What does IgE do on re-exposure in Type 1 or Immediate Hypersensitivity?

What else is released during this process?

• IgE produced in "sensitized" individuals
• IgE binds to mast cells and other cell son re-exposure
• histamine and other inflammatory causing substances released (degranulation)

Type 1/Immediate Hypersensitivity

most severe = anaphylaxis (systemic)

type 1/immediate hypersensitivity reaction in the skin

flare - wheal - flare

• biogenic amines (eg. histamines) and lipid mediators (eg. PAF, PGD₂, LTC₄) ---- > cause vascular leak, bronchoconstriction and intestinal hypermotility
• cytokines (eg. TNF) and Lipid mediators --- > Inflammation
• Enzymes (eg. tryptase) --- > tissue remodeling

• antibodies produced to a target (foreign or from host)
• binding antibody causes activation of cell mediated or complement mediated (cause destruction/damage to target)
• reaction onset = 8 hrs or chronic in autoimmune

1. complement-mediated
2. antibody-dependent cellular cytotoxicity (ADCC)
3. antibody-mediated cellular dysfunction

Type II

IgG

Fast

the mother is RhD negative but fetus is RhD positive; when first birth, RhD positive cells in mothers blood stream and mother makes anti-RhD IgG antibodies

For the next pregnancy; the anti-RhD IgG attack fetus

How does Type 3 (or Immune Complex Mediated Hypersensitivity) work? 

large amount of soluble antigen in plasma reacts with antibody and forms large antigen-antibody complexes

these overwhelm normal ability of RBC to take them up for transport and removal in liver

trapped in capillaries (esp. kidneys and lungs) and activate complement cascade

- PMN are attracted but unable to phagocytose complex; release granules of damaging enzymes (cause local tissue damage)

- mast cell degranulate and cause inflammation

- rxn onset within 6 hrs of exposure

Type III

IgG

Slow

List examples of Type III hypersensitivity

• serum sickness (result of passive immunization with animal serum to treat disease)
• autoimmune disease (lupus and RA)
• glomerulonephritis

• sensitization (to antigen) occurs when antigen processed by phagocytic cell and presented to T lymph in local lymph node
• re-exposure = T cells initiate cell mediated response (using monocytes, macrophages and lymphocytes) which invade area with antigen = local inflammation

Type IV (4)

T cell

Delayed

occurs in 24-48 hours

- if chronic (antigen cannot be cleared), area surrounded by macrophages with lymphocytes and fibrosis occurs = granuloma

1. Primary = genetic

2. Secondary = therapy, cancer, preggers, etc

• may occur as result of lack of any complement component
• causes failure of cascade

• predispose to bacterial infections
• causes Chronic Granulomatous Disease (inability to kill organisms that have been ingested)
• staphylococci and other catalase-producing organisms tend to cause infections 

a group of diseases in which there are low antibody levels, and lack of lymphoid tissue becuase failure of development

as maternal immunity transferred at birth wears off 

ex. SCID and others

• affect lymphocytes in particular (interfere with cell division = inhibit regeneration of cells that have rapid turnover (eg. PMN)
• after treatment = number of PMN (and other blood cells) drop = increased risk of infection

• Iatrogenic (secondary)
• prednisone, dexamethosone
• damp down inflammation by many mechanisms (ex. anti-macrophage and anti-T lymph) and interupt presentation of antigents = decrease antibody response

What are the commonly used post transplant medications?

What do they do?

What type of cell is then predisposed to infection?

cyclosporin A, tacrolimus, serolimus

- inhibit lymphocyte function

- immunosuppressed w/ predisposition to infection of T cell deficiency

Why might a spleen be removed? What does it do? 

• trauma or treatment for malignancies or congenitally absent (rare)
• removes circulating microorganisms, immune complexes and old blood cells (main site of opsonizing antibody)

What does a splenectomy increase the risk of?

List some examples. 

life threatening infections with encapsulated organisms

ex. Strept pneumo, Haemophilus influenzae, Neisseria Meningitidis, salmonella, etc

splenectomy

S. pneumoniae, H. influenzae, N. meningitidis

1. heat
2. pain
3. redness
4. swelling

microorganism gain entry (breach in innate defense)

phagocytose bacteria and present antigen to T cells (local lymph nodes)

complement activated = MAC = punch holes in cell membrane

histamine, tumor necrosis factor α (TNF-α)

- release cells that increase vascular permeability and increase blood flow

part of first exposure response

• complement components diffuse out site of infection, attract PMN (patrolling in blood)
• PMN migrate to site of infection (chemotaxis)
• PMN roll along endothelial linning of blood vessel and bind more closely as attracted and activated by inflammatory signals (diapedesis - they enter the tissues)
• PMN phagocytose organism then kill in "phagocytic vacuole" by "oxidative burst" 
• accumulation of PMN = pus

• T cells activated = defend against intracellular organisms
• B cells activated = develop into plasma cells (produce antibodies 5-7 days after) (initially IgM but "class switching" to IgG

T cells activate macrophages so become more effective at kililng organism by producing more reactive substance to fuse to phagocytic vacuoles

- 1-3 days after infection arrive at site

If organisms have spilled into the blood, what will clear them?

production of cytokines = fever and production of acute phase reactants

- bone marrow produces more PMN = increase WBCs

interferon; results in inhibition of viral replication, "warns" adjoining cells, renders them resistant to infection, activates immune system, host experiences malais and muscle aches and fever

may activate NK killer cells (eliminate infected cells)

• destroying complement components (Gp A Streptococci)
• destroying immunoglobulin (Neisseria may produce IgA protease)
• preventing phagocytosis (encapsulated organisms)
• preventing intracellular killing after being phagocytosed (examples on other slide
• bacteria growing in cytoplasms of cells protected (listeria)
• bacteria (or other) may change surface antigen rapidly 

• Neisseria may produce IgA protease

• encapsulated organisms

• listeria