Immunology is a branch of bio medical science that covers the study of all aspects of the immune system in all organisms.

1. AyeshaArshad
2015
Immunology
Immunology is a branch of biomedical science that
covers the study of all aspects of the immune system in
all organisms. Itdeals with the physiologicalfunctioning
of the immune systemin states of both health and
diseases; malfunctions of the immune systemin
immunological disorders (autoimmune
diseases, hypersensitivities, immune
deficiency, transplantrejection); the physical, chemical
and physiologicalcharacteristics of the components of
the immune system in vitro, in situ and in vivo.
Immunology has applications in severaldisciplines of
science, and as such is further divided.

2. Immunology:
Immunology is a branch of biomedical science that covers the study of all aspects
of the immune systemin all organisms.
Components of immune system:
CD (cell designator):
This is used to designate different cells i.e. which cell is which.
Determinant:
The site on the surfaceof an antigen molecule to which an antibody
attaches itself.
Primary and Secondary organs:
There are two groups of immune systemorgans.
-Primary (central)--organswhereimmaturelymphocytes develop
Thypmus
Bone marrow
-Secondary (eripheral)--tissueswhereantigen is localized so that it can be
effectively exposed to mature lymphocytes
Lymph nodes
Appendix
Peyer's Patches (of GI tract)
Tonsils
Adenoids
Spleen
MALT (Mucosal-Associated Lymphoid Tissue)
GALT (Gut-Associated Lymphoid Tissue)
BALT(Bronchial/Tracheal’Associated Lymphoid Tissue)
NALT (Nose-Associated Lymphoid Tissue)
VALT (Vulvovaginal-Associated Lymphoid Tissue)
Discovery of ABO system:

3. The A, B, and O blood groups werefirst identified by Austrian immunologist Karl
Landsteiner in 1901.
49 different blood groups.
10 are studied.
2 are major.
Major Blood GroupSystems:
ABO
Rh
Minor blood Group systems:
Kidd
Kell
Duffy
Bombay
K,l,M,Netc
Importance of Minor blood types:
There are over 100 other blood subtypes. Mosthavelittle or no effect on blood
transfusions, buta few of them may be the main causes of mild transfusion
reactions. Mild transfusion reactions arefrightening, but they are rarely life-
threatening when treated quickly.
The ABO groupsystem
The blood is classified as type A, B, AB, or O respectively.
Under the ABO system, the absenceof a particular antigen corresponds to the
presenceof an antibody for that antigen.If a person is blood group A, they will
have A antigens on their red blood cells and they will have antibodies to antigen B
in their plasma.
Likewise, if they are blood group B, they will haveB antigens on their red blood
cells and antibodies to antigen A in their plasma.
People with blood type AB have both A and B antigens on their red blood cells, so
they do not have antibodies to either A or B in their plasma.

4. People with blood type O, who haveno A or B antigens, haveantibodies to both A
and B in their plasma.
Subtypesof Group A are A1, A2, A1B and A2B.
RH bloodsystem:
The Rh blood group systemrefers to a set of 50 antigens, but Rh factor
refers only to the D antigen. If you are Rh positive, you have the D antigen and
don't producethe corresponding antibody. This can causeproblems if an Rh-
mother has an Rh+ baby.
Importance of the rhesus (Rh) system:
Another antigen known as the Rhesusfactor (abbreviated as Rh factor) is found on
the surfaces of red blood cells. Named because it was firstdiscovered in rhesus
monkeys, it is presentin some people’s blood but not in others. Thosewho have
it are said to be Rh positive, thosewho do not haveit are said to be Rh negative.
One difference between the Rh systemand the ABO group systemis that Rh
negative people don't usually possess Rh antibodies, whereas in the ABO group
systemif the antigen is absent, the antibody to it is present. In any of the 4 ABO
groups, a person can be Rh positive or Rh negative, meaning that a person’s blood
can be classified as one of 8 possibletypes (O+, O-, A+, A-, B+, B-, AB+, AB-).
Antiserums usedfor BloodgroupIdentificationTesting:
Antiserums
Antibodies
Agglutination/Reaction
Results/Blood groups
AntiserumA (Blue in color)
Contains Antibody B
Agglutinates Antigen A
Grp.A
AntiserumB (Yellow in Color)
Contains Antibody A
Agglutinates Antigen B

5. Grp.B
Both Antiserum A & B
No Antibody
Agglutinates Ag. A & B
Grp. AB
Both Antiserum A & B
Both Antibodies
No Agglutination
Grp.O
AntiserumD (Transparent)
Contains Antibody D
Agglutinates Antigen D
Rh+,-
O- Testing benefits:
Ithas no antigen.
Easily controlled.
Can be donated to any blood type.
Chromosomes which controlproduction
Our gene determines which type of antigen is presentin our body. Glycoproteins
will determine that which antigenic determinant we possess.
Rh is produced by chromosomenumber 1.
ABO is produced by chromosomenumber 9.
HLA is produced by chromosomenumber 6.
BloodGroup Alter: Blood group can be altered by the D-acetyl Enzymepresentin
some Bacteriawhich removes acetyl group .
As Ag-Determinant of Ag. Ais N-Acetyl Glucosamine& that of Ag. Bis D-Galactose.
These can be altered by bacterial enzymeto N-Acetyl Galactosamine& D-Glucose.
Bacteremia:(Bacteria in Blood)
Septicemia:(Toxins or Secretions of microbes in Blood)
Rh basedDisorders:
After the ABO system, the Rh (Rhesus) blood group systemis regarded as the
second most important blood group system, as some of the severe hemolytic

6. transfusion reactions and most hemolytic diseaseof the fetus and
newborn (HDFN) cases areassociated with antibodies to the Rh group antigens.
Two separategenes for the Rh systemare found on chromosome1. Onegene,
RHD, encodes for the D antigen. Individuals with the D antigen presenton their
red blood cells are labeled as "Rh (D)–positive." Thosewho do not have the D
antigen are labeled as "Rh (D)–negative."
The frequency of "Rh-negative" individuals varies among different ethnic groups,
largely becauseof the different molecular mechanisms that causethe absent
expression of the D antigen. For example, Mechanisms of Rh-negativity in
theethnic groups may include gene deletion, gene rearrangement, gene
duplication, and gene mutation .
Rh Disease:
Hemolyticdiseaseof newborn:
What is Rh disease?
Rh disease occurs during pregnancy when there is an incompatibility between the
blood types of the mother and baby.Ito ccurs in new born but linked tomother
because of AB transfer.
What causes Rh disease?
Rh factors are genetically determined. A baby may havethe blood type and Rh
factor of either parent, or a combination of both parents. Rh factors follow a
common pattern of genetic inheritance. The Rh positive gene is dominant
(stronger) and even when paired with an Rh negative gene, the positive gene
takes over. For example:
If a person has the genes + +, the Rh factor in the blood will be positive.
If a person has the genes + -, the Rh factor will be positive.
If a person has the genes - -, the Rh factor will be negative.
A baby receives one gene from the father and one fromthe mother.
If a father's Rh factor genes are + +, and the mother's are + +, the baby will have
one + fromthe father and one + gene fromthe mother. The baby will be + + Rh
positive.
If a father's Rh factor genes are + +, and the mother's are - -, the baby will have
one + fromthe father and one - gene fromthe mother. The baby will be + - Rh
positive.

7. If the father's genes are + - Rh positive, and the mother's are + - Rh positive, the
baby can be:
+ + Rh positive
+ - Rh positive
- - Rh negative
If the father's genes are - -, and the mother's are + -, the baby can be:
+ - Rh positive
- - Rh negative
If the father's genes are - -, and the mother's are - -, the baby will be:
- - Rh negative
Problems with the Rh factor occur only when the mother's Rh factor is negative
and the baby's is positive.
Reticulocyte:
PrematureRBC’s.
Retics:
RbC’s with nucleus in baby.
At birth Reticulocyte rate is high in new born.
Retics Stain:
After 1stpregnancy testis performed for mother, to identify the retics delivered,
between 50-100% is safe, if exceeds than dangerous.
No. of Reticulocyte in blood/Total amount if cells
1stpregnancy:
Mother will be safeafter small diseases like jaundice & fever etc.
1stpregnancy is safe.
2ndPregnancy:
Itis disaster because now Ab will destroy the baby. i.e, baby Rh-, Ab Rh +
Diseases during 2ndpregnancy can be:
A mother has no physicalsigns of Rh disease, but her Rh positive baby can have
problems if the mother has developed antibodies.
Hydrops Fetalis
Anemia
Heart Disease
Lung Destruction
Myopathy

8. Anemia:
Heart beat will be fast called ‘Tachycardia’. Heartsupply is direct. Blood deficiency
occurs becauseheart needs more work & there are more heartbeats which
effects lung and heart de-shape ‘Myopathy’.
O-supply willbe problematic.
Low blood pressureand expulsion of water. In periphery, water expels and
protein remains inside called ‘edema’. Causeswelling becauseof low and direct
filtration of glomerulus/kidney.
Baby swells and cause organ failure. ‘Intrauterinedeath’.
If baby is timely delivered, mother is safe. Otherwisecauses ‘Toxemia’ if dead
body is under womb for 1-2 days.
Hydrops fetalis
Hydrops fetalis is a serious condition. Itoccurs when abnormal amounts of fluid
buildup in two or more body areas of a fetus or newborn. Itis a symptomof
underlying problems.
Derived from Hydro (Baby filled with water). Prematurebirth symptoms butit can
be cured after causeswelling, it is rare in 2000 babies, if problemstarts in 1stby
chance then in 2 ndpregnancy wedeliver Du Ag. (Immunoglobulin) to safethe
pregnancy.
Hemolytic Anemia- Pathophysiology:
In a healthy person, a red blood cell survives 90 to 120 days in the circulation, so
about 1% of human red blood cells break down each day. The spleen (part of the
reticulo-endothelial system) is the main organ that removes old and damaged
RBCs fromthe circulation. In healthy individuals, the breakdown and removalof
RBCs fromthe circulation is matched by the production of new RBCs in the bone
marrow.
In conditions where the rate of RBC breakdown is increased, the body initially
compensates by producing more RBCs; however, breakdown of RBCs can exceed
the rate that the body can make RBCs, and so anemia can develop. Bilirubin, a
breakdown productof hemoglobin, can accumulate in the blood,
causing jaundice, and be excreted in the urine causing the urineto become a dark
brown color.

9. In general, hemolytic anemia occurs as a modification of the RBC life cycle. That
is, instead of being collected at the end of its useful life and disposed of normally,
the RBC disintegrates in a manner allowing free iron-containing molecules to
reach the blood. Itis perhaps then helpful to understand the physiology of the
RBC and things that can go wrong to causeit to "die" prematurely.
The distinguishing feature of intravascular hemolysis is the release of RBC
contents into the blood stream. The metabolism and elimination of these
products, largely iron-containing compounds capable of doing damage
through Fenton reactions, is an important partof the condition. The heme is
ultimately converted to bilirubin and removed in stool and urine. Hemoglobin
may be cleared directly by the kidneys resulting in fastclearance of free
hemoglobin but causing the continued loss of hemosiderin loaded renal tubular
cells for many days.
Intrinsic causes:
Hereditary (inherited) hemolytic anemia can be due to:
Defects of red blood cell membrane production (as in hereditary
spherocytosis and hereditary elliptocytosis)
Defects in hemoglobin production (as in thalassemia, sickle-cell
diseaseand congenital dyserythropoietic anemia)
Defective red cell metabolism (as in glucose-6-phosphatedehydrogenase
deficiency and pyruvatekinasedeficiency)
Extrinsic causes:
Acquired hemolytic anemia may be caused by immune-mediated causes, drugs
and other miscellaneous causes.
Any of the causes of hypersplenism (increased activity of the spleen), such
as portal hypertension.
Acquired hemolytic anemia is also encountered in burns and as a resultof certain
infections.
Lead poisoning resulting fromthe environmentcauses non-immunehemolytic
anemia.
Low-gradehemolytic anemia occurs in 70% of prosthetic heart valverecipients,
and severehemolytic anemia occurs in 3%.
Treatment:

10. Definitive therapy depends on the cause:
Symptomatic treatment can be given by blood transfusion, if there is marked
anemia.
In severeimmune-related hemolytic anemia, steroid therapy is sometimes
necessary.
Sometimes splenectomy can be helpful whereextravascular hemolysis,
or hereditary spherocytosis, is predominant(i.e., mostof the red blood cells are
being removed by the spleen).
Cross matching:
Testing of RBC’s of recipient againstthe serumof donor to identify previously
unreacted antibodies which can destroy the cells of recipient.
Plasma can’t be taken because of excess amount of proteins in it.
Saline phase:(0.9% NaCl) – Isotonic Environment
Dilute blood, centrifuge, shakethen false coating of antigen or blood groups is
released.
Complete Ab detection.
(Side armalpha-helix of antibodies across thestructureare complete)
Albuminphase:
Adjuvant(Binding or bridging) of recipient RBC’s & donor’s serum.
Intermittent step which works for binding of Ab & Ab (Less than 1ml Ab should be
present).
Bovine Albumin is used 22%.
Coombs test:
Coombs reagent is added. Also known as ‘Anti-Human Anti-Globulins’. LISS (Low
ionic strength sol.) is an alternative.
Detects the incomplete Ab.
Result:
RBC shrinkage
Clumping
Rolex Formation
Cold antibodies Induction:
Below 34’c.
Warm antibodies Induction:
No temperature based induction.
Compliment fixation.
More dangerous of the two is warmantibodies induction. Onceinduced, it can’t
be stopped.

11. Only 2 Antibodies are enough to rupture a cell.
Hematology or Clinical Immunology:
Itis the branch of medicine concerned with the study, diagnosis, treatment, and
prevention of diseases related to the blood.
Autoimmune Disorders:
Diseasein which our immune systemreacts againstour own cells, causing
pathological effects.
WarmAb
Cold Ab
WarmAb:(68% disorder causes)
Idiopathic:
When we don’tknow the causeit is ‘Idiopathic’.
Secondary:
CLL: (Chronic Lymphocytic Leukemia)– Cancer of Lymphocytes
Itis a lymphocytic disorder, they loses their capability & generate misleading or
fake Ag. Itis a disease due to the consequences of primary disease.
Lymphoma:
Disorder of lymphocytes associated with lymph nodes.
Disseminated Lupus Erythematosus:
Disseminated disease after viralinfection.
OvarianTumor:
Tumor of Ovaries.
Cold Ab: (16% disorder causes)
Cold Heme AgglutinationDisease:
Cold Agglutination combines with red cell Ag and cells become sanitized with
complement (C3 & C4). When Red cells return to circulation at 37oCAb dissociate
but red cells are damaged by complement components and cell lysis occurs or
complement coated red cells are removed.
Transitory Hemolytic Anemia due to pneumonia & Mycoplasma:
Patient with this disorder areoften elderly with mild to moderate H.A. When
diseaseis going away and induce another problem. When infection finishes it
induce Ab.
Infectious Mono-nuclease:
Consequenceof Cytomegalovirus.
Some others are;
DCT –ve H.A: (Hemolytic Anemia)
Direct Coombs test negative Hemolytic Anemia.

12. Drug InducedAIHA (Autoimmune Hemolytic Anemia):
In somecases, a drug can cause the immune systemto mistakenly think the
body's own red blood cells are dangerous, foreign substances. Antibodies then
develop against the red blood cells.
Autoimmune hemolytic anemia:
A disorder causing lysis of own blood and ultimately deficiency of blood or leading
to anemia.
Autoimmune hemolytic anemia (AIHA)occurswhen antibodies directed against
the person's own red blood cells (RBCs) cause them to burst(lyse), leading to
insufficient plasma concentration. The lifetime of the RBCs is reduced fromthe
normal 100–120 days to justa few days in serious cases. Theintracellular
components of the RBCs are released into the circulating blood and into tissues,
leading to someof the characteristic symptoms of this condition. The antibodies
are usually directed against high-incidence antigens, therefore they also
commonly act on allogenic RBCs (RBCs originating fromoutside the person
themselves, e.g. in the caseof a blood transfusion)
AIHA can be caused by a number of different classes of antibody,
with IgG and IgMantibodies being the main causativeclasses.
Treatment:
Corticosteroids.
Ab for cold H.A: Donath Landsteiner Ab. (Ab with Kappa-arm).
Indirect DonathLandsteiner Test:
No Transfusion
Positive Coombs Test
HLA (Human Leukocyte Antigens):
HLA also known as tissue or transplantation antigens are glycoproteins in nature
that are present on the membranes of most nucleated cells and platelets. Acute
rejection of foreign tissues is controlled by a small chromosomalregion in which
numerous genes which controls immune reactions are found. This region on
chromosomeno. 6 in man is known as ‘MHC’.
The antigens of HLA are genetically determined and each chromosomeno. 6
possess 5 closely linked genes termed as A, B, C, D and DR. Each of the loci is
associated with series of alleles and information contained by one chromosome
originates fromone parent and 2ndhomologous chromosomecomes from2
ndparent. Therefore, there are 4 different genes combinations possible.
HLA & MHC difference:

13. HLA & MHC is basically samething, HLA is conventional name and MHCis recent
one. The main differencebetween the two groups is that MHCis often found in
vertebrates while HLA is found only in humans. To simplify, HLA is the human
body’s version of MHC. Part of the responsibility of these antigens is to
detect cells entering the body. They are found in all nucleated cells.
The major histocompatibility complex (MHC) is a set of cell surfacemolecules
encoded by a large gene family which controls a major part of the immune
system in all vertebrates. The major function of MHCs is to bind to peptide
fragments derived from pathogens and display them on the cell surfacefor
recognition by the appropriateT-cells. MHC molecules mediate interactions
of leukocytes, also called white blood cells (WBCs), which are immune cells, with
other leukocytes or with body cells. The MHC determines compatibility of donors
for organ transplant, as well as one's susceptibility to an autoimmune disease via
cross-reacting immunization. In humans, theMHC is also called the human
leukocyte antigen (HLA).
AB, AC, AD, BB, BC, BD together gives 6 MHC when Dr and Drw comes then HLA
forms sameas MHC.
Transplant:
RBC Maturation:
Blood frombone marrow comes in transition phasein blood, Most of the white
cells mature and comes fromblood.
90% Maturation of RBC’s takes place in Bone Marrow
10% Maturation in Blood.
Though RBC’s doesn’thave any nucleus else than their Formation or maturation
phasei.e, during Erythropoiesis.
Erythropoiesis:
In Bone marrow, RBC’s aresimilar to WBC’s. Thereare about 6 stages of
maturation in which internal lining shrinksand DNA is extracted .
The phase in which the fragment of DNA is seen in the cell is known as
‘Reticulocyte’.
Reticulocyte normally stain for blood are not visible, only 2% arenormal.
Hypoxia:Deficiency of o in blood.
Nephropathy: Nephrons stop functioning.
Threshold Level:Level of any molecule in kidney that is tolerable to our body and
is re quired for normalfunctionality. i.e,

14. Glucose=180g/dl, if exceeds than it will be excreted.
Same is the case with Na+=5.5and K +=1.8.
Disturbancein Levels:
Non-protein nitrogenous compound containing urea which is byproductof
ammonia. Ammonia is volatile substanceand is dangerous becauseour blood
may cross thebrain barrier. Only selective molecules can cross the barrier of
brain.
Basically there is no blood supply directly in brain but can be disturbed with high
conc. Of ammonia and the patient will be in coma.Samecase is with Glucoseconc.
As compared to adults, children have partially developed barrier, and molecules
mayeasily pass and cause disease.
In caseof Na and K level, if exceeds leads to continuous vomiting till death.
There are various glands on our kidney, through which glucocorticoids are
secreted.
Glucocorticoids:Thereare the hormones that maintain glucoseas well as Na and K
metabolism. They give signalto our brain.
Erythropoietin:Signals RBC production.
Cyclosporine:Evolved from cyclospora, a naturalcompound in fungus, it releases
in our tissues and HLA on our cells block. If MHCwill not give signal, immune
systemwill not be activated.
Complications:
Bone marrow transplanthave so many complications, kidney transplantis
relatively simple procedure.
Types of Blood cancer in which Transplantis needed:
Acute Lymphocytic Leukemia
Chronic Lymphocytic Leukemia
Recurrent Lymphocytic Leukemia in Children
Hodgkin Lymphoma (Hairy Cell Leukemia)
Myelocytic Leukemia (DNA Alter)
In all these conditions,
Alternation on DNA occurs, Apoptosis stops, Cells becomeimmortal (Not normal
cell death). Then Bone marrow is transplanted.
The problem is bone marrow is already faulty, we can’t replace the whole bone
marrow.

15. Bone marrow is reddish thick blood and is presentonly in long bones (Radius &
ulna).
To get rid of all the problems we eradicate the bone marrow by radiation, cells
become non-functional.
HLA typing of donor is matched and importance is siblings.
If HLA typing is not matched, doctors suggestfor moresiblings as sacrificeto
achieve HLA matching.
Blood cancer once cured, against formin 3 to 5 years may be its form changes to
lung cancer etc. becauseof mutated DNA.
10-15mlof bone marrow is taken fromidentical sibling and insertthrough vein,
they settle and producenew cells for patient life (only 1 year of extra life).
HLA paternity test haveaccuracy of 80% for 100% surety DNA testis performed.
Paternity Test:
Paternity test determines the 80% matching or HLA compatibility among the
patient and parents or siblings. There are 25% chances of same allele
arrangementpresent in the siblings. Hence, 85% chances of successfultransplant.
Futurediseases are predicted.
Cord blood of newly born baby is taken and froze(Cryopreserved) and
manipulated in lab, which is again transferred to the patient as bone marrow and
life span increases 3-5 years.
Futurediseases HLA types Prediction:
Alleles for Minor rejection of Transplant:
(Rodger, Bf, C2, 4, 8) these are presentin all the cells and decreases the minor
rejection chances.
MicrolymphocytotoxicityTest:
Microlymphocytotoxicity testing is used to detect class I MHCantigens in order to
"match" as many class I antigens between the donor and recipient as possible.
When 2 people sharethe sameHLAs, they are said to "match." In other words,
their tissues are immunologically compatible with each other.
Ankylosing Spondilitis:
HLA Type:B27 Chances: 96%
Deformation of joints, immature growth.
Hodgkin’s lymphoma:
HLA Type:BW35 Chances: 33%

16. Bone marrow transplantis required in case of cancerous patient, if child is not
affected by cancerous preservecord blood or bone marrow, thereis probability of
developing cancer.
Gluten Enteropathy:
HLA Type:B8 Chances: 88%
Gluten is present in wheat, it is suggested that upto 1 year no wheatshould be
given to child.
Allergic reactions starts in the intestinal tract, if there would be intake of wheat,
cell bursts and intestinal walls shrinks, becomes non-functional. Unableto digest
anything, Continuous vomiting, diarrhea.
Systemic lupus Erythematosus(SLE) :
HLA Type:BW15 Chances: 46%
All joints stiffs.
Insulin IndependentDiabetes Mellitus (IDDM):
HLA Type:DRW3 Chances: Very strong
Common disease, DRW3 expression presencein body confirms this disease.
Autoimmune Hemolytic Anemia (AIHA):
HLA Type:DRW2 & 3 Chances: 75%
A disorder causing lysis of own blood and ultimately deficiency of blood or leading
to anemia.