Introduction to immunology and serology |

What is Immunology? 1885 – Louis Pasteur

• Is defined as resistance to disease, specifically infectious disease.  Therapeutic vaccination; First report of live “attenuated” vaccine for rabies
• The study of a host’s reactions when foreign substances are introduced into the body. Consists of the  there are multiple doses when given Anti-rabies vaccination
following:
 The study of the molecules, cells, organs, and systems responsible for the recognition and 1890 – Emil von Behring & Shibasaburo Kitasato
disposal of foreign materials  Humoral Theory of Immunity
 How body components respond and interact  certain serum protein coats antibody production ??
 The desirable and undesirable consequences of immune interactions  humor – fluid
- desirable consequences is when a person is healthy and can fight off infections whereas for
undesirable consequences is when it attacks our own cells such as autoimmune reactions 1891 – Robert Koch  Demonstration of Cutaneous (delayed-type) Hypersensitivity
 The ways in which the immune system can be advantageously manipulated to protect or treat
disease 1900 – Paul Ehrlich  Antibody Formation Theory
- the understanding of how the immune system works, led us to the understanding and
availability of the vaccines 1902 – Charles Richet & Paul Portier  Hypersentivitiy Anaphylaxis

What is Serology? 1903 – Maurice Arthus  Arthus Reaction of Intermediate Hypersensitivity

• Is the study of blood serum
- although serology is the study of the blood serum, it is not limited to serum. Human secretions 1944 – Hypothesis of Allograft Rejection
can also be applied such as: whole blood and plasma samples
• Serology/serologic test – tests that look for the presence of antibodies in the blood. This is applied 1949 – Jonas Salk & Albert Sabin  Development of Polio Vaccine
when studying a blood serum
- such as kits or rapid kits which are tests that look for antibodies in the blood
1951 – Walter Reed  Yellow Vaccine
1953 – Graft – versus – Host reaction
Vaccines 1957 – Macfarlane Burnet  Clonal Selection theory
• can be inactivated or attenuated. 1958 – 1962 Human Leukocyte Antigens
• Attenuated – actual virus but weakened. Attenuated vaccines give more immunity to the body
compared to inactivated vaccines 1964 – 1968 T-cell and B-cell cooperation in immune response
• Inactivated – virus are killed 1972 – Identification of antibody molecule
1975 – Georges J.F. Kohler  First monoclonal antibodies
1978 – Edward Jenner
 Smallpox vaccination 1985-1987 – Identification of genes for T cell receptor
 instead of using the actual smallpox virus for the vaccine, he used Cowpox because as he 1986 – Monoclonal hepatitis B vaccine
experimented in infected cows with cowpox virus, he discovered that they are not affected with 1986 – Tim Mosmann  Th1 versus Th2 model of the T helper cell function
smallpox virus 1996 – 1998: Identification of toll-like helper cell function
1880-1881 – Louis Pasteur 2001 – FOXP3, the gene directing regulatory T cell development
 Live, attenuated chicken cholera and anthrax vaccines 2005 – Ian Frazer  Development of human papillomavirus vaccine
1883-1905 – Ellie Metchnikoff
 Cellular Theory of immunity through phagocytosis
 he observed that a cell can engulf another cell = Cellular Immunity
 he proposed that the main component of an Immune System are cells

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Adaptive Defense Mechanism

 is specific and has memory

 it needs to be “primed” or a first exposure through the action of macrophages then small
amount of antibodies and memory cell will be produced against an antigen
 the next time that the body meets the same antigen or pathogen, the body will automatically
recognize that antigen or pathogen
 since an antibody has already been made against that antigen or pathogen through the
memory cells, they will then be specific to that certain pathogen or automatically recognize it
 memory cells will proliferate or rise then become plasma cells and some will become memory
cells that will produce antibodies specific to that pathogen making the immune reaction faster
and quicker in fighting off that same antigen or pathogen

Primary Lymphoid Organs

 Bone Marrow
 The main source of hematopoietic stem cells, which develops
into erythrocytes, granulocytes, monocytes, platelets, and
lymphocytes
 Functions as the center for antigen-independent lymphopoiesis
 at this point, lymphocytes are not exposed to certain antigens
they will be exposed once they move into secondary lymphoid
organs
 other organs as a source of hematopoiesis other than BM like
Innate Defense Mechanism spleen
 Where B – cell maturation takes place
 is nonspecific or natural means we are born with it and has immediate reaction
- it is called “B-cell” because they develop in the Bone
 if it recognizes a pathogen, it automatically attacks
marrow
 can be divided into two: First Line of Defense and Second Line of Defense
 Thymus
 First Line of Defense  Where T cells develop their identifying characteristics
 basically the physical barriers of the body; skin, mucous membranes, etc  this the last place where the T cells are eliminated
 once the physical barrier/s is breached, the second line of defense comes in to play  Has thymic lobules, each containing an outer cortex and an inner medulla.
 Most thymic cells are lymphocytes which are densely packed in the cortical regions with a few
 Second Line of Defense macrophages scattered among them
 basically phagocytes but the role of these cells are not only limited to the innate defense
mechanism Secondary Lymphoid Organs
 macrophages are antigen presenting cells. They will be the one to process the antigen that it
met then present it to the lymphocytes (T cells and B cells). From there, the adaptive immune  Spleen
system then decides on what to do to that certain antigen  Removes old and damaged cells and foreign antigens from the blood (graveyard if RBCs)
 Provides a site for lymphocyte proliferation and immune surveillance and response
- after the maturation of lymphocytes in the bone marrow and thymus, they will migrate to
otherareas or lymphoid organs such as the spleen which is where there is a higher chance
for them to meet antigens
- they have to meet antigens inorder for them to proliferate or para dili sila mamatay

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- if they are unable to meet antigens, they will have a specific lifespan then will undergo  Tonsils
apoptosis , but during infection, they will have a longer lifespan  Contains follicles with obvious germinal centers
surrounded by diffusely scattered lymphocytes.
 Stores some of the breakdown products of RBCs for later use  The tonsillar crypts trap bacteria and particular
 Stores blood platelets and monocytes for release into the blood when needed matter
- if there is a severe decrease of platelets, spleen can release the platelets stored in it - that’s why tonsilitis will occur if a person is severly
 Composition: infected

o White pulp – contains the lymphoid tissue, which is  Peyer’s Patches / Aggregated Lymphoid
arranged around arterioles in a periarteriolar Nodules
lymphoid sheath (PALS). This sheath contains mainly  Located in the wall of the distal portion of the small
T cells. Attached to the sheath are primary follicles, intestine and are structurally similar to the tonsils
which contain B cells that are not yet stimulated by - areas where a posible entry of pathogens will take
antigen place like the intestines where parasites mostly
take place. That’s when Peyer’s Patches will
- most important for lymphocytes help fight off those parasites

 Appendix
o Red pulp – where worn-out RBCs and bloodborne
 Contains high concentration of lymphoid follicles.
pathogens are destroyed
- intracellular pathogens that are carried by RBCs are destroyed such as: Dengue Fever,  It is an ideal position
Malaria, Plasmodium 1. to destroy bacteria before these pathogens can breach the intestinal wall, and
2. to generate many “memory” lymphocytes for long term immunity
- there are many B-cells in this area since it is able to generate many memory cells for long term
 Lymph Nodes immunity
 Serve as central collecting points for
lymph fluid from adjacent tissues.
 The lymph fluid flows slowly through
spaces called sinuses, which are lined
First Line of Defense
with macrophages
- if there are pathogens carried together 1. Protective Secretions
with lymph fluid then the  Sebum and Lactic Acid
macrophages are ready to - sebum is produced by sebaceous gland that lines
phagocytose them because they are and protects mucous membranes and
found in the lining epithelial cells so that the pathogens cannot
directly penetrate that area
 The tissue is organized into an outer
cortex, a paracortex, and an inner medulla  Hydrochloric acid and protein-digesting enzymes of the stomach mucosa
- The cortex contains macrophages and - incase there are pathogens that are ingested = HCl digests that
aggregations of resting B cells in
 Saliva and Lacrimal Fluid
primary follicles.
- contains digestive enzymes
- Secondary follicles consist of antigen-stimulated proliferating B cells
 Mucin, Cerumin – mucin, cerumen and defensins help in protecting mucous membranes and skin
- B cells will not automatically proliferate to become plasma cells and memory cells, it must
 Defensins
be exposed to an antigen or pathogen to stimulate it to become plasma and memory cells
then if it is exposed, antibodies will then be produced
- The germinal center of the secondary follicles is where the blast transformation of the B cells
takes place
- T lymphocytes are mainly localized in the paracortex

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2. Structural Modifications  Toll-like Receptors – found on human leukocyte and some nonleukocytes cell types and the highest
 Mucous-coated vibrissae/ hair of the nasal cavity concentration occurs on monocytes, macrophages, and neutrophils
- it helps in entrapping inhaled pathogens so that it won’t go directly to the lungs or bronchial - not a cell. It is important mediators of inflammatory pathways in the gut which play a major
tree. It will be trapped through the hairs of the nasal cavity role in mediating the immune responses towards a wide variety of pathogen-derived
 Cilia of the respiratory mucosa ligands and link adaptive immunity with the innate immunity.
- cilia – those that are trapped in the nasal cavity or respiratory area will be pushed out of the
- helps in the recognition of pathogens
body through the reflex reactions of the body by coughing or sneezing when there are
- there is also another receptor found in WBCs other than TLRs. The Pathogen Recognition
foreign substances inside
- cilia doesn’t move but it propels foreign substances Receptors – they are proteins capable of recognizing molecules frequently found in
 Keratinization of the upper layer of the skin and its constant repair pathogens (the so-called Pathogen-Associated Molecular Patterns—PAMPs), or molecules
- if there are pathogens, it will shed off the pathogens released by damaged cells (the Damage-Associated Molecular Patterns—DAMPs)

3. Normal Flora  Acute-Phase Reactants

- normal flora are natural bacterias of the body. For example, Lactobacillus sp. for the girls that  Are normal serum constituents that increase rapidly by at least 25% due to infection, injury, or
will help the pH of balance of the vaginal area (= acidic.) If it is disturbed, it can lead to trauma to the tissues.
overgrowth of other opportunistic pathogens. If it is absent, the pH will be alkaline which  Enhances phagocytosis
promotes the growth of other pathogens leading to vaginosis.  Produced by the hepatocytes in response to increase cytokines (interleukin - 1β (IL-1β), interleukin-
- normal flora are territorial in nature, they don’t want the presence of other bacteria in the 6 (IL-6), and tumor necrosis factor – alpha (TNF-α)
area. It will mean that their nutrients from the host will lessen that’s why it is their job to
“shoo them away”
Protein Response Normal Increase Function
Time Conc.
Second Line of Defense (mg/dL)
C-Reactive Protein 6-10 0.5 1000x Opsonization, complement activation
 Cellular Components Nonspecific - CRP is tested and increased during inflammation
Increased regardless of the
cause of inflammation
Serum Amyloid A 24 3.0 1000x Removes cholesterol
- has high affinity to HDL; transports HDL
Alpha1-Antitrypsin 24 200-400 2.5x Protease Inhibitor
- most protease are digestive enzymes. That’s
- Neutrophils increases in acute infection and bacterial infections. They are the first one to why if it will have an uncontrolled reaction, it will
respond in acute infection cause tissue damage. To counter these proteases
- Eosinophils are non-phagocytic. They increase in parasitic infection. Their granules contain and Alpha1-Antitrypsin also increases & will take
release digestive enzymes if there are parasites action
- Basophils produce histamine during allergic reactions along with the mast cells Fibrinogen 24 110-400 2.5x Clot formation
- Monocyte’s distinguished character is its vacuoles Haptoglobin 24 40-200 2-10x Binds hemoglobin
- Macrophage is the activated version of monocytes. If there are no pathogens or any foreign - haptoglobin binds free hemoglobin because it
substance, then it will not progress into macrophage. causes oxidative reactions that causes tissue
- Mast cells looks like basophils however, it is bigger and more granulated than basophils. It also damage
produces histamine. Ceruloplasmin 48-72 20-40 2x Binds Copper and oxidizes Iron
Complement C3 48-72 60-140 2x Opsonization & lysis
- complements and antibodies usually make
 Mast cells – plays a role in the hypersensitivity reactions binding IgE similar to basophils
the opsonization process
Mannose-binding ? 0.15-1.0 ? Complement Activation
 Dendritic Cells – main function is to phagocytose antigen and present it to the helper T cells protein
- it has longer pseudopods or false-feet that will catch the pathogens easier

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 Inflammation
 Prevents the spread of damaging agents to nearby tissues – it contains to that area
 Disposes of cell debris and pathogens
 Alerts the adaptive immune system
 Sets the stage for repair or healing
- the main reason for inflammation is to help lead the neutrophils and macrophages to the area
of injury or infection
- increase of metabolic rate will lead to healing

Cardinal Signs of Inflammation

 Calor – heat
- local increase in temperature which also increase in metabolic rates because of the leukocyte
inducing factor which leads the neutrophils and macrophage to the area of injury which will
phagocytose the infecting agents
 Rubor – redness
 Tumor – swelling
 Dolor – pain
 Functio laesa – temporary or permanent loss of function
- when the arterioles are dilated during inflammation, there will be local hyperemia or increase
of blood flow to the area which will lead to the cardinal signs of inflammation

PHAGOCYTE MOBILIZATION
Major Events:
a. Leukocytosis –injured cells release chemicals called leukocytosis-inducing factors
- during tissue injury, the body will produce the release of certain inflammatory chemicals and
- with LIF, it will attract the release of neutrophils and macrophages to the site
leukocytosis inducing factors.
b. Margination – refers to this phenomenon of phagocytosis when phagocytes clings to the inner walls
- Inflammatory chemicals – Ex: histamine and complement. These will lead to three reactions.
of the capillaries and postcapillary venules.
1. Dilation of arterioles
c. Diapedesis – continued chemical signaling
2. Increase capillary permeability
prompts the neutrophils to flatten and
3. Attraction of Neutrophils to the area of injury
squeeze between the endothelial cells of the
- since the arterioles are dilated it will cause:
capillary walls
d. Chemotaxis – neutrophils and other WBCs
1. Increased blood supply to the infected area
migrate up the gradient of chemotactic agents
2. Increased capillary permeability caused by retraction of endothelial cells lining the vessels
to the site of injury
- helps to mobilize the neutrophils to the area of infection or injury hence, they will move faster
- chemotactic or pro-inflammatory
- increase capillary permeability will lead to capillary leakage which also leads to the cardinal
chemicals will lead neutrophils and
signs of inflammation because the nerves will compress therefore, it will lead to temporary
macrophages to the area of infection.
loss of function because of pain and swelling
That’s why inflammation will only have
3. Migration of white blood cells from capillaries to the surrounding tissue
localized effects
- phagocytic mobilization
4. Migration of macrophages to the injured area
- due to the presence of the leukocyte inducing factors and other inflammatory chemicals like
macrophages and other WBCs will be led to the area of injury
- Neutrophils are the first ones to react then the macrophage then acute phase reactants will
stimulate phagocytosis of the microorganisms that are present in the area of injury

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 Phagocytosis
 Opsonins are serum proteins that attach to a foreign substance and help
prepare it for phagocytosis
- opsonins can be antibodies or complement Third Line of Defense
- sometimes opsonins are not present but mostly, naa jud na siya
hehe  3 Important Aspects:
- it will be easier for phagocytes to engulf foreign substances o It is Specific
because of the attachment of opsonins to them - it can launch a specific immune response to a specific
- the coating of opsonins to the pathogen is known as opsonization antigen
- opsonins serve as the markers for phagocytes that will then adhere to pathogens and make it o It is Systemic
faster and easier to engulf the pathogens = phagocytosis o It has “Memory”
- once it will adhere to pathogens, it will form pseudopods. These pseudopods will engulf the - it can remember the pathogen during the first exposure then in the second exposure, it can
particles forming the phagosome (phagocyte + pathogen = phagosome) the phagosome launch an immediate attack
will now contain the pathogen o it can be divided into two:
- Macrophages contain the lysosomes that contains digestive enzymes
- Lysosome and Phagosome will bind releasing the contents of the lysosome into the phagosome
= Phagolysosome. When the contents of
the lysosome will release into the  Humoral Immunity or Antibody-Mediated Immunity
phagosome, it will be digested - B cells – major player since we need antibody production
 When pathogens cannot be digested with
o Is provided by antibodies present in the body’s “humors”, or fluids
lysosomal enzymes, helper T cells activate
- antibodies are present in the body fluid like serum, plasma and other body secretions
(macrophages) enzymes that produce a lethal
o Antibodies circulate freely in the blood and lymph, where they bind primarily to extracellular
respiratory burst which promotes killing of
targets, inactivating them temporarily and marking them for destruction by phagocytes or
pathogens by:
complement
o Liberating a deluge of highly destructive
- “marking” – basically opsonization or coating
free radicals
o Producing oxidizing chemicals
o Increasing the phagolysosome’s pH and
osmolarity  Cellular or Cell-mediated Immunity
- this is where T lymphocytes play its role
 Antimicrobial Proteins - virus infected, parasitic infected or foreign grafts (Graft-versus-Host Transplantation during
 Interferons (IFN) transplantation)
 These are proteins that are released by virus-infected cells to signal and help protect cells that - Graft – organ transplanted to the recipient. If the recipient’s body recognizes the organ to be
have not yet been infected foreign = Graft-v-Host Transplantation
 IFN alpha and beta have antiviral effects and activate NK cells.
 IFN gamma, or immune interferon, is secreted by lymphocytes and has widespread immune o Lymphocytes act against the targets either directly, by killing the infected cells, or indirectly, by
mobilizing effects such as activating macrophages releasing chemicals that enhance the inflammatory response or activate other lymphocytes or
macrophages
 Complement - Cytotoxic T Cells – can kill directly
 Provides a major mechanism in destroying foreign substances in the body. Its activation - Helper T cells – kill indirectly by the release of chemicals
unleashes inflammatory chemicals that amplify virtually all aspects of the inflammatory o Has cellular targets – virus-infected or parasite-infected tissue cells, cancer cells, and cells of
process. foreign grafts.
 Activated complements also lyses and kills certain bacteria and other cell types
- helps in the opsonization process and induces inflammatory response

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Lymphocytes Surface Markers on Lymphocytes
Development, Maturation, and Activation - morphologically, we cannot differentiate B-cells and T-cells
- B lymphocytes will undergo different process but has the same origin with T lymphocytes in the
Bone Marrow  used as markers to differentiate T cell and B cells
- their maturation process will differ  used to distinguish the developmental stages of the two types of cells according to when these
o B-cells – Bone Marrow proteins appear
o T-cells – migrate to the Thymus - we will know what type of B cell is present if they posses this certain surface marker
- one of the most important surface markers is the clusters of differentiation or CD Markers
1. Origin
Antigen Cell Type (found in) Function
2. Maturation CD2 Thymocytes, T cells, NK cells Involved in T-cell differentiation
 Immunocompetence – each lymphocyte must be able to recognize its one specific antigen by
binding to it CD4 Helper T cells, monocytes, macrophages Coreceptor for MHC Class II; Receptor for
- if it cannot recognize then it will undergo apoptosis HIV
 Self-tolerance – each lymphocyte must be relatively unresponsive to self-antigens so that it does CD8 Thymocyte subsets, cytotoxic T cells Coreceptor for MHC Class I
not attack the body’s own cells CD19 Macrophages, NK cells, neutrophils Part of B cell coreceptor, signal
transduction
- self-tolerance – lymphocytes must be unresponsive to self-antigens
molecule that regulates B-cell
- it must recognize its self-antigens and must be unresponsive because if not, it will cause an
development
immune reaction = autoimmune reactions or the cells attacking each other
CD25 Activated T, B cells, monocytes Receptor for IL-2
CD45R Different forms on all hematopoietic cells Essential in T and B cell antigen-
3. Seeding Secondary Lymphoid Organs and Circulation stimulated
- migrate to secondary lymphoid organs such as lymph nodes, spleen and tonsils to meet activation
antigens/pathogens
CD21 B cells, follicular dendritic cells Receptor for complement component
- they will not bet activated if they won’t meet antigens
C3d; part of B-cell coreceptor with CD19

4. Antigen Encounter and Activation

- in the secondary lymphoid organs, Stages in B-cell Differentiation
then if they meet antigens:  Pro-B Cells

5. Proliferation and Differentiation

- will occur

 Can be recognized by the presence of a surface molecule called CD45R.

 Go through the antigen-independent phase up to the immature B-cells
- occurs in the Bone Marrow
- they will not be exposed to antigens but they will develop antigenic characteristics and these
will be needed by lymphocytes
 Factors necessary to differentiate common lymphoid precursors into pro-B cells:
o E2A o paired box protein 5 (PAX)
o EBF o Interleukin – 7
 Rearrangement of genes that codeofor the heavy and light chains of an antibody molecule happen

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- the antibody production in the Pro-B Cells are not the antibodies that will be released against a  Mature B Cells
certain antigen these antibodies will appear on the surface of pro-b cells which will serve as - they’re already in the secondary lymphoid organs
a receptor for future antigens  Marginal zone B cells  mature B cells in the spleen
- remember that antibodies can work as a receptor aside from it being a substance against an  Follicular B cells  found in lymph nodes and other secondary organs and are constantly
antigen recirculating throughout the secondary lymphoid organs.
- pro-B cells will need to develop receptors which are the immunoglobulin classes to detect  In addition to IgM, all mature B cells exhibit IgD on their surface.
antigens  Life span is only a few days unless contact with antigen occurs
- during pro-B cell stage, there will be a rearrangement of gene that will code for the heavy and  Antigen – dependent phase of B-cell development – because it has already met an antigen
light genes of an antibody molecule
- the heavy and light chains will be rearranged and later in the Pre-B cell stage, it can determine
if either the , ,  will develop  Activated B Cells
o  - IgM  Antigen-dependent activation occurs
o  - IgA when antigens cross-link several
o  - IgD surface immunoglobulins on select B
cells.
 Intracellular proteins found in pro-B cells:  Exhibit identifying markers that include
o Terminal Deoxynucleotide Transferase (TdT) CD25, which act as a receptor for
o Recombination-activating genes RAG-1 and RAG-2 interleukin-2
– which code for enzymes involved in gene rearrangement  Will give rise to both plasma cells and
memory cells
 Pre-B Cells - since they are active, they
 Begins when synthesis of the heavy chain part of the antibody molecule occurs proliferate or give rise
- if the first antibody molecule is IgM in nature on the surface of the B cells = Pre-B cells - remember: B-cells will not
 The first heavy chains synthesized are the μ chains, which belong to the IgM class automatically proliferate to
 May also express μ chain on the cell surface, accompanied by an unusual light chain molecule become plasma and memory
called surrogate light chain. cells unless they have met an antigen to give rise to plasma and memory cells
 The combination of the two heavy chains with
 surrogate light chains + two very short chains, Ig-α/Ig-β = pre-B cell receptor
 Plasma Cells
 Once the pre-B receptor (preBCR) is expressed, neighboring pre-B cells may send signals for  Spherical or ellipsoidal cells between 10-20 um in size
further maturation and stimulates a burst of clonal expansion  Characterized by the presence of abundant cytoplasmic immunoglobulin and little to no surface
immunoglobulins
 Immature B cells  Nucleus: eccentric or oval with dark, heavily clumped chromatin.
 Distinguished by the appearance of complete IgM molecules on the cell surface.  Abundant endoplasmic reticulum and a clear well – defined Golgi zone
 Completion of light chain rearrangement commits a cell to produce an antibody molecule with
specificity for a particular antigen or group of antigens. Variable regions determine the
specificity of the antibody  Memory Cells
- the variable will change depending on the type of antigen therefore it determines the specificity  Represent progeny of antigen-stimulated B cells that are capable of
 Other surface proteins responding to an antigen with increased speed and intensity
o CD21 - memory B-cells will be important in secondary exposure because
o CD40 pro-B cell and pre-B cells are not needed during the secondary exposure
o major histocompatibility complex (MHC) class II molecules - memory cells will automatically give rise to plasma cells and other memory cells
 At this stage, evidence that self-antigens give a negative signal to immature B cells, resulting in
arrested maturation and cell death
- apoptosis

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Immunological Memory Humoral Immunity

Active Immunity
 body is actively producing antibodies
 need to encounter the antigen it could be naturally or artificially
 artificially – immunization, vaccination. Either attenuated, inactivated or mRNA vaccines
- these are still antigens so the body will respond by making antibodies

Passive Immunity
 the antibodies are passed on to the body
Primary Response or Exposure  can either be naturally or artificially acquired
 conception or breastfeeding – a baby cannot produce antibodies in around 0-6 months. They can
Antigen and B cells meet  Activated B cells  proliferate to plasma cells and memory B cells  secrete only produce antibodies during 6 months and above
few Antibody molecule  Lag Phase  artificially acquired passive immunity – ex: rogam, anti-tetanus, prophylaxis for mothers and baby
(since it is the first time in encountering that certain antigen) with different Rh type
- plasma cells and memory cells are known as effector cells of B cells
- antibody production and antibody titer is low Cellular Immunity
 T-Cell Differentiation
Secondary Response or Exposure  Lymphocyte precursors: Thymocytes
The memory B cells that were formed during the primary response will proliferate and will give rise to  Driver of migration: Chemochines
plasma cells and another batch of memory cells. The process from pro-B cells, pre-B cells, Immature B cells - chemochines help migrate thymocytes to migrate
and Activated B cells are not necessary anymore since the memory cells remembered that the body has  Surface markers of thymocytes committed to becoming T cells:
already encountered that certain pathogen. o CD44
o CD25
That’s why after immunization and a person is infected again, the immune reaction will be faster because  Maturation takes place over a 3-week period
the memory B cells are already stored.
 97% of the cortical cells die intrathymically before becoming mature T cells – 3% survive
This time there are more antibodies will be released. Antibody titer is higher than the first exposure. - elimination process for T cells is more vigorous

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Double – Negative Stage  Only 1-3% of the double-positive thymocytes in the cortex survive.
 Early thymocytes lack CD4 and CD8 markers: double-negative thymocytes (DN)
 The large double-negative thymocytes actively proliferate in Mature T cells
the outer cortex under the influence of Interleukin-7  Survivors of selection exhibit only one type of marker, either CD4 or CD8, and they migrate to the
 Rearrangement of the genes for the antigen receptor TCR medulla.
begins at this stage  CD4+ T cells are termed helper or inducer T cells
 CD3 – the complex that serves as the main part of the T-cell - CD4 – Helper T Cells
receptor consists of 8 noncovalently associated chains - CD8 – Cytotoxic T cells
 Alpha () and beta () chains contain variable regions that
recognize specific antigens o CD4+ Classes:
 The combination of β chain with the rest of CD3 forms the pre-  Th1 produce interferon gamma (IFN-) and tumor necrosis factor beta, which protect cells
TCR receptor. against intracellular pathogens
 Signaling by the chain also triggers the thymocyte to become  Th2 cells produce a variety of interleukins (IL-4, IL-5, IL-10, and IL-13). Help B cells produce
CD4-positive (CD4+) and CD-positive (CD8+) antibody against extracellular pathogens
 Thymocytes (10%) express gamma (γ) and delta (δ):
o Remain negative both CD4 and CD8
o Represent the dominant T-cell population in the skin, intestinal
epithelium, and pulmonary epithelium when mature
o May act like Natural Killer cells (NK)
o Capable of recognizing antigens without being
presented by MHC proteins

Double – Positive Stage

 Thymocytes express both CD4 and CD8 antigens
 When CD3 – receptor complex (TCR) is expressed on the
cell surface, a positive selection process takes place.
- positive selection process – all T cells must undergo
and recognize all major MHC proteins or self-
MHC
- if self-MHC is not recognized, it will undergo
apoptosis
- if self-MHC is recognized it will proceed to negative
selection  CD8+ population consists of cytotoxic T cells.
- if self-antigen is recognized = autoimmunity  T regulatory cells (T reg) – possess the CD4 antigen and CD25 and plays an important role in the
immune response to self-antigens.
- Negative Selection – process for T cells to develop  Single positive T cells spend approximately 12 days in the medulla
self-tolerance. T cells must not recognize self- - if there are no antigens = mamatay
antigens because if it will recognize the self-  T cells remain metabolically active through continuous contact with self- peptide / MHC complexes
antigen = apoptosis on APCs and the action of IL-7

 TCR binding transmits a signal that results in the

activation of kinases.
 Negative selection takes place among the surviving double-positive T cells.
 Strong reactions with self-peptides will result to the cell’s apoptosis

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 Introduction to immunology and serology |
 Natural-Killer Cells
Characteristics:
 Larger than either T cells or B cells (15 um in diameter) and contain kidney-shaped nuclei with
condensed chromatin and prominent nucleoli Density Gradient Centrifugation with Ficoll-Hypaque
- whole blood and special tube with Ficoll-Hypaque
 Higher N:C Ratio, and cytoplasm contains a number of azurophilic granules
- Ficoll-Hypaque – help separate mononuclear cells, RBCs, granulocytes, after centrifugation at
 NK cells arise from the common lymphocyte precursor
400 rpm ; 30 mins
 Have a half-life of 7 to 10 days
 Found in the uterus, peripheral blood, the spleen, and the liver

Markers: Flow Cytometry

 CD16 is a receptor for the fragment crystallizable portion, or non-specific end, of the
immunoglobin molecule IgG. The other marker is CD56  Relies on the use of labeled monoclonal antibodies against specific surface antigens
 NK cells with a high level of CD56 and low or no CD16 produce more cytokines and help support  Cell Flow Cytometry – based on the scattering of
antibody production light as cells flow in single file through a laser
 NK cells with some CD56 and high levels of CD16 have a higher cytotoxic activity beam
 Are used to screen Fluorescent antibodies for
Functions: subpopulations
 Have the ability mediate cytolytic reactions and kill target cells without prior exposure to them.
 Capable of recognizing any foreign cell and destroying it without regard to MHC restriction
 May paly a role in maintaining pregnancy because they accumulate at the maternal-fetal
pregnancy.
 Activity is stimulated by exposure to cytokines (IL-12, Interferon-gamma, and IFN-beta)
 Respond early during a viral infection and activity peaks in about 3 days, before antibody Manual Method: Rosette Technique
production or a cytotoxic T cell response.

Mechanism of Cytotoxicity:
 Inhibitory Receptors
o Based on recognition of MHC class I proteins
o Receptors include killer cell immunoglobulin-like-receptor (KIRs), ILT/LIR and CD94 / NKG2A
 Activatory Receptors
o Proteins produced by cells under stress named MICA and MICB activates NK cells
o Receptors called CD94/NKG2C and CD94/NKG2D on NK cells bind MICA or MICB
 Release perforins and granzymes

Antibody-Dependent Cell Cytotoxicity

 Recognition and lysis of antibody-coated cells
 Binding occurs through CD16 receptor for IgG  from a whole blood sample create RBC suspension
 Using a counting chamber, 200 cells are counted and the percent forming rosettes is calculated.
This represents the percentage of T cells, and the percentage of B cells is calculated by
subtracting this number from 100.

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 Introduction to immunology and serology |
5. Acute Phase Reactants are produced by:
- Hepatocytes
Location Substance Recognized Target Microorganism 6. This acute phase reactant counteracts the effects of neutrophil invasion during
Cell surface Lipopeptides Mycobacteria
TLR1 inflammatory response – basically a protease inhibitor
Cell surface Peptidoglycan Gram-Positive Bacteria
TLR2 Lipoproteins Mycobacteria
- Serum Amyloid A
7. Increased capillary permeability leads to the manifestation of what cardinal signs or
Zymosan Yeasts
Endosomal Double-Strandded RNA Rna Viruses inflammation?
TLR3 compartment of a cell - Tumor / Dolor
Cell surface Lipopolysaccharide, Gram-Negative Bacteria 8. Leukocytosis inducing factors are produced by what cells?
TLR4 Fusion Proteins, RSV Fungi - Injured Cells !!
Mannan Flagellin
9. In phagocytosis, the fusion of lysosomes and phagocytic vesicle is known as 
Cell surface Flagellin Bacteria With Flagellae
TLR5 - Phagolysosome
Cell surface Lipopeptides Mycobacteria
TLR6 Lipoteichoic Acid Gram-Positive Bacteria
10. These are proteins that are release by virus-infected cells to help protect cells that have
Zymosan Yeasts not been infected
Endosomal Single-Strandded RNA Rna Viruses - Interferons
TLR7 compartment of a cell 11. A surface marker on lymphocyte that acts as a correceptor for Class I MHC
Endosomal Single-Strandded RNA Rna Viruses - CD8
TLR8 compartment of a cell
12. Antigen-independent phase of B-cell differentiation occurs in what organ?
Endosomal Double-Strandded RNA Dna, Viruses
TLR9 compartment of a cell Bacterial Dna - Bone Marrow
Endosomal Unknown Unknown 13. True or False: The body’s response to antigen B is independent of the response to
TLR10 compartment of a cell antigen A.
- True
14. Thymocytes that lack CD8 and CD4 markers are in what stage of T cell differentiation?
What are Pathogen-Recognition Receptors (PRRs)? Give their importance. (10 pts)
 Toll-like receptors (TLRs) - Double-Negative Stage
 C-type lectin receptors (CLRs 15. T cells must recognize self-MHC is a process called?
 Nucleotide-binding Oligomerization Domain-like Receptors (NLRs) - Positive Selection
 Retinoic Acid-inducible gene-I-like receptors (RLRs)
16. T cells differentiate or matures in what organ?
 AIM2-like receptor (ALR)
- Thymus
- Pathogen recognition receptors (PRRs) are specialized receptors that can identify pathogen- 17. True of False: Inactive humoral immunity the body does not need to be exposed to
associated molecular patterns (PAMPs). These receptors are essential for the initiation of antigen
innate immunity, which is a type of defense that helps protect us from harmful bacteria - False
and viruses
18. Activated B cells proliferate to become:
- Memory Cells and Plasma Cells
19. & 20. What are the surface immunoglobulins found on Mature B-cells?
- IgD and IgM
1. This refers to the diagnostic identification of antibodies in serum
- Serology
2. He pioneered therapeutic vaccination
- Louis Pasteur
3. In the spleen, the T cells are mostly found in what area?
- White Pulp – Periaretiolar Lymphoid Sheath (PALS)
4. The enzyme found in saliva and lacrimal fluid that is destroys cell walls of bacteria
- Lysozyme

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