Week 6 Pathology

Hypersensitivity Types 1-4

Types Mechanism Effect Example
Type 1 immediate(mins), IgE mediated response to an antigen in a previously sensitised host vasoactive agents and cytokines released for acute inflammation- oedema, smooth muscle spasm, mucus production allergy, anaphylaxis
Type 2 delayed type, antibody formed against an antigen that is on cell surface or ECM The IgG and IgM Ab causes phagocytosis(opsonisation, Fc receptor, Complement), cell lysis by activated complement(MAC) or dysfunction. Leukocyte recruitment/fc inflammation. ADCC Auto immune haemolytic anaemia, good pastures syn, Graves disease, Myasthenia gravis, Rheumatic heart disease,  glomerulonephritis, Tx reaction
Type 3 delayed type, antigen-antibody complexes are formed that deposit in tissues cause inflammation via complement–> recruit Leukocytes, produce toxic metabolites and enzymes post strep glomerulonephritis, SLE, Arthurs disease, Serum sickness(systemic), joints
Type 4 delayed type, T cell mediated inflammation Cytotoxic t cells and activated macrophages–> perivascular cellular infiltrates, oedema, cell destruction, granuloma TB, transplant rejection, Multiple sclerosis, T1DM, contact dermatitis, RA
  • Type I
    • Immediate – vasodilation, vascular leakage, and depending on the location, smooth muscle spasm or glandular secretions. These changes usually become evident within 5 to 30 minutes after exposure to an allergen and tend to subside in 60 minutes.
    • In many instances (e.g., allergic rhinitis and bronchial asthma), a second, late-phase reaction sets in 2 to 24 hours later without additional exposure to antigen and may last for several days. This late- phase reaction is characterized by infiltration of tissues with eosinophils, neutrophils, basophils, monocytes, and CD4+ T cells as well as tissue destruction, typically in the form of mucosal epithelial cell damage.


Transplant rejection

  • Direct pathway
    • APC on graft have high density of MHC II with the foreign antigen in them which stimulate host  CD8 cell+++
    • Host T cells also recognise the donor tissue as having foreign proteins in their MHC I
    • Both lead to T cell activation, first more so –> Activated (costimulators)–> cell death, increased vasc permeability, endothelial injury –> important in acute rejection
  • Indirect pathway
    • APC of Host –> donor protein on MHC II –> CD4 cell –> increased IF gamma –> increase activated macrophages, MHC presentation, B cells–> plasma cells –> Abs -> endothelial injury –> seen in chronic or late acute rejection.
  • Amplitude of rejection depends on level of genetic disparity – HLA incompatibility gives strong rejection
  • Speed increases with increasingly vascularised tissues.
  • 25% chance that siblings have identical HLA – because you inherit HLA genes and express from both parents
  • Sensitisation then effector stage


Stages of rejection

  • Hyper-acute
    • the transplanted tissue is rejected within minutes to hours because vascularization is rapidly destroyed.
    • the recipient has preexisting antibodies against the graft, which can be induced by prior blood transfusions, multiple pregnancies, prior transplantation, or xenografts against which humans already have antibodies.
    • The antigen-antibody complexes activate the complement system, causing massive thrombosis in the capillaries, which prevents the vascularization of the graft.
    • The kidney is most susceptible to hyperacute rejection; the liver is relatively resistant
  • Acute
    • Manifests in first 6mo
    • Direct pathway via donor dendritic cells becoming APC and activating cellular immunity esp in lymphoid tissues
    • Indirect pathway via Ab and complement. Can occur in first week
    • Proteinuria
  • Chronic
    • Months to years
    • Antibody and cell mediated
    • Manifests as fibrosis in the grafts eg accelerated CAD, bronchiolitis obliterans, vanishing bile ducts, glomerulopathy


Graft vs host disease

Passenger immunocompetent T lymphocytes on graft recognise host as foreign and begin attacking, host has weak immune system

  • Acute GVHD
    • Dermatitis – pruritic or painful
    • Hepatitis – itch
    • Enteritis – diarrhoea, interstinal bleeding, cramps, ileus
    • Within 100 days after allogeneic hematopoietic-cell transplantation (HCT).
  • Chronic GVHD describes a more diverse syndrome developing after day 100.
    • Ocular– Burning, irritation, photophobia, and pain from lack of tear secretion
    • Oral and GI– Mouth dryness, sensitivity to acidic or spicy foods, dysphagia, odynophagia, and insidious weight loss
    • Pulmonary– Obstructive lung disease, with symptoms of wheezing, dyspnea, and chronic cough that is usually nonresponsive to bronchodilator therapy
    • Neuromuscular– Weakness, neuropathic pain, and muscle cramps
  • High risk of GVHD
    • Allogenic HCT
    • transplantation of solid organs containing lymphoid tissue
    • transfusion of unirradiated blood products.



Auto-immune diseases: Know some for MCQs

SLE:- know the major clinical manifestations.

  • Relapsing and remitting disease – affects mainly women and starts in child bearing age.
  • Classic triad – fever, joint pain and rash
  • Symptoms- relapsing and remitting 
    • malaise, fatigue, myaligia, fever
    • LN, weight loss, Alopecia, nail fold infarcts, Reynaud’s, non infective endocarditis, stroke, migraine, retinal exudates.
    • Sulphonamides and OCP may worsen symptoms.
  • Ix- CDE
    • C3 and C4 levels(should be down)
    • Anti dsDNA titres(high)
    • ESR(raised, CRP normal),
  •  We offer a mnemonic that contains the 11 categories used by the American College of Rheumatology, from which four or more must be present to diagnose

    • Arthritis
    • Renal disease (proteinuria, cellular casts)
    • ANA (positive antinuclear antibody)
    • Serositis (pleurisy or pericarditis)
    • H aematological disorders (haemolytic anaemia or leucopenia or lymphopenia or thrombocytopenia)
    • Photosensitivity
    • Oral ulcers
    • I mmunological disorder (positive LE cell, anti-DNA, anti-Sm, false positive serological test for syphilis)
    • N eurological disorders (seizures or psychosis, in the absence of other causes)
    • Malar rash
    • Discoid rashBecause the malar rash is the most easily recalled finding, this mnemonic uses that word and an accompanying message that it “points an MD to a possible diagnosis.”


Immunodeficiency syndromes: 1′ vs. 2′. What types of immune deficiency are you aware of ?

  • Primary/congenital
    • X-linked agammaglobulinemia (XLA)
    • severe combined immunodeficiency (SCID disorders)
    • common variable immunodeficiency
    • Alymphocytosis (“boy in a bubble” disease)
  • Secondary/acquired
    • HIV
    • Immunologic cancers eg leukaemia, multiple myeloma
    • Severe burn



  • Risk groups
    • Multiple sex partners
    • Unprotected sex
    • IVDU
    • Health care workers – needle stick injury
    • Mother to child – intrapartum and breastfeeding
    • Blood Tx before 1985
  • Viral structure
    • HIV – 1 and HIV -2: Lentivirus(retrovirus)
    • enveloped, diploid, single-stranded, RNA viruses with a DNA intermediate, which is an integrated viral genome (a provirus) that persists within the host-cell DNA.
  • Mechanism of immunopathogenesis.
    • Infect and kill CD4 cells  when replicating
    • Infected CD4 cells recognised and killed by other T cells
    • Activation of noinfected CD4 cells –> activation induced apoptosis
  • Major abnormalities of immune function
    • Dysregulation of B cell Ab production
    • Lymphopenia
    • Altered activity of macrophages and monocytes
    • Increase in CD8: CD4
    • Opportunistic infections, more viral and fungal than bacterial.
  • Natural history
    • 2-8wks acute HIV syndrome
    • Asymptomatic or flu-like illness during seroconversion – fever, malaise, generalised rash.
    • Asymptomatic HIV infection
    • Constitutional Sx
    • AIDS defining illness – CD4 <200
  • Clinical features.
    • Recurrent, severe opportunistic infections in an otherwise healthy person
    • Generalised lymphadenopathy
    • Wt loss
    • Candida, genital herpes
  • AIDS-defining illnesses:
    • Candidiasis
    • CMV
    • TB
    • Cancers – cervical, lymphomas
    • Kaposi
    • Pneumocystic Jerovici
    • Herpes simplex