Medical Immunology

1
Medical Immunology

• Vaccines, Immune disorders, and in vitro
  applications

2
Immunization for disease prevention

• Active immunization for potential future exposure
• Passive immunization for (recently) past exposure
  prior to disease onset
• First vaccinations by Edward Jenner (1796)
  against smallpox
• Most recent vaccine licensed
• human papilloma virus 16 (Nov. 20,2002)

3
Types of vaccines
Viruses

• Attenuated live agent with reduced
  pathogenicity due to multiple mutations
• Killed Inactivated with heat or formalin

Proteins

• Subunit purified macromolecules from pathogen
  includes recombinant DNA expressed in lab
• Recombinant vector, often carrying genes of
  multiple agents
• Anti-idiotype vaccine pathogen molecular mimic

DNA

• DNA vaccines expressed by host cells

4
(No Transcript)
5
Immune Disorders

• Hypersensitivities
• Exaggerated immune response
• Results in tissue damage
• Autoimmune diseases
• Transplantation rejection
• Immune deficiency

6
Type I hypersensitivity

• Allergic reaction due to IgE production in
  response to innocuous antigen
• IgE binds to mast cells (also eosinophils,
  basophils)
• Degranulation triggers anaphylaxis
• Local hay fever, bronchial asthma
• Systemic circulatory shock
• Examples allergies to food, penicillin, insect
  venom

7
(No Transcript)
8
Type II Hypersensitivity

• Cytotoxic/cytolytic
• IgG or IgM-mediated
• Activation of complement pathway and effector
  cells (platelets, neutrophils, eosinophils,
  macrophages, etc)
• Example non-matched blood transfusion

9
(No Transcript)
10
Type III Hypersensitivity

• Immune complex formation
• Accumulation of excess results in damage to blood
  vessels, kidneys, skin
• Due to 1) persistent infection and weak Ab
• 2) continued synthesis of autoantibody
• 3) repeated inhalation of allergens
• Examples lupus erythematosus, Farmers lung

11
(No Transcript)
12
Type IV hypersensitivity

• Delayed type, T cell mediated
• Special subset of TH1 cell migrate to site
• Recognition of antigens bound to tissue cells
• Activation of TH1 cells to release cytokines
• Recruitment of lymphocytes, macrophages,
  basophils
• Examples TB skin test, poison ivy, leprosy

13
(No Transcript)
14
Autoimmune Disease

• Loss of immunologic tolerance
• Activation of autoreactive T and B cells results
  in acute tissue damage
• Influenced by genetic, viral, endocrine, and
  psychoneuroimmunolgical factors

15
(No Transcript)
16
AUTOIMMUNITY mild to life-threatening disorders
Tolerance immune system held in check a)
antigen not exposed (inside cell, behind
barrier) b) antigen not produced early c) B
cells T cells deleted Autoimmunity -
breakdown of Tolerance, system failure a)
antigen exposed b) antigen produced (viral
infection, cancer) c) B T cells not deleted
17
Autoimmune hemolytic anemia antibody against RBC
surface antigen opsonization - macrophages
engulf RBC complement cascade - RBC
lysis Myasthenia gravis antibody to
acetylcholine receptors in the
neuromuscular junction muscle weakness
difficulty chewing, swallowing, breathing -
respiratory failure
18
Systemic lupus erythematosus red wolf reddish
rash on the cheeks - early symptom
resembles a butterfly fever, joint pain damage
to CNS, heart, and kidneys Antibodies to
double-stranded DNA DNA released on cell death
binds to antibody Ag-Ab complexes filtered by
kidney, against basement membrane of
glomerulus activate complement cascade - tissue
damage
19
Rheumatoid arthritis abnormal IgM - rheumatoid
factor reacts with the Fc portion of
IgG Ag-Ab complexes deposited in synovia
activate complement cascade inflammatory
response with increased vascular
permeability - swelling pain proteolytic
enzymes of neutrophils degrade collagen repeated
bouts lead to fibrous tissue replacing collagen
joint fusion
20
Hashimotos thyroiditis antibodies against
thyroid epithelial cells thyroglobulin
in serum thyroid follicles infiltrated with B
cells T cells macrophages - follicles
destroyed damage by humoral cell-mediated
immune systems Multiple sclerosis
?? demyelinization of CNS tissue, progressive
paralysis lesions resemble cellular infiltrates
associated with delayed hypersensitivity
reactions Juvenile or Type I diabetes T cells
attack the ?-cells of the pancreas
21
Etiology of Autoimmune disseases Tolerance -
T suppressors hold system in check clonal
deletion eliminates cells able to respond to
self Autoimmunity - clones not
deleted hidden antigen now exposed antigens not
made early now produced viral induced
changes cross-reactive antigens - bacterial or
viral infection triggers antibody
production to cell components -
22
Transplantation Rejection

• Allografts from different individuals
• Xenograft from different species
• Tissue rejection may occur by TH cells
  recognizing different MHC II, aid TC to destroy
  graft (recognize MHC I)
• TH cells also release cytokines, cue macrophages
• Graft vs host disease (bone marrow transplants)

23
(No Transcript)
24
Immunodeficiencies
25
In vitro applications

• Agglutination reactions
• Tests using secondary antibody
• Liposome tests

26
Agglutination tests

• Drug tests measure ability of sample to compete
  antibody away from latex agglutination complex
• Pregnancy tests measure competition by human
  chorionic gonadotropin in urine for
  antibody-binding latex beads
• Tests for serum antibody (eg, against rubella-
  German measles)

27
(No Transcript)
28
(No Transcript)
29
(No Transcript)
30
Hemagglutination inhibition assay
31
(No Transcript)
32
Tests using secondary antibody

• ELISA
• Flow cytometry
• Western blot

33
ELISA
34
Flow cytometry
35
Western blot

• Proteins separated by SDS-polyacrylamide gel
  electrophoesis
• Transfer to membrane
• Treat membrane with specific antibody against
  protein of interest (or test antiserum)
• Detect antibody using labeled secondary Ab
  (radioactive or enzyme label)

36
Liposomes