Langerhans cell granulomatosis (histocytosis X)
a. A group of diseases that are caused by the proliferation of Langerhans’ cells (previously known as histocytes).
b. Most commonly causes bone lesions; however, other tissues can be affected.
c. Histologic findings include Langerhans’ cells containing Birbeck granules and eosinophils.

d. Three types:
(1) Letterer-Siwe disease—an acute, disseminated form that is fatal in infants.
(2) Hand-Schüller-Christian disease—a chronic, disseminated form that has a better prognosis than LettererSiwe disease. It usually presents
before the age of 5 and is characterized by a triad of symptoms:
(a) Bone lesions—found in skull, mandible (loose teeth).
(b) Exophthalmos.
(c) Diabetes insipidus.
(3) Eosinophilic granuloma of bone—a localized, least severe form of the three. Lesions may heal without treatment.
(a) Most commonly occurs in young adults.
(b) Lesions in the mandible may cause loose teeth.

Glycogen storage diseases (glycogenoses)

1. Genetic transmission: autosomal recessive.

2. This group of diseases is characterized by a deficiency of a particular enzyme involved in either glycogen production or degradative pathways.

Diseases include:
on Gierke disease (type I)
(a) Deficient enzyme: glucose-6-phosphatase.
(b) Major organ affected by the buildup of glycogen: liver.

Pompe disease (type II)

(1) Deficient enzyme: α-glucosidase(acid maltase).
(2) Major organ affected by the buildup of glycogen: heart.

Cori disease (type III)
(1) Deficient enzyme: debranching enzyme (amylo-1,6-glucosidase).
(2) Organs affected by the buildup of glycogen: varies between the heart, liver, or skeletal muscle.

Brancher glycogenosis (type IV)
(1) Deficient enzyme: branching enzyme.
(2) Organs affected by the buildup of glycogen: liver, heart, skeletal muscle, and brain.

McArdle syndrome (type V)
(1) Deficient enzyme: muscle phosphorylase.
(2) Major organ affected by the buildup of glycogen: skeletal muscle.

Psoriasis is a chronic disorder characterized by scaly, erythematous plaques, which histologically are secondary to epidermal proliferation.
 - genetic factors (HLA relationships), environmental (physical injury, infection, drugs, photosensitivity), abnormal cellular proliferation (deregulation of epidermal proliferation) and microcirculatory changes in the papillary dermis (diapedesis of neutrophils into the epidermis) are all interrelated.
 - the plaques of psoriasis are characteristically well-demarcated pink or salmon colored lesions covered by a loosely-adherent silver-white scale which, when picked off, reveals pinpoint bleeding sites (Auspitz sign).
 - the nail changes in psoriasis include pitting, dimpling, thickening and crumbling with a yellowish-brown discoloration of the nail plate.
 - the characteristic histologic features of psoriasis include:
 - hyperkeratosis
 - absence of the granulosa cells (present in lichen planus).
 - parakeratosis
 - regular, club-shaped elongation of the rete pegs (irregular and saw toothed in lichen planus) with vessel proliferation in the papillary dermis (reason for the bleeding associated with Auspitz sign).
 - characteristic subcorneal collection of neutrophils called a Munro's microabscess (diapedesis from vessels in papillary dermi).
 - 7% develop HLA B27 positive psoriatic arthritis

 IMMUNO PATHOLOGY

Abnormalities of immune reactions are of 3 main groups

• Hypersensitivity,
• Immuno deficiency,
• Auto immunity.

Hypersensitivity (ALLERGY)

This is an exaggerated or altered immune response resulting in adverse effects

They are classified into 4 main types.

I. Type I-(reaginic, anaphylactic). This is mediated by cytophylic Ig E antibodies, which get bound to mast cells. On re-exposure, the Ag-Ab reaction occurs on the mast cell surface releasing histamine.

Clinical  situations

I. Systemic anaphylaxis, presenting with bronchospasm oedema hypertension, and even death.

2. Local (atopic) allergy.

• Allergic rhinitis (hay fever)
• Asthma
• Urticaria.
• Food allergies.

2. Type II. (cytotoxic). Antibody combines with antigen present on-cell surface. The antigen may be naturally present on the surface or an extrinsic substance (e.g.drug) attached to cell surface.

The cell is then destroyed by complement mediated lysis (C89) or phagocytosis of the antibody coated cell.

Clinical situations

• Haemolytic anemia.
• Transfusion reaction
• Auto immune haemolytic anemia.
• Haemolysis due to some drugs like Alpha methyl dopa

Drug induced thrombocytopenia (especially sedormid).

Agranulocytosis due to sensitivity to some drugs.

Goodpasture’s syndrome-glomermerulonephritis due to anti basement membrane antibodies.

3. Type III. (Immune complex disease). Circulating immune complexes especially

small soluble complexes tend to deposit in tissues especially kidney, joints, heart and

arteries.

These then cause clumping of platelets with subsequent release of histamine. and

serotonin resulting in increased permeability. Also, complement activation occurs which

being chemotactic results in aggregation of polymorphs and necrotising vasculitis due to

release of lysosmal enzymes

Clinical situations

• Serum sickness.
• Immune complex glomerulonephritis.
• Systemic lupus erythematosus.
• Allergic alveolitis.
• Immune based vasculitis like
  • Drug induced vasculitis.
  • Henoch – Schonlein purpura

4. Type IV. (Cell mediated). The sensitized lymphocytes may cause damage by

cytotoxicity or by lymphokines and secondarily involving macrophages in the reaction.

Clinical situations

I. Caseation necrosis in tuberculosis.

2. Contact dermatitis to

• Metals.
• Rubber.
• Drugs (topical).
• Dinitrochlorbenzene (DNCB).

5. Type V. (stimulatory) This is classed by some workers separately and by other with

cytotoxic type (Type II) with a stimulatory instead of toxic effect

Clinical Situations :

LATS (long acting thyroid stimulator) results in thyrotoxicosis (Grave’s disease)

Monocytosis:
Causes

-Infections causing lymphocytosis, especialy tuberculosis and typhoid. 
-Monocytic leukaemia.
-Some auto immune diseases.

Human immunodeficiency virus (HIV)
1. Part of the Retroviridae family (i.e., it is a retrovirus).
2. Basic virion structure
a. The nucleocapsid contains single stranded RNA and three enzymes: reverse transcriptase, integrase, and protease.

b. An exterior consists of two glycoproteins, gp120 and gp41, which are imbedded in the lipid bilayer. This lipid bilayer was obtained from the host cell via budding.

3. Virion characteristics

a. The HIV genome includes:

(1) gag gene—codes for core proteins.
(2) pol gene—codes for its three enzymes.
(3) env gene—codes for its two envelope glycoproteins.

b. HIV enzymes

(1) Reverse transcriptase—reverse transcription of RNA to viral DNA.
(2) Integrase—responsible for integrating viral DNA into host DNA.
(3) Protease—responsible for cleaving precursor proteins. 

4. Pathogenicity

a. HIV mainly infects CD4 lymphocytes, or helper T cells. Its envelope protein, gp120, binds specifically with CD4 surface
receptors. After entry, viral RNA is transcribed by reverse transcriptase to viral DNA and integrated into  the host DNA. New virions are synthesized and released by lysis of the host cell.

b. The predominant site of HIV replication is lymphoid tissues.
c. Although HIV mainly infects CD4 helper T cells, it can bind to any cell with a CD4 receptor, including macrophages, monocytes, lymph node dendritic cells, and a selected number of nerve cells. Macrophages are the first cells infected by HIV.

5. HIV infection versus acquired immunodeficiency syndrome (AIDS).

a. AIDS describes an HIV-infected person who has one of the following conditions:

(1) A CD4 lymphocyte count of less than 200.
(2) The person is infected with an opportunistic infection or other AIDS-defining illness, including (but not limited to) tuberculosis, recurrent pneumonia infections, or invasive cervical cancer.
b. The cause of death in an AIDS patient is most likely due to an opportunistic infection.

6. Common opportunistic infections associated with AIDS:
a. Pneumonia caused by Pneumocystis jiroveci (carinii). 
b. Tuberculosis.
c. Periodontal disease—severe gingivitis, periodontitis, ANUG, necrotizing stomatitis.
d. Candidiasis.
e. Oral hairy leukoplakia (EBV).
f. Kaposi’s sarcoma (HHV-8).
g. Recurrent VZV infections.
h. Condyloma acuminatum or verruca vulgaris (warts, HPV)—less common.
i. CMV infections.
j. Disseminated herpes simplex, herpes zoster.
k. Hodgkin’s, non-Hodgkin’s lymphoma.

7. Laboratory diagnosis of HIV

a. ELISA test—detects HIV antibodies.
False negatives do occur.

b. Western blot—detects HIV proteins.
There is a 99% accuracy rate when both the ELISA test and Western blot are used to diagnose HIV infection.
c. PCR—more sensitive; can amplify and identify the virus at an early stage.

8. Treatment
a. Inhibitors of reverse transcriptase.

(1) Nucleoside analogs
(a) Inhibit viral replication via competitive inhibition.
(b) Examples: zidovudine (AZT), didanosine, lami- vudine, stavudine.

(2) Nonnucleoside inhibitors.
(a) Act by binding directly to reverse transcriptase.
(b) Examples: nevirapine, delavirdine.
b. Protease inhibitor.
c. “Triple cocktail” therapy—often consists of two nucleoside inhibitors and a protease inhibitor.