susceptible to recurrent, severe infections by a wide range of
pathogens, including Candida albicans, Pneumocystis jiroveci, Pseudomonas,
cytomegalovirus, varicella, and a whole host of bacteria. Without HSC
transplantation, death occurs within the first year of life. Despite the common
clinical manifestations, the underlying defects are quite varied in different forms of
SCID, and in many cases the genetic lesion is not known. Often, the SCID defect
resides in the T-cell compartment, with a secondary impairment of humoral
immunity.
Treatment
- Human Stem cell transplantation
SECONDARY IMMUNO DEFICIENCY DISEASES:

Cause
Human immuno
deficiency virus
Irradiation and
Chemotherapy treatment
for cancer
Involvement of bone
marrow by cancer
(Metastasis, Leukaemias)
Protein calorie
malnutrition
Removal of spleen
Mechanism
Depletion of CD4+ helper
T cells
Decreased bone marrow
precursors for all
leukocytes
Reduced site of leukocyte
development
Metabolic derangements
inhibit lymphocyte
maturation and function
Decreased phagocytosis
of microbes

Acquired Immno Deficiency Syndrome:

Etiologic agent: Human Immuno Deficiency Virus

Mode Of transmission:
- sexual transmission
- transmission via blood and blood products
- transmission via other body fluids
- perinatal transmission
Structure of HIV

Pathogenesis
1. Infection by HIV virus
2. Selective tropism of gp120 for CD4 molecule receptor leads the virus to
attack CD4+ T cells of Immune system
3. gp41 of HIV Virus internalised into the CD4+ T cell membrane
4. Once virion has entered into the T cell cytoplasm, reverse transcriptase of
the viral RNA forms a single stranded DNA. Then DNA polymerase copies the
single stranded DNA to make it to double stranded DNA, while destroying its
own RNA strands.
5. Formed viral DNA inserted and integrated into the host T cell nucleus by viral
integrase protein
6. Host cell DNA transcripts for viral RNA
7. Replicated virus particles detach from the host cell damages the cell
membrane of host cell and cause death of host CD4+ T Cells by apoptosis.
8. Released viral particles infects more CD4+ T cells and produces viremia
Clinical features
• Lymphadenopathy (PGL)
• Weight Loss
• Fever
• Mucocutaneous Disease
• GI Lesions
• Pulmonary Tuberculosis
• Meningitis
• Opportunistic Infections

Investigations
• ELISA
• WESTERN BLOT

Treatment

• Reverse Transcriptase inhibitors

• Protease Inhibitors
• Anti- Microbial Agents
• Combined drug therapy

ART

 Anti retroviral therapy

 Two NRTI s together with an NNRTI, Protease Inhibitor (PI) or Integrase
inhibitor
 Classes Drugs

Nucleoside reverse transcriptase Abacavir(300mg bd),

inhibitor (NRTI) Emitricitabine(200 mg),
Lamivudine(150mg bd), Tenofovir,
Zidovudine
Non-nucleoside reverse transcriptase Efavirenz(600mg OD on empty
inhibitor (NNRTI) stomach), Nevirapine(200 mg /day),
Etravirine,
Protease Inhibitors (PI) Atazanavir, Darunavir, Lopinavir( 400mg
with ritonavir 100 mg bd)
Integrase Inhibitors Raltegravir

Chemokine receptor inhibitor Maraviroc

HYPERSENSITIVITY

Type I – Anaphylactic Hypersensitivity

It is defined as a state of rapidly developing or Anaphylactic type of immune
response to an antigen to which the individual is previously sensitised. The reaction
appears within 15-30 minutes.
Type II – Cytotoxic Hypersensitivity
It is defined as reaction by humoral antibody that attack cell surface antigens on
the specific cells and tissues and cause lysis of target cells. Appears generally within
15-30 minutes after exposure.
Type III – Immune complex Hypersensitivity
It results from deposition of antigen antibody complexes on tissues, which is
followed by activation of complement system and inflammatory reaction, resulting
in cell injury. Reaction takes place about 6 hours after exposure to the antigen.
Type IV – Cell mediated Hypersensitivity
In this type, tissue injury occurs by T cell mediated immune response without
formation of antibodies. The reaction occurs about 24 hours after exposure to the
antigen and the effect is prolonged which may last upto 14 days.

AUTO IMMUNE DISEASES

Autoimmunity is a state in which body’s immune system fail to distinguish between
self and non self and reacts by formation of autoantibodies against one’s own tissue
antigens.
It results from the failure of immunological tolerance.

Types :
Organ Specific
1.Grave’s Disease
2.Myasthenia gravis
3.Diabetes mellitus Type 1
4.Crohn’s Disease
Organ Non-specific
1.SLE
2.Rheumatoid arthritis
3.Sjogren’s Syndrome
4.systemic sclerosis
1.Grave's Disease
Graves disease is characterized by breakdown in self-tolerance to thyroid
autoantigens, of which the most important is the TSH receptor. The result is the
production of multiple autoantibodies, including:
Thyroid-stimulating immunoglobulin:
An IgG antibody that binds to the TSH receptor and mimics the action of TSH,
stimulating adenyl cyclase, with resultant increased release of thyroid hormones.
Almost all persons with Graves disease have detectable amounts of this auto -
antibody, which is relatively specific for Graves disease.
Thyroid growth-stimulating immunoglobulins:
Also directed against the TSH receptor, these antibodies have been implicated in
the proliferation of thyroid follicular epithelium.
TSH-binding inhibitor immunoglobulins:
These anti-TSH receptor antibodies prevent TSH from binding to its receptor on
thyroid epithelial cells and in so doing may actually inhibit thyroid cell function. The
coexistence of stimulating and inhibiting immunoglobulins in the serum of the same
patient is not unusual—a finding that may explain why some patients with Graves
disease spontaneously develop episodes of hypothyroidism.

Clinical features:
• Hyperthyroidism
• Diffuse thyroid enlargement
• Opthalmopathy ( exophthalmos)
• Peritibial myxoedema
Investigations:
 T4
 TSH
Management:
• Anti thyroid drugs
 • Carbimazole 40- 60 mg daily or Preopylthiouracil 400- 600 mg daily
• Subjective Improvement within 10-14 days
• Patient become euthyroid within 3- 4 weeks
• In most patients carbimazole continued at 5-20 mg per day for 12-18
months in the hope that remission will occur
2.Myasthenia gravis
It is a disease of neuro muscular junction
Myasthenia gravis is caused by autoantibodies that block the function of
postsynaptic acetylcholine receptors at motor end plates, which results in the
degradation and depletion of the receptors.
Clinical features:
• Muscle weakness
• Fatigue
• Initial weakness in Ocular muscles
• Later it spreads to involvement in trunk and limbs
• Respiratory muscle weakness
Management:
 Intravenous Immunoglobulin
 Plasma Exchange
 Corticosteroids
 Immunosuppressors – Azathioprine 2.5 mg/day
 Pyridostigmine to inhibit acetylcholinesterase
 Side effects controlled by propantheline

3.SYSTEMIC LUPUS ERYTHEMETOSIS

The fundamental defect in SLE is a failure to maintain self-tolerance, leading to the
production of a large number of autoantibodies that can damage tissues either
directly or in the form of immune complex deposits. As in other autoimmune
diseases, the pathogenesis of SLE involves a combination of genetic and
environmental factors.
Spectrum of Auto antibodies in SLE:
1. Anti nuclear antibodies (ANA)
2. Antibodies to double stranded DNA (Anti ds DNA)
3. Anti Smith antibodies
Clinical features:
 Arthritis
 Raynaud’s phenomenon
 Butterfly facial rash
 Proliferative glomerulonephritis
 Photosensitivity
 Oral ulcers
 Proteinuria
 Fatigue
 Headache
 Serositis

Typical facies of SLE:

Investigations:
 ANA
 Raised ESR
 Leukopenia
 CRP normal except in case of serositis

Management:
Mild to moderate:
• Analgesics, NSAIDs and hydroxychloroquine (200 to 400 mg daily)
• Corticosteroids (prednisolone 5-20 mg/ day) often in combination with
immunosuppressant such as methotrexate, azathioprine or
mycophenolate mofetil(MMF)
• Increased dosage of steroid may be required in serositis.
Life threatening disease:
• High dose corticosteroids and immunosuppressants in renal, CNS, cardiac
involvement
• Methylprednisolone(10mg/kg IV) , coupled with cyclophospamide(15mg
/ kg IV) repeated at 2-3 weekly intervals for 6 cycles
• MMF in combination with high dose steroids for renal involvement
Maintanance theraphy:
• Oral immuno suppressive medications given
• Prednisolone 40 -60 mg , then reduced to 10 -15 mg over 3 months
• Azathioprine 2-2.5 mg /kg/day
• Methotrexate 10-25 mg /week
• MMF 2-3 g/day

3.Rheumatoid arthritis:
Rheumatoid arthritis (RA) is a systemic, chronic inflammatory autoimmune disease
affecting many tissues but principally attacking the joints. It causes a
nonsuppurative proliferative synovitis that frequently progresses to destroy
articular cartilage and underlying bone with resulting disabling arthritis. When
extraarticular involvement develops—for example, of the skin, heart, blood
vessels, muscles, and lungs—RA may resemble lupus or scleroderma.
RA is caused by an autoimmune response against self-antigen(s) such as
citrullinated proteins, which leads to T cell reactions in the joint with production of
cytokines that activate phagocytes that damage tissues and stimulate proliferation
of synovial cells (synovitis). The cytokine TNF plays a central role, and antagonists
against TNF are of great clinical benefit. Antibodies may also contribute to the
disease.
Clinical features:
 Pain and swelling in the small joints
 Initially aching and stiffness in the joint especially in the morning
 As the disease advances, Joints become enlarged and motion limited
 Complete ankylosis may appear
 Ulnar deviation in the fingers (Chronic)
 Swan neck deformities (Chronic)
 Rheumatoid Nodules
 Generalized weakness
 Malaise
 Morning stiffness
 Weight loss
Investigations:
 RA factor
 Anti CCP
 CRP
 ESR
 CBC
 Radiograph
Treatment:
The mainstay of treatment in RA comprises the early use of small-molecule disease-
modifying anti-rheumatic drugs (DMARDs), and corticosteroids for induction of
remission.
 Methotrexate 5-25mg /week
 Sulfasalazine 2-4g /day
 Hydrochloroquine 200- 400 mg/day
  Leflunomide 10- 20 mg/day
 D- Penicillamine 250-750 mg/ day
 Cyclosporine 150-300 mg/ day

व्याधिक्षमत्वं
व्याधिक्षमत्वं नाम व्याधिबलधिरोधित्वं व्याध्युत्पादकप्रधिबन्धकत्वधमधि ।
C.Su 28/7 Chakra.
Vyaadhikshamatva is the ability to resist against the vyaadhibala and to prevent the
occurrence of other diseases.
General concept of Bala:

प्राकृिस्तु बलं शलेष्मा धिकृिो मल उच्यिे ।

स चैिोजः स्मृिः काये स च पाप्मोपधदश्यिे ।।

C.Su 17/117
The Kapha dosha in its state of normalcy ( Prakruta avastha) is known as the Bala
but when abnormal it becomes Mala.The normal kapha is considered as Ojas but
while the abnormal one is sinful (cause various of diseases)
Types of Bala:

धिधििं बलधमधि – सहजं कालाजं युक्ति कृिम् च । कालकृिं ऋिु धिभागं ियकृिं च ।
C.su 11/36

• सहजं
• ऋिु
• ियस्
• युक्ति
बल िृक्तिकर भािा:

बलिृिीकरास्तु इमे भािा भिक्ति । िद्यथा बलित्पुरुषे दे शे जन्म बलित्पुरुषे काले च,

सुखश्च कालयोग: बीजक्षेिगुणसंपच्च, आहारसंपच्च, शरीरसंपच्च, सात्म्यसंपच्च, सत्वसंपच्च,
स्वभािसंधसक्तिश्च, यौिनं च, कमम च, संहषमश्चेधि ।।
C.sha 6:13
The factors lead to the increase of strength such as – birth in a place having strong
persons, that in a time conductive for strength, favourable time, excellence of
shukra and artava, excellence of diet , body, suitability and psyche , natural
mechanism, toughness, physical exercise and cheerfulness
Gunas of Kapha dosha:
धिग्धः शीिो गुरुममन्दःश्लक्ष्णो मृत्स्नः क्तथथरः कफः ।
A.Hr 1/11
Functions of Kapha dosha:
श्लेष्मा क्तथथरत्वधिग्धत्वसक्तन्धबन्धक्षमाधदधभः
A.H 11/3

Sleshma provides stability, unctuousness, binding together of joints and

forbearance.

सक्तन्धसंश्लेषणिे हनरोपणपूरणबलथथै यमकृि् श्लेष्मा पञ्चिा प्रधिभि उदककममणाऽनुग्रहं

करोधि ।
S.Su 15.4
Kapha gives stability to the sandhis, it does snehana, ropana, poorana, balakrita,
sthairyakrita
It is divided into five types and these subtypes performs the functions of various
body fluids.
The Concept of Ojas:
िि रसादीनां शु क्रािानां यत्परं िे जः िि् खलु ओजः । यि् खलु ओजः िदे ि बलम् इधि
उच्यिे स्वशास्त्राधसिािाि् ।

सु. सू 15/19 डल्

Essence of all the seven dhatus is called as Ojas, it is also known as bala.
Gunas of Ojas:

गुरु शीिं मृदु श्लक्ष्णं बहलं मिुरं क्तथथरम् । प्रसन्नं धपक्तिलं धिग्धमोजो दशगुणं स्मृिम्।

च. धच 24/31
Disorders of Ojas:
a) Ojovisramsam:

सक्तन्धधिष्ले षो गािाणां सदनं दोषच्यिनं धक्रया सधन्नरोिश्च धिस्रंसे

सु. सू 15/24
Flaccidity of joints, displacement of doshas and sluggish activity occurs in
ojovisramsam
b) Ojovyapat:

स्तब्ध गुरु गाििा िािशोफो िणम भेदो ग्लाधनस्तन्द्रा धनद्रा च व्यापन्ने

सु. सू 15/24
Stiffness and heaviness of the body, vata type of shopha, discolouration, fatigue,
drowsiness and sleepiness occurs in ojovyapat
c)Ojokshaya:

मूिाम मां सक्षयो मोहः प्रलापो मरणधमधि च क्षये

सु. सू 15/24
Fainting, loss of musculature, delirium, coma and death occurs in ojokshaya

Chikitsa for disorders of Ojas:

िि धिस्रंसे व्यापन्ने च धक्रयाधिशे षैरधिरुिै बमलमाप्याययेि् इिरं िु मूढसंज्ञं िजम येि् ।।

सु. सू 15/28
The chikitsa of visramsa and vyapat of ojas (bala) consists in its replenishment by
such specific measures which are not incompatible; the other one ( ojo kshaya) ,
however should be discarded , if it has reached the stage of moodhasamnja.

Chikitsa to improve Bala:

 Rasayana chikitsa
 Vajeekarana chikitsa