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Ontogeny and Phylogeny of Immune System

: (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

* 5 counterpart of the bone marrow in avian


* stem cell comes from 6
* thymus found at the 7
8
9

antibody-mediated immune reaction Bone Marrow


cell-mediated immune reaction - Thymus

Percent Cell Distribution of


Different Tissues in HumansMorphology
Tissue
Thymus
Lymph Node
Spleen
Blood
Electron Microscope
Thoracic Duct
IgE recruitment
Bone Marrow
C3 recruitment
Tonsil
Fc rep
Lymph Fluid
Immunoglobulin in surface
Method of identification
Effect in CMI

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
+
+
+
+
-

Cells of immune system:


a Hematopoetic system
(bone marrow) RBC, WBC, platelet
b Monocytic (mononuclear) Phagocytic system
c Granulocytic system

1 Primary Lymphoid Organs


2 Secondary Lymphoid Organs
3 GALT (Gut-assoc Lymphoid Tissue)
4 Salmonella typhi in ileum
5 Bursa of Fabricius
6 bone marrow
7 back of sternum
8 B cell
9 T-cell

T-cell
+
+
+
+

Lymphoid system

10

(1) Blood monocyte and (2) free and fixed macrophages


Represent 1-3% of circulating wbc in normal adults
Remain in blood (11) then migrate to tissue (12) and become mature macrophages divide in 13, do not 14, do not
produce 15
Classification of Macrophage:
1 16 (body Cavities) peritoneal, pleural, alveolar, synovial macrophages
2 17 kupffer cells, splenic, lymph nodes, bone marrow
3 18 histiocytes (19), microglial (20) and mesangial cells (21)
Functions:
1 Phagocytosis and antigen processors process of converting into a highly potent form recognized by
lymphocytes.

Process antigen highly potent form recognize lymphocytes introduce to phagocytes


(e.g. 22)
2
3

AnG presentation to AnG sensitive lymphocyte (23)


Secretory cells monokines e.g 24

Molecules secreted by macrophages:


1 Enzymes
a Lysozomal enzymes
b Acid hydrolase
c Lysozymes
d Proteinases
2 Plasma proteins
a. 25 (universal opsonin)
b. coagulation function
c. complement cascades
3 Monokines
a 26 activates resting T cells & acts as endogenous pyrogen
b 27 viral infection and prevention

10 Mononuclear Phagocytic System


11 1-3 days
12 months/years
13 tissue
14 recirculate
15 memory cells
16 Free cells
17 Sinus-lining cells
18 Tissue macrophages
19 connective tissue
20 CNS
21 kidney
22 opsonization
23 T&B cells
24 TNF
25 fibronectin
26 IL-1
27 Interferons

Granulocytic Phagocytes (Polymorphonuclear cells)


A 28
- 60-70% of WBC in peripheral blood
- Predominant phagocyte but not capable of sustained phagocytic activity
- Cant process antigens
- Half-life: 12 hrs, additional 2 days in tissue
- Cytoplasm: has granules with enzyme
- Increased in acute bacterial infection
29
B
- 3% of WBC
- Less efficient in phagocytic activity
- Control allergic & inflammatory reaction
- Half-life: 30 mins, 12 days in tissues
- Has granules with enzymes & eosinophilic proteins
C 30
- 1% of WBC
- Little or no phagocytic act
- Granules: contain chemical mediators (vasoactive amines) like 31
Lymphoid System
Principal cells: 32
Classification:
- 33
- Regulate production & differentiation of lymphocytes
- Site for maturation of lymphocytes in the absence of antigenic stimulation.
- Responsible for the acquisition of lymphocytes of the ability to recognize self and non-self antigen.
- Include: 34
35
- Lymph nodes round or bean shaped
Size:

(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

population cells or null cells or non-T or non-B cells

- Bone marrow-derived unclassified cells


- 9% of circulating lymphocytes
Types of Null Cell
1. 59
= Natural Killer cells (kills cancer cells through Fc receptor)
2. 60
= any cells which destroy cells coated with antibody (Tumor cells/Virus infected cells)
= 61: process of attracting antibody (62)
Nature of AnG and AnB
Types:
1. 63
- in the body already
- can be generalized (fever, interferon, inflammatory) or local (serum in ear, stomach activity, intact skin, etc)
2. 64
- Highly diverse and more specialized mechanism of Immune response
- Response in minutes against a specific agent not recognized by the host itself
- There is interaction between antigen and specific antibody (specific meaning it solely reacts to one antigen)
Chars of specific Immune response
1 65
- Highly selective. Highly discriminating immune response
- The product of immune response will react solely with the configuration identical or similar to that which stimulate
the response
- Sample: 66(similar to) 67= tonsil antibodies target the heart valves
2 68
- Wide variety of all types & cell products and produced to interact with diversity of responses
3 69
- Property of accelerated /qaaugmented specific immune response upon subsequent exposure to similar immunogens
- Booster doses of vaccination (augment)
Mechanisms that mediate specific immune response:
1 70
- AnB mediated immune response
- Governed by thymus-independent B cells
- End products of B cell stimulation are AnB
- How?
1 Neutralization of toxins, virus (e.g. 71)
2 Direct bactericidal/lytic with complement (AnB-AnG complex activation of complement system)
3 Agglutinate microorganisms making them more of a subject
4 Opsonize microorganisms to facilitate phagocytosis
2 72
- Cell mediated immunity
- Governed by thymus-dependent T cells

59 Large Granular Lymphocyte


60 Killer cells
61 Opsonization
62 opsonin
63 Non-specific or innate immune response
64 Specific or Adoptive immune response
65 Specificity
66 Recurrent tonsilitis antigen
67 rheumatic heart disease heart valves
68 Heterogenity
69 Memory
70 Humoral immune response (antibody-mediated immunity)
71 tetanus pasmi
72 Cellular immune response (CMI)

T cells stimulation lead to production and sensitized (introduced to antigen already) T cells, proliferation and T cell
release of lymphokines (inflammatory substances)

Mononuclear inflammatory reaction (macrophage monokines)


Cytotoxic destruction of invading cells (in microorganisms, or transformed cells or grafted cells)
Activation of macrophages which permit then to destroy intracellular org & target cells.
Delayed type of hypersensitivity reaction in man

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

An antigen could be:


1 76 can elicit specific immune response (high molecular weight)
2 77 immunogenes only when coupled to a large protein molecule (carrier called 78)

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

73 T cell mediated responses


74 Antigen (generic)
75 Immunogens (specific)
76 Complete
77 Incomplete antigen
78 HAPTEN
79 10,000 daltons
80 capsule
81 gelatin
82 T cell independent (TI Ag)
83 T cell dependent (TD Ag)
84 Exogenous antigens
85 cell wall, capsule, flagellum, toxin
86 capsid, envelope, antigens

- 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.

AnB sensitized lymphocytes maybe produced in response to normal self AnG


E.g 91

Present in an animal species but are not shared by all members of that species
Ex.93.

92

Difference between Thymus-Independent and Thymus-Dependent Antigen


TI
T cell
No
Memory Response
No
Structure
Simple, repetition
Antibody formed
IgM, IgG3
Metabolism
catabolized slow
Induction of Tolerance
Easy
Antigen-Processing
May not be required
Examples
-pneumococcal capsule
-polysaccharide
-dextran
-LPS

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

Special form of proteins Ig


Present in highest concentration in serum (gamma globulin protein) but are also found in fluids
Detected in many body function
a. tears
b. respiratory secretions
c. saliva
d. intestinal content
e. milk
f. CSF
g. urine
Highly specific reaction
Molecules of protein is measured by ultracentrifugation
Act as antigen since they are proteins and therefore stimulates production of AnB or Antiglobulin.

Structure:
-Y-shaped
- monomer: baric unit
- 80 to 90 % polypeptide

87 Heterologous or xeno antigens or Forssman antigen


88 Proteus Vulgari OX-19 strain across
89 Streptococcal Org
90 autologous / autoantigens
91 lens proteins, sperm cells, nucleic acids, thyroglobulin
92 Homologous antigen / alloantigens
93 ABO bld group antigen. Histocompatibility AnG

- 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
-

Second most abundant (100-400 mg/dL)


15% of total Ig
Defending exposed body and portals of entry
Monomer/dimer
Subclass: IgA secretion/IgA serum
Saliva, tears, colustrum, bile, intestinal, respiratory and urogenital tracts
Half-life: 6 days
Secretory IgA: predominant Ig in the intestine. Secretions that serve:
Protect the IgA from proteolytic digestion
Facilitate transport across secretions

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

MICROBIOLOGY (Dr. Esquivel)


Serology study of AnG-AnB reaction
AnG & AnB REACTIONS, IL & COMPONENT SYSTEM
AnG & AnB include:
1 Precipitation of soluble AnG
2 Agglutination of particulate AnG
3 Neutralization of bacteria, virus and toxins
4 Neutralization of the Complement system (lysis of the cell)
Precipitation:
Immonological precipitates are insoluble complexes formed by a union of AnB (precipitin) and soluble antigen
(precipitinogens).
Lattice formation requires that both AnG and AnB be at least bivalent.
Reactants must be present in optional proportion in order to build a lattice of sufficient size. (should be equal
concentration between AnG and AnB.)
IgG good precipitating antibody.
Precipitated to form rapidly as the temperature is increased 40-45C. (serves as CATALYST. Denatures proteins if beyond)
A dose response relationship is observed if increasing amounts of
soluble AnG are
mixed with a constant amount of AnB.
3 Phases of precipatation curve
1 Prozone (zone of AnB excess)
2 Zone of Equivalence maximum precipitation between AnB
3 Post zone ( zone of AnG excess)
Agglutination
Refers to immunological aggregation or clumping of insoluble particles.
Antigen: Agglutinogen
Antibody: Agglutinin- (good) Blood groups AnB.
3 Major categories of Agglutination reactions:
1 Direct immune Agglutination
Involves AnB reactions with antigen of the native particle.
Ex: ABO blood grouping
Presence
Ag (RBC)
Ab(serum)
A
A+Ag
Anti-B
B
B+Ag
Anti-A
AB
A+ B+ Ag
None
O
A- B- Ag
Anti-B & Anti-A

and AnG.

2
3

Direct non-immune agglutination


use of lectins or phytohemagglutinins (plant extract), hemagglutination by virus
Indirect (Passive)
Agglutination of soluble Ag coated or insert particles which act as carrier.
Charcoal, latex particle
IgM is a good agglutinating Ab.
Quantification of degree of agglutination is done by titration.
Titration refers to be process in which the serum under test is make up in a series of increasing dilutions and
each dilution is then tested for activity.
Titer: refers to the reciprocal of the highest dilution giving a (-) reaction which provides the measure of the
amount of Ab present in the serum. (visible reaction)
Fourfold increase in the titer is considered significant.
(Reactions)
o Turbidity formation
o Differ in intensity of turbidity decreasing in serial dilutions
E.g. 320 todd units titer reported
Direct immune Agglutination
1 Hema agglutination
a Cold hema tests (colder than 37o)
b Heterophile agglu test (for syphilis)
2 Bacterial agglutination
Direct non-immune agglutination
1 Viral hema
Based on the non-serological hema agg properties of some viruses (influenza, vacinia, variola, dengue,
mumps, corseki groups, rabies etc.)
Indirect passive agglutination
Soluble Ag reacts with Ab.
Uses carrier particles: RBC, latex particle, colloidal charcoal.

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:

Directly activate C3.


Activates polysaccharides, bacterial components (LPS, capsule, cell wall) virus, fungi, parasites
Cobra venom factor (intravascular hemolysis).
C3 recognition unit (instead of C1)

C5 C9: membrane attak unit (MAU)


* C5 meeting pt of 2 pathways
Bacterial activities of the products of CS activation:
1 Cytolysis
Caused by the MAU (C5-C9)
Resistant
- Yeast cells, mammalian cells
- plant cells
Sensitive (intravenous)
- leukocytes
- thrombocytes
- RBC
- gram (-)
2 Enzyme formation:
C1 esterase (C1s, Clr, C1q)
C3 & C5 convertase
Factor D
3 Anaphylatoxins (SRS-A)
C3a, C4a, C5a
4 Chemotoxins (phagocytes orderly migration to the site of infection)
C5a, C3a, C567
5 Opsonization
C3b
6 Immune adherence
7 Virus neutralization
Control Complement Mediated Functions
2 Principal Control systems: all are normal serum proteins and are complement components.
1 Inactivations
a Factor I : inactivate C3b and C4b
b Factor H: accelerate inactivation of C3b and C4b
c ANA inactivate
Carboxy peptidase enzyme
Inactivates C4a, C3a, C5a
d C4 binding proteins presents participation in the complement cascade activation.
e C6 inactivation: inactivates C6.
2 Inhibitors:
a C1s inhibitor: inhibits C1s activity
b S-proteins
Has the ability to bind surface lipids and interfere with the attachment of C5, C6, C7, C9.
Hypersensitivity Rxns
Immunity
- State wherein there is prior contact of a person against an agent, obtain protection that would otherwise harm him
- rxn specific for particular agent & benefit comes from immune set-up
Sensitization period formation of IgE; no manifestation of reaction first
Allergy/hypersensitivity
- Altered reactivity to antigen pathologic rxns upon subsequent exposure to that particular antigen
Allergen
- Sensitizer
- Antigenic substance trigger allergic state
- Protein/non-protein of low molecular weight
Routes of entry of allergen
- Resp. tract
- Digestive tract

Injection (ATS Skin Test)


Skin contact (exposed area to allergen)

Classes: Allergic response


Immediate type
- Rxns appear w/in mins. (20-30 mins.)
- After intercutaneous injxn/cutaneous application of allergen
- Mediated by antibodies
Delayed type
- Slow response 24-48H
- Mediated by sensitized lymphocytes/macrophages
- w/ Ab /Ab-like molec. attachment to the cells surface
- cell-mediated immunity
Clinical types: Allergic rxns
* based on manifestation
Type I: Anaphylactic type
- immediate
- most common
Type 2: Cytotoxic type
- due to toxic effects of anti-cell & anti-tissue Ab
Type 3: Complex-mediated type
- due to toxic effects of Ag-Ab complexes
Type 4: Cell-mediated (delayed type)

Type I Hypersensitivity Rxn


- mediated by IgE bound to mast cells (differentiated basophil) & basophils histamine production
- rxn results from release of pharmacologically active factors
- Ag w/c has potent stimulators: pollen, helminths Ag, and proteins from insect venoms
- genetic = most impt factor influence devt of allergic rxn
- genetic basis
- major IgE regulator locus influence overall IgE prodxn probably through T-cell mediated mech.
- assoc. bet. certain HLE region haptocytes & occurrence of atopy (e.g. skin asthma)
- Ir gene of HLA region influenced allergic trait of individual
Mechanism Anaphylaxis
Susceptible person

Exposure to Ag

Ab (IgE) prodxn attached to mast cells & basophils

Re-exposure to same Ag sensitized person


Ag-Ab rxns leading to degranulation of mast cells & basophils

Release vasoactive amines:


* Histamine
* Serotonin
* Leukotrienes
* Prostaglandin
* Eosinic Chemotaxic Factor (ECF)
* Platelet Activating Factor (PAF)
* Neutrophil Chemotactic Factor Anaphylaxis (NCF-A)
* Kinins
Biological effects
- capillary permeability

- 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

3 Factors derived from arachidonic acid


Leukotrienes from macrophages
A1. LTB4 stimulate neutrophils & eosinophil chemotaxis
A2. LTC4, D4, E4
- slow reacting substance of anaphylaxis
- vascular permeability 2
- provoke slow contracxn of sm mm
4

ECF-A: eosinophilic chemotactic factor of anaphylaxis


- attract eosinophils to site of mast cell degranulaton
- promote eosinophil superoxide prodxn

PAF: platelet activating factor


- platelet aggregate & release their contents esp serotonin
- promote platelet prostaglandin synthesis
- promote neutrophil aggreg.

Other biologically active factors


1 neutrophil chemotactic factors (NCF) of anaphylaxis
2 neutrophil immobilization factor (neutralizes NCF-A)
3 heparin
4 kinins
- bradykinin
- vascular permeability
- stimulate SM contacxn
Types Anaphylaxis in Humans
Generalized/systemic
- 20-30 mins after admin of inciting agent
- s/sx: urticaria, wheezing, paroxysmal cough, dyspnea, cyanosis, vomiting, circ collapse, shock
Causes:
- drugs (penicillin)
- biologicals (animal serum)

- foods (seafoods, chicken)


- insect sting
Cause of death:
- laryngeal edema
- massive airway edema
Localized/spontaneous clinical allergy
- few mins after contact w/ inciting allergen inhalation/ingestion
- s/sx: hay fever, urticaria, asthma, vomiting
- marked familial disposition
- cross rxns bet unrelated Ag are frequent
Cutaneous anaphylaxis
- skin tests
Itchiness @ injexn site

Elevated, blanched irregular wheal surrounded by zone of erythema (flare)


Dx:
1.

2.
3.
4.
5.

direct allergen skin test


a. epicutaneous (scratch/prick) skin test
b. intradermal
oral/inhalation test of allergen
RIST (radioimmunosorbent test)
- for total IgE conc
RAST (radioallergosorbent test)
-spec IgE conc
Prausner-Kustner (PK) rxn
Serum for allergic ind

Injected to non-allergic ind

After 24-48H: Ag injected @ site of serum injxn

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

Type II (Cytotoxic type)


- interacxn bet Ab & w/ either an Ag component of a tissue cell or w/ an Ag/hapten w/c has been intimately assoc w/ tissue
cells
- AnB circ in blood
- IgG/IgM
- presence of complement to effect cellular damage
- example: blood transfusion of wrong blood type
Mechanism: Tissue injury Type II
1 Rxn of Ab w/ tissue cells
- Ab induces direct cytolysis & killing by inactivation of complement system
- ex: hemolytic rxns
2

involved participation of cell (neutrophil & macrophages)


- Ag-Ab interacxn stimulates phagocytes

rxns against specific receptors on cell


- ex: Myasthenia gravis = presence of Ab against Ach receptors

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

Type III Complex-mediated hypersensitivity


- cells/tissues injured by complex results from interaxn bet Ab & its corresponding Ag
Pathology:
Initiated when Ag react w/ precipitating Ab in tissue fluids

Formaxn toxic complexes

Formaxn microprecipitates in & around small vessel walls

(1) activate phagocyte


(2) neutrophil activation

Eat AgAb
inflammatory reaction

Destroy wall of BV
Arthus type of reactivity (Ab excess)
Ag-Ab complexes precipitated in blood vessels

Release: lysozymes & proteolytic enzymes from phagocytic cells

Damage blood vessel walls

Hemorrhage, necrosis, vascular permeability


- an influx of neutrophils = primary factor responsible for observed tissue damage
- ex: Lupus, Arthritis, Leprosy
Type IV Cell-mediated/delayed hypersensitivity rxn
- based on interacxn of Ag w/ primed T cells
- manifestations: due to release of mediator substances (lymphokines) by activated T cells
- involved in formaxn of induction & erythematous rxn (24-48H)
- mononuclear lymphocytes & phagocytes, granuloma formation
Mediators of delayed hypersensitivity
1 migration-inhibiting factor
- inhibits macrophages
2 leukocyte inhibiting factor
3 macrophage chemotactic factor
- IL 8 = stimulates infiltration of macrophages
4 IL 2 = activates cytotoxic lymphocytes & macrophages
5 TNF-B (lymphotoxin)
- lyse tumor cells
6 macrophage activating factors
a interferon gamma
b macrophage-granulocyte colony stimulating factor
c tumor necrosis factor alpha (enhances the cytolytic microbicidal activation of macrophage)
Examples Type IV
- contact dermatitis
- leprosy
- tuberculin skin test
DTH Type
Contact

Reaction Time
48-72 hours

Characteristics
Histological
Clinical Appearance
Appearance
Eczema
Infiltration of

Antigen
Epidermal (e.g. nickel,

lymphocytes and later,


macrophages, edema
of epidermis

Tuberculin

Granulomatous

END

48-72 hours

4 weeks

Local Hardening and


swelling +/- fever

Infiltration of
lymphocytes and later,
macrophages

Hardening e.g. in skin


and lungs

Granuloma containing
epitheloid cells, giant
cells and
macrophages, fibrosis
+/- necrosis

rubber, poison ivy


usually hapten)
Intradermal injection
used diagnostically:
tuberculin,
myobacterial*
leishmanial antigens
Persistent Ag or AgAb complexes in
macrophages; or nonimmunological, e.g.
talcium powder