Immunology Physiology
Primary lymphoid tissue
Cell mediated (see UTD art)
Humoral (substances from humor ie antibodies) (See UTD art)
Inn and Ada both involve both.
Innate immunity
Adaptive aka acquired
- cell mediated
APCs have MHCII which activate CD4+ T cells
t-cell receptors recognised antigen complexes with MHC (major histocompatibility) on APCs
IgG only one that crosses placenta to protect infant
IgA (70% of total body Ig) secreted into gut and mucous membranes
IgE in allergy and helmiths
IgG (75% serum) T1/2 23d monomer (also smallest)
IgA (12% of serum but predominant serum Ig) T1/2 6d monomer or dimer (highest rate of production as high secretion and turnover)
IgD (<1%) T1/2 3d, like IgM on b-cell menbrane, activated b-cell
IgE (<0.1% serum) T1/2 3d
(cryoglobinaemic: reversable precipitation of Ig in the cold, occurs in HIV/HepC/lymphoproliferative disease)
After IgG /M binding of antigen,
Fc portion of IgG (1, 3 well, 2 somewhat, 4 not at all) and M binds C1q (on C1) complement activating the classic pathway
IgA can bind lectin or alternate
Secretory IgA from breastmilk is found in and provides protection to the infant GIT and Resp tracts
Lymphocytes (subsets look at CD3/4/8/16/19)
B-Lymphocytes (CD19)
Phagocytic cells (see UTD art)
- deficiency if recurrent staph abscesses or gm neg infections
Complement pathway
Classic Ag-Ab (C1, 2, 4)
Lectin Pathway Lectin-Mannose (MASP, 2, 4) (Mannose on antigen bound by lectin which activated lectin path)
Alternate Pathogen/apoptotic tissue (FB, FD, Properdin) (constant 'ticking over' independently bind self >inactivated, binds non self > pos feedback > alternate activated
Common from here
C3 covertase: C3 > C3a + b
C5 convertase: C5 > C5a+b
results in membrane attack complex (MAC) (C5b/6/7/8/9)
CH50 measure classic pathway C1-9
- low = deficiency in pathway
C3/4 tests available but not others (C4 usful for heretitary angioedema)
Properdin is X-linked, all other complement deficiencies are Autosomal
AH50 measures alternate pathway
Aquired immunity
Naturally: passive - cross placenta, breast milk, active - exposure to infection
Artificially: passive - Immunoglobulin, active - immunisation
C-reactive protein
- Bone marrow (B- and T-cells birth place, B-cells mature here)
- Thymus (progenitors migrate to thymus and mature here as thymocytes)
- thymocytes initially double neg (ie CD3 but no4/80
- then double positive (CD3, and 4 and 8)
- then single pos (CD3 and either 4 OR 8)
- lymph nodes (100-200 in body): APCs present to T-cells
- tonsils
- spleen
- Peyer's patches of small intestine
- mucosa associated lymphoid tissue (MALT)
Cell mediated (see UTD art)
Humoral (substances from humor ie antibodies) (See UTD art)
Inn and Ada both involve both.
Innate immunity
- Complement
- Natural Killer Cells (Lymphocyte)
Adaptive aka acquired
- cell mediated
- intracellular pathogens
- neoplasms
- allogenic cells (transplant rejection)
- autoimmunity
- type 4 hypersensitivity
- contact dermatitis
- have pattern recognition receptors including toll-like receptors, recognise Ig:antigen complexes
- process antigen and present
- intracellular antigen: on MHCI (>CD8 cytotoxic Tcell)
- extracellular antigen: on MHCII
APCs have MHCII which activate CD4+ T cells
- Professional APCs include: dendritic cells, macrophages, B-cells
t-cell receptors recognised antigen complexes with MHC (major histocompatibility) on APCs
- All Tcells have CD3: signal t-cell receptor contact
- CD4: on T helper cells, ligand MHCII (the target of HIV which when depleted > AIDS)
- Th1 cytokines proinflammatory: IFN gamma (inflammatory)
- Th2 cytokines: IL 4,5,13 (IgE/Atopy) and 10 (antiinflammatory)
- Th1:2 balance is important ?atopy related to Th2>1 influence
- Th cells involved in class switching in B-cells
- CD8: on Cytotoxic T cells, ligand MHCI (ie intracellular)
- B-cells produce antibody
- Some migrate to blood as plasma cells to specialised in Ig production
- Others become memory B cell awaiting future inoculation for quick response
- Antibody aka IgGAMED (serology)
- binds to Fc receptor on immune cell
- induced phagocytosis or cytoxicity
- binds to Fc receptor on immune cell
IgG only one that crosses placenta to protect infant
IgA (70% of total body Ig) secreted into gut and mucous membranes
IgE in allergy and helmiths
IgG (75% serum) T1/2 23d monomer (also smallest)
- IgG1,2,3,4
IgA (12% of serum but predominant serum Ig) T1/2 6d monomer or dimer (highest rate of production as high secretion and turnover)
IgD (<1%) T1/2 3d, like IgM on b-cell menbrane, activated b-cell
IgE (<0.1% serum) T1/2 3d
(cryoglobinaemic: reversable precipitation of Ig in the cold, occurs in HIV/HepC/lymphoproliferative disease)
After IgG /M binding of antigen,
Fc portion of IgG (1, 3 well, 2 somewhat, 4 not at all) and M binds C1q (on C1) complement activating the classic pathway
IgA can bind lectin or alternate
Secretory IgA from breastmilk is found in and provides protection to the infant GIT and Resp tracts
Lymphocytes (subsets look at CD3/4/8/16/19)
B-Lymphocytes (CD19)
- test function
- IgGAMED level (G subsets only if absent of specific polysaccaride vaccine response ?IgG2 def)
- Protein and polysaccaride vaccines IgG (BEFORE any type of transfusion, IVIG has Ig from ~60,000 donors)
- Protein vaccine antibody responses to tetanus and diptheria 2w post reimmunisation if initial low
- Polysaccaride vaccine antibody response to pneumococcal 3w post reimmunisation if initial low
- (do pre and post at same lab)
- helps identify SADNI, and also IgG low due to protein loss (antibody response normal despite low Ig)
- A and B blood type IgM (nb normally low <2y OR absent in blood type AB)
- IgA def (B-cells present)
- Common variable immunodeficiency = low IgG AND low IgA or M AND B-cells present (assoc with autoimmunity and lymphoid hyperplasia)
- HyperIgM (IgM high, rest low, b-cells present)
- Primary hypogammaglobulinaemias
- Transient hypogammaglobulinemia of infancy = same as CVID but normalises by 2y (ie hard to differentiate before)
- x-linked agammaglobulinemia = low Ig's AND near absence of B-cells (suscept to enterovirus)
- Selective antibody deficiency with normal immunoglobulin levels (SADNI)
- Normal Ig levels, but absent polysaccaride OR protein antigen antibodies (antibody responses variable until 5yo so cant diagnose until then
- (1 or more Ig level high ?HIV, chronic granulomatous disease, chronic inflammation, or autoimmune lymphoproliferative syndrome (ALPS))
- T Helper cells (CD4)
- Cytotoxic T cells (CD8)
- candida skin test is best screening test
- SCID (T-cell lymphopenia)
- CD16 (and CD56) are specific to NK cells
Phagocytic cells (see UTD art)
- deficiency if recurrent staph abscesses or gm neg infections
- Ix neutrophil function testing
- early diagnosis essential for survival > Rx stem cell transplant
- defect in phagocytes nicotinamide adenine dinucleotide phosphate (NADPH) oxidase
- ie impaired oxidative aka respiratory burst ie cant kill phagocytosed cell
- predisposition to catylase pos ie fungus and most bacterial
Complement pathway
Classic Ag-Ab (C1, 2, 4)
Lectin Pathway Lectin-Mannose (MASP, 2, 4) (Mannose on antigen bound by lectin which activated lectin path)
Alternate Pathogen/apoptotic tissue (FB, FD, Properdin) (constant 'ticking over' independently bind self >inactivated, binds non self > pos feedback > alternate activated
Common from here
C3 covertase: C3 > C3a + b
C5 convertase: C5 > C5a+b
results in membrane attack complex (MAC) (C5b/6/7/8/9)
CH50 measure classic pathway C1-9
- low = deficiency in pathway
C3/4 tests available but not others (C4 usful for heretitary angioedema)
Properdin is X-linked, all other complement deficiencies are Autosomal
AH50 measures alternate pathway
Aquired immunity
Naturally: passive - cross placenta, breast milk, active - exposure to infection
Artificially: passive - Immunoglobulin, active - immunisation
C-reactive protein
- made in liver
- recognises foreign protein and self protein from damaged cells
- can activate complement system (humoral)
- can bind Fc receptors on phagocytes (cellular)