Chapter #1 IMMUNOLOGY
Word Origin
Derived from the Latin word "Immunis" which means free of burden.
Historical Background
● Immunology was first introduced by Edward Jenner in 1796.
● Jenner discovered a vaccine against smallpox, which induced immunity and helped prevent
smallpox (an often fatal human disease).
● The term Immunology was first coined by the Russian Biologist Ilya Ilyich Mechnikov.
● Mechnikov received the Nobel prize for his work in 1908 along with his colleague Paul Ehrlich.
● Mechnikov is the first discoverer of Phagocytosis.
● Immunology has various applications in the field of medicine, particularly in organ
transplantation, oncology, and rheumatology (Study of Joints).
Definition
● It's a very important branch of medical & biological sciences which deals with the study of the
immune system (i.e., the components of the Immune system).
● OR The study of all pathways of action taken by a body when a foreign invader enters into our
body.
Immune System
● It's a complex network of cells, tissues, organs, & substances that help the body to fight
disease and other infections.
● Function: This system protects the body from infections.
● Organs of Immune system: WBCs, lymphatic system, tonsils, thymus, spleen, lymph nodes,
lymph vessels, and bone marrow.
Introduction to Immunity
Definition
● Immunity is the state or process of being insusceptible or resistant to a disease-producing
agent, especially an infection.
● OR The ability of our body to resist all types of infections, pathogens, antigens, or many
unfavourable changes.
● Immunity may be produced naturally in the body by exposure OR immunization. ● Defensive
ability of a body is called Immunity.
Basic Principles of Work of Immunity
Healthy immunity accomplishes four essential principles in a body:
1. Ability to detect and fight off infections.
2. Ability to recognize a host's own cell as "self" thereby preventing them.
3. Memory from previous foreign infection.
4. Ability to limit the response after the pathogen has been removed.
Types of Immunity
There are two basic types of Immunity:
1. Innate / Natural / Non-specific Immunity
2. Acquired / Artificial / Adoptive Immunity or Specific Immunity
I. Innate / Natural / Non-specific Immunity ● It has further divided
into 2 divisions on 2 bases:
(A) On the basis of Out-Source.
● Defensive mechanism:
0 (i) Physical barriers (e.g., Skin).
○ (ii) Chemical barriers (e.g., Acid, Saliva).
○ (iii) Cell-mediated (White Blood Cells, Phagocytosis).
(B) On the basis of Time of Encountering a Pathogen
● Natural Immunity:
0 Short term, temporary, rapid, with hours and days. ○ Chronic (long term, slower).
Components of Innate Immunity
● Types of Barriers: ○ Physical
0 Chemical
○ Cell-mediated
● Other cells of Innate Immunity:
0 Macrophages, Eosinophils, Mast cells, Basophils, Neutrophils, Dendritic cells.
○ Macrophages: Attract other immune cells to the infection site and pass signals.
○ Mast cells: Release Histamine, help in wound healing, and their oversecretion can cause
allergy.
○ Neutrophils: Most abundant cell in blood, Granulocytes.
○ Eosinophils: Secrete highly toxic protein to kill virus and bacteria.
○ Basophils: Kill multicellular parasites.
○ Dendritic cells: Secrete protein and kill the viral infected cells.
● Cytokines: Virally infected cells are killed by the help of interferons.
Defense Mechanism
● Inflammation: Non-specific immune response to a physical or chemical tissue damage because
of exposure to radiations, injury; or drug intake.
● Types of Inflammation: Active (Short term), Chronic (Long term, Permanent).
Fever (Pyrexia)
● Means elevation of body temperature.
● Temperature set point: Hypothalamus.
● Abnormal body temperature: > 45^{\circ} \text{C}.
● Purpose: To kill microbes & bacteria.
● Indication: That there is something wrong in the body.
● Pyrogen: Substance causing temperature secreted by toxic bacteria/damaged tissue.
Species Immunity
● The condition of resistance which is well developed in one kind of species but not in other
species.
● Different species resist disease in different ways (e.g., Chicken, Cattle, Human 36^{\circ} \
text{C}).
Racial Immunity
● More resistant toward disease (e.g., Tick fever: Brahman cattle can't be affected; African (black
people) are more resistant toward malaria because of Genetics and environment).
II. Acquired / Adoptive / Specific / Artificial Immunity
General Introduction & Characteristics
● This kind of immunity develops after exposure to an antigen.
● It's brought by the interaction of a specific antigen and our immune system.
● All advancements inside the health control are brought together by this kind of adoptive
immunity.
● This kind of immunity resists or shows resistance to a particular foreign Antigen.
● Adoptive or Acquired Immunity is gained through the lifetime of an individual.
● This kind of Immunity improves on repeated exposure towards the same antigen.
● This type of immunity is highly specific and has memory which is developed
within a few weeks.
Basic Ways of Work of Adoptive Immunity
Adoptive immunity is based on 3 main steps/divisions:
1. Recognition:
○ It recognizes anything which is foreign to your body.
○ This recognition is highly specific.
○ It differentiates body self from Non-self (pathogen from other, and body's own cells from
cancerous cells).
2. Response/Tackling: It tackles/shows a response to this foreign invader.
3. Memory: It forms memory cells for that one particular foreign invader (antigen).
Differentiation of Innate from Adoptive Immunity (Adoptive Immunity
Characteristics)
1. Specificity: This kind of immunity only works for a specific antigen.
2. Memory: After 1^{\text{st}} exposure to an antigen, it recalls memory upon 2^{\text{nd}} exposure
for that same antigen. This memory for some antigens is life-long.
3. Diversity: This kind of immunity deals with a million/billion kinds of pathogens & produces a
variety of immune responses.
4. Discrimination: This type of immunity discriminates one type of pathogen from the other type; it
differentiates body's own cells from cancerous cells (i.e., Discriminates body's self from Non-
self).
Types of Adoptive Immunity (On the basis of pattern of encountering a Pathogen)
● Cells Involved: T-lymphocytes (formed in the thymus) and B-lymphocytes (Antibody/plasma
cells).
(i) Cell-mediated Immunity (CMI)
● Consists of T-cells (Helper T-cells & Cytotoxic T-cells).
● The immune response is produced with the help of T-cells, thus ensuring the defense mechanism
by 3 kinds of lymphocytes.
● In this way, the body cell becomes activated & kills the invading pathogens. ● It helps in providing
defense from Virus, Bacteria, Fungi.
(ii) Antibody-mediated Immunity (AMI) / Humoral Immunity
● This immune response is brought by B-cells (i.e., Antibody Plasma cells).
● In this kind, the B-cell (lymphocytes) produces soluble proteins (Antibodies) which are
secreted in body fluids and circulate in the bloodstream.
● Antibodies encounter pathogens wherever they are present in the body.
Types of Adoptive Immunity (On the basis of Out-Source)
(I) Active Acquired Immunity
● It is the kind of acquired active immunity in which the body starts making antibodies upon
exposure to the antigen by its own system.
● The production of antibodies and activation of lymphocytes takes place. ● It is further divided
into 2 classes:
(i) Natural Acquired Active Immunity
● In this kind of immunity, the body's lymphocytes become activated and antibodies production
naturally takes place.
● Examples: Clinical & Sub-Clinical Infection, Resistance toward common cold.
(ii) Acquired Active Artificial Immunity
● In this way, the production of antibodies & lymphocytes takes place by antigen presentation.
● Examples: Vaccine preparation administration into the body in the form of live & killed disease,
Immunity to Polio, Chicken Pox, and Hepatitis-B.
(II) Acquired Passive Immunity
● In acquired passive immunity, upon an antigen exposure, we take ready-made antibodies from
out-sources.
● It is further divided into 2 classes:
(i) Natural Acquired Passive Immunity
● In this kind of immunity, antibodies transfer from mother's body toward the fetus.
● Examples: Through Placenta, through Colostrum (first mother's breast milk).
(ii) Artificial Acquired Passive Immunity
● Note: This section is incomplete in the provided text.
(II) Acquired Passive Immunity.
● In acquired passive immunity, upon an antigen exposure, we take ready-made
antibodies from out-sources. ● Types:
(i) Natural Acquired Passive Immunity
● In this kind of immunity, antibodies transfer from mother's body toward the
fetus.
● Examples: Through Placenta, through Colostrum (first mother's breast milk).
(ii) Artificial Acquired Passive Immunity
● Note: The full content for this section is not fully present in the provided text.
● This involves administration of synthetically prepared ready-made antibodies or
globulins.
● Example: Delivery of ready-made serum/antibodies to a person.
● This type of immunity is short term (temporary).
● It helps in providing immediate defense mechanism.
Explanation of Immune Response
An immune response is a physiological reaction which occurs within an organism for the
purpose of defending against exogenous substances. It's the way the body recognizes
and defends itself against any foreign invaders threatening it. It involves a complex
system of cells, tissues, organs & organ system working together.
Aims/Objectives/Functions in Our Body
The immune response system aims to:
1. Recognize the threat (antigens).
2. Activate the immune cells.
3. Eliminate or neutralize the threat (antigens).
4. Protect against future infections (threat).
Types of Immune Response
1. Innate Immune Response.
2. Adoptive Immune Response.
(A) Innate Immune Response
● It is Immediate and non-specific.
Components:
○ Physical barriers (Skin, Mucus, Cilia).
○ Chemical barriers (Gastric juices, Urine, Bile).
○ Cellular barriers (Monocytes, Macrophages, Interferon, Antibodies, Dendritic
cells etc.).
(B) Adoptive Immune Responses
● It is a delayed and a very specific kind of immune response.
● It is comprised of lymphocytes (T-cell & B-cells). ● It involves Immunological
memory.
(1) Primary Immune Response
● Occurs on the basis of an antigen entering for the first time.
● It is a delayed response (recognizes antibodies). ● Antibody level rapidly decline.
(2) Secondary Immune Response
● Occurs when the antigen enters for the second time.
● The immune cells have memory.
● Antibodies are formed.
● Antibody level remains for longer time.
Components of Inflammation (Chemical Mediators)
● (Note: The flow of the text suggests these are components related to the
inflammatory response).
1. Prostaglandins: Fatty acids/lipids in nature help to enhance physiology of active
lipid molecules.
2. Leukotrienes: These were first seen inside leukocytes. They are lipid molecules
that resolve inflammation. They are present in WBCs.
3. Transcriptional factor: Group of proteins that involve in genetic control.
Overall Process of Inflammation
The overall process is composed of a step-by-step mechanism to preserve the tissue
integrity.
● Resident cells are firstly involved, and once activated, they induce pro-
inflammatory mediators and cytokines.
● The production of pro-inflammatory mediators and cytokines in turn activate down-
stream pro-inflammatory signals.
● Blood cells are recruited into the inflammatory environment and active
phagocytosis mechanism.
● By phagocytosis mechanism the debris and micro-organisms are eliminated.
Stages of Inflammation
● Stage 3: Inflammation: Blood vessels dilate; tissue permeability increases.
Chemical signals (cytokines & chemokines) attract more WBCs.
●
● Stage 4: Pus formation: Dead cells, pathogens & debris accumulate. Protein-rich
fluid from blood vessels & tissue leakage mixes with debris. Fibrinogen is converted
to fibrin, creating a network that traps debris.
● Stage 5: Maturation: Pus becomes more concentrated as fluid is absorbed or
drained. The immune system continues to fight with the infection.
Immunoglobulins (Antibodies)
● (Note: The text jumps into the characteristics and structure of different
Immunoglobulins starting with IgM).
Immunoglobulin M (IgM)
● General Characteristics:
0 It is a pentamer molecule (5 antibodies joined by a J-chain).
○ It is the first immunoglobulin produced in the body during primary immune
response.
○ It is the most efficient in causing bacteria death.
○ It has a short half-life of 3-5 days.
○ Its normal serum level is 0.5-2.0 mg/ml.
○ Its molecular weight is 900,000 dalton.
● Functions:
1. Although IgM can't cross the placenta, it helps to activate the classical
pathway.
2. IgM increases the ingestion of pathogens by phagocytic cells.
3. It acts as an acid receptor and recognizes foreign antigens.
4. IgM is much efficient than IgG in causing the death of bacteria.
5. The joining chain of IgM is responsible for polymerization, which makes the
IgM more stable, so it's more stable than IgG.
6. The IgM is more active in activation of Type-II hypersensitivity.
Immunoglobulin A (IgA)
● General Features/Characteristics:
0 It's a dimer molecule (2 antibodies join through a J-chain).
○ IgA is named due to its heavy chain being a globulin.
○ It is the second most abundant class.
○ Present almost 15%.
○ It is majorly found inside mucous secretion.
○ Its normal serum level is 0.6-4.2 mg/ml.
○ Its molecular weight is 1,60,000 dalton.
○ It has a half-life of 6-8 days.
Structure:
○ IgA occurs in two forms: Serum IgA and Secretory IgA.
○ The serum IgA is a monomer (7S with molecular weight 160 KDa).
○ But Secretory IgA usually found on mucosal surfaces & in secretions is a
dimer.
○ It is formed by two 7S IgA monomers joined at their carboxy terminus of Fc
region by a "J" chain & also with a secretory component.
○ The dimer IgA is much longer.
○ IgA molecule has two \alpha heavy chains containing 3 constant regions (\
text{CH}1, \text{CH}2, \text{CH}3) & either two \kappa or two \lambda light
chains.
● Functions:
1. It is present inside internal secretion & epithelial cells.
2. It prevent pathogen attachment.
3. It stops colonization of pathogens.
4. It is present inside breast milk (Colostrum) which provides protection to the
new born baby.
5. It prevents local infection (e.g., in many microbes).
6. It prevents entry of virus.
7. It promotes phagocytosis & intracellular killing of microbes.
Immunoglobulin D (IgD)
● General Characteristics:
0 It has a delta (\delta) heavy chain.
○ 13% of Carbohydrates are present in its delta chain.
○ Present in trace amount inside blood serum.
○ Its normal level inside blood is \approx 0.3 \text{mg/ml}.
○ It has a molecular weight of 1,80,000 dalton.
○ It has a half-life of 3 days.
○ IgD in combination with IgM is present on the surface of B-cells.
● Structure:
0 Its structure is similar to IgG in nature.
○ It exists in monomeric nature.
○ It has a heavy chain and a light chain.
● Functions:
1. IgD binds antigen & signals B-cells to produce antibodies.
2. It involves in the maturation & activation of B-cells.
3. It is involved inside humoral immunity.
4. Its individual function is unknown.
Immunoglobulin E (IgE)
● General Features:
0 It's heavy chain is comprised of \varepsilon.
○ It is a monomeric molecule.
○ 13% carbohydrate is present in it.
○ The hinge region of IgE is flexible in nature.
●
○ It has a low serum concentration.
○ It has a half-life of 7-10 days.
○ It has high affinity for allergens.
○ It has a molecular weight of 1,90,000 dalton (1.90 \times 10^{5} dalton).
○ IgE abundance is about 0.002%.
● Structure:
0 IgE exists as a monomer & has an extra region in the constant region.
○ It has a heavy and a light chain.
○ Its structure is similar to IgG.
○ It has 3 constant regions & 1 variable region.
● Functions:
1. It deals with hypersensitivity.
2. Allergic reactions inside the body.
3. It has parasite immunity.
4. It releases histamine & other chemical mediators.
5. It has a great affinity to bind with allergens.
Lymphocyte Development & Diversity (Unit #5)
Lymphocytes
● Meaning: Derived from Latin words: Lymph means water, cytes means cells.
● Definition: Lymphocytes are white blood cells that are also one of the body's
main types of immune cells.
● They are made in the bone marrow & found in the blood & lymphoid tissue (except
Central Nervous System (CNS)).
● They are 5-15 \mum in diameter.
● They may be short-lived (\mathbf{2-3} days).
● They may be long-lived (100-200 days or up to years).
Types of Lymphocyte Cells
1. B-lymphocytes (B-cells) (Bone marrow or Bursa derived).
2. T-lymphocytes (T-cells) (Thymus cell).
3. Natural killer cells (NK cells, Killer cell, K-cell).
(1) B-lymphocytes
● Named after their site of origin in the Bursa of Fabricius in birds or in the bone
marrow in humans.
● They recognize antigen & become plasma cells that produce antibody.
● These are arise from stem cells inside the bone marrow.
● These cells are not involved in the immune response until they are fully
developed.
Upon maturation they migrate towards the lymphatic system, where upon
interaction with an antigen they become antibody producing 'Plasma cells'.
(2) T-cell (T-lymphocytes)
● T-cells originate inside the bone marrow & then migrate towards the thymus for
the purpose of maturation.
● After maturation they remain inside the thymus & circulate in the blood & travel
towards the site of infection.
● They circulate inside the body to the areas where they are needed.
Types of T-cells
● (a) Memory T-cells:
0 These long-lived cells survive after the infection has been neutralized &
provide cell-mediated immunity by responding rapidly to another encounter
with the same antigen.
● (b) Cytotoxic T-cells:
0 These directly inactivate any cells carrying antigens.
○ They attach themselves to the target cell & release powerful toxins called
Perforin which make holes in the target cells & kill them.
○ The main role of cytotoxic T-cells is the destruction of abnormal body cells
(e.g., infected cells & cancer cells).
● (c) Helper T-cells:
0 These are essential for the correct function of not only the cell-mediated
immunity but also antibody-mediated immunity.
○ The production of special chemical called Cytokines & co-operation with B-
lymphocytes to produce antibodies are the function of helper T-cells.
● (d) Suppressor T-cell:
0 These cells act as "brakes," turning off activated T- & B-lymphocytes.
○ This limits the powerful & potentially damaging effects of the immune system.
(3) Natural Killer Cells (NKSc)
● NK cells are a component of the Innate Immune System.
● NK cells play a major role in the host rejection of both tumours & virally
infected cells.
● They are present in bone marrow, liver, uterus, spleen, lung & thymus.
● Role of NK-cells:
0 NK cells are cytotoxic in nature & small granules in their cytoplasm contain
special proteins such as Perforin & Proteases known as Granzymes.
○ Perforin chemical form pores in the cell membrane of the target cell through
which the granzymes can enter the cell. This leads to the destruction of the
virus inside.
○ NK-cells are also activated for destructive action in response to Interferons or
Macrophage derived Cytokines.
●
Steps in Lymphocyte Development
Development of lymphocytes, also known as Lymphopoiesis, is a complex process that
involves the coordinated action of multiple cell types.
1. Hematopoietic Stem Cell (HSCs): The development of lymphocytes begins with
hematopoietic stem cells which give rise to lymphoid progenitor cells.
2. Lymphoid Progenitor Cells: HSCs differentiate into lymphoid progenitor cells,
which are committed to becoming lymphocytes.
3. T-cell Development: Lymphoid progenitor cells migrate to the thymus, where they
undergo T-cell development. This involves the expression of T-cell-specific genes,
such as TCR$\alpha$ & TCR$\beta$.
4. B-cell Development: Lymphoid progenitor cells that remain in the bone marrow
undergo B-cell development. This involves the expression of B-cell-specific genes,
such as IgM & IgD.
Difference between T-lymphocytes & B-lymphocytes
Feature T-Cells B-Cells
Origin Originate in the bone Originate in the bone
marrow. marrow.
Maturation Mature in the thymus. Mature in the bone marrow.
Function Play a role in Cell-mediated Play a role in Antibody
immunity. mediated (Humoral)
immunity.
Recognition It recognizes antigen through It directly involves in
T-cell receptors on its recognizing antigens on their
surface. surface. It differentiates body
self from non-self
(differentiates pathogen from
other & body's own cells
from cancerous cells). It
bears BCR receptor.
Receptors It bears TCR receptor. It bears BCR receptor.
Activation Activation takes place by Activation takes place by
antigens. antigen presenting cells,
T-Helper cells & cytokines.
Use Markers T-cell use markers for B-cell use markers for
identification of CD4+ identification of CD19.
(\text{CD}4, \text{CD}8), CD.
Types Helper T-cells, Cytotoxic T- Certain memory cells &
cells, Naive T-cells, Plasma Regulatory cells.
cells.
Target It directly target any It produces antibodies to
antigen. target any antigen.
Feature T-Cells B-Cells
Response It produce response to It differentiate into Helper
plasma cells which secrete T-cells, Cytotoxic T-cells &
antibodies. memory T-cells.
Lifespan Have longer life spans. Have shorter lifespans.
Percentage 80% of the blood 20% of the blood
lymphocytes are T-cells. lymphocytes are B-cells.
Effect Have an inhibitory effect on Don't have any inhibitory
the immune system. effect on the immune system.
Clonal Selection & Expansion
Clones
Clones are a genetically identical group of cells, an organism, or an individual arising
from a single parent.
Clonal Selection & Expansion
● These are general concepts in the field of Immunology, that explain how your
immune system selects special, specific immune cells for a pathogen & then
their spreading takes place.
● This concept was introduced by an Australian doctor Frank Macfarlane Burnet in
1957.
● It involves B-cells, Antigen Presenting Cells (APCs), & memory cells.
● B-cells (B-lymphocytes) involve through humoral immunity.
● T-cells (Helper T-cells) activate cytotoxic activity.
● Memory cells involve through Adoptive Immunity.
Steps of Clonal Selection
1. Antigen Presentation: It is the first step in which the entry of an antigen takes
place/starts.
2. Recognition: When antigens enter the body, immune cells recognize these
specific antigens.
3. Activation: Recognizing cells become activated. Cellular activity and cytotoxic
activity takes place.
4. Proliferation: In this step, activated cells start dividing.
Multiplication/division/expansion takes place.
5. Differentiation: B-cells involve in the production of antibody in plasma cells.
Steps of Clonal Expansion
1. Rapid Cell Division: Selected cells proliferate extensively and divide in a rapid
increase in numbers.
2. Increased Cell No.: The cells no. is increased by extensively dividing immune
cells & dominate the immune response.
3. Affinity Maturation: Dividing cells mature and their attraction towards the antigen
increases.
4. Memory Cells Formation: Cells that become long-lived develop into memory
cells. E.g., T-cells form memory cells.
T-Cell Activation by Antigens (Chapter #6)
T-cell Activation
T-cell activation is a complex interaction of molecular signals & cellular responses
that trigger the immune system.
Activation Site
T-cell activation occurs in the secondary lymphoid organs: Spleen, Lymph nodes,
Tonsils & unique Lymphoid structure within mucosal tissues.
Why Is Human T-cell Activation Necessary?
Human T-cell activation is imperative to a successful adaptive immune response &
allows for the resilience of human immunity to developing diseases. Human T-cells are
therefore an essential subject to study & can help us further understand the mechanisms
underlying effective immunity.
T-B Interaction
● (Note: This section describes a diagram of T-B interaction).
● \text{CD}4\text{0L} & \text{CD}4\text{0}.
● Signal 2: Naive B-cell excretes a new antigen in the Spleen & Lymphoid organs.
● Primary response (\text{T-cell} + \text{B-cell}): \text{IL}2, \text{IL}4 & \text{IL}5 \
rightarrow \text{plasma cell} \& \text{memory cell}.
● Memory cell is produced for any infection.
● Antigen capture & presentation: B-cell capture antigen.
