Coupon Accepted Successfully!


Type IV Hypersensitivity (Cell mediated)

Initiated by specifically sensitized T lymphocytes
2 Type s Q
  1. Classic delayed type HS - by CD4 T cells          
  2. Direct cell cytotoxicity - by CD8 T cells
Disease Specificity of Pathogenic T cells Clinicopathologic Manifestations
Type 1 diabetes mellitus Antigens of pancreatic islet βcells (insulin, glutamic acid decarboxylase, others) Insulitis (chronic inflammation in islets), destruction of βcells; diabetes
Multiple sclerosis Protein antigens in CNS myelin (myelin basic protein, proteolipid protein) Demyelination in CNS with perivascular inflammation; paralysis, ocular lesions
Rheumatoid arthritis Unknown antigen in joint synovium (type II collagen?); role of antibodies? Chronic arthritis with inflammation, destruction of articular cartilage and bone
Peripheral neuropathy; Guillain-Barré syndrome Protein antigens of peripheral nerve myelin Neuritis, paralysis
Inflammatory bowel disease (Crohn's disease) Unknown antigen; may be derived from intestinal microbes Chronic inflammation of ileum and colon, often with granulomas; fibrosis, stricture
Contact dermatitis Environmental chemicals, e.g., poison ivy (pentadecylcatechol) Dermatitis, with itching; usually short-lived, may be chronic with persistent exposure

Delayed type HS e.g. tuberculin reaction
  1. Exposure to tubercle bacillus
  2. With MHC Class II molecules on Ag pres. Cell
  3. Naive CD4 ------------ → TH1 cell
  4. Some TH1 cells enter the circulation → Memory pool
  5. Intradermal. inj. of tuberculin to prev. exposed individual
  6. Some THI cell interaction with Ag on surface of Ag presenting cell
  7. And produce TNF - alpha, lymphotoxin, Gamma interferon.
  8. TNF-α& lymphotoxins: - Endothelial effects, lead to extravasation of lymphocyte and
  • monocytes
  1. Secretion of PGI2 vasodilation
  2. Expression of E-selection and P- selectin
  3. Induction & secretion of chemotactic factors IL-8
  4. IFN - gamma - Power activator of macrophages.
  5. IL - 2 - Proliferation of antigen specific T-cell
Tuberculin Reaction: Microvascular permeability, edema, deposition of fibrin leading to erythema and induration of skin:
Most common –
  1. Mononuclear cells around veins and venules (Perivascular cuffing) Q
  2. With persistent or non - degradability antigens (eg T.B bacilli) colonizing lungs or other tissues, the initial perivascular cuffing is replaced by granuloma over 2 - 3 weeks.
  3. Granuloma has epithelioid cells, grant cells and mononuclear cells.
    1. TB, fungi, certain parasites, transplant rejection, tumor immunity
    2. Contact Dermatitis: Contact with Urshiol (Ag component of poison ivy of poison oak
    3. Delayed type HS reaction
T cell mediated cytotoxicity
  1. CD8 + T cells kill antigen bearing target cells
  2. Role in viral inf., tumor immunity - viral peptides associate with class I molecule which are transported to cell membrane.
  3. These are recognized by TCR which engulf and kill the virus Mechanism:
  4. Puforin granzyme depending killing;
    Contained in lysosome like granules of CTLS Q
    Puforin  => drilling holes → Pore formation
    Granzyme → Proteases
Fas-Fas ligand dependent killing - apoptosis by stimulating TNF β like effect Q

  1. Definition: Soluble substances, produced by lymphoid & / or non - lymphoid cells that exercise specific effects on target cells
    1. Predominant Action: Paracrine & Autocrine. Rarely Endocrine
    2. Produced by many cell types, principally activated lymphocytes, macrophages also endothelium, epithelium, connective tissue cells
  2. According to source
    1. By mononuclear phagocyte: Monokines Q
    2. By activated lymphocytes: Lymphokines Q 
  1. According to innate or adaptive
  1. Cytokines that mediate innate [natural] immunity - IL -1 and TNF alpha, type 1 interferon and 1L-6.
  2. Others like IL -12 and Gamma interferon are involved in both innate and adaptive immunity Q.
  3. Cytokines that regulate lymphocyte growth, activation and differentiation, IL-2, IL-4, IL-12, IL-15 and TGF -bet Q
  1. IL-2 Important growth factor for T cellsQ
  2. IL-4 Stimulate differentiation to TH2 subset and act on. B cell as wellQ
  3. IL-12  Stimulate differentiation to Th1 pathwayQ 
  4. IL-15  Stimulate growth and activity of NK cellsQ
  1. Cytokines that activate inflammatory cells.
  1. Gamma interferon Activate macrophagesQ
  2. IL-5 Activate EosinophilsQ
  3. Tumor necrosis factor – beta Induce inflammation by acting onQ
    (Lymphotoxin) neutrophils and endothelial cellsQ
  1. Chemokines
Cytokines that stimulate hematopoiesis like colony stimulating factors eg. GM CSF, G- CSF, C kit ligand.
  1. Toll like receptors
  1. The Toll-like receptors are membrane proteins that recognize a variety of microbe-derived molecules and stimulate innate immune responses against the microbes.
  2. The Toll-like receptors are expressed on many different cell types that participate in innate immune responses including macrophages, dendritic cells, neutrophils, NK cells, mucosal epithelial cells and endothelial cells.
  3. Signalling by Toll like receptors results in the activation of transcription factors notably NF-KB.
  4. The genes that are expressed in response to TLR signalling encode proteins important in many different components of innate immune response.
  1. These include :-
  1. Inflammatory cytokines (TNF, IL-l, IL-2)
  2. Endothelial adhesion molecules (E-selection) and
  3. Proteins involved in microbial killing mechanisms.

Test Your Skills Now!
Take a Quiz now
Reviewer Name