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Immunology 090341

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IMMUNE SYSTEM

AND ITS RESPONSES

DR. ENJOY
OBJECTIVES
At the end of this presentation you should be able to
1. Describe immune response (adaptive and innate immunity
2. Describe of immune functions
- Cell mediated immunity
-
Humoral mediated immunity
3. Explain types of immunoglobulins (Ig)- A,D,E,G,M
4. Explain types of hypersensitivity
5. Explain autoimmune diseases
6. Explain immune deficiency diseases
INTRODUCTION.
• Immunity refers to protection against infections
• Deficiencies in immune defenses result in an increased
susceptibility to infections, which can be life-threatening if the
deficits are not corrected.
• On the other hand, the immune system is itself capable of
causing great harm and is the root cause of some of the most
worrisome and intractable diseases of the modern world.
• Thus, diseases of immunity range from those caused by too little
to those caused by too much or inappropriate immune activity.
TYPES OF IMMUNE SYESTEM

Defense against microbes consists of two types of reactions


1. Innate/Non specific immunity
2. Adaptive/specific immunity

Immune System

Innate Adaptive
(Nonspecific) (Specific)
1o line of defense 2o line of defense
THE INNATE/NON SPECIFIC IMMUNITY

 Innate immunity (also called natural, or native, immunity)


 It is the 1st line of body defense
 Many pathogenic microbes have evolved to overcome innate immune
defenses, and protection against these infections requires the more
powerful mechanisms of adaptive immunity (also called acquired, or
specific, immunity).
 Is mediated by mechanisms that are always present and poised to fight
against microbes which involves;
 Anatomic
 Physiologic
 Phagocytic
COMPONENTS OF INNATE BARRIERS TO INFECTIONS…

1) Anatomic
Intestinal epithel.
skin -> epidermis
mucus membranes. ->inner surfaces
2) Physiological
temperature, acids, enzymes.
3) Phagocytes
blood monocytes, and neutrophils
4) Inflammatory response
triggered by wound/foreign particle
5 Cardinal signs reflect 3 major events of inflam response:
-vasodilation
- >capillary permeability
-influx of phagocytes
COMPONENTS OF INNATE IMMUNITY;

1. Epithelial Barriers Of The Skin


2. Epithelia and acid secretion by Gastrointestinal Tract
3. Epithelium and cilia of Respiratory Tract
4. Phagocytic Leukocytes (Neutrophils And Macrophages)
5. Specialized Cell Type Called The Natural Killer (NK) Cell,
6. Plasma Proteins, Which Are The Proteins Of The Complement
System.
ADAPTIVE IMMUNITY
• It is the second line defense.
• It is normally silent and responds (or ‘adapts’) to the presence of
infectious microbes by becoming active, expanding, and generating
potent mechanisms for neutralizing and eliminating the microbes.
• Unlike the innate immune system, the adaptive immune system
relies on fewer types of cells to carry out its tasks: B cells and T cells
• By convention, the terms ‘immune system’ and ‘immune response’
refer to adaptive immunity
Adaptive Immunity
Displays four (4) Characteristics:
1) antibody specificity – distinguishes minute differences in
molecular structure to determine non-self antigens.
2) diversity – the immune system can produce a hugely diverse set of
recognition molecules which allows us to recognize literally billions of
molecular shapes
3) memory – once it has responded to an antigen, the system
maintains a memory of that Ag
4) self-nonself recognition –the system typically responds only to
foreign molecules
*adaptive IR is not independent of innate IR – they’re connected
TYPES OF ADAPTIVE IMMUNE RESPONSES:

i. Humoral immunity
mediated by soluble antibody proteins that are produced by B-
lymphocytes (also called B cells). Antibodies provide protection
against extracellular microbes in the blood, mucosal secretions,
and tissues.

ii. Cell-mediated (or cellular) immunity


mediated by T lymphocytes (also called T cells).
THE ADAPTIVE - HUMORAL IMMUNITY

• The humoral immune system deals with antigens


from pathogens that are freely circulating, or outside
the infected cells.
• “humor” is a medieval term for body fluid
..

• Antibodies produced by the B cells will bind to


antigens, neutralizing them, or causing lysis or
phagocytosis
• B cells express antibodies on their cell surface,
which can also be called membrane-bound
antibodies.
THE ADAPTIVE - CELL MEDIATED IMMUNITY

• Cellular immunity occurs inside infected cells and is mediated by T


lymphocytes.
• The pathogen's antigens are expressed on the cell surface or on an antigen-
presenting cell
• Unlike antibodies, which can bind to antigens directly, T cell receptors can only
recognize antigens that are bound to certain receptor molecules, called Major
Histocompatibility Complex -MHC
• These MHC molecules are membrane-bound surface receptors on antigen-
presenting cells, like dendritic cells and macrophages.
• CD4 and CD8 play a role in T cell recognition and activation by binding to MHC.
.

• Mature T cells should recognize


only foreign antigens combined
with self-MHC molecules in order
to mount an appropriate immune
response.
ASSIGNMENT
Write an essay to Describe the DIFERRENCES of immune
functions
Cell mediated immunity AND humoral mediated
immunity
Innate immunity vs Adaptive Immunity

Innate Immunity Adaptive Immunity


(first line of defense) (second line of defense)

• No time lag • A lag period

• Not antigen specific • Antigen specific

No memory • Development
of memory
THE IMMUNOGLOBINS

.
IMMUNOGLOBINS/ANTIBODIES
 immunoglobulin (Ig), is a Y-shaped protein used by the immune system to
identify and neutralize foreign objects such as pathogenic bacteria and
viruses.
 The antibody recognizes a unique molecule of the pathogen, called an
antigen.
 Each tip of the "Y" of an antibody contains a paratope (analogous to a lock)
that is specific for one particular epitope (analogous to a key) on an antigen,
 This lock and key allow these two structures to bind together.
 Immunoglobins occur in two forms:
i. attached to a B cell or
ii. soluble form in extracellular fluids such as blood plasma
TYPES OF IMMUNOGLOBINS
,
THE HYPERSENSITIVITY REACTIONS.

.
Hypersensitivity reactions overview
 Is An exaggerated immune response that results in tissue injury
 This term originated from the idea that individuals who mount
immune responses against an antigen are said to be ‘sensitized’ to
that antigen,
 Body system of checks and balances optimizes the eradication of
infecting organisms without serious injury to host tissues.
 Immune responses may be inadequately controlled or inappropriately
targeted to host tissues, and in these situations, the normally
beneficial response is the cause of disease.
Causes of Hypersensitivity Diseases

1. Autoimmunity causing autoimmune diseases


2. Reactions against microbes e. g. post-streptococcal
glomerulonephritis
3. Cross-reaction of antibodies and/or T cells reactive with a microbe
with a host tissue(s) e.g. rheumatic heart disease (RHD)
4. Injured host tissues during the process of eradicating infection e. g.
viral hepatitis
5. Reactions against environmental antigens e. g. allergic reactions
TYPES OF HYPERSENTIVITY REACTIONS
Classified According to Gell and Comb’s classification
Traditionally subdivided into four types;
Types – I II, and III reactions are dependent on the interaction of
specific antibodies with the given antigen, whereas, in type IV
reactions recognition is achieved by antigen receptors on T-cells.
The types are numbered into
TYPE-I (Immediate type)
TYPE II, (Antibody mediated type)
TYPE III, (Immune complex type)
TYPE IV. (Delayed type type)
Type I
 Immediate (Type I) Hypersensitivity
 This results from the activation of the CD4+ helper T 2 cells by
environmental antigens, leading to the production of IgE antibodies,
which become attached to mast cells.
 When these Ig-E molecules bind the antigen (allergen), the mast
cells are triggered to release mediators of inflammation like
histamines, leukotrienes
 These diseases are commonly called allergies.
 The common forms of skin and food allergies, hay fever, and
asthma are examples of localized allergic reactions.
TYPE I

.
TYPE II

Antibody-Mediated (Type II) Hypersensitivity


These disorders are caused by antibodies that bind to fixed tissue or cell surface antigens and promote
phagocytosis and destruction of the coated cells or trigger pathologic inflammation in tissues.
The destruction of host cells in this way can lead to tissue-specific damage.
Type 2 hypersensitivity reactions may occur in response to host cells (i.e. autoimmune) or to non-self cells,
as occurs in blood transfusion reactions.
Antibody-mediated abnormalities are the underlying cause of many human diseases, examples of these are
1. Autoimmune haemolytic anaemia
2. Autoimmune thrombocytopenic purpura
3. Graves disease (hyperthyroidism)
4. Insulin-resistant diabetes mellitus
5. Goodpasture syndrome
.
.
TYPE III

 Type 3 is distinguished from type 2 by the location of the antigens


 In type 2, the antigens are cell bound, whereas in type 3 the antigens are soluble.
 The disorders are caused by antibodies binding to antigens to form complexes
that circulate and may deposit in vascular beds and stimulate inflammation.
 Immune complex diseases are some of the most common immunologic diseases
such as
1. Acute post-streptococcal glomerulonephritis
2. Serum Sickness
3. Polyarteritis nodosa (PAN)
4. Reactive arthritis
5. Systemic lupus erythematosus (SLE)
TYPE IV
• T-Cell-Mediated (Type IV) Hypersensitivity
• The disorders are cell-mediated immune responses in which T
lymphocytes cause tissue injury, either by producing cytokines
that induce inflammation and activate macrophages,or by
directly killing host cells.
• This reaction is also known as delayed-type hypersensitivity
due to its characteristic longer time period to appear following
antigen exposure.
.
THE AUTOIMMUNE DISEASES

 Autoimmune diseases are disorders in which the body's immune


system reacts against its own tissue and produces antibodies to
attack itself.
 These are diseases due to immune reaction to self-antigens
 Autoimmunity is a state in which the body’s immune system fails
to distinguish between self and non self by formation of auto
antibodies against one’s own tissues.
CAUSE/MECHANISMS OF AUTOIMMUNE DISEASE

1. Genetic factors in autoimmunity


• o Autoimmune diseases have a tendency to run in families, and there is a greater incidence
of the same disease in monozygotic than in dizygotic twins.

2. Infections and tissue injury


 A variety of microbes, including bacteria, mycoplasmas, and viruses, have been implicated as
triggers for autoimmunity.
 Microbes may induce autoimmune reactions by several mechanisms.
 Viruses and other microbes, particularly certain bacteria such as streptococci and Klebsiella
organisms, may share cross-reacting with self-antigens, such that responses to the microbial
antigen may attack self-tissues.
TYPES OF AUTOIMMUNE DISEASES
• Broadly classified into two groups depending on the type of auto antibody
formation
1.Organ specific diseases
2. Non organ specific diseases

Organ Specific Diseases Non Organ Specific Diseases


Examples;
1.Endocrine • • A number of auto antibodies are
Insulin dependent diabetes formed which reacts with antigens
mellitus
(Ags) in many tissues thus
causing systemic lesions
2.Alimentary tract • Example
pernicious anaemia
1. Systemic lupus erythematosus
3. Heart
2. Rheumatoid arthritis
Rheumatic heart disease
IMMUNE DEFICIENCY DISEASES
• The term immunodeficiency covers a group of disorders of
specific immune responses, neutrophil, macrophage and natural
killer cells functions, as well as defects in the compliment system
that lead to impaired resistance to microbial infections.
• Classification – These diseases are crudely classified according to
the causes into two types
1. primary immunodeficiency diseases and
2. secondary immunodeficiency disease types.
PRIMARY IMMUNODEFICIENCY DISEASES

 These disorders usually manifest in early childhood and are almost always
genetically determined.
 They affect either adaptive immunity (i.e. humoral or cellular)
or innate host defence mechanisms, including complement
proteins and cells such as phagocytes and NK cells
 Though, some overlap exists primary immunodeficiency diseases are
manifested by
1. Deficiencies of antibody (B – cells) immunity.
2. Deficiencies of cell mediated (T-cell) Immunity :
3. Combined T-cell and B-cell deficiencies
SECONDARY IMMUNODEFICIENCIES

These immunodeficiency states may be acquired secondary to


various disease processes or drug effects
The acquired immunodeficiency syndrome (AIDS), the most
devastating example of
secondary immune deficiency.
ETIOLOGY OF SECONDRY IMMUNODEFICIENCY DISEASES

1. Infections eg. TB.


2. Cancer
3. Malnutrition
4. Aging
5. Immunosuppression process. Eg. During organ transplant
6. Autoimmunity
7. Chemotherapy
8. Steroids drugs. Eg Prednisolone, Hydrocortisone
Sample questions;
5. The ability of the immune system to recognize self antigens versus
nonself antigen is an example of:
1. Naturally acquired active immunity would be most likely acquired a. Specific immunity
through which of the following processes? b. Tolerance
A. Vaccination c. Cell mediated immunity
B. Breast milk d. Antigenic immunity
C. natural birth e. Humoral immunity
D. Infections
6. Which of the following Antibodies cross the placenta?
E. immunisation A: IgA.
2. B and T cells are produced by stem cells that are formed in: B: IgE.
a. Bone marrow C: IgG.
b. The liver
D: IgD.
c. The circulatory system
d. The spleen E. Ig M
e. The lymph nodes
3. Which of the following immune cells/molecules are most effective at destroying 7.Which of thr following hypersensitivity type is NOT associated with antibodies
intracellular pathogens? A. Type I
a. T helper cells B. Type II
b. B cells
c. Antibodies
C. Type III
d. Complement D. Type IV
e. T cytolytic cells E. Type V
4. Cell mediated immunity is carried out by………….. while humoral immunity is
mainly carried out by……………….. 8. Hypersensitivity reactions are broadly classified into four different types. Which of the
a. B cells/T cells following hypersensitivity occurs via IgE antibody?
b. Epitopes/Antigens
c. T cells/B cells a) Type I hypersensitivity
d. Antibodies/Antigens b) Type II hypersensitivity
e. Antibodies/Phagocytes c) Type III hypersensitivity
d) Type IV hypersensitivity
9. The T helper 1 cells release cytokines to activate macrophage or T
cells and cause direct cellular damage. Which of the following
hypersensitivity reactions are mediated by sensitized T helper-1 cells?
a) Type I hypersensitivity
b) Type II hypersensitivity 13During a blood transfusion, ABO incompatibilities lead to the recognition
c) Type III hypersensitivity of A or B antigens present on the RBC resulting in complement-mediated
d) Type IV hypersensitivity cell lysis. Which of the following antibody isotype is primarily involved in
10. Which of the following hypersensitivity reactions is a result of this type II hypersensitivity reaction?
massive deposition of immune complex in various tissues? These a) IgG
immune complex induce complement activation and inflammation b) IgM
response c) IgE
a) Type I hypersensitivity d) IgA
b) Type II hypersensitivity
c) Type III hypersensitivity 14. Which of the following the disease is not the example of type III
hypersensitivity reaction?
d) Type IV hypersensitivity
a) Systemic Lupus Erythematosus
11. A hereditary predisposition of the development of immediate hypersensitivity b) Rheumatoid Arthritis
reaction against common environmental antigens are called
a) Atrophy c) Good Pasture’s syndrome
b) Atopy d) Down Syndrome
c) Anergy
d) Synergy 15. Which of the following statement is not true regarding the sensitization
12. The type I early response occur within minutes of allergic response. Which of the phase of delayed-type hypersensitivity (DTH)?
following is the early mediator of type I hypersensitivity reaction?
a) The sensitization phase begins 1-2 weeks after the primary contact with
a) Histamine
b) Leukotrienes antigens
c) Prostaglandins b) T cell undergo activation and clonal expansion after interacting with
d) Nitric oxide antigen-MHC complex
c) CD8+ T Helper-1 cells are primarily activated after exposure to antigen
d) CD4+ T Helper-1 cells are primarily activated after exposure to antigen
.
.

THE END
REFERENCES
1. Cotran RS, Kumar V, Collins T. Robins pathologic basis of
diseases. Philadelphia, J.B. Saunders Company. 6th edition 1999
2. Mac Sween RNM, Whaley K. Muir’s Textbook of pathology.
London, Edward Arlond 13th edition 1992
3. Rubin E, Farber JC. Pathology Philadelphia, J.B. Lippincott
Company 6th edition 1994
4. Dey NC, Dey TK. A Textbook of Pathology Calcatta, Messers
Allied agency 10th edition 1994.

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