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: (further differentiation)
Bone marrow (adults)
Thymus (adult)
Fetal liver (young)
Spleen
Lymph nodes
3
o
o
o
o
Tonsils
Appendix
Payers patches (e.g. 4)
Lymphoid follicles
B-Cell
<0.5
20-40
30-40
B-Cell
30-40
Numerous Projection
10-15
+
40
+
50
+
<25
+++
immunoflourescence
T-Cell
> 99
60-80
40-65
60-80
85
1-7
50
>75
T-Cell (carrier)
Flat Surface
+/+/Rossette form
with Sheeps RBC
+
Functions
Target Cell
Antibody
Carrier Specificity
Hapten Specificity
ConA
Phytohema
LPS
Mixed Lymph Culture
B-cell
+
+
+
+
-
T-cell
+
+
+
+
Lymphoid system
10
(usually)
1. Large 36
2. Small 37
Functions:
1. B-lymphocyte related
2. T-lymphocyte related
Central or Primary Lymphoid Tissues
(1) 38
-master organ
- fully functional: birth
Atrophy: puberty (becomes 39)
- cells: 1. 40 (mass of lymphocytes)
2. Epithelial cells
- layers:
1.41: divide and differentiate
28 Neutrophils
29 Eosinophils
30 Basophils
31 histamine
32 Lymphocyte
33 Central or Primary Lymphoid tissue
34 thymus, bone marrow, bursa of Fabricius & fetal liver
35 Peripheral or secondary LT
36 T-lymphocytes
37 B-lymphocytes
38 Thymus
39 thyrothymic ligament
40 Thymocytes
2.42: further maturation (acquire surface markers and ability to recognize self antigens)
43
- :
- recirculate to blood and are distributed to different peripheral lymphoid organs
- most die within the thymus
- 44:
- secrete hormone-like substances which regulate the differentiation and maturation of T cells
(2) 45
- B-cell differentiation and maturation
- also has macrophages (can also be considered as secondary lymphoid organ)
(3) Fetal Liver
Peripheral or Secondary Lymphoid Tissues
(1) Lymph Node
1 46 predominantly B cells
2 47 few T & B cells, macrophages & plasma cells
3. 48 ill defined area bet cortex and medulla, mainly T-cells
(2) Lymph Circulation
- lymph flow to thoracic duct (49)
- lymphocytes
* 50 (blood)
51
* to complete 1 cycle
(3) Spleen
1 52 destruction of aged RBC
2 53 lymphoid tissue around a central arteriole called periarterial lymphoid sheath containing T cells
54
scattered
Separated by a marginal zone with macrophages
(4) GALT
- B cells are found 55
- T cells are found in the 56
==
57
- 30% of WBC
Types:
1 T & B lymphocytes
2 58
41 Cortex
42 medulla
43 T cells
44 epithelial cells
45 Bone Marrow
46 Peripheral cortex
47 Central medulla
48 Paracortical zone or deep cortex
49 500 mL/hour; 1x10 cells/mL
8
50 2-12
51 24-48 hours
52 Red pulp
53 White pulp
54 B cells
55 within the follicles
56 interfollicullar areas
57 Lymphocytes
58 3
rd
T cells stimulation lead to production and sensitized (introduced to antigen already) T cells, proliferation and T cell
release of lymphokines (inflammatory substances)
73
74
Substance which have the ability to bind with products of specific immune response. (AnG-AnB Reaction)
Subs that stimulate a specific immune response either humoral or cellular response
75
Properties of Antigen
1 Macromolecular size
- 79 (least)
- Large protein & polysaccharides of natural origin (e.g.80); excellent immunization
2 Molecular complexity
- The more complex, the better
3 Solubility
- The more insoluble, the more immunogenic
4 Structural stability
-flexible molecules are weakly antigenic (e.g. 81)
5.Degradability
- rapidly digested = poor immunogenic
6. Foreignness
7. Recognized by 2 lymphocytes types
a 82 antigens that stimulate B cells w/o intervention of T cells (antibody)
b 83 CMI
Kinds of Antigens:
1 84 come from MO, drugs, pollens, pollutants
a Bacterial agents 85
b Viral 86
2 Endogenous antigen
a 87
- Similar/ identical determinants are found in 2 completely unrelated cells so that AnB formed against one
antigen react with other antigen
- Principle of cross-reactivity
- E.g 1. 88, reacts with ricketssia typhi
2. 89: share with antigenic, determined with heart muscles (in recurrent
tonsilitis) and glomerulus of kidneys (PSGN -Poststreptococcal glomerulonephritis- from skin
infection)
b. 90
c.
Present in an animal species but are not shared by all members of that species
Ex.93.
92
TD
Yes
Yes
More complex
IgM, IgG, IgA
Fast
Difficult
Require
-most proteins
-bovine serum albumin
Antibodies:
- Immunoglobulins (Ig) --- formed in the globulin structure
- Molecules produced by the body in response to an immunogen which has the specific property of combining with the AnG
which induced their formation
Properties
1
2
3
4
5
6
Structure:
-Y-shaped
- monomer: baric unit
- 80 to 90 % polypeptide
- 10 to 20% carbohydrates
- regions: a. Fab antigen-binding hands varies antigen-bound
b. Fc crystallizable foot constant complement-bound
1. complement fixation
2. degranulation of mast cells
3. attachment to phagocytic cells
- J chain
- 2 to 3/5 monomers
- low in molecular wgt
- composition:
a. shorter chain/light chain
- few amino acid
- types: (1) kappa, (2) lambda
b. longer chain/heavy chain
- 5 classifications:
- IgM: pentamer
IgG: monomer
IgE: monomer
IgD: monomer
IgA serum: monomer
Secretory: dimer/trimer
Ig A
-
Ig M (agglutinating)
- Half-life: 5 days
- 10% of total Ig
- Multivalent, largely confined in IV spaces because of large size
- 1st AnB detected/produced
- Appears transiently in immune response
- Can fix complement
- Efficient agglutinator of particulate antigen-like bacteria
- Increased in uterine malfunctions
- No role in memory
Ig D
- Sensitive to proteolytic enzyme & heat
- No biologic role
- Against thyroid, insulin (destroy B cell of Islet of Langerhan), penicillin, nuclear antigens
- Primary cell membrane antigen of B cells together with IgM as antigen receptor
Ig E
- Abundant on surface of mast cells
- Attach to human skin
- Mediate type I or immediate type of hypersensitivity (allergic) reactions
- Shortest half-life: 2-5 days.
- Heat Labile
IgG
- Bivalent
- Most abundant (75%)
- Longest life span: halflife: 23 days in the serum except G3 which has 8 days
- Types: IgG1, IgG2, IgG3, IgG4
- Functions:
o Fix complement via classical pathway
o Participate in the production of immunologic memory
o Provide the bulk of immunity against infectious agents
o Can diffuse to all tissues
Titer refers to concentration of antibody
and AnG.
2
3
Complement system
Properties:
1 Normal serum proteins present in blood but not active
2 There are at least 20 components: 9 major components designated as C1-C9.
3 Synthesis by the:
a Epithelial cells of the intestine
b Macrophages
c Fibroblasts
d Liver cells
4 They circulate in plasma as inactive forms and when activated they are converted as active enzymes.
5 End results of complement activation is Cell Lysis.
6 Complement is activated by heating at 56 C for 30 minutes.
7 Complement is non-specific serologic reagents
8 Complement system has major roles in host defense (eg. Opsonization production, anaphylactic activity, activation of
inflammatory cells, lysis of target cells virus, tumors, cancer cells)
9 Activation of CS by 2 pathways:
a Classical pathway
b Alternate pathway
Classical Pathway:
Requires binding with Ag-Ab complex
Other activates:
Lipid A of the LPS
RNA retro virus, C-reactive proteins
Dextran (blood expander), heparin (anti-coagulant)
Mitochondrial membrane
C1: recognition unit
C4, C2 & C3: Activation unit (activated by C1)
C5 to C9: membrane attack unit.
Alternative Pathway:
Exposure to Ag
- edema
- vasodilation (erythema)
- contraction smooth muscle (except in blood vessel smooth muscles)
- migration of PMNs
- aggregation of eosinophils
- basochonstriction
Clinical manifestations
Anaphylaxis
- Loss of concentration decreased oxygen to brain
- swelling: tongue, inability to swallo
- rapid swelling of throat tissues
- urticaria
- bronchial asthma
- allergic rhinitis/hay fever (sneezing early in the morning)
- angioneurotic edema
Mast cell
- in brain, eye, nose, lung, stomach, intestine, bladder, skin
Functions of chemical mediator substances
1 Histamine
- dilates & induces permeability of small BV production: wheal & flare rxn
- smooth mm contraction bronchi, GUT, uterus, bladder
- potent stimulator exocrine secretions bronchial, gastric, lacrimation & salivation
- enhances response basophils to C5a & promotes helminthicidal act. Of eosinophils
- chemotactic for eosinophils
2
Serotonin
- stimulates heart
- BP ff vasoconstriction
- produced by platelets as pre-formed serotonin
2.
3.
4.
5.
Immediate type hypersensitivity rxn d/t presence of skin sensitizing Ab called Reagin & IgE
Anaphylactoid rxn
- resembles anaphylactic rxn
- observed ff injection of colloids/finely suspended material into blood stream
- absence: Ag-Ab rxn
- liberation: vasoactive subs consequence of colloid injection
Inactivation
Examples: Type II HR
1 Isoimmune rxns
A transfusion rxns
B Rh incompatibility (hemolytic dse of newborns)
C
2
Mom (Rh-) + Dad (Rh+) (1) Rh+ not affected; (2) Rh+ affected, (3) Rh +
*mom injected with Rohgam injection to destroy the fetal Rh (sensitization)
Organ transplant rejection
Autoimmune rxns
A Autoimmune Hemolytic Anemia
B Hashimotos dse
- autoantibodies directed against thyroglobulin
Eat AgAb
inflammatory reaction
Destroy wall of BV
Arthus type of reactivity (Ab excess)
Ag-Ab complexes precipitated in blood vessels
Reaction Time
48-72 hours
Characteristics
Histological
Clinical Appearance
Appearance
Eczema
Infiltration of
Antigen
Epidermal (e.g. nickel,
Tuberculin
Granulomatous
END
48-72 hours
4 weeks
Infiltration of
lymphocytes and later,
macrophages
Granuloma containing
epitheloid cells, giant
cells and
macrophages, fibrosis
+/- necrosis