Learning objectives:
1.
Distinguish between innate (nonspecific) and adaptive (specific) defenses, and explain
2.
the role of lymphocytes in the immune response.
Identify the major components of the lymphatic system, describe the structure and
3.
4.
functions of each component, and discuss the importance of lymphocytes.
List the body’s innate (nonspecific) defenses, and describe the components, mechanisms, and functions of each.
Define adaptive (specific) defenses, identify the forms and properties of im-munity, and
5.
6.
7.
distinguish between cell-mediated (cellular) immunity and antibody-mediated (humoral) immunity.
Discuss the types of T cells and their roles in the immune response, and describe the mechanisms of T cell activation and differentiation.
Discuss the mechanisms of B cell activation and differentiation, describe the structure and function of antibodies, and explain the primary and secondary responses to antigen exposure.
Describe the development of immunological competence, list and explain examples of
8.
9.
immune disorders and allergies, and discuss the effects of stress on immune function.
Describe the effects of aging on the lymphatic system and the immune response.
Give examples of interactions between the lymphatic system and other organ sys-tems we have studied so far and explain how the nervous and endocrine systems influence the immune response.
Body's defenese Mechanisms
The ability of the body to protect itself from damage or disease is called resistance .
Two main types of resistance are:
• Nonspecific resistance (innate defenses): provide defense mechanism against a range of
• pathogens in a general way.
Specific resistance (adaptive/immunity): provides defense mechanism against a specific pathogen by specialized lymphocytes. The system of the body responsible for specific resistance is the lymphatic system.
1. Innate (nonspecific) defense mechanisms
Prevent entry, limit the spread of microorganisms or other environmental hazards. There are seven major categories of innate defenses.
1. Physical barriers
2. Phagocytes
3. Immunological surveillance
4. Interferons
5. Complement
6. Inflammatory response
7. Fever
Physical Barrier
Prevent entry of microbes in the body. Provided by the skin and mucous membrane.
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Intact skin is a physical barrier to entrance of microbes.
Mucous membrane that lines the digestive respiratory and urogenital tract secrete a
• viscous mucus that prevents entry of potentially harmful microbes.
In addition many of the secretions like saliva, tears etc. also contain proteins like lysozyme which digest cell wall of microbes and destroy it.

Phagocytes
Phagocytes are specialized cells that perform phagocytosis. Phagocytosis takes place in 5 steps chemotaxis, adherence, ingestion, digestion, and killing. Cells involved in this process include:
• Neutrophils:- 60-70% of all WBCs. They leave blood and migrate to the infected area, attracted to the chemicals released by the damaged cells. They self destruct on destroying foreign invaders.
• Monocytes:- 5% of WBC. They leave the blood, migrate into tissues and develop into macrophages. Some macrophages are wandering (moving around the body) and others are fixed (stationary). They extend pseudopodia and pull the microbes in.
Immunological surveillance
Is carried out by natural killer (NK) cells. They attack cancer cells and body cells infected with viruses. Their mechanism of action is outlined below:
1.
Activated NK Cells identify and attach to abnormal cell (nonselective)
2.
Golgi apparatus in NK cell forms perforin vesicles
3.
Vesicles release proteins called perforins (exocytosis)
4.
Perforins lyse abnormal plasma membrane
Interferons
Proteins (cytokines) released by activated lymphocytes and macrophages.
Complement System
Plasma contains 11 special complement (C) proteins. These proteins form complement system and complement antibody action. Complement proteins work together in cascades.
Two pathways activate the complement system: Classical pathway and Alternative pathway
Effects of Complement Activation
• Pore formation: Destruction of target plasma membranes. Five complement proteins join to form membrane attack complex (MAC)
• Enhancement of phagocytosis by opsonization. Complements working with antibodies
(opsonins)
• Histamine release: Increases the degree of local inflammation and blood flow
Inflammation
It is triggered by a physical injury, such as a cut, or by entry of microorganisms. Symptoms include redness, pain, heat and swelling. An injury to white blood cells called, basophils & mast cells causes release of histamine which triggers vasodilations. Small blood vessels near the injury dilate, increasing the blood supply (causing redness & heat). Fluids from the dilated vessels also move into neighboring tissues, causing swelling. Inflammatory response also involves the migration of phagocyte from the blood into the infected tissues, which eliminate the pathogens by phagocytosis.
Products of Inflammation:
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Necrosis: Local tissue destruction in area of injury
Pus: Mixture of debris and necrotic tissue
Abscess: Pus accumulated in an enclosed space
Fever
It is defined as a maintained body temperature above 37
0
C (99
0
F)
Pyrogens: Any material that causes the hypothalamus to raise body temperature.
A variety of stimuli either act as pyrogens themselves or stimulate macrophages to release pyrogens, e.g. Circulating pathogens, toxins, or antibody complexes.
Active macrophages release cytokine called endogenous pyrogens or interleukin-1 (IL-1).

2. Specifc (adaptive) defense mechanisms
Specific resistance (immunity)
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Responds to specific antigens
With coordinated action of T cells and B cells
Specific Defenses
• T Cells: Provide cell-mediated immunity
Defend against abnormal cells and pathogens inside cells
• B Cells: Provide antibody-mediated immunity
Defend against antigens and pathogens in body fluids
Types of Adaptive Immunity
Adaptive Immunity can be divided into two types:
1.
Active immunity: is when the body's immune system is stimulated to make antibodies and other immune cells (killer cells). Although this immunity takes time to work, it generates memory cells which remain in the body to protect against future encounters with the same antigen. Active immunity can be naturally acquired or artificially. o
Naturally acquired active immunity: is seen when the individual is exposed to the o antigen in a natural manner. Body responds to this antigen by activating B and/or
T cells, and memory cells are made. e.g. being exposed to chicken pox virus through a friend.
Artificially acquired active immunity: is when a weak or killed antigen is injected into the individual. Individual responds by activating a specific B and/or T cell, and antigen is inactivated. In this process memory cells are also made for future encounters. This type of immunity forms the basis for vaccination.
2.
Passive immunity : is when prepared antibodies are received by an individual. This immunity provides immediate protection but lasts for a short term, since antibodies are proteins and undergo breakdown. Body's immune system is not involved in this immunity and hence no memory cells are produced. Because of this fact no protection is there for future encounters. o
Naturally acquired passive immunity: e.g. when IgG naturally crosses the placenta to go from the mother's blood to fetus blood or when IgA is fed to the new born through the breast milk. These antibodies protect the fetus as well as the new born for the first few months of their life, until the newborn's immune system kicks in o and starts making its own antibodies.
Artificially acquired passive immunity: is when an individual is given shots of prepared antibodies or serum to treat or prevent infections. Shots of gamma globulins are often given to hospital patients and travelers for temporary protection against hepatitis.
Properties of Immunity
Four characteristic features of the immune system are:-
1.
Specificity :- recognition of a specific pathogen or toxin and then destroying it. Each lymphocyte is highly specific in responding to a particular pathogen or toxin.
2.
Verstality/Diversity :- Immune system on the whole has the ability to respond to millions of different kind of invaders.
3.
Memory :- Immune system has the ability to ‘remember’ pathogens or toxins it encounters. This property is carried out by specialized cells termed the memory cells.
4.
Tolerance OR Self/Nonself recognition :- Immune system distinguishes the body's own molecules (self) from foreign molecules (nonself).
Overview of Immune response
• Cell mediated immunity : works best against intracellular antigens which invade and are present in an infected cell. e.g. viruses, parasites, fungi and cancer cells and tissue transplants. Antigens bind to a specific T-cell receptor --> T-cell becomes activated and differentiates into Killer cell and directly attacks the infected cell causing its lysis.

• Humoral or antibody mediated response : In this response antigens trigger and activate a specific B-cell --> which differentiates into plasma cells & reacts by producing antibodies --> which are released in the blood and lymph. These antibodies then inactivate the foreign antigen by a number of possible mechanisms. This type of immune response works against extracellular antigens circulating in body's fluid.
Key terminologies used in immunity
• Antigen : A foreign molecule capable of triggering a response form the adaptive
Immunity . e.g. of antigens - bacteria, viruses, fungi, protozoa, pollens, & transplanted tissue.
• Epitope :- localized region on the surface of an antigen capable of initiating immune response, is called epitope. A single antigen can have several effective epitopes.
• Hapten : are small molecules that bind to larger molecules within the body and then stimulate an adaptive Immunity response. E.g. penicillin
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Foreign antigens : not produced in the body.
Allergens : cause an overreaction of the Immune system.
Self antigens : molecules within the body triggering immune system. Can prove to be dangerous – autoimmune diseases.
Cell dediated immunity - Types of T cells
Main types of T cells:
• Helper T (T
H
) cells : recognize antigen fragments associated with MHC-II molecules, and secrete several cytokines, most important, interleukin-2, which acts as a costimulator
•
• for other helper T cells, cytotoxic T cells, and B cells.
Memory T cells help to recognize the antigen which invades for the second time.
Cytotoxic T (T
C
) cells : kill infected body cells that display the antigen on their surface.
When cytotoxic T cells encounter a cell displaying a microbial antigen, they can release granzymes which trigger apoptosis . The microbe is then destroyed by phagocytes.
Cytotoxic T cells can also bind to infected cells and release perforin and granulysin.
Perforin causes cytolysis while granulysin destroys the microbe.
Antigen Presentation
Pathway of Antigen Processing: To produce an immune response, the first step is for B and T cells to recognize the antigen.
T cells however recognize pieces of antigens that are processed and attached to MHC selfantigen.
• Major Histocompatibility Complex (MHC) Antigens are glycoproteins present on the cell surface. They serve as identity markers, since no two individuals can have the same
MHCs except identical twins. B and T-cell receptors do not elicit any response against body's own MHCs, but when the MHC is attached to a foreign antigen it initiates an immune response in the body.
There are two types of MHC antigens: o
MHC Class I molecules: found on nucleated cells, display antigens produced o inside their cells on their surface.
MHC Class II molecules: found on the surface of antigen presenting cells.
Processing of exogenous antigens : Exogenous antigens are the ones present outside body cells, e.g. bacteria, parasitic worms, bacterial toxins. Cells that help to process and present exogenous antigens are called the antigen-presenting cells (APCs) which include include macrophages, B cells, and dendritic cells. The steps in this process are:
- APCs ingest antigens by phagocytosis.
- Inside the APCs, the antigen is digested into shorter pieces.
- APCs synthesize MHC-II molecules.
- Inside the APCs, MHC-II molecules and the antigen pieces bind to one another.

- MHC-II-antigen complex is then inserted in the plasma membrane of the APC. This APC then migrates to lymphatic tissue to present the antigen to the T cells.
Processing of endogenous antigens : Endogenous antigens are synthesized within the body and include viral proteins or proteins produced by cancer cells.
- Most of the cells of the body can process endogenous antigens
- Fragments of endogenous antigen are associated with MHCI molecules inside the cell.
- The antigen MHCI complex moves to the cell’s surface.
- This complex signals the lymphatic system that a cell has been infected and needs help.
Antigen Recognition, Costimulation and Activation of T cells
Antigen Recognition
• T cell receptors recognize antigen fragments associated with MHC molecules on the surface of a body cell.
• CD Markers are cluster of proteins on T cell membranes that play an important role in antigen recognition.
Two important CD markers are: o
CD8 Markers: Found on cytotoxic T cells and suppressor T cells. Respond to antigens on Class I MHC proteins. o
Costimulation
CD4 Markers: Found on helper T cells. Respond to antigens on Class II MHC proteins
Proliferation of T cells requires costimulation, by cytokines such as interleukin-1 (IL-1) and interleukin-2 (IL-2), or by pairs of plasma membrane molecules, one on the surface of the T cell and a second on the surface of an APC.
Activation of CD8 Cells
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•
Activated by exposure to antigens on MHC protein.
Results in the production of two types of T cells: TC and Memory T cells
Cytotoxic T cells Seek out and immediately destroy target cells by using several different mechanisms.
• Memory TC Cells: Stay in circulation and Immediately form cytotoxic T cells if same antige n appears again.
Activation of CD 4 cells.
Upon activation, undergo a series of divisions and differentiate into:
• Active helper T cells (TH cells): Secrete cytokines that stimulate both cell-mediated and antibody-mediated immunity.
• Memory helper (TH) cells: Remain in reserve
Antibody mediated Immunity
B Cells
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Responsible for antibody-mediated immunity
Attack antigens by producing specific antibodies
Millions of populations, each with different antibody molecules
This type of immune response works against extra cellular antigens circulating in body's fluid.
B cell sensitization and Activation
Sensitization
• Corresponding antigens in interstitial fluids bind to B cell receptors

• B cell prepares for activation, preparation process is sensitization. During sensitization, antigens are: o
Taken into the B cell o o
Processed
Reappear on surface, bound to Class II MHC protein
B Cell Activation
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Helper T cell binds to MHC complex
Secretes cytokines that promote B cell activation and division
B Cell Differentiation
Activated B cell divides into:
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Plasma cells: Synthesize and secrete antibodies into interstitial fluid
Memory B cells: Like memory T cells, remain in reserve to respond to next infection
Antibody Structure
Antibodies are proteins that bind specifically to the antigen that triggered its production.
Structure : Antibodies constitute a class of proteins called Immunoglobulins (Ig ) .
Each immunoglobulin molecule is made up 2 light chains and 2 heavy chains .
Each chain has two regions; a constant regionvariable region (V) which varies from one antibody to the other.
V region from each chain has the antigen binding site to recognize and specifically attach to a particular antigen.
Antibody Classes
Based on chemistry and structure, antibodies are grouped into five principal classes each with specific biological roles (IgG, IgA, IgM, IgD, and IgE).
Antibody action
Antigen–Antibody Complexes can destroy the antigen in one of the following ways:
• Neutralization of antigen binding sites: antibodies bind to specific sites on bacteria and viruses which prevents them from attaching to a body cell.
• Precipitation and agglutination - antibodies link large number of antigens togetehr, resulting in the formation of immune complex which becomes too large and therefore precipitates.
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Activation of complement
Attraction of phagocytes
Opsonization: coating of an antigen by antibodies is called opsonization, which increases phagocyte efficiency
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Stimulation of inflammation by stimulating basophils and mast cells.
Prevention of bacterial and viral adhesion.
Primary Immune Response: first exposure to an antigen,
Takes time to develop - can take 2 weeks
Antigens activate B cells resulting in proliferation of lymphocytes
Plasma cells differentiate
Antibody titer (level) slowly rises.
Secondary immune response:
If the body is exposed to same antigen at some later time, the response is faster and more prolonged.
This is due to long-lived memory cells.

Immune Disorders
Autoimmune Disorders : A malfunction of system that recognizes and ignores “normal” antigens
Activated B cells make autoantibodies against body cells
Examples:
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Thyroiditis
Rheumatoid arthritis
Insulin-dependent diabetes mellitus (IDDM).
Immunodeficiency Diseases
Result from:
Problems with embryological development of lymphoid tissues
Can result in severe combined immunodeficiency disease (SCID)
Viral infections such as HIV
Can result in AIDS
Immunosuppressive drugs or radiation treatments
Can lead to complete immunological failure
Allergies
Inappropriate or excessive immune responses to antigens
Allergens
Antigens that trigger allergic reactions
Age Related Changes
Immune System Diminishes with Age
Increasing vulnerability to infections and cancer
Four Effects of Aging:
Thymic hormone production is greatly reduced
T cells become less responsive to antigens
Fewer T cells reduces responsiveness of B cells
Immune surveillance against tumor cells declines