Immunology for MBBS

128 Pages·2021·26.04 MB·English

by  S.K. Gupta, Binita Goswami

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SYLLABUS
Competency BI-10.3
Describe the cellular and humoral components of the immune system and describe the types of antibodies.
The immune system consists of many components. The main ones are:
* Cells of the immune system
* Lymphoid tissues and organs of the immune system
¢ Antibodies
* Major histocompatibility complex
° Complement system
* Cytokines
The cells, lymphoid tissues and organs constitute the cellular components. The remaining components, viz.,
antibodies, complement system and cytokines are the main constituents of humoral components. These are
described in specific chapters to cover this competency.
Competency BI-10.4
“Describe and discuss innate and adaptive immune responses, self/non-self recognition and the central role
of helper T-cells in immune responses.”
¢ This competency includes major area of immunity which needs to be discussed in order to have a good
understanding.
¢ The major areas with subsections included in this competency are:
1. Innate immunity
2. Self and non-self recognition with the following subsections:
e Antigen }
¢ MHC
e Antigen processing and presentation
e Mechanism of self / non-self recognition
3. Adaptive immunity with the following subsections:
¢ Role of helper T-cells
e Humoral immune response
e Cellular immune response
These are discussed in the specific chapters to cover this competency
Competency BI-10.5
“Describe antigens and concepts involved in vaccine development.”
This chapter focuses on vaccine development concepts. ‘Antigen’ is already described in Chapter 7.
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CONTENTS
Chapter 1 Immunity — An Overview
Chapter 2 Immune System — Cellular Components
Chapter 3 Antibodies
Chapter 4 Complement System
Chapter 5 Cytokines
Chapter 6 Innate Immunity
Chapter 7 Antigen
Chapter 8 Major Histocompatibility Complex
Chapter 9 Antigen Processing and Presentation
Chapter 10 Mechanism of Self- and Non-self Recognition
Chapter 11 Adaptive Immunity and the Central Role of Helper T-cells
Chapter 12 Humoral Immune Response
Chapter 13 Cellular Immune Response
100
Chapter 14 Vaccine
109
Additional Reading 118
Index 129
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Immunity — An Overview
IMMUNITY augmented by highly specific receptors present

Immunology is the science that deals with the study on T-cells and B-cells. Together, all these receptors
of protective and surveillance mechanisms against differentiate between self and non-self and enable
disease-producing microorganisms. This state of the immune system to react to non-self only. Usually
protection of the body against pathogens is called this is a finely tuned system and does not lead to
immunity. It is the result of a normally functioning any aberration.
Immune system which is highly efficient but
complex. It generates a variety of molecules and cells
INNATE AND ADAPTIVE IMMUNITIES
which recognise the foreign pathogens in a highly

Immune system works at two levels to produce
specific manner and then eliminates them without
immunity. The first is called innate immunity or
any damage to the host. Not only that, it generates
natural immunity. It is present since birth in all
the memory of this pathogen for future in the host
individuals and its main focus is to prevent the entry
immune system,
of pathogens into the host to establish infection. There
are well-defined mechanisms which are of general
ANTIGENS nature and act in the same way against all organisms
as barriers.
Immune response is developed not only against
pathogens but also against a vast variety of other
In contrast to innate immunity, there is the
agents. These include biological products of plant
second level called adaptive immunity or acquired
and animal origins, chemicals of diverse nature, food
immunity. It develops only after the pathogen has
items and even body's own cells and molecules which
entered the host and has activated the immune
have been damaged or altered due to mutations,
system. This leads to the development of an immune
cancers, etc. All such agents against which the body
response suited to eliminate the invading organism.
produces an immune response are known as antigens
Hence, it is highly specific.
or immunogens.
Normally, the immune system reacts only to the HUMORAL AND CELLULAR IMMUNITIES
foreign antigens and not against the body’s own
Both the innate and acquired immunities function
molecules. There are mechanisms to identify these by two main mechanisms: (a) by soluble or secreted
foreign antigens and to generate an immune response molecules which combat the antigen. This is called
against them for their neutralisation and removal. humoral immunity. This is operative in most body
fluids, including vascular compartment and at the
mucosal surfaces of gastrointestinal tract (GIT),
RECOGNITION OF SELF AND NON-SELF
respiratory and genitourinary mucosa, etc. and (b)
Most foreign pathogens exhibit at least few chemical
by specific cytotoxic cells that kill the pathogen or
molecules which have unique structural patterns not
antigen. This is called cellular immunity or cell-
found on mammalian cells. These are called pathogen-
mediated immunity.
associated molecular patterns (PAMPs). They are
recognised by unique receptors called pattern These are clearly demarcated in adaptive immunity,
recognition receptors (PRRs). Such receptors are i.e, cellular immunity is mediated by cytotoxic
present on various cells like leukocytes and even as T-lymphocytes and humoral immunity is mediated
by antibodies. Both antibodies and cytotoxic T-cells
soluble receptors on molecules such as complement,
CRP, etc. They participate in the development of are produced after the stimulation of the immune
immunity. This recognition mechanism is further system by the antigen.

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response, need the help of MHC to recognise the
Various anatomical barriers, phagocytosis,
foreign antigen.
inflammation, etc., constitute the cellular mechanisms
of innate immunity, while the various mediators
produced by them and the acute phase response COMPLEMENT SYSTEM

proteins, cytokines, etc., constitute the humoral Complement system represents a group of proteins
mechanism. which react in a sequential cascade to generate
products which augment both cellular and humoral
IMMUNOLOGICAL MEMORY immunity. This system is activated by the antigen
A great attribute of acquired immunity is the directly (alternative pathway) to augment the
development of memory of the pathogen to which innate immunity. It is also activated by antibodies
it has interacted with, for future. This is achieved to reinforce the acquired immune response (classical
by producing effector memory cells. They have pathway).
unique features suited to their function. Two such
key properties are: (1) their long life which can extend CYTOKINES
even up to the lifetime of the organism, contrary to Like the endocrine system, which has its messengers,
the limited lifespan of most cells; (2) their very low the hormones, the immune system has its chemical
threshold for activation. Also, they produce a much mediators called cytokines. They have several
stronger and long-lasting immune response. It is a common features vis-a-vis hormones and growth
very crucial element of immunity. factors. On the other hand, they have distinguishing
features as well. Besides, cytokines are also needed
IMMUNOCOMPETENT CELLS - T AND in cell differentiation, haemopoiesis and regulation
B-LYMPHOCYTES of immune response.
Even though all leukocytes and many other cells are
involved in the immune response, T-lymphocytes LYMPHOID ORGANS AND LYMPHATIC
(T-cells) and B-lymphocytes (B-cells) are the main SYSTEM
cells involved in adaptive immunity. Both are derived The lymphoid organs and the lymphatic system are
from small lymphocytes and each has a distinct
directly connected with the immune system and
receptor on its surface to capture antigen and to
immunity. Bone marrow, thymus, lymph nodes and
produce immune response.
spleen are at the centre of activity along with the
B-cells are responsible for humoral immune lymphatic vessels network. Bone marrow and thymus
response. T-cells are involved in both cellular
provide all the cells of the immune system, including
immunity as well as humoral immunity. These are
the leukocytes. The spleen and lymph nodes act as
discussed in appropriate chapters.
filters to trap the antigen. Spleen filters the vascular
compartment, whereas the lymph nodes screen the
MAJOR HISTOCOMPATIBILITY lymph. It is in these organs that the antigen and
COMPLEX M OLECULES immune cells interact and the immune response is
generated against the antigen to remove it. Thus, they
¢ Major histocompatibility complex (MHC)
not only provide the all important ‘T- and B-cells’
molecules represent the self molecules. They have
pool, they are also the sites where the antigen is killed
an important role in recognition of self and non-
for final and complete elimination.
self by the immune system.
* MHC molecules also determine the compatibility
of grafted tissue into the recipient, such as in ABNORMAL IMMUNE RESPONSE
the kidney transplant. This matching of MHC AND DISEASES
molecules between donor and recipient is ¢ Development o f immunit y is a subtle physiological
determined by the technique called HLA-typing. If
response and we are not conscious or aware of it.
there is a match between the tissues, it is accepted.
However, if the immune response development
Otherwise, the grafted tissue is rejected.
is exaggerated or abnormal, it leads to unusual
* MHC molecules also play a role in the development manifestations or even cliseases. Allergy is one
of adaptive immune response. T-cells, which are such example. It can be even fatal if severe. Some
crucial for both humoral and cellular immune other examples are:

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Immunity = AT Overview 3
8 sedan diseases like type 1 diabetes mellitus, immune response are seen during allergy, blood
ashimoto’s thyroiditis, rheumatoid arthritis, etc. transfusion and drug reactions, etc.
These result when imm
antigens tne system reacts to self- Diseases also result from the deficiency of various
components, e.g., complement deficiency diseases,
¢ Hypersensitivity reactions due to exaggerated hypogammaglobulinaemias, etc. Such persons
have frequent and often severe infections.

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Competency: B1-10/3
“Describe the cellular and humoral components of the immune
system and describe the types of antibodies.”
The immune system consists of many components. The main
ones are:
e Cells of the immune system
e Lymphoid tissues and organs of the immune system

e Antibodies
e¢ Major histocompatibility complex

e Complement system

e Cytokines
The cells, lymphoid tissues and organs constitute the cellular
components. The remaining components, viz. antibodiés, major
histocompatibility complex, complement system and cytokines
are the main noncellular or humoral components. These are
described in the following chapters to cover this competency.
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Immune System — Cellular Components
At the end of this chapter, the students should be able to:

e Explain the concept of immune system and name its main components

¢ Enumerate the cellular components of the immune system and enlist
their roles in immunity
¢ Briefly describe the cells of the immune system, including lymphocytes,
T-cells, B-cells, NK cells, macrophages and dendritic cells
¢ Explain the organisation and functions of lymphoid organs of the
immune svstem
Outline the process of lymphocyte trafficking and its importance

IMMUNE SYSTEM Table 2.1: Components of the immune system
a

Anatomically, the immune system consists of different
Cells
lymphoid organs and tissues present throughout the
Leukocytes, dendritic cells, macrophages
body and interconnected by blood and lymph vessels
(Table 2.1). These tissues perform two basic functions. Lymphoid organs and tissues
* They provide the various cells involved in (a) Primary or central
immunity, including immunocompetent T- and Bone marrow and thymus
B-lymphocytes, which are most important. (b) Secondary or Peripheral

¢ They are also the sites where the antigen 1s first Spleen, lymph nodes
trapped and then lymphocytes interact with it to MALT: Mucosa-associated lymphoid tissues
develop an immune response. GALT: Gut-associated lymphoid tissues
CALT: Cutaneous-associated lymphoid tissues
This development of an adequate immune
response to an antigen also requires the participation MHC proteins
of other molecules like complement proteins, major Complement system
histocompatibility complex molecules and chemical Chemical mediators, e.g., cytokines, etc.
mediators like cytokines. Hence, a working knowledge

of the various cells, the structure and function of
lymphoid tissues and other components is essential
for a good understanding of immunological concepts.

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Bil
CELLS OF THE IMMUNE SYSTEM marrow but mature differently. Some lymphocytes
migrate from bone marrow to thymus where they
LEUCOCYTES
mature and become fully functional T-lymphocytes
All leucocytes are involved in the immune system or T-cells. The lymphocytes which remain in the bone
(Table 2.2). Out of these, lymphocytes play a central
marrow and mature in the bone marrow itself are
role, particularly in acquired immunity. Other referred to as B-lymphocytes or B-cells.
leucocytes play a supportive role in phagocytosis,
antigen presentation, cytokine secretion, etc.
Table 2.3: Features of small and large lymphocytes.

Characteristics Large Small

Table 2.2: Role of leucocytes in immunity
lymphocyte lymphocyte

Leucocytes Role in immunity
Size 14-16 pm 6-10 um
Neutrophils Phagocytosis of pyogenic
Appearance Large nucleus _—‘ The cytoplasm
| microorganisms
with thin rim is more as

| Eosinophils Phagocytosis of parasites of cytoplasm compared

to small
Basophils Delayed hypersensitivity
lymphocyte.
Monocytes and Phagocytosis
Post-maturation Null cells or T- and B-
macrophages
fate NK cells lympohcytes
Lymphocytes Acquired immune response

LYMPHOCYTES
All lymphocytes arise from a common lymphoid
stem cell (Flow chart 2.1). They make up 20-40%
of the total blood leucocytes and 99% of all the

cells found in lymph. Peripheral blood contains

two types of lymphocytes — small lymphocyte
and large lymphocytes — also called large granular
lymphocytes because they have granules in their
cytoplasm. As shown in Fig. 2.1, small lymphocytes
have a very thin rim of cytoplasm as compared to
large lymphocytes. Important differences are given in

Table 2.3.
Fig. 2.1: Large lymphocyte (4), small lymphocyte (4) and
Both B- and T- lymphocytes originate in the bone large granular lymphocyte (A)

Haemopoietic stem cells |
v
v
Lymphoid stem cells | Myeloid stem cell |
|
v y y
Small lymphocyte Large lymphocyte | Large granular RBCs

lymphocyte Platelets
¥ y — i — Neutrophils
Eosinophils
T-lymphocyte B-lymphocyte | Null cells or Basophils
——— a
NK cells Monocytes

y Y Y oe Mast cells
Ty cell | To cell | Treg cell | — SS

Flow chart 2.1: Origin of blood cells

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