UNIT TWO

ALTRATION IN BODY DEFENCE

Inflammation
Definition:
- is a local response (reaction) of living vascularized tissues to endogenous and exogenous
stimuli (the same stimuli causing cell injury).
- The term is derived from the Latin "inflammare" meaning to burn.
- Inflammation is fundamentally a protective (Physiologic) response destined to localize
and eliminate the causative agent and to limit tissue injury
 Causes:
- The same as causes of cell injury or diseases.
 Nomenclature:
- The name of the inflamed tissue or organ is suffixed with 'itis'.
- Thus inflammation of appendix is called appendicitis and of meninges as meningitis, etc.
- Exceptions = Pleura -- pleurisy, rectum – proctitis, lung – pneumonia, etc.
 Inflammation accomplishes its missions by
- trying to dilute,
- destroy or
- otherwise neutralize the offending agents.
 The inflammatory response is followed by a set of repair processes designed to regenerate the
damaged tissue and/or fill the gaps with fibrous tissue (scar).
Acute Inflammation
- Transient and early response to injury (e.g., bacterial infection)
- Involves release of chemical mediators, causing stereotypic vessel and leukocyte
responses.
Cardinal signs of inflammation
- Rubor (redness): histamine-mediated vasodilation of arterioles
- Calor (heat): histamine-mediated vasodilation of arterioles
- Tumor (swelling): histamine-mediated increase in permeability of venules
- Dolor (pain): caused by prostaglandin E2 and bradykinin
Vascular events
1. Transient vasoconstriction of arterioles lasts only seconds
2. Vasodilation of arterioles mast cells release histamine, which acts on vascular smooth muscle and
causes increased blood flow.
3. Increased permeability of venules: histamine contracts endothelial cells of the vessels, causing
movement of a transudate into interstitial tissue.
4. Swelling of tissue: outflow of fluid surpasses lymphatic ability to remove fluid.
5. Reduced blood flow: caused by outflow of fluid from blood vessels
Cellular events
1. Margination:
- Red blood cells (RBCs) aggregate into rouleaux ("stacks of coins") in venules, with the
neutrophils pushed to the periphery.
2. Rolling:
- Selectin molecules on the cell surfaces cause the neutrophils to "roll" along the endothelium
or to adhere to it temporarily.
3. Adhesion: neutrophils adhere to endothelial cells
4. Transmigration:
- neutrophils move through the basement membrane of venules and release type IV
collagenase, producing an exudate in the interstitial tissue.

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5. Chemotaxis: neutrophils migrate toward bacteria.
6. Phagocytosis: neutrophils ingest opsonized bacteria.
7. Bacterial killing by neutrophils
PNEUMONIA
 Microbial invasion of the lung parenchyma evoking exudative solidification (consolidation) of
the lung tissues.
 Etiology: Pneumonia can be caused by bacteria, viruses, fungi, parasites, chemicals etc...
 Classification
 Based on etiologic agents
- bacterial: pneumococcal, staphylococcal, mycoplasma, etc:
- viral: iffluenza, respiratory syncythial virus etc
- fungal: Histolasopasma captulatum, Aspagilla Fumigatus, etc
- paracytic:
- chemicals:
 Based on the gross anatomic distribution of the disease
- broncho pneumonia and lobar pneumonia
PATHOGENESIS
 The resparatory airways and alveoli are exposed air containing hazardous dusts,chemicals and
micro-organisms.
 Small particles about the size of most bacteria 1-5µm are deposited in the terminal airways and
alveoli.
 The normal lung is free from bacteria
 There are potent defence mechanisms that clear or destroy any bacteria inhaled with with air.
- Nasal clearance- Sneezing,or blowing.
- Tracheo-brnchial clearance: Mucocilliary action that eventually expectoriated or
swallowed.
- Alveolar clearance: Bacteria or solid particles deposited in alveoliare phagocytosed by
alveolar macrophages.
 Pneunonia can result whenever
- these defencesmechanisms are impaired or
- the resistance of the host in general is lowered.
 Factors that affect the resistance in general include
- chronic diseases,
- immunologic deffieciencies,
- treatment with immunosuppressive agnts and
- unusal virulent infections
 The Clearance mechamims can be interfered by many factors including
- Loss or suppression of cough reflex, as a result of
 coma,
 anesthsea,
 neuromuscular disorders,
 drugs or chest pain (this may lead to aspiration of gastric contents).
- Injury of mucocilliary apparatus
 Owing to cigarette smok
 Inhalation of hot or corrosive gases,
 Viral diseases
 Intrefrance with phagocytic or bactericidal action of alveolar macrophages
- Alcohol
- Tobacco s

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 - anoxia
LOBAR peumonia Brochopeumonia

Route First L ung infection First bronchi and bronchioles then lung
parenchyma
Age Young adult Extremes of age

Organisms Pnumococci, and occasionally Any organism

Klebssella
Health status Healthy Predisposed by viral infection,
(previous) bronchitis, cancer etc..
Site any lobe Most lower lobes or bilaterally

Gross Consolidative Patchy (3 - 4 cm elevatel, granular)

Prognosis Bad Worse

Resolution Common Uncommon, with complications

Morphology of lobar pneumonia

 Pneumooococci and Klebsiela mainly cause lobar pneumonia
 Lolar pneumonia is characterized by four stages.
‒ Acute congesition
 lasts - 2 days.
 The lung heals, dark and firm.
 The alveoli are filled with eosinophilic edema, containing many gram-positive
diplococci and PMNs
‒ Red hepatization
 lasts 2nd to 4th day.
 Lung is dry, firm, red and granular.
 The pleural surface, grey-white and friable.
 The capillaries engorged, filled with fibrin exudates, RBC and numerous
neutrophils.
‒ Grey hepatization –
 lasts 4th - 8th day:
 Cut surface is dry, granular and grey.
 Alveoli contain fibrins, dead and live neutrophiles and occasionally degenerating
erythrocytes.
‒ Resolution –
 after 8th day:
 migration of macrophages from the alveolar space into the exudate, which latter
liquefied by fibrinolytic system
 Complete resolution and aeration takes 1-3 weeks, but pleural adhesion between
the two layers usually persists.

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 These classic stages (phases) of lobar pneumonia are now infrequent owing to effective antibiotic
thrapy that prevent the deveopment of full blown lobar consolidations.
Malaria
 Mosquito- born, hemolytic, febrile illness.
 It infects over 200 million persons per year and kills more than 1 million
 Four species of plasmodium cause malaria:
‒ P. falciparum
‒ P. Vivax
‒ P. Ovale
‒ P. Malariae
 P. falciparum causes more severe disease than the others.
Epidemiology
 Common in tropical and subtropical areas especially in African, South and central America, and
South East Asia.
 If is transmitted by the bite of female Anopheles mosquito.
 P. fellciparum and P. Vivax are the most common causes in Ethiopia
Pathogenesis
 Sporozoites inside
Anopheles mosquito

Human skin

Sporozoites

Liver
Gametocytes
Schizonts
Merozoites

Rupture of
RBCs Schizonts RBCs
Inside RBCs

P. Falciparum
 the cause of severe malaria
 is distinguished from other malarial parasites in four aspects:
‒ has no secondary hepatic stage.
‒ there is high parasitemia and anemia.
‒ there may be several parasites in a single RBC.
‒ it charges the flow characteristics and adhesive qualities of infected RBC so that
 they adhere to the endothelial cells of small blood vessels.
 The obstruction of small blood vessels frequently produces severe tissue
ischemia,
 which is probably the most important factor , in the virulence of P.
falciparum
Pathology
 Enlargement of the liver & spleen by sequestered red blood cells.

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 These organs appear dark because of macrophages filled with hemosiderin and malarial
pigment.
 Obstruction of Capillaries of deep organs by P. falciparum infected RBCs leading to
ischemia of different organs ( Kidneys, lungs, brain, etc)
 Intravascular hemolysis causes hemoglobinuric nephrosis (“ black water fever”)
 In the lungs damage to alveolar Capillaries leads to pulmonary edema and acute alveolar damage.
Clinical Feature
 High grade intermittent fever
 Chills
 Headache
 nausea, Vomiting and abdominal Pain
 Hypotension
 hepatosplenomegally
 anemia
 P. falciparum:-
 Ischemic injury to the brain
 Somnolence
 Hallucinations
 Seizure & coma.
 the mortality is 20 % to 50 %
Chronic Inflammation
‒ Inflammation of prolonged duration (weeks to years)
‒ most often results from persistence of an injury-causing agent.
‒ Injurious agents include infectious diseases (e.g., hepatitis C, tuberculosis) and alcohol.
Morphology
1. Cell types:
- Monocytes and/or macrophages,
- Lymphocytes and/or plasma cells, eosinophils, fibroblasts, endothelial cells
2. Necrosis:
- not as prominent a feature as in acute inflammation
3. Destruction of parenchyma:
- loss of functional tissue,with repair by fibrosis
Granulomatous inflammation
1. Causes
- Infectious agents
 include tuberculosis and systemic fungal infection;
 usually associated with caseous necrosis
- Noninfectious causes include
 sarcoidosis and Crohn's disease;
 associated with noncaseating necrosis
2. Morphology
- Gross: pale
 white nodule with or without central caseation
- Microscopic
 Usually well-circumscribed
 Cell types:
 epithelioid cells (activated macrophages),

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  mononuclear (round cell) infiltrate(CD4 helper T cells, or TH cells of the
TH 1 type)
 Multinucleated giant cells: fusion of epithelioid cells; nuclei usually at the
periphery

TUBERCULOSIS
 Tuberculosis is a chronic communicable disease
 Etiology
- M. tuberculosis (Principal)
- M. bovis (rare)
- M. hominis (rare)
 The lungs are the prime target, but any organ may be infected.
 M. tuberculosis is a slender beaded, non- motile acid fast bacillus.
Epidemiology
 Disrupted through out the world
 Annual incidence:
- USA: 12/100,000
- Some developing countries 450/100.000
 It is transmitted by aerosolized depletes during coughing, sneezing and talking all create
aerosolized respiratory droplets.
 Tuberculosis can also be caused by
- M. bovis
- Humans acquire infection by these rare organisms following ingestion of raw milk
 Generally, tuberculosis infection is divided into two.
1. Primary infection
 This is an infection of persons who have not had prior contact with the tubercle bacillus.
Pathogenesis
1. Inhaled droplets containing M. tuberculosis are deposited in the alveoli.
2. The organisms are phagocytosed by alveolar macrophages but resist Killing by these
unsensitized cells.
3. Proliferation of the organisms with in the macrophage
4. Degeneration of macrophages and release of organisms attracting additional macrophages and
lymphocytes and eventually producing inflammation.
5. Some macrophages carry organisms from the lung to regional (hilar or mediastinal)
lymphondes, and from their they may be disseminated by the blood stream to other sites in the
body (kidneys, meninges, bones and other parts of the lungs)
6. Infected macrophages present tuberculous antigens to lymphotytes, which are then transformed
and produce cytokines.
7. Cytokines activate macrophages increasing their concentration of lytic enzymes and
augmenting their capacity to kill mycobacteria.
- The lytic enzymes also destroy host tissues.
- Epithelioid cells and Langhan’s giant cells are activated macrophages
- The development of a population of activated lymphocytes constitutes the
hypersensitivity response to the organism.
- The related development of activated macrophages capable of ingesting and destroying
the organism comprises the cell medicated immune responses.
Pathology
 Macroscopic:

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 - Ghon focus is a small ill- defined area of inflammatory consolidation which is found on
the lower lobe.
- Ghon complex is the combination of Ghon focus and involved hilar or mediastinal
lymph node.
 Microscopic
- Caseous granuloma is the classic lesion.
- It has soft Semisolid core surrounded by epithelioid cells, Langhan’s giant cells,
lymphocytes and peripheral fibrous tissue.
 Out Come:
- > 90% have a self- limited course
- Progressive primary tuberculosis in which the immune system fails to control the primary
infection
- Miliary tuberculosis refers to infection at disseminated sites that produces multiple,
small, yellow and nodular lesions in several organs.
 Clinical Picture of Primary Tuberculosis
- Primary tuberculosis is generally asymptomatic.
2. Secondary (Cavitary) Tuberculosis
 This results from the proliferation of the organisms in a person who has been previously infected
and has mounted an immunologic response.
 The sources of infection are:
- Dormant organisms from old granuloma.
- Newly acquired bacilli.
 Causes: - Cancer,Chemotherapy, AIDS, Malnutrition, Old age & Others
Pathology
- The lungs are the commonest sites
- The apical lobe is mainly affected
- Hypersensitivity and cell-mediated immunity lead to tissue necrosis and the production of
tuberculous cavities.
- Cavities are typically 2 to 4cm in diameter.
Clinical picture
- Cough, low grade fever, malaise, fatigue, anorexia, weight loss night sweats.
- Hemoptysis (Coughing up of blood)
- Chest x- ray shows apical cavities.
Leprosy (Hansen’s Disease)
- Is a chronic slowly progressive, distractive process involving peripheral nerves, skin, and
mucous membranes.
Etiology:
- M. leprae (slender, acid- fast rod)
Epidemiology:
- M. leprae is shed in nasal secretions or from ulcerated lesions of an infected person.
- The mode of infection is unclear, but it probably involves inoculation of bacilli into the
respiratory tract or into open wounds.
- Years of close contact with an infected person are required for successful transmission of
the disease.
- 15 million people are infected world wide
Pathogenesis
- M. leprae multiplies best at temperatures colder than core human body temperature and
lesions tend to occur in coaler parts of the body (e.g, the hands and the face)

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 - Depending on the differences in immune reactivity, the lesions of leprosy may vary from
small, insignificant and self healing macules of tuberculosis leprosy to the diffuse,
disfiguring lepromatous.
- 95% of all persons have a natural protective immunity to M. lepae and are not infected
even though there is intimate and prolonged exposure
 Susceptible people (5%) may develop any one of the following three clinical varieties of leprosy:
1.Anergic patients (those with little or no resistance) have lepromatous leprosy.
2.Hyperegic patients (those with high resistance) develop tuberculous leprosy.
3.Border line leprosy falls in between. The majority of patients belong to this group.
1. Tuberculosis leprosy
 This occurs in infected persons who manifest an effective graunlomatous response that
limits the proliferation of the bacillus and the extent of the disease.
Pathology
 Single lesion or very few lesions on the skin are characteristics.
 The lesions appear on the face, trunk or extremities.
 Microscopic :
- Well- formed, circumscribed. dermal granulomas.
- Composed of epitheliod cells, Langhans giant cells, and lymphocytes.
- There is no caseaus necrosis.
- Neurons are swollen and infiltrated with lymphocytes which is responsible for sensory
loss.
- Bacilli are rare and often not found with acid fast stain.
Clinical picture.
 Skin:
- Well- demarcated hypopigmented or erythematous, dry, hair-less patches with raised
outer edges.
- There is diminished sensation with in the patches.
- The lesions are not infectious.
- They cause only minimal disfigurement.
2. Lepromatous leprosy
 Occurs in persons who fail to develop adequate immune response to the bacteria.
 There are progressive destructive lesions filled with mycobacteria.
Pathology
- Multiple tumor- like lesions of the skin eyes, testes, nerves, lymph nodes, and spleen.
- There is nodular or diffuse infiltrates of foamy macrophages which contain the bacilli.
- The epidermis stretched thinly over the nodules
- There is a clear- zone of dermis between the tumor and the epidermis.
- Globi is the name given to aggregates of acid- fast materials with in the foamy
macrophages.
Clinical picture
- Nodular skin lesions with or without ulceration
- Claw- shaped hands
- Hammer toes
- Saddle- nose
- Pendulous ear lobes
- Lion- like appearance (leonine facies)
- Chronic nasal discharge & voice change
- Blindness.
3. Border line leprosy

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 These patients have variable combination of features of both lepromatous and tuberculoid
leprosy.
Wound Healing
 Demonstrates
- Epithelial regeneration (healing of the epidermis) and
- Repair by scarring (healing of the dermis).
 Two patterns of wound healing
1. Healing by first intention (primary union)
- Occurs with clean wounds when there has been little tissue damage and
- The wound edges are closely approximated
- The classicexampleis asurgicalincision
 Day 1:
- fibrin clot (hematoma) develops.
- Neutrophils infiltrate the wound margins.
- There is increased mitotic activity of basal cells of squamous epithelium in the apposing
wound margins.
 Day 2:
- squamous cells from apposing basal cell layers migrate under the fibrin clot and seal off
the wound after 48 hours
- Macrophages emigrate into the wound.
 Day 3:
- granulation tissue begins to form.
- Initial deposition of type III collagen begins but does not bridge the incision site.
- Macrophages replace neutrophils.
 Days 4-6:
- granulation tissue formation peaks, and collagen bridges the incision site.
 Week 2:
- collagen compresses blood vessels in fibrous tissue, resulting in reduced blood flow.
- Tensile strength is about 10%.
 Month 1:
- collagenase remodeling of the wound occurs, with replacement of type III collagen by
type I collagen
- Tensile strength increases, reaching 80% within 3 months.
- Scar tissue is devoid of adnexal structures (e.g., hair, sweat glands) and inflammatory
cells
2. Secondary union (healing by secondary intention)
- Occurs in wounds that have large tissue defects and when the two skin edges are not in
contact
- requires larger amounts of granulation tissue to fill in the defect
- Often accompanied by significant wound contraction
- Often results in larger residual scars
Factors affecting Healing:
Systemic
- Nutrition
- Vitamin def.
- Age
- Immune status
- Other diseases
Local

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 - necrosis
- Infection
- apposition
- Blood supply
- Mobility
- Foreign body
Defects in immune response
Plan of Topic
- Definition
- Terms used
- Components of Immune system
- Mechanism or pathogenesis
- Diseases of immunity
Definition
- It is the study of immune system.
- Immune system protects against exogenous substances, microbial invasion & tumors.
- Sometimes immune response damages the host tissue, which forms the basis of autoimmune
diseases.
Terms used
- Antigen(Ag)- a protein, when introduced into tissues stimulates antibody production.
- Antibody(Ab)- a protein substance produced as a result of antigenic stimulation.
- Immunopathology- study of derangements in the immune system.
- Hapten- Is a non-protein, which has no antigenic properties, but on combination with protein
can form antigen- forming antibodies
- Antigen-antibody complex: the antigen may combines with antibody to form antigen-
antibody complex.
- Immunity- Protection from particular diseases/injury (resistance).
- Hypersensitivity- state of exaggerated or altered immune response to a given agent (allergy).
Components of Immune system
- Lymphocytes
- Neutrophils
- Macrophages
- Complement system
Lymphocytes
- They are of 2 types- T & B lymphocytes
- B cells differentiates into plasma cells- forms specific antibodies
- Both cannot be differentiated by light or electron microscopy, but can be differentiated by
immunologic methods
- Functions- B cells: expresses specific antibodies as
immoglobulins & role of humoral immunity
T cells:CMI, delayed hypersensitivity &
immunoregulation of T & B cells
Macrophages
 They have different name in various tissues like- in blood – monocytes, skin- Langerhans cells,
lymphnodes- dendritic cells, etc,.
 Functions- * process the antigen for presenting to
immune competent T or B cells
* Act as powerful effector cell in CMI
* Produces IL-1-differentiation of T & B cells

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 * Capable of lysing tumor cells by toxic
metabolites
* Phagocytic function
Polymorphonuclear leucocytes
- Are granulocytes- containing many substances like-
proteases,myeloperoxidase,lysozyme,esterases, aryl sulfatase, acid & alkaline phosphatase and
cations.
- Functions- First line of defense by initial phagocytosis followed by engulfment of foreign cells.
- Demerit- destruction of basement membrane of glomeruli & small blood vessels.

Compliment System
- It is a series of plasma proteins that react together to bring about rupture of cell membrane.
- Activated by –Classic pathway: through antigen-
antibody complex.
Alternate pathway: via non-
immunological agents like bacterial
toxins, cobra venom & IgA.
* Yeilds anaphylatoxin, C3a, C5a & membrane attack complex(MAC

Functions
- Anaphylatoxins- release of histamine from mast cells & basophils,causes- vascular permeability
--> edema
C3a- augments phagocytosis
C5a- chemo tactic for leucocytes
- MAC – causes pores in cell membrane of invading
organisms
Mechanism
- Body has 2 defense mechanism
* Nonspecific or innate- means ‘inborn’ or present at
birth, which does not require activation by disease
agents.
Acts by Humoral- comprised by complement
Cellular – neutrophils,macrophage & NK cell
* Specific or adaptive- requires activation by disease
agents through several mechanism
Acts by Humoral- antibodies followed by B cells
Cellular – mediated by T cells
Diseases of Immunity
- They are classified into 4 groups:
I. Immunodeficiency disorders- deficient cellular &
humoral immune functions
II. Hypersensitivity reactions- hyperfunction of immune
system
III.Autoimmune diseases- when immune system fails to
recognise ‘self’ from ‘non-self’
IV.Possible immune disorders- when immunological
mechanism is suspected.
Hypersensitivity Reactions
- Type I - Anaphylactic
- Type II - Cytotoxic

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 - Type III- Immune complex
- Type IV- Cell mediated
Type I- Anaphylactic
- It causes anaphylaxis and bronchial asthma.
- Mechanism-formation of IgE(cytotoxic) antibody àrelease of vasoactive amines & other
mediators from basophil & mast cell
- Types-i)Systemic-parentral/oral use of allergen-
>bronchoconstriction,, laryngeal edema, shock
& death
ii)Local(atopic)-due to inhaled or ingested allergens
Type II - Cytoxic
- Causes autoimmune hemolytic anemia,EF, goodpastuers syndrome
- Mechanism- Formation of IgG,IgM antibodiesàbinds to antigen on target cell
surfaceàphagocytosis or lysis by C8,9 of compliment or ADCC
Type III – Immune comple
- Mechanism- Forms antigen-antibody complex àactivates compliment àNeutrophils are
attracted à release of lysosomal enzymes & other toxic moities.
- Types- a) Systemic IC disease- Eg.Serum sickness- due to use of heavy dose of
serum(foreign).
b) Local IC disease- Arthus reaction, causing localised vasculitis & necrosis due to
deposition of IC.
Type IV – Cell Mediated(delayed hypersensitivity)
- Causes- Tb,contact dermatitis,transplant rejection
- Mechanism- sensitised T cells(thymic) àrelease of lymphokines à T cell mediated
cytotoxity.
Autoimmune disease
- Autoimmunity is the state in which the body's immune system fails to distinguish
between ‘self’ & ‘non-self’.
- Reacts by formation of auto-antibodies against one’s own tissue agents.
- In other words, means ‘loss of tolerance to one’s own tissue’.
- Immune tolerance- is a normal phenomena present since fetal life.
- It is defined as ability of an individual to recognize self tissue and antigen
Immune tolerance- mechanism
- Clonal elimination- recognizing & responding to antigen à elimination of cells.
- Suppressor cells- do not allow antigen responsive cells to proliferate & differentiate.
- Blocking antibodies- by antigen-antibody complexes or circulating antigen.
- Anti-idiotype network control- are specific antibodies against antigenic
determinants(idiotype) on T & B cells à reacts à non-responsive or tolerant.
Mechanism – autoimmune diseases
Immune tolerance can be interrupted by following:
 Immunological factors
 Genetic factors
 Microbial factors
a) Immunological factors:
Failure of immunological tolerance initiates autoimmunity

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- Polyclonal activation of B cells- bypasses T cell tolerance
- Generation of self reacting B cell clones
- Decreased T suppressor & increased T helper cell –loss of T suppressor cell àhigh
helper cell activationàincreased levels of autoantibody production à autoimmunity.
- Fluctuation of anti-idiotype network control
- Sequestrated antigen release from tissue
b) Genetic factors:
- Increased familial incidence of some AI diseases.
- Increased expression of class II HLA antigens on tissue in autoimmunity
c) Microbial factors:
- Evidence of infection with micro-organism – virus like EBV, streptococci, klebsella &
mycoplasma- is lacking.
Autoimmune diseases
- Examples are SLE, Rheumatoid arthritis, scleroderma, sjogrens syndrome,
etc,.
SYSTEMIC LUPUS ERYTHEMATOSIS (SLE)
- It is an example of systemic autoimmune or collagen disease.
- ‘Lupus’ in Latin means ‘wolf’, which affects the skin and eat away the skin
like wolf.
Types- 1. Systemic/disseminated form
2. Discoid form- seen in bridge of nose & cheek
Etiology-Exact cause is not known
-Auto-antibodies against nuclear & cytoplasmic
components are seen under fluorescence test.
-Anti-nuclear antibody is important.
Mechanism-type II hypersensitivity- autoantibodies against blood
cellsàhematological disorders
-type III hypersensitivity-Ag-Ab complex to
DNA, anti-DNA antibody & IgG-anti-IgGà
deposits in renal glomeruli, small vessel wall,
Microscopy-SLE
- Fibrinoid necrosis- seen in connective tissue,under synovial lining cells or
endothelium of blood vessels.
- LE cells- is diagnostic test & is a phagocytic leucocyte
- round pink homogenous nuclear material of
injured cell with peripheral nuclear lobes
( LE body / hematoxylin body)
CLINICAL FEATURES:
- Multisystem disease, women of 2 to 3rd decade.
- fever, painful joints, chest pain, butterfly rash – face
- hematuria,proteinuria, seizures, psychosis.

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 Rheumatoid Arthritis (RA)
- A chronic multisystem disease of unknown etiology
- Females commonly in 3 to 4th decades of life
- Familial aggregation associated with HLA-DR4,DR1
- 80% of cases are sero-positive for Rheumatoid factor
- Mechanism/pathogenesis-exact cause is unknown, but autoimmunity,
hypersensitivity reactions, postinfectious immunologic reactions,
heriditary,etc, play role.
- Immunologic factors- circulating auto-antibody-RF,IgG
-presence of Ag-Ab complex- IgG-RF
- activation of CMI –CD4+ T cells & macrophage
- presence of anti-nuclear factor, antibodies to collagen type II, cytoskeleton.
 Triggering factor- autoimmunity with destruction of articular cartilage by-
EBV,CMV,rubella,mycoplasma
 Microscopy- villous hypertrophy, thickening of synovial
membrane,inflammatory cells-follicles,fibrinoid necrosis
 Features-small joint pain & swelling, cervical spine involved, fever.
- Failure or decreased immune system, manifested by repeated infections
- Types- 1)Primary- genetic or developmental
abnormality of immune system
2)Secondary- Acquired suppression of immune
system
- Primary was seen in 1952, whereas secondary acquired immune deficiency
was seen in 1981 in United States, a deadly syndrome
Acquired Immune Deficiency Syndrome (AIDS)
- Is secondary form of immunodeficiency caused by HIV1
- Profound suppression of T cell mediated immunity, opportunistic
infection,neoplasm & neurologic disease
Modes of transmission-
- Sexual contact
- Parental inoculation
- Mother to fetus
Risk factors- homosexuals/bisexual males (60%)
-IV drug users (23%),hemophiliacs (1%),
-blood & blood component recipients (2%)
Biology of HIV-
- non-transforming cytopathic retro virus-destruction of target T cells
- It has lipid envelope- viral glycoprotein gp120 & gp 41
- Has several genes not present in other virus- which regulates transcriptase

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- Virus is isolated from-semen,lymphoid cells,CSF and secretions of infected
person
AIDS-infection in lymphocytes & macrophages
- Path-Depletion of CD4+ helper T cells(also present in macrophages &
monocytes) has receptor for gp120 on HIV1
- Binds to virus à internalization à genome undergoes àreverse
transcriptase àproviral DNA integrated into host genome
- CNS- is a major targetà via infected monocytes àcirculate in brainà
activates release of cytokines directly or recruità inflammatory cells &
cause damage to neurons
Stages of HIV infection
- 3 phases, based on host immune system
Early acute-
- transient viremia & seeding of lymphoids
- Temporary fall of CD4+ T cells à sero-conversion à generation of CD8+
antiviral T cells, controls viral replication
- Lasts for 6 to 12 weeks
- C/f-sore throat, nonspecific myalagia, septic meningitis
Middle chronic
- gradual decline in CD4+ counts
- Lasts for 7 to 10 years
- C/f-lymphnodes ++ without constitutional symptoms
- Later- fever, erythematous rash, fatigue,viremia.
Final crisis
- low CD4+ count
- rapid decline in host defense
- < 200 cells/ul
- Is a full blown AIDS- following features
- Loss of weight, diarrhea,oppurtunistic infestions, secondary neoplasm(20%)
- CNS involvement- 30-50%-aseptic meningitis, peripheral neuropathy,
myelopathy & progressive encephalopathy
- 5 year mortality is 85%
HLA System
- Human Leukocyte Antigen- though not a component of immune system, but
regulates it, discovered on leukocyte
- Histocompatibility antigens are located in portion of chromosome 6, called
as HLA complex or MHC
- It has 4 loci/region-ABCD which exhibit variation in allelic genes, are
highly polymorphic.

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Types
- Class I-
 located on all nucleated cells of body
 have HLA-A, HLA-B & HLA-C.
- Class II-
 found on all sub-population of macrophages,T & B cells
 Have single locus on HLA-D, also DR,DQ & DP loci.
- Class III-
 are components of complement system coded on HLA complex
Functions-
- Organ transplantation- matching of donor & recepient for tissue
transplantation
- Regulation of immune system- class I(CD8 Cytotoxic) & II(CD4 helper),
regulate cellular & humoral immunity
- associated with diseases like ankylosing spondylitis, RA, IDDM,etc,.

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